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What is a Literature Review? How to Write It (with Examples)

A literature review is a critical analysis and synthesis of existing research on a particular topic. It provides an overview of the current state of knowledge, identifies gaps, and highlights key findings in the literature. 1 The purpose of a literature review is to situate your own research within the context of existing scholarship, demonstrating your understanding of the topic and showing how your work contributes to the ongoing conversation in the field. Learning how to write a literature review is a critical tool for successful research. Your ability to summarize and synthesize prior research pertaining to a certain topic demonstrates your grasp on the topic of study, and assists in the learning process. 

Table of Contents

• What is the purpose of literature review? 
• a. Habitat Loss and Species Extinction: 
• b. Range Shifts and Phenological Changes: 
• c. Ocean Acidification and Coral Reefs: 
• d. Adaptive Strategies and Conservation Efforts: 

How to write a good literature review 

• Choose a Topic and Define the Research Question: 
• Decide on the Scope of Your Review: 
• Select Databases for Searches: 
• Conduct Searches and Keep Track: 
• Review the Literature: 
• Organize and Write Your Literature Review: 
• How to write a literature review faster with Paperpal? 
• Frequently asked questions 

What is a literature review?

A well-conducted literature review demonstrates the researcher’s familiarity with the existing literature, establishes the context for their own research, and contributes to scholarly conversations on the topic. One of the purposes of a literature review is also to help researchers avoid duplicating previous work and ensure that their research is informed by and builds upon the existing body of knowledge.

What is the purpose of literature review?

A literature review serves several important purposes within academic and research contexts. Here are some key objectives and functions of a literature review: 2  

1. Contextualizing the Research Problem: The literature review provides a background and context for the research problem under investigation. It helps to situate the study within the existing body of knowledge. 

2. Identifying Gaps in Knowledge: By identifying gaps, contradictions, or areas requiring further research, the researcher can shape the research question and justify the significance of the study. This is crucial for ensuring that the new research contributes something novel to the field. 

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3. Understanding Theoretical and Conceptual Frameworks: Literature reviews help researchers gain an understanding of the theoretical and conceptual frameworks used in previous studies. This aids in the development of a theoretical framework for the current research. 

4. Providing Methodological Insights: Another purpose of literature reviews is that it allows researchers to learn about the methodologies employed in previous studies. This can help in choosing appropriate research methods for the current study and avoiding pitfalls that others may have encountered. 

5. Establishing Credibility: A well-conducted literature review demonstrates the researcher’s familiarity with existing scholarship, establishing their credibility and expertise in the field. It also helps in building a solid foundation for the new research. 

6. Informing Hypotheses or Research Questions: The literature review guides the formulation of hypotheses or research questions by highlighting relevant findings and areas of uncertainty in existing literature. 

Literature review example

Let’s delve deeper with a literature review example: Let’s say your literature review is about the impact of climate change on biodiversity. You might format your literature review into sections such as the effects of climate change on habitat loss and species extinction, phenological changes, and marine biodiversity. Each section would then summarize and analyze relevant studies in those areas, highlighting key findings and identifying gaps in the research. The review would conclude by emphasizing the need for further research on specific aspects of the relationship between climate change and biodiversity. The following literature review template provides a glimpse into the recommended literature review structure and content, demonstrating how research findings are organized around specific themes within a broader topic. 

Literature Review on Climate Change Impacts on Biodiversity:

Climate change is a global phenomenon with far-reaching consequences, including significant impacts on biodiversity. This literature review synthesizes key findings from various studies: 

a. Habitat Loss and Species Extinction:

Climate change-induced alterations in temperature and precipitation patterns contribute to habitat loss, affecting numerous species (Thomas et al., 2004). The review discusses how these changes increase the risk of extinction, particularly for species with specific habitat requirements. 

b. Range Shifts and Phenological Changes:

Observations of range shifts and changes in the timing of biological events (phenology) are documented in response to changing climatic conditions (Parmesan & Yohe, 2003). These shifts affect ecosystems and may lead to mismatches between species and their resources. 

c. Ocean Acidification and Coral Reefs:

The review explores the impact of climate change on marine biodiversity, emphasizing ocean acidification’s threat to coral reefs (Hoegh-Guldberg et al., 2007). Changes in pH levels negatively affect coral calcification, disrupting the delicate balance of marine ecosystems. 

d. Adaptive Strategies and Conservation Efforts:

Recognizing the urgency of the situation, the literature review discusses various adaptive strategies adopted by species and conservation efforts aimed at mitigating the impacts of climate change on biodiversity (Hannah et al., 2007). It emphasizes the importance of interdisciplinary approaches for effective conservation planning. 

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Writing a literature review involves summarizing and synthesizing existing research on a particular topic. A good literature review format should include the following elements. 

Introduction: The introduction sets the stage for your literature review, providing context and introducing the main focus of your review. 

• Opening Statement: Begin with a general statement about the broader topic and its significance in the field. 
• Scope and Purpose: Clearly define the scope of your literature review. Explain the specific research question or objective you aim to address. 
• Organizational Framework: Briefly outline the structure of your literature review, indicating how you will categorize and discuss the existing research. 
• Significance of the Study: Highlight why your literature review is important and how it contributes to the understanding of the chosen topic. 
• Thesis Statement: Conclude the introduction with a concise thesis statement that outlines the main argument or perspective you will develop in the body of the literature review. 

Body: The body of the literature review is where you provide a comprehensive analysis of existing literature, grouping studies based on themes, methodologies, or other relevant criteria. 

• Organize by Theme or Concept: Group studies that share common themes, concepts, or methodologies. Discuss each theme or concept in detail, summarizing key findings and identifying gaps or areas of disagreement. 
• Critical Analysis: Evaluate the strengths and weaknesses of each study. Discuss the methodologies used, the quality of evidence, and the overall contribution of each work to the understanding of the topic. 
• Synthesis of Findings: Synthesize the information from different studies to highlight trends, patterns, or areas of consensus in the literature. 
• Identification of Gaps: Discuss any gaps or limitations in the existing research and explain how your review contributes to filling these gaps. 
• Transition between Sections: Provide smooth transitions between different themes or concepts to maintain the flow of your literature review. 

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Conclusion: The conclusion of your literature review should summarize the main findings, highlight the contributions of the review, and suggest avenues for future research. 

• Summary of Key Findings: Recap the main findings from the literature and restate how they contribute to your research question or objective. 
• Contributions to the Field: Discuss the overall contribution of your literature review to the existing knowledge in the field. 
• Implications and Applications: Explore the practical implications of the findings and suggest how they might impact future research or practice. 
• Recommendations for Future Research: Identify areas that require further investigation and propose potential directions for future research in the field. 
• Final Thoughts: Conclude with a final reflection on the importance of your literature review and its relevance to the broader academic community. 

Conducting a literature review

Conducting a literature review is an essential step in research that involves reviewing and analyzing existing literature on a specific topic. It’s important to know how to do a literature review effectively, so here are the steps to follow: 1  

Choose a Topic and Define the Research Question:

• Select a topic that is relevant to your field of study. 
• Clearly define your research question or objective. Determine what specific aspect of the topic do you want to explore? 

Decide on the Scope of Your Review:

• Determine the timeframe for your literature review. Are you focusing on recent developments, or do you want a historical overview? 
• Consider the geographical scope. Is your review global, or are you focusing on a specific region? 
• Define the inclusion and exclusion criteria. What types of sources will you include? Are there specific types of studies or publications you will exclude? 

Select Databases for Searches:

• Identify relevant databases for your field. Examples include PubMed, IEEE Xplore, Scopus, Web of Science, and Google Scholar. 
• Consider searching in library catalogs, institutional repositories, and specialized databases related to your topic. 

Conduct Searches and Keep Track:

• Develop a systematic search strategy using keywords, Boolean operators (AND, OR, NOT), and other search techniques. 
• Record and document your search strategy for transparency and replicability. 
• Keep track of the articles, including publication details, abstracts, and links. Use citation management tools like EndNote, Zotero, or Mendeley to organize your references. 

Review the Literature:

• Evaluate the relevance and quality of each source. Consider the methodology, sample size, and results of studies. 
• Organize the literature by themes or key concepts. Identify patterns, trends, and gaps in the existing research. 
• Summarize key findings and arguments from each source. Compare and contrast different perspectives. 
• Identify areas where there is a consensus in the literature and where there are conflicting opinions. 
• Provide critical analysis and synthesis of the literature. What are the strengths and weaknesses of existing research? 

Organize and Write Your Literature Review:

• Literature review outline should be based on themes, chronological order, or methodological approaches. 
• Write a clear and coherent narrative that synthesizes the information gathered. 
• Use proper citations for each source and ensure consistency in your citation style (APA, MLA, Chicago, etc.). 
• Conclude your literature review by summarizing key findings, identifying gaps, and suggesting areas for future research. 

Whether you’re exploring a new research field or finding new angles to develop an existing topic, sifting through hundreds of papers can take more time than you have to spare. But what if you could find science-backed insights with verified citations in seconds? That’s the power of Paperpal’s new Research feature!  

How to write a literature review faster with Paperpal?

Paperpal, an AI writing assistant, integrates powerful academic search capabilities within its writing platform. With the Research feature, you get 100% factual insights, with citations backed by 250M+ verified research articles, directly within your writing interface with the option to save relevant references in your Citation Library. By eliminating the need to switch tabs to find answers to all your research questions, Paperpal saves time and helps you stay focused on your writing.   

Here’s how to use the Research feature:  

• Ask a question: Get started with a new document on paperpal.com. Click on the “Research” feature and type your question in plain English. Paperpal will scour over 250 million research articles, including conference papers and preprints, to provide you with accurate insights and citations. 
• Review and Save: Paperpal summarizes the information, while citing sources and listing relevant reads. You can quickly scan the results to identify relevant references and save these directly to your built-in citations library for later access. 
• Cite with Confidence: Paperpal makes it easy to incorporate relevant citations and references into your writing, ensuring your arguments are well-supported by credible sources. This translates to a polished, well-researched literature review. 

The literature review sample and detailed advice on writing and conducting a review will help you produce a well-structured report. But remember that a good literature review is an ongoing process, and it may be necessary to revisit and update it as your research progresses. By combining effortless research with an easy citation process, Paperpal Research streamlines the literature review process and empowers you to write faster and with more confidence. Try Paperpal Research now and see for yourself.  

Frequently asked questions

A literature review is a critical and comprehensive analysis of existing literature (published and unpublished works) on a specific topic or research question and provides a synthesis of the current state of knowledge in a particular field. A well-conducted literature review is crucial for researchers to build upon existing knowledge, avoid duplication of efforts, and contribute to the advancement of their field. It also helps researchers situate their work within a broader context and facilitates the development of a sound theoretical and conceptual framework for their studies.

Literature review is a crucial component of research writing, providing a solid background for a research paper’s investigation. The aim is to keep professionals up to date by providing an understanding of ongoing developments within a specific field, including research methods, and experimental techniques used in that field, and present that knowledge in the form of a written report. Also, the depth and breadth of the literature review emphasizes the credibility of the scholar in his or her field.  

Before writing a literature review, it’s essential to undertake several preparatory steps to ensure that your review is well-researched, organized, and focused. This includes choosing a topic of general interest to you and doing exploratory research on that topic, writing an annotated bibliography, and noting major points, especially those that relate to the position you have taken on the topic. 

Literature reviews and academic research papers are essential components of scholarly work but serve different purposes within the academic realm. 3 A literature review aims to provide a foundation for understanding the current state of research on a particular topic, identify gaps or controversies, and lay the groundwork for future research. Therefore, it draws heavily from existing academic sources, including books, journal articles, and other scholarly publications. In contrast, an academic research paper aims to present new knowledge, contribute to the academic discourse, and advance the understanding of a specific research question. Therefore, it involves a mix of existing literature (in the introduction and literature review sections) and original data or findings obtained through research methods. 

Literature reviews are essential components of academic and research papers, and various strategies can be employed to conduct them effectively. If you want to know how to write a literature review for a research paper, here are four common approaches that are often used by researchers.  Chronological Review: This strategy involves organizing the literature based on the chronological order of publication. It helps to trace the development of a topic over time, showing how ideas, theories, and research have evolved.  Thematic Review: Thematic reviews focus on identifying and analyzing themes or topics that cut across different studies. Instead of organizing the literature chronologically, it is grouped by key themes or concepts, allowing for a comprehensive exploration of various aspects of the topic.  Methodological Review: This strategy involves organizing the literature based on the research methods employed in different studies. It helps to highlight the strengths and weaknesses of various methodologies and allows the reader to evaluate the reliability and validity of the research findings.  Theoretical Review: A theoretical review examines the literature based on the theoretical frameworks used in different studies. This approach helps to identify the key theories that have been applied to the topic and assess their contributions to the understanding of the subject.  It’s important to note that these strategies are not mutually exclusive, and a literature review may combine elements of more than one approach. The choice of strategy depends on the research question, the nature of the literature available, and the goals of the review. Additionally, other strategies, such as integrative reviews or systematic reviews, may be employed depending on the specific requirements of the research.

The literature review format can vary depending on the specific publication guidelines. However, there are some common elements and structures that are often followed. Here is a general guideline for the format of a literature review:  Introduction:   Provide an overview of the topic.  Define the scope and purpose of the literature review.  State the research question or objective.  Body:   Organize the literature by themes, concepts, or chronology.  Critically analyze and evaluate each source.  Discuss the strengths and weaknesses of the studies.  Highlight any methodological limitations or biases.  Identify patterns, connections, or contradictions in the existing research.  Conclusion:   Summarize the key points discussed in the literature review.  Highlight the research gap.  Address the research question or objective stated in the introduction.  Highlight the contributions of the review and suggest directions for future research.

Both annotated bibliographies and literature reviews involve the examination of scholarly sources. While annotated bibliographies focus on individual sources with brief annotations, literature reviews provide a more in-depth, integrated, and comprehensive analysis of existing literature on a specific topic. The key differences are as follows: 

References 

• Denney, A. S., & Tewksbury, R. (2013). How to write a literature review.  Journal of criminal justice education ,  24 (2), 218-234. 
• Pan, M. L. (2016).  Preparing literature reviews: Qualitative and quantitative approaches . Taylor & Francis. 
• Cantero, C. (2019). How to write a literature review.  San José State University Writing Center . 

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Writing a Literature Review

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A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

• An introductory paragraph that explains what your working topic and thesis is
• A forecast of key topics or texts that will appear in the review
• Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
• Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
• Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
• Critically Evaluate: Mention the strengths and weaknesses of your sources
• Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

• Summarize the key findings you have taken from the literature and emphasize their significance
• Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

• Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
• Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
• Qualitative versus quantitative research
• Empirical versus theoretical scholarship
• Divide the research by sociological, historical, or cultural sources
• Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

• It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
• Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
• Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
• Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

How to Write a Literature Review

What is a literature review.

• What Is the Literature
• Writing the Review

A literature review is much more than an annotated bibliography or a list of separate reviews of articles and books. It is a critical, analytical summary and synthesis of the current knowledge of a topic. Thus it should compare and relate different theories, findings, etc, rather than just summarize them individually. In addition, it should have a particular focus or theme to organize the review. It does not have to be an exhaustive account of everything published on the topic, but it should discuss all the significant academic literature and other relevant sources important for that focus.

This is meant to be a general guide to writing a literature review: ways to structure one, what to include, how it supplements other research. For more specific help on writing a review, and especially for help on finding the literature to review, sign up for a Personal Research Session .

The specific organization of a literature review depends on the type and purpose of the review, as well as on the specific field or topic being reviewed. But in general, it is a relatively brief but thorough exploration of past and current work on a topic. Rather than a chronological listing of previous work, though, literature reviews are usually organized thematically, such as different theoretical approaches, methodologies, or specific issues or concepts involved in the topic. A thematic organization makes it much easier to examine contrasting perspectives, theoretical approaches, methodologies, findings, etc, and to analyze the strengths and weaknesses of, and point out any gaps in, previous research. And this is the heart of what a literature review is about. A literature review may offer new interpretations, theoretical approaches, or other ideas; if it is part of a research proposal or report it should demonstrate the relationship of the proposed or reported research to others' work; but whatever else it does, it must provide a critical overview of the current state of research efforts. 

Literature reviews are common and very important in the sciences and social sciences. They are less common and have a less important role in the humanities, but they do have a place, especially stand-alone reviews.

Types of Literature Reviews

There are different types of literature reviews, and different purposes for writing a review, but the most common are:

• Stand-alone literature review articles . These provide an overview and analysis of the current state of research on a topic or question. The goal is to evaluate and compare previous research on a topic to provide an analysis of what is currently known, and also to reveal controversies, weaknesses, and gaps in current work, thus pointing to directions for future research. You can find examples published in any number of academic journals, but there is a series of Annual Reviews of *Subject* which are specifically devoted to literature review articles. Writing a stand-alone review is often an effective way to get a good handle on a topic and to develop ideas for your own research program. For example, contrasting theoretical approaches or conflicting interpretations of findings can be the basis of your research project: can you find evidence supporting one interpretation against another, or can you propose an alternative interpretation that overcomes their limitations?
• Part of a research proposal . This could be a proposal for a PhD dissertation, a senior thesis, or a class project. It could also be a submission for a grant. The literature review, by pointing out the current issues and questions concerning a topic, is a crucial part of demonstrating how your proposed research will contribute to the field, and thus of convincing your thesis committee to allow you to pursue the topic of your interest or a funding agency to pay for your research efforts.
• Part of a research report . When you finish your research and write your thesis or paper to present your findings, it should include a literature review to provide the context to which your work is a contribution. Your report, in addition to detailing the methods, results, etc. of your research, should show how your work relates to others' work.

A literature review for a research report is often a revision of the review for a research proposal, which can be a revision of a stand-alone review. Each revision should be a fairly extensive revision. With the increased knowledge of and experience in the topic as you proceed, your understanding of the topic will increase. Thus, you will be in a better position to analyze and critique the literature. In addition, your focus will change as you proceed in your research. Some areas of the literature you initially reviewed will be marginal or irrelevant for your eventual research, and you will need to explore other areas more thoroughly. 

Examples of Literature Reviews

See the series of Annual Reviews of *Subject* which are specifically devoted to literature review articles to find many examples of stand-alone literature reviews in the biomedical, physical, and social sciences. 

Research report articles vary in how they are organized, but a common general structure is to have sections such as:

• Abstract - Brief summary of the contents of the article
• Introduction - A explanation of the purpose of the study, a statement of the research question(s) the study intends to address
• Literature review - A critical assessment of the work done so far on this topic, to show how the current study relates to what has already been done
• Methods - How the study was carried out (e.g. instruments or equipment, procedures, methods to gather and analyze data)
• Results - What was found in the course of the study
• Discussion - What do the results mean
• Conclusion - State the conclusions and implications of the results, and discuss how it relates to the work reviewed in the literature review; also, point to directions for further work in the area

Here are some articles that illustrate variations on this theme. There is no need to read the entire articles (unless the contents interest you); just quickly browse through to see the sections, and see how each section is introduced and what is contained in them.

The Determinants of Undergraduate Grade Point Average: The Relative Importance of Family Background, High School Resources, and Peer Group Effects , in The Journal of Human Resources , v. 34 no. 2 (Spring 1999), p. 268-293.

This article has a standard breakdown of sections:

• Introduction
• Literature Review
• Some discussion sections

First Encounters of the Bureaucratic Kind: Early Freshman Experiences with a Campus Bureaucracy , in The Journal of Higher Education , v. 67 no. 6 (Nov-Dec 1996), p. 660-691.

This one does not have a section specifically labeled as a "literature review" or "review of the literature," but the first few sections cite a long list of other sources discussing previous research in the area before the authors present their own study they are reporting.

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• Last Updated: Jan 11, 2024 9:48 AM
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• 04 December 2020
• Correction 09 December 2020

How to write a superb literature review

Andy Tay is a freelance writer based in Singapore.

You can also search for this author in PubMed   Google Scholar

Literature reviews are important resources for scientists. They provide historical context for a field while offering opinions on its future trajectory. Creating them can provide inspiration for one’s own research, as well as some practice in writing. But few scientists are trained in how to write a review — or in what constitutes an excellent one. Even picking the appropriate software to use can be an involved decision (see ‘Tools and techniques’). So Nature asked editors and working scientists with well-cited reviews for their tips.

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doi: https://doi.org/10.1038/d41586-020-03422-x

Interviews have been edited for length and clarity.

Updates & Corrections

Correction 09 December 2020 : An earlier version of the tables in this article included some incorrect details about the programs Zotero, Endnote and Manubot. These have now been corrected.

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Ledesma, H. A. et al. Nature Nanotechnol. 14 , 645–657 (2019).

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Choi, Y. & Lee, S. Y. Nature Rev. Chem . https://doi.org/10.1038/s41570-020-00221-w (2020).

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• What is a Literature Review? | Guide, Template, & Examples

What is a Literature Review? | Guide, Template, & Examples

Published on 22 February 2022 by Shona McCombes . Revised on 7 June 2022.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research.

There are five key steps to writing a literature review:

• Search for relevant literature
• Evaluate sources
• Identify themes, debates and gaps
• Outline the structure
• Write your literature review

A good literature review doesn’t just summarise sources – it analyses, synthesises, and critically evaluates to give a clear picture of the state of knowledge on the subject.

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Table of contents

Why write a literature review, examples of literature reviews, step 1: search for relevant literature, step 2: evaluate and select sources, step 3: identify themes, debates and gaps, step 4: outline your literature review’s structure, step 5: write your literature review, frequently asked questions about literature reviews, introduction.

• Quick Run-through
• Step 1 & 2

When you write a dissertation or thesis, you will have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

• Demonstrate your familiarity with the topic and scholarly context
• Develop a theoretical framework and methodology for your research
• Position yourself in relation to other researchers and theorists
• Show how your dissertation addresses a gap or contributes to a debate

You might also have to write a literature review as a stand-alone assignment. In this case, the purpose is to evaluate the current state of research and demonstrate your knowledge of scholarly debates around a topic.

The content will look slightly different in each case, but the process of conducting a literature review follows the same steps. We’ve written a step-by-step guide that you can follow below.

Prevent plagiarism, run a free check.

Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

• Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
• Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
• Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
• Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research objectives and questions .

If you are writing a literature review as a stand-alone assignment, you will have to choose a focus and develop a central question to direct your search. Unlike a dissertation research question, this question has to be answerable without collecting original data. You should be able to answer it based only on a review of existing publications.

Make a list of keywords

Start by creating a list of keywords related to your research topic. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list if you discover new keywords in the process of your literature search.

• Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
• Body image, self-perception, self-esteem, mental health
• Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some databases to search for journals and articles include:

• Your university’s library catalogue
• Google Scholar
• Project Muse (humanities and social sciences)
• Medline (life sciences and biomedicine)
• EconLit (economics)
• Inspec (physics, engineering and computer science)

You can use boolean operators to help narrow down your search:

Read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

To identify the most important publications on your topic, take note of recurring citations. If the same authors, books or articles keep appearing in your reading, make sure to seek them out.

You probably won’t be able to read absolutely everything that has been written on the topic – you’ll have to evaluate which sources are most relevant to your questions.

For each publication, ask yourself:

• What question or problem is the author addressing?
• What are the key concepts and how are they defined?
• What are the key theories, models and methods? Does the research use established frameworks or take an innovative approach?
• What are the results and conclusions of the study?
• How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
• How does the publication contribute to your understanding of the topic? What are its key insights and arguments?
• What are the strengths and weaknesses of the research?

Make sure the sources you use are credible, and make sure you read any landmark studies and major theories in your field of research.

You can find out how many times an article has been cited on Google Scholar – a high citation count means the article has been influential in the field, and should certainly be included in your literature review.

The scope of your review will depend on your topic and discipline: in the sciences you usually only review recent literature, but in the humanities you might take a long historical perspective (for example, to trace how a concept has changed in meaning over time).

Remember that you can use our template to summarise and evaluate sources you’re thinking about using!

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It’s important to keep track of your sources with references to avoid plagiarism . It can be helpful to make an annotated bibliography, where you compile full reference information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

You can use our free APA Reference Generator for quick, correct, consistent citations.

To begin organising your literature review’s argument and structure, you need to understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

• Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
• Themes: what questions or concepts recur across the literature?
• Debates, conflicts and contradictions: where do sources disagree?
• Pivotal publications: are there any influential theories or studies that changed the direction of the field?
• Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

• Most research has focused on young women.
• There is an increasing interest in the visual aspects of social media.
• But there is still a lack of robust research on highly-visual platforms like Instagram and Snapchat – this is a gap that you could address in your own research.

There are various approaches to organising the body of a literature review. You should have a rough idea of your strategy before you start writing.

Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarising sources in order.

Try to analyse patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organise your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

• Look at what results have emerged in qualitative versus quantitative research
• Discuss how the topic has been approached by empirical versus theoretical scholarship
• Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text, your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

If you are writing the literature review as part of your dissertation or thesis, reiterate your central problem or research question and give a brief summary of the scholarly context. You can emphasise the timeliness of the topic (“many recent studies have focused on the problem of x”) or highlight a gap in the literature (“while there has been much research on x, few researchers have taken y into consideration”).

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, make sure to follow these tips:

• Summarise and synthesise: give an overview of the main points of each source and combine them into a coherent whole.
• Analyse and interpret: don’t just paraphrase other researchers – add your own interpretations, discussing the significance of findings in relation to the literature as a whole.
• Critically evaluate: mention the strengths and weaknesses of your sources.
• Write in well-structured paragraphs: use transitions and topic sentences to draw connections, comparisons and contrasts.

In the conclusion, you should summarise the key findings you have taken from the literature and emphasise their significance.

If the literature review is part of your dissertation or thesis, reiterate how your research addresses gaps and contributes new knowledge, or discuss how you have drawn on existing theories and methods to build a framework for your research. This can lead directly into your methodology section.

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a dissertation , thesis, research paper , or proposal .

There are several reasons to conduct a literature review at the beginning of a research project:

• To familiarise yourself with the current state of knowledge on your topic
• To ensure that you’re not just repeating what others have already done
• To identify gaps in knowledge and unresolved problems that your research can address
• To develop your theoretical framework and methodology
• To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your  dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

Cite this Scribbr article

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• UConn Library
• Literature Review: The What, Why and How-to Guide
• Introduction

Literature Review: The What, Why and How-to Guide — Introduction

• Getting Started
• How to Pick a Topic
• Strategies to Find Sources
• Evaluating Sources & Lit. Reviews
• Tips for Writing Literature Reviews
• Writing Literature Review: Useful Sites
• Citation Resources
• Other Academic Writings

What are Literature Reviews?

So, what is a literature review? "A literature review is an account of what has been published on a topic by accredited scholars and researchers. In writing the literature review, your purpose is to convey to your reader what knowledge and ideas have been established on a topic, and what their strengths and weaknesses are. As a piece of writing, the literature review must be defined by a guiding concept (e.g., your research objective, the problem or issue you are discussing, or your argumentative thesis). It is not just a descriptive list of the material available, or a set of summaries." Taylor, D.  The literature review: A few tips on conducting it . University of Toronto Health Sciences Writing Centre.

Goals of Literature Reviews

What are the goals of creating a Literature Review?  A literature could be written to accomplish different aims:

• To develop a theory or evaluate an existing theory
• To summarize the historical or existing state of a research topic
• Identify a problem in a field of research 

Baumeister, R. F., & Leary, M. R. (1997). Writing narrative literature reviews .  Review of General Psychology , 1 (3), 311-320.

What kinds of sources require a Literature Review?

• A research paper assigned in a course
• A thesis or dissertation
• A grant proposal
• An article intended for publication in a journal

All these instances require you to collect what has been written about your research topic so that you can demonstrate how your own research sheds new light on the topic.

Types of Literature Reviews

What kinds of literature reviews are written?

Narrative review: The purpose of this type of review is to describe the current state of the research on a specific topic/research and to offer a critical analysis of the literature reviewed. Studies are grouped by research/theoretical categories, and themes and trends, strengths and weakness, and gaps are identified. The review ends with a conclusion section which summarizes the findings regarding the state of the research of the specific study, the gaps identify and if applicable, explains how the author's research will address gaps identify in the review and expand the knowledge on the topic reviewed.

• Example : Predictors and Outcomes of U.S. Quality Maternity Leave: A Review and Conceptual Framework:  10.1177/08948453211037398  

Systematic review : "The authors of a systematic review use a specific procedure to search the research literature, select the studies to include in their review, and critically evaluate the studies they find." (p. 139). Nelson, L. K. (2013). Research in Communication Sciences and Disorders . Plural Publishing.

• Example : The effect of leave policies on increasing fertility: a systematic review:  10.1057/s41599-022-01270-w

Meta-analysis : "Meta-analysis is a method of reviewing research findings in a quantitative fashion by transforming the data from individual studies into what is called an effect size and then pooling and analyzing this information. The basic goal in meta-analysis is to explain why different outcomes have occurred in different studies." (p. 197). Roberts, M. C., & Ilardi, S. S. (2003). Handbook of Research Methods in Clinical Psychology . Blackwell Publishing.

• Example : Employment Instability and Fertility in Europe: A Meta-Analysis:  10.1215/00703370-9164737

Meta-synthesis : "Qualitative meta-synthesis is a type of qualitative study that uses as data the findings from other qualitative studies linked by the same or related topic." (p.312). Zimmer, L. (2006). Qualitative meta-synthesis: A question of dialoguing with texts .  Journal of Advanced Nursing , 53 (3), 311-318.

• Example : Women’s perspectives on career successes and barriers: A qualitative meta-synthesis:  10.1177/05390184221113735

Literature Reviews in the Health Sciences

• UConn Health subject guide on systematic reviews Explanation of the different review types used in health sciences literature as well as tools to help you find the right review type
• << Previous: Getting Started
• Next: How to Pick a Topic >>
• Last Updated: Sep 21, 2022 2:16 PM
• URL: https://guides.lib.uconn.edu/literaturereview

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Organizing Your Social Sciences Research Paper

• 5. The Literature Review
• Purpose of Guide
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• Glossary of Research Terms
• Reading Research Effectively
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• Bibliography

A literature review surveys prior research published in books, scholarly articles, and any other sources relevant to a particular issue, area of research, or theory, and by so doing, provides a description, summary, and critical evaluation of these works in relation to the research problem being investigated. Literature reviews are designed to provide an overview of sources you have used in researching a particular topic and to demonstrate to your readers how your research fits within existing scholarship about the topic.

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . Fourth edition. Thousand Oaks, CA: SAGE, 2014.

Importance of a Good Literature Review

A literature review may consist of simply a summary of key sources, but in the social sciences, a literature review usually has an organizational pattern and combines both summary and synthesis, often within specific conceptual categories . A summary is a recap of the important information of the source, but a synthesis is a re-organization, or a reshuffling, of that information in a way that informs how you are planning to investigate a research problem. The analytical features of a literature review might:

• Give a new interpretation of old material or combine new with old interpretations,
• Trace the intellectual progression of the field, including major debates,
• Depending on the situation, evaluate the sources and advise the reader on the most pertinent or relevant research, or
• Usually in the conclusion of a literature review, identify where gaps exist in how a problem has been researched to date.

Given this, the purpose of a literature review is to:

• Place each work in the context of its contribution to understanding the research problem being studied.
• Describe the relationship of each work to the others under consideration.
• Identify new ways to interpret prior research.
• Reveal any gaps that exist in the literature.
• Resolve conflicts amongst seemingly contradictory previous studies.
• Identify areas of prior scholarship to prevent duplication of effort.
• Point the way in fulfilling a need for additional research.
• Locate your own research within the context of existing literature [very important].

Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper. 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . Los Angeles, CA: SAGE, 2011; Knopf, Jeffrey W. "Doing a Literature Review." PS: Political Science and Politics 39 (January 2006): 127-132; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012.

Types of Literature Reviews

It is important to think of knowledge in a given field as consisting of three layers. First, there are the primary studies that researchers conduct and publish. Second are the reviews of those studies that summarize and offer new interpretations built from and often extending beyond the primary studies. Third, there are the perceptions, conclusions, opinion, and interpretations that are shared informally among scholars that become part of the body of epistemological traditions within the field.

In composing a literature review, it is important to note that it is often this third layer of knowledge that is cited as "true" even though it often has only a loose relationship to the primary studies and secondary literature reviews. Given this, while literature reviews are designed to provide an overview and synthesis of pertinent sources you have explored, there are a number of approaches you could adopt depending upon the type of analysis underpinning your study.

Argumentative Review This form examines literature selectively in order to support or refute an argument, deeply embedded assumption, or philosophical problem already established in the literature. The purpose is to develop a body of literature that establishes a contrarian viewpoint. Given the value-laden nature of some social science research [e.g., educational reform; immigration control], argumentative approaches to analyzing the literature can be a legitimate and important form of discourse. However, note that they can also introduce problems of bias when they are used to make summary claims of the sort found in systematic reviews [see below].

Integrative Review Considered a form of research that reviews, critiques, and synthesizes representative literature on a topic in an integrated way such that new frameworks and perspectives on the topic are generated. The body of literature includes all studies that address related or identical hypotheses or research problems. A well-done integrative review meets the same standards as primary research in regard to clarity, rigor, and replication. This is the most common form of review in the social sciences.

Historical Review Few things rest in isolation from historical precedent. Historical literature reviews focus on examining research throughout a period of time, often starting with the first time an issue, concept, theory, phenomena emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and to identify the likely directions for future research.

Methodological Review A review does not always focus on what someone said [findings], but how they came about saying what they say [method of analysis]. Reviewing methods of analysis provides a framework of understanding at different levels [i.e. those of theory, substantive fields, research approaches, and data collection and analysis techniques], how researchers draw upon a wide variety of knowledge ranging from the conceptual level to practical documents for use in fieldwork in the areas of ontological and epistemological consideration, quantitative and qualitative integration, sampling, interviewing, data collection, and data analysis. This approach helps highlight ethical issues which you should be aware of and consider as you go through your own study.

Systematic Review This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research, and to collect, report, and analyze data from the studies that are included in the review. The goal is to deliberately document, critically evaluate, and summarize scientifically all of the research about a clearly defined research problem . Typically it focuses on a very specific empirical question, often posed in a cause-and-effect form, such as "To what extent does A contribute to B?" This type of literature review is primarily applied to examining prior research studies in clinical medicine and allied health fields, but it is increasingly being used in the social sciences.

Theoretical Review The purpose of this form is to examine the corpus of theory that has accumulated in regard to an issue, concept, theory, phenomena. The theoretical literature review helps to establish what theories already exist, the relationships between them, to what degree the existing theories have been investigated, and to develop new hypotheses to be tested. Often this form is used to help establish a lack of appropriate theories or reveal that current theories are inadequate for explaining new or emerging research problems. The unit of analysis can focus on a theoretical concept or a whole theory or framework.

NOTE: Most often the literature review will incorporate some combination of types. For example, a review that examines literature supporting or refuting an argument, assumption, or philosophical problem related to the research problem will also need to include writing supported by sources that establish the history of these arguments in the literature.

Baumeister, Roy F. and Mark R. Leary. "Writing Narrative Literature Reviews."  Review of General Psychology 1 (September 1997): 311-320; Mark R. Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Kennedy, Mary M. "Defining a Literature." Educational Researcher 36 (April 2007): 139-147; Petticrew, Mark and Helen Roberts. Systematic Reviews in the Social Sciences: A Practical Guide . Malden, MA: Blackwell Publishers, 2006; Torracro, Richard. "Writing Integrative Literature Reviews: Guidelines and Examples." Human Resource Development Review 4 (September 2005): 356-367; Rocco, Tonette S. and Maria S. Plakhotnik. "Literature Reviews, Conceptual Frameworks, and Theoretical Frameworks: Terms, Functions, and Distinctions." Human Ressource Development Review 8 (March 2008): 120-130; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

Structure and Writing Style

I.  Thinking About Your Literature Review

The structure of a literature review should include the following in support of understanding the research problem :

• An overview of the subject, issue, or theory under consideration, along with the objectives of the literature review,
• Division of works under review into themes or categories [e.g. works that support a particular position, those against, and those offering alternative approaches entirely],
• An explanation of how each work is similar to and how it varies from the others,
• Conclusions as to which pieces are best considered in their argument, are most convincing of their opinions, and make the greatest contribution to the understanding and development of their area of research.

The critical evaluation of each work should consider :

• Provenance -- what are the author's credentials? Are the author's arguments supported by evidence [e.g. primary historical material, case studies, narratives, statistics, recent scientific findings]?
• Methodology -- were the techniques used to identify, gather, and analyze the data appropriate to addressing the research problem? Was the sample size appropriate? Were the results effectively interpreted and reported?
• Objectivity -- is the author's perspective even-handed or prejudicial? Is contrary data considered or is certain pertinent information ignored to prove the author's point?
• Persuasiveness -- which of the author's theses are most convincing or least convincing?
• Validity -- are the author's arguments and conclusions convincing? Does the work ultimately contribute in any significant way to an understanding of the subject?

II.  Development of the Literature Review

Four Basic Stages of Writing 1.  Problem formulation -- which topic or field is being examined and what are its component issues? 2.  Literature search -- finding materials relevant to the subject being explored. 3.  Data evaluation -- determining which literature makes a significant contribution to the understanding of the topic. 4.  Analysis and interpretation -- discussing the findings and conclusions of pertinent literature.

Consider the following issues before writing the literature review: Clarify If your assignment is not specific about what form your literature review should take, seek clarification from your professor by asking these questions: 1.  Roughly how many sources would be appropriate to include? 2.  What types of sources should I review (books, journal articles, websites; scholarly versus popular sources)? 3.  Should I summarize, synthesize, or critique sources by discussing a common theme or issue? 4.  Should I evaluate the sources in any way beyond evaluating how they relate to understanding the research problem? 5.  Should I provide subheadings and other background information, such as definitions and/or a history? Find Models Use the exercise of reviewing the literature to examine how authors in your discipline or area of interest have composed their literature review sections. Read them to get a sense of the types of themes you might want to look for in your own research or to identify ways to organize your final review. The bibliography or reference section of sources you've already read, such as required readings in the course syllabus, are also excellent entry points into your own research. Narrow the Topic The narrower your topic, the easier it will be to limit the number of sources you need to read in order to obtain a good survey of relevant resources. Your professor will probably not expect you to read everything that's available about the topic, but you'll make the act of reviewing easier if you first limit scope of the research problem. A good strategy is to begin by searching the USC Libraries Catalog for recent books about the topic and review the table of contents for chapters that focuses on specific issues. You can also review the indexes of books to find references to specific issues that can serve as the focus of your research. For example, a book surveying the history of the Israeli-Palestinian conflict may include a chapter on the role Egypt has played in mediating the conflict, or look in the index for the pages where Egypt is mentioned in the text. Consider Whether Your Sources are Current Some disciplines require that you use information that is as current as possible. This is particularly true in disciplines in medicine and the sciences where research conducted becomes obsolete very quickly as new discoveries are made. However, when writing a review in the social sciences, a survey of the history of the literature may be required. In other words, a complete understanding the research problem requires you to deliberately examine how knowledge and perspectives have changed over time. Sort through other current bibliographies or literature reviews in the field to get a sense of what your discipline expects. You can also use this method to explore what is considered by scholars to be a "hot topic" and what is not.

III.  Ways to Organize Your Literature Review

Chronology of Events If your review follows the chronological method, you could write about the materials according to when they were published. This approach should only be followed if a clear path of research building on previous research can be identified and that these trends follow a clear chronological order of development. For example, a literature review that focuses on continuing research about the emergence of German economic power after the fall of the Soviet Union. By Publication Order your sources by publication chronology, then, only if the order demonstrates a more important trend. For instance, you could order a review of literature on environmental studies of brown fields if the progression revealed, for example, a change in the soil collection practices of the researchers who wrote and/or conducted the studies. Thematic [“conceptual categories”] A thematic literature review is the most common approach to summarizing prior research in the social and behavioral sciences. Thematic reviews are organized around a topic or issue, rather than the progression of time, although the progression of time may still be incorporated into a thematic review. For example, a review of the Internet’s impact on American presidential politics could focus on the development of online political satire. While the study focuses on one topic, the Internet’s impact on American presidential politics, it would still be organized chronologically reflecting technological developments in media. The difference in this example between a "chronological" and a "thematic" approach is what is emphasized the most: themes related to the role of the Internet in presidential politics. Note that more authentic thematic reviews tend to break away from chronological order. A review organized in this manner would shift between time periods within each section according to the point being made. Methodological A methodological approach focuses on the methods utilized by the researcher. For the Internet in American presidential politics project, one methodological approach would be to look at cultural differences between the portrayal of American presidents on American, British, and French websites. Or the review might focus on the fundraising impact of the Internet on a particular political party. A methodological scope will influence either the types of documents in the review or the way in which these documents are discussed.

Other Sections of Your Literature Review Once you've decided on the organizational method for your literature review, the sections you need to include in the paper should be easy to figure out because they arise from your organizational strategy. In other words, a chronological review would have subsections for each vital time period; a thematic review would have subtopics based upon factors that relate to the theme or issue. However, sometimes you may need to add additional sections that are necessary for your study, but do not fit in the organizational strategy of the body. What other sections you include in the body is up to you. However, only include what is necessary for the reader to locate your study within the larger scholarship about the research problem.

Here are examples of other sections, usually in the form of a single paragraph, you may need to include depending on the type of review you write:

• Current Situation : Information necessary to understand the current topic or focus of the literature review.
• Sources Used : Describes the methods and resources [e.g., databases] you used to identify the literature you reviewed.
• History : The chronological progression of the field, the research literature, or an idea that is necessary to understand the literature review, if the body of the literature review is not already a chronology.
• Selection Methods : Criteria you used to select (and perhaps exclude) sources in your literature review. For instance, you might explain that your review includes only peer-reviewed [i.e., scholarly] sources.
• Standards : Description of the way in which you present your information.
• Questions for Further Research : What questions about the field has the review sparked? How will you further your research as a result of the review?

IV.  Writing Your Literature Review

Once you've settled on how to organize your literature review, you're ready to write each section. When writing your review, keep in mind these issues.

Use Evidence A literature review section is, in this sense, just like any other academic research paper. Your interpretation of the available sources must be backed up with evidence [citations] that demonstrates that what you are saying is valid. Be Selective Select only the most important points in each source to highlight in the review. The type of information you choose to mention should relate directly to the research problem, whether it is thematic, methodological, or chronological. Related items that provide additional information, but that are not key to understanding the research problem, can be included in a list of further readings . Use Quotes Sparingly Some short quotes are appropriate if you want to emphasize a point, or if what an author stated cannot be easily paraphrased. Sometimes you may need to quote certain terminology that was coined by the author, is not common knowledge, or taken directly from the study. Do not use extensive quotes as a substitute for using your own words in reviewing the literature. Summarize and Synthesize Remember to summarize and synthesize your sources within each thematic paragraph as well as throughout the review. Recapitulate important features of a research study, but then synthesize it by rephrasing the study's significance and relating it to your own work and the work of others. Keep Your Own Voice While the literature review presents others' ideas, your voice [the writer's] should remain front and center. For example, weave references to other sources into what you are writing but maintain your own voice by starting and ending the paragraph with your own ideas and wording. Use Caution When Paraphrasing When paraphrasing a source that is not your own, be sure to represent the author's information or opinions accurately and in your own words. Even when paraphrasing an author’s work, you still must provide a citation to that work.

V.  Common Mistakes to Avoid

These are the most common mistakes made in reviewing social science research literature.

• Sources in your literature review do not clearly relate to the research problem;
• You do not take sufficient time to define and identify the most relevant sources to use in the literature review related to the research problem;
• Relies exclusively on secondary analytical sources rather than including relevant primary research studies or data;
• Uncritically accepts another researcher's findings and interpretations as valid, rather than examining critically all aspects of the research design and analysis;
• Does not describe the search procedures that were used in identifying the literature to review;
• Reports isolated statistical results rather than synthesizing them in chi-squared or meta-analytic methods; and,
• Only includes research that validates assumptions and does not consider contrary findings and alternative interpretations found in the literature.

Cook, Kathleen E. and Elise Murowchick. “Do Literature Review Skills Transfer from One Course to Another?” Psychology Learning and Teaching 13 (March 2014): 3-11; Fink, Arlene. Conducting Research Literature Reviews: From the Internet to Paper . 2nd ed. Thousand Oaks, CA: Sage, 2005; Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1998; Jesson, Jill. Doing Your Literature Review: Traditional and Systematic Techniques . London: SAGE, 2011; Literature Review Handout. Online Writing Center. Liberty University; Literature Reviews. The Writing Center. University of North Carolina; Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: SAGE, 2016; Ridley, Diana. The Literature Review: A Step-by-Step Guide for Students . 2nd ed. Los Angeles, CA: SAGE, 2012; Randolph, Justus J. “A Guide to Writing the Dissertation Literature Review." Practical Assessment, Research, and Evaluation. vol. 14, June 2009; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016; Taylor, Dena. The Literature Review: A Few Tips On Conducting It. University College Writing Centre. University of Toronto; Writing a Literature Review. Academic Skills Centre. University of Canberra.

Writing Tip

Break Out of Your Disciplinary Box!

Thinking interdisciplinarily about a research problem can be a rewarding exercise in applying new ideas, theories, or concepts to an old problem. For example, what might cultural anthropologists say about the continuing conflict in the Middle East? In what ways might geographers view the need for better distribution of social service agencies in large cities than how social workers might study the issue? You don’t want to substitute a thorough review of core research literature in your discipline for studies conducted in other fields of study. However, particularly in the social sciences, thinking about research problems from multiple vectors is a key strategy for finding new solutions to a problem or gaining a new perspective. Consult with a librarian about identifying research databases in other disciplines; almost every field of study has at least one comprehensive database devoted to indexing its research literature.

Frodeman, Robert. The Oxford Handbook of Interdisciplinarity . New York: Oxford University Press, 2010.

Another Writing Tip

Don't Just Review for Content!

While conducting a review of the literature, maximize the time you devote to writing this part of your paper by thinking broadly about what you should be looking for and evaluating. Review not just what scholars are saying, but how are they saying it. Some questions to ask:

• How are they organizing their ideas?
• What methods have they used to study the problem?
• What theories have been used to explain, predict, or understand their research problem?
• What sources have they cited to support their conclusions?
• How have they used non-textual elements [e.g., charts, graphs, figures, etc.] to illustrate key points?

When you begin to write your literature review section, you'll be glad you dug deeper into how the research was designed and constructed because it establishes a means for developing more substantial analysis and interpretation of the research problem.

Hart, Chris. Doing a Literature Review: Releasing the Social Science Research Imagination . Thousand Oaks, CA: Sage Publications, 1 998.

Yet Another Writing Tip

When Do I Know I Can Stop Looking and Move On?

Here are several strategies you can utilize to assess whether you've thoroughly reviewed the literature:

• Look for repeating patterns in the research findings . If the same thing is being said, just by different people, then this likely demonstrates that the research problem has hit a conceptual dead end. At this point consider: Does your study extend current research?  Does it forge a new path? Or, does is merely add more of the same thing being said?
• Look at sources the authors cite to in their work . If you begin to see the same researchers cited again and again, then this is often an indication that no new ideas have been generated to address the research problem.
• Search Google Scholar to identify who has subsequently cited leading scholars already identified in your literature review [see next sub-tab]. This is called citation tracking and there are a number of sources that can help you identify who has cited whom, particularly scholars from outside of your discipline. Here again, if the same authors are being cited again and again, this may indicate no new literature has been written on the topic.

Onwuegbuzie, Anthony J. and Rebecca Frels. Seven Steps to a Comprehensive Literature Review: A Multimodal and Cultural Approach . Los Angeles, CA: Sage, 2016; Sutton, Anthea. Systematic Approaches to a Successful Literature Review . Los Angeles, CA: Sage Publications, 2016.

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Literature Reviews

• What is a literature review?
• Steps in the Literature Review Process
• Define your research question
• Determine inclusion and exclusion criteria
• Choose databases and search
• Review Results
• Synthesize Results
• Analyze Results
• Librarian Support

What is a Literature Review?

A literature or narrative review is a comprehensive review and analysis of the published literature on a specific topic or research question. The literature that is reviewed contains: books, articles, academic articles, conference proceedings, association papers, and dissertations. It contains the most pertinent studies and points to important past and current research and practices. It provides background and context, and shows how your research will contribute to the field. 

A literature review should: 

• Provide a comprehensive and updated review of the literature;
• Explain why this review has taken place;
• Articulate a position or hypothesis;
• Acknowledge and account for conflicting and corroborating points of view

From  S age Research Methods

Purpose of a Literature Review

A literature review can be written as an introduction to a study to:

• Demonstrate how a study fills a gap in research
• Compare a study with other research that's been done

Or it can be a separate work (a research article on its own) which:

• Organizes or describes a topic
• Describes variables within a particular issue/problem

Limitations of a Literature Review

Some of the limitations of a literature review are:

• It's a snapshot in time. Unlike other reviews, this one has beginning, a middle and an end. There may be future developments that could make your work less relevant.
• It may be too focused. Some niche studies may miss the bigger picture.
• It can be difficult to be comprehensive. There is no way to make sure all the literature on a topic was considered.
• It is easy to be biased if you stick to top tier journals. There may be other places where people are publishing exemplary research. Look to open access publications and conferences to reflect a more inclusive collection. Also, make sure to include opposing views (and not just supporting evidence).

Source: Grant, Maria J., and Andrew Booth. “A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies.” Health Information & Libraries Journal, vol. 26, no. 2, June 2009, pp. 91–108. Wiley Online Library, doi:10.1111/j.1471-1842.2009.00848.x.

Meryl Brodsky : Communication and Information Studies

Hannah Chapman Tripp : Biology, Neuroscience

Carolyn Cunningham : Human Development & Family Sciences, Psychology, Sociology

Larayne Dallas : Engineering

Janelle Hedstrom : Special Education, Curriculum & Instruction, Ed Leadership & Policy ​

Susan Macicak : Linguistics

Imelda Vetter : Dell Medical School

For help in other subject areas, please see the guide to library specialists by subject .

Periodically, UT Libraries runs a workshop covering the basics and library support for literature reviews. While we try to offer these once per academic year, we find providing the recording to be helpful to community members who have missed the session. Following is the most recent recording of the workshop, Conducting a Literature Review. To view the recording, a UT login is required.

• October 26, 2022 recording
• Last Updated: Oct 26, 2022 2:49 PM
• URL: https://guides.lib.utexas.edu/literaturereviews

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Literature reviews, what is a literature review, learning more about how to do a literature review.

• Planning the Review
• The Research Question
• Choosing Where to Search
• Organizing the Review
• Writing the Review

A literature review is a review and synthesis of existing research on a topic or research question. A literature review is meant to analyze the scholarly literature, make connections across writings and identify strengths, weaknesses, trends, and missing conversations. A literature review should address different aspects of a topic as it relates to your research question. A literature review goes beyond a description or summary of the literature you have read. 

• Sage Research Methods Core Collection This link opens in a new window SAGE Research Methods supports research at all levels by providing material to guide users through every step of the research process. SAGE Research Methods is the ultimate methods library with more than 1000 books, reference works, journal articles, and instructional videos by world-leading academics from across the social sciences, including the largest collection of qualitative methods books available online from any scholarly publisher. – Publisher

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How to write a good scientific review article

Affiliation.

• 1 The FEBS Journal Editorial Office, Cambridge, UK.
• PMID: 35792782
• DOI: 10.1111/febs.16565

Literature reviews are valuable resources for the scientific community. With research accelerating at an unprecedented speed in recent years and more and more original papers being published, review articles have become increasingly important as a means to keep up to date with developments in a particular area of research. A good review article provides readers with an in-depth understanding of a field and highlights key gaps and challenges to address with future research. Writing a review article also helps to expand the writer's knowledge of their specialist area and to develop their analytical and communication skills, amongst other benefits. Thus, the importance of building review-writing into a scientific career cannot be overstated. In this instalment of The FEBS Journal's Words of Advice series, I provide detailed guidance on planning and writing an informative and engaging literature review.

© 2022 Federation of European Biochemical Societies.

Publication types

• Review Literature as Topic*

How To Structure Your Literature Review

3 options to help structure your chapter.

By: Amy Rommelspacher (PhD) | Reviewer: Dr Eunice Rautenbach | November 2020 (Updated May 2023)

Writing the literature review chapter can seem pretty daunting when you’re piecing together your dissertation or thesis. As  we’ve discussed before , a good literature review needs to achieve a few very important objectives – it should:

• Demonstrate your knowledge of the research topic
• Identify the gaps in the literature and show how your research links to these
• Provide the foundation for your conceptual framework (if you have one)
• Inform your own  methodology and research design

To achieve this, your literature review needs a well-thought-out structure . Get the structure of your literature review chapter wrong and you’ll struggle to achieve these objectives. Don’t worry though – in this post, we’ll look at how to structure your literature review for maximum impact (and marks!).

But wait – is this the right time?

Deciding on the structure of your literature review should come towards the end of the literature review process – after you have collected and digested the literature, but before you start writing the chapter. 

In other words, you need to first develop a rich understanding of the literature before you even attempt to map out a structure. There’s no use trying to develop a structure before you’ve fully wrapped your head around the existing research.

Equally importantly, you need to have a structure in place before you start writing , or your literature review will most likely end up a rambling, disjointed mess. 

Importantly, don’t feel that once you’ve defined a structure you can’t iterate on it. It’s perfectly natural to adjust as you engage in the writing process. As we’ve discussed before , writing is a way of developing your thinking, so it’s quite common for your thinking to change – and therefore, for your chapter structure to change – as you write. 

Need a helping hand?

Like any other chapter in your thesis or dissertation, your literature review needs to have a clear, logical structure. At a minimum, it should have three essential components – an  introduction , a  body   and a  conclusion . 

Let’s take a closer look at each of these.

1: The Introduction Section

Just like any good introduction, the introduction section of your literature review should introduce the purpose and layout (organisation) of the chapter. In other words, your introduction needs to give the reader a taste of what’s to come, and how you’re going to lay that out. Essentially, you should provide the reader with a high-level roadmap of your chapter to give them a taste of the journey that lies ahead.

Here’s an example of the layout visualised in a literature review introduction:

Your introduction should also outline your topic (including any tricky terminology or jargon) and provide an explanation of the scope of your literature review – in other words, what you  will   and  won’t   be covering (the delimitations ). This helps ringfence your review and achieve a clear focus . The clearer and narrower your focus, the deeper you can dive into the topic (which is typically where the magic lies). 

Depending on the nature of your project, you could also present your stance or point of view at this stage. In other words, after grappling with the literature you’ll have an opinion about what the trends and concerns are in the field as well as what’s lacking. The introduction section can then present these ideas so that it is clear to examiners that you’re aware of how your research connects with existing knowledge .

2: The Body Section

The body of your literature review is the centre of your work. This is where you’ll present, analyse, evaluate and synthesise the existing research. In other words, this is where you’re going to earn (or lose) the most marks. Therefore, it’s important to carefully think about how you will organise your discussion to present it in a clear way. 

The body of your literature review should do just as the description of this chapter suggests. It should “review” the literature – in other words, identify, analyse, and synthesise it. So, when thinking about structuring your literature review, you need to think about which structural approach will provide the best “review” for your specific type of research and objectives (we’ll get to this shortly).

There are (broadly speaking)  three options  for organising your literature review.

Option 1: Chronological (according to date)

Organising the literature chronologically is one of the simplest ways to structure your literature review. You start with what was published first and work your way through the literature until you reach the work published most recently. Pretty straightforward.

The benefit of this option is that it makes it easy to discuss the developments and debates in the field as they emerged over time. Organising your literature chronologically also allows you to highlight how specific articles or pieces of work might have changed the course of the field – in other words, which research has had the most impact . Therefore, this approach is very useful when your research is aimed at understanding how the topic has unfolded over time and is often used by scholars in the field of history. That said, this approach can be utilised by anyone that wants to explore change over time .

For example , if a student of politics is investigating how the understanding of democracy has evolved over time, they could use the chronological approach to provide a narrative that demonstrates how this understanding has changed through the ages.

Here are some questions you can ask yourself to help you structure your literature review chronologically.

• What is the earliest literature published relating to this topic?
• How has the field changed over time? Why?
• What are the most recent discoveries/theories?

In some ways, chronology plays a part whichever way you decide to structure your literature review, because you will always, to a certain extent, be analysing how the literature has developed. However, with the chronological approach, the emphasis is very firmly on how the discussion has evolved over time , as opposed to how all the literature links together (which we’ll discuss next ).

Option 2: Thematic (grouped by theme)

The thematic approach to structuring a literature review means organising your literature by theme or category – for example, by independent variables (i.e. factors that have an impact on a specific outcome).

As you’ve been collecting and synthesising literature , you’ll likely have started seeing some themes or patterns emerging. You can then use these themes or patterns as a structure for your body discussion. The thematic approach is the most common approach and is useful for structuring literature reviews in most fields.

For example, if you were researching which factors contributed towards people trusting an organisation, you might find themes such as consumers’ perceptions of an organisation’s competence, benevolence and integrity. Structuring your literature review thematically would mean structuring your literature review’s body section to discuss each of these themes, one section at a time.

Here are some questions to ask yourself when structuring your literature review by themes:

• Are there any patterns that have come to light in the literature?
• What are the central themes and categories used by the researchers?
• Do I have enough evidence of these themes?

PS – you can see an example of a thematically structured literature review in our literature review sample walkthrough video here.

Option 3: Methodological

The methodological option is a way of structuring your literature review by the research methodologies used . In other words, organising your discussion based on the angle from which each piece of research was approached – for example, qualitative , quantitative or mixed  methodologies.

Structuring your literature review by methodology can be useful if you are drawing research from a variety of disciplines and are critiquing different methodologies. The point of this approach is to question  how  existing research has been conducted, as opposed to  what  the conclusions and/or findings the research were.

For example, a sociologist might centre their research around critiquing specific fieldwork practices. Their literature review will then be a summary of the fieldwork methodologies used by different studies.

Here are some questions you can ask yourself when structuring your literature review according to methodology:

• Which methodologies have been utilised in this field?
• Which methodology is the most popular (and why)?
• What are the strengths and weaknesses of the various methodologies?
• How can the existing methodologies inform my own methodology?

3: The Conclusion Section

Once you’ve completed the body section of your literature review using one of the structural approaches we discussed above, you’ll need to “wrap up” your literature review and pull all the pieces together to set the direction for the rest of your dissertation or thesis.

The conclusion is where you’ll present the key findings of your literature review. In this section, you should emphasise the research that is especially important to your research questions and highlight the gaps that exist in the literature. Based on this, you need to make it clear what you will add to the literature – in other words, justify your own research by showing how it will help fill one or more of the gaps you just identified.

Last but not least, if it’s your intention to develop a conceptual framework for your dissertation or thesis, the conclusion section is a good place to present this.

Example: Thematically Structured Review

In the video below, we unpack a literature review chapter so that you can see an example of a thematically structure review in practice.

Let’s Recap

In this article, we’ve  discussed how to structure your literature review for maximum impact. Here’s a quick recap of what  you need to keep in mind when deciding on your literature review structure:

• Just like other chapters, your literature review needs a clear introduction , body and conclusion .
• The introduction section should provide an overview of what you will discuss in your literature review.
• The body section of your literature review can be organised by chronology , theme or methodology . The right structural approach depends on what you’re trying to achieve with your research.
• The conclusion section should draw together the key findings of your literature review and link them to your research questions.

If you’re ready to get started, be sure to download our free literature review template to fast-track your chapter outline.

Psst… there’s more!

This post is an extract from our bestselling short course, Literature Review Bootcamp . If you want to work smart, you don't want to miss this .

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27 Comments

Great work. This is exactly what I was looking for and helps a lot together with your previous post on literature review. One last thing is missing: a link to a great literature chapter of an journal article (maybe with comments of the different sections in this review chapter). Do you know any great literature review chapters?

I agree with you Marin… A great piece

I agree with Marin. This would be quite helpful if you annotate a nicely structured literature from previously published research articles.

Awesome article for my research.

I thank you immensely for this wonderful guide

It is indeed thought and supportive work for the futurist researcher and students

Very educative and good time to get guide. Thank you

Great work, very insightful. Thank you.

Thanks for this wonderful presentation. My question is that do I put all the variables into a single conceptual framework or each hypothesis will have it own conceptual framework?

Thank you very much, very helpful

This is very educative and precise . Thank you very much for dropping this kind of write up .

Pheeww, so damn helpful, thank you for this informative piece.

I’m doing a research project topic ; stool analysis for parasitic worm (enteric) worm, how do I structure it, thanks.

comprehensive explanation. Help us by pasting the URL of some good “literature review” for better understanding.

great piece. thanks for the awesome explanation. it is really worth sharing. I have a little question, if anyone can help me out, which of the options in the body of literature can be best fit if you are writing an architectural thesis that deals with design?

I am doing a research on nanofluids how can l structure it?

Beautifully clear.nThank you!

Lucid! Thankyou!

Brilliant work, well understood, many thanks

I like how this was so clear with simple language 😊😊 thank you so much 😊 for these information 😊

Insightful. I was struggling to come up with a sensible literature review but this has been really helpful. Thank you!

You have given thought-provoking information about the review of the literature.

Thank you. It has made my own research better and to impart your work to students I teach

I learnt a lot from this teaching. It’s a great piece.

I am doing research on EFL teacher motivation for his/her job. How Can I structure it? Is there any detailed template, additional to this?

You are so cool! I do not think I’ve read through something like this before. So nice to find somebody with some genuine thoughts on this issue. Seriously.. thank you for starting this up. This site is one thing that is required on the internet, someone with a little originality!

I’m asked to do conceptual, theoretical and empirical literature, and i just don’t know how to structure it

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Literature Review: Conducting & Writing

• Sample Literature Reviews
• Steps for Conducting a Lit Review
• Finding "The Literature"
• Organizing/Writing
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Sample Lit Reviews from Communication Arts

Have an exemplary literature review.

• Literature Review Sample 1
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Have you written a stellar literature review you care to share for teaching purposes?

Are you an instructor who has received an exemplary literature review and have permission from the student to post?

Please contact Britt McGowan at [email protected] for inclusion in this guide. All disciplines welcome and encouraged.

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• Open access
• Published: 24 May 2024

Vertebral hemangiomas: a review on diagnosis and management

• Kyle Kato 1 ,
• Nahom Teferi 2 ,
• Meron Challa 1 ,
• Kathryn Eschbacher 3 &
• Satoshi Yamaguchi 2  

Journal of Orthopaedic Surgery and Research volume  19 , Article number:  310 ( 2024 ) Cite this article

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Metrics details

Vertebral hemangiomas (VHs) are the most common benign tumors of the spinal column and are often encountered incidentally during routine spinal imaging.

A retrospective review of the inpatient and outpatient hospital records at our institution was performed for the diagnosis of VHs from January 2005 to September 2023. Search filters included “vertebral hemangioma,” "back pain,” “weakness,” “radiculopathy,” and “focal neurological deficits.” Radiographic evaluation of these patients included plain X-rays, CT, and MRI. Following confirmation of a diagnosis of VH, these images were used to generate the figures used in this manuscript. Moreover, an extensive literature search was conducted using PubMed for the literature review portion of the manuscript.

VHs are benign vascular proliferations that cause remodeling of bony trabeculae in the vertebral body of the spinal column. Horizontal trabeculae deteriorate leading to thickening of vertical trabeculae which causes a striated appearance on sagittal magnetic resonance imaging (MRI) and computed tomography (CT), “Corduroy sign,” and a punctuated appearance on axial imaging, “Polka dot sign.” These findings are seen in “typical vertebral hemangiomas” due to a low vascular-to-fat ratio of the lesion. Contrarily, atypical vertebral hemangiomas may or may not demonstrate the “Corduroy” or “Polka-dot” signs due to lower amounts of fat and a higher vascular component. Atypical vertebral hemangiomas often mimic other neoplastic pathologies, making diagnosis challenging. Although most VHs are asymptomatic, aggressive vertebral hemangiomas can present with neurologic sequelae such as myelopathy and radiculopathy due to nerve root and/or spinal cord compression. Asymptomatic vertebral hemangiomas do not require therapy, and there are many treatment options for vertebral hemangiomas causing pain, radiculopathy, and/or myelopathy. Surgery (corpectomy, laminectomy), percutaneous techniques (vertebroplasty, sclerotherapy, embolization), and radiotherapy can be used in combination or isolation as appropriate. Specific treatment options depend on the lesion's size/location and the extent of neural element compression. There is no consensus on the optimal treatment plan for symptomatic vertebral hemangioma patients, although management algorithms have been proposed.

While typical vertebral hemangioma diagnosis is relatively straightforward, the differential diagnosis is broad for atypical and aggressive lesions. There is an ongoing debate as to the best approach for managing symptomatic cases, however, surgical resection is often considered first line treatment for patients with neurologic deficit.

Introduction

Vertebral hemangiomas (VHs) are benign vascular lesions formed from vascular proliferation in bone marrow spaces that are limited by bony trabeculae [ 1 ]. VHs are quite common and are often incidental findings on spinal computed tomography (CT) and magnetic resonance imaging (MRI) of patients presenting with back or neck pain [ 2 , 3 ]. Previous, large autopsy series such as Schmorl (1926) and Junghanns (1932) found a VH prevalence of 11% in adult specimens [ 1 , 4 ]. However, the prevalence is believed to be higher as modern imaging techniques allow for better detection of small VHs that may not be easily diagnosed on autopsy specimens [ 5 ]. They can occur at any age but are most often seen in individuals in their 5th decade of life with a slight female preponderance [ 2 , 6 , 7 ]. Most VHs are found in the thoracic or lumbar spinal column and often involve the vertebral body, though they can extend to the pedicle, lamina, or spinous process, and may span multiple spinal segments [ 5 ].

The vast majority of VHs are asymptomatic, quiescent lesions [ 3 ]. Prior studies have stated less than 5% of VHs are symptomatic [ 8 , 9 ], although the 2023 study by Teferi et. al. demonstrated 35% of their 75 VH patients presented with symptoms including localized pain, numbness, and/or paresthesia [ 1 ]. 85% of symptomatic cases in this series were found to have VHs localized in the thoracic spine [ 1 ].

Among symptomatic VHs, up to 20–45% of cases may exhibit aggressive features including damage to surrounding bone and soft tissue or demonstrate rapid growth that extends beyond the vertebral body and invades the paravertebral and/or epidural space [ 1 , 5 , 10 , 11 ]. When “aggressive”, VHs may compress the spinal cord and nerve roots causing severe symptoms [ 1 , 5 ]. 45% of symptomatic VH patients present with neurologic deficits secondary to compressive lesions, bony expansion, disrupted blood flow, or vertebral body collapse while the remaining 55% present solely with back pain [ 8 , 12 , 13 , 14 , 15 ].

VHs are primarily diagnosed with radiographs, CT, and MRI, although other studies such as angiography, nuclear medicine studies, and positron emission—computed tomography (PET-CT) have been previously utilized to a lesser extent [ 1 , 15 , 16 , 17 , 18 , 19 ]. Radiologically, these lesions can be grouped into Typical, Atypical, and Aggressive subtypes (see radiological features). Histologically, VHs are composed of varying proportions of adipocytes, blood vessels, and interstitial edema which leads to thickening of vertical trabeculae in the affected vertebra [ 5 ]. This histopathology leads to the characteristic “polka-dot” sign on axial CT/MRI and “corduroy” sign on coronal and sagittal CT/MRI [ 5 , 20 ].

In terms of management, conservative treatment with observation and pain control are the mainstay of treatment for asymptomatic VH patients and those with mild-to-moderate pain respectively [ 21 ]. Surgical decompression is indicated for patients with neurologic deficits including compressive myelopathy or radiculopathy [ 22 ]. Other symptomatic patients have a wide variety of treatment options available including sclerotherapy, embolization, radiotherapy, and/or vertebroplasty [ 1 , 5 , 23 ]. The best approach in managing an individual patient with a symptomatic VH has not been elucidated and there have been different management algorithms suggested based on varying institutional experiences [ 1 , 5 , 24 , 25 ].

This article will review what is currently known regarding VHs. Diagnostic techniques and challenges will be highlighted as well as current treatment recommendations from the literature.

A retrospective review of the inpatient and outpatient hospital records at our institution was performed for the diagnosis of VHs from January 2005 to September 2023. Search filters included “vertebral hemangioma” "back pain,” “weakness,” “radiculopathy,” and “focal neurological deficits.” Radiographic evaluation of these patients included plain X-rays, CT, and MRI. Following confirmation of a diagnosis of VH, these images were used to generate the figures used in this manuscript. Moreover, an extensive literature search was conducted using PubMed for the literature review portion of the manuscript.

68 Articles were selected from our PubMed search. This article will review what is currently known about VHs. Diagnostic techniques and challenges will be highlighted as well as current treatment recommendations from the literature.

Histopathological features

VHs are benign tumors composed of various sized blood vessels, adipocytes, smooth muscle, fibrous tissue, hemosiderin, interstitial edema, and remodeled bone [ 5 , 7 , 26 , 27 ]. Macroscopically, they appear as soft, well-demarcated, dark red masses with intralesional, sclerotic boney trabeculae and scattered blood-filled cavities lending to a honeycomb appearance [ 5 , 6 , 7 ].

Microscopically, there are four subtypes of hemangiomas based on vascular composition: capillary, cavernous, arteriovenous (AV), and venous hemangiomas [ 28 ] (Fig.  1 ). Capillary hemangiomas are composed of small, capillary-sized blood vessels while cavernous hemangiomas present with collections of larger, dilated blood vessels [ 1 ]. AV hemangiomas are composed of interconnected arterial and venous networks while an abnormal collection of veins comprises venous hemangiomas [ 1 ]. VHs are predominately capillary and cavernous subtypes with thin-walled blood vessels surrounded by edematous stroma and boney trabeculae that permeate the bone marrow space [ 1 , 7 , 27 ]. In a sample of 64 surgically treated VHs cases, Pastushyn et al. reported 50% were capillary subtype, 28% were cavernous subtype, and 22% were mixed [ 29 ]. Occasionally, secondary reactive phenomena such as fibrous and/or adipose involution of bone marrow and remodeling of bone trabeculae may be seen [ 7 , 26 ]. Symptomatic VHs can be caused by all hemangioma subtypes, and there are no distinguishing features between subtypes on imaging [ 1 ]. However, cavernous and capillary subtypes are associated with favorable postsurgical outcomes [ 29 ].

Capillary hemangioma ( A and B ): A H&E 200× magnification showing proliferation of small caliber vessels within a fibrous stroma with surrounding bone, B CD34 immunohistochemical stain, 200× magnification highlighting small caliber vascular spaces. Cavernous hemangioma ( C and D ): C H&E 100× magnification showing proliferation of thin-walled, dilated, blood filled vascular channels, D H&E 200× magnification: Thin-walled, dilated vascular channels within a loose stroma with adjacent mature bone. Venous hemangioma ( E and F ): E H&E 100 ×  magnification showing abnormal proliferation of thick-walled vessels with dilated lumens. F H&E 100× magnification reveals tightly packed, thick-walled vessels with adjacent fragments of mature bone

Radiographic features

The histopathology of VHs gives rise to imaging features used to classify VHs as typical, atypical, or aggressive [ 13 ]. Typical and atypical MRI findings are correlated with the intralesional ratio of fat to vascular components [ 20 ]. Lesions with a high fat content are more likely to demonstrate features of typical VHs while those with a high vascular content (atypical VHs) tend to present without these findings [ 5 , 30 , 31 ]. Aggressive VHs have features including destruction of the cortex, invasion of the epidural and paravertebral spaces, and lesions extending beyond the vertebral body [ 13 , 15 , 20 ].

Laredo et al. demonstrated that VHs with a higher fatty content are generally quiescent lesions, while those with a higher vascular content are more likely to display “active” behavior and potentially evolve into compressive lesions [ 20 ]. Therefore, asymptomatic VHs can display both typical or atypical imaging findings while symptomatic lesions are more likely to present with atypical or aggressive findings [ 1 ]. Despite radiographically typical VHs being relatively easy to diagnose, atypical and aggressive VHs are much more challenging to recognize as they do not present with classic imaging findings and often mimic other pathologies such as multiple myeloma, metastatic bone lesions, and inflammatory conditions [ 5 , 30 , 31 ]. Compressive VHs often have coinciding radiologic and clinical classifications due to the correlation between aggressive behavior and compressive symptoms [ 5 ].

While MRI, CT, and radiographs are the primary imaging modalities used in the workup of VHs, other studies have also been used. Angiography will occasionally be performed to identify feeding/draining vessels and evaluate the blood supply to the spinal cord [ 5 ]. Multiphase technetium 99-methyl diphosphonate ( 99 Tc-MDP) bone scintigraphy may show increased tracer uptake in all phases (perfusion, blood pool, and delayed) due to technetium 99-labeled red blood cell accumulation in the tumors, which occurs in all hemangiomas [ 16 ]. PET-CT has been used to classify VHs as “hot” or “cold” lesions based on the degree of 18-FDG and 68-Ga DOTATATE uptake [ 17 , 18 , 19 ]. Although angiography is useful in clarifying the vascular network of aggressive VHs primarily, nuclear medicine studies offer a much more limited contribution to diagnosis when compared to CT and MRI [ 5 ].

Typical VHs

The collection of thin-walled, blood-filled spaces that comprise VHs cause resorption of horizontal trabeculae and reinforcement of vertical trabeculae, leading to a pattern of thickened vertical trabeculae interspersed with lower density bone of the nonexpanding vertebral body [ 15 , 31 , 32 ]. This composition is responsible for the “corduroy cloth” appearance seen in typical VHs on radiographic images [ 31 ].

On unenhanced axial CT images, typical VHs are characterized by a “polka dot” appearance, termed polka-dot sign. This is caused by small, punctate areas of high attenuation from hyperdense trabeculae surrounded by hypodense stroma [ 20 , 33 ] (Fig.  2 ). Like radiographs, sagittal and coronal CT images display the “corduroy” sign caused by thickened trabeculae in a field of hypodense bone (Fig.  2 ). There is no extraosseous extension of the hemangioma in typical VHs [ 5 ].

Sagittal ( A ) and axial ( B ) CT scans of a typical VH in an asymptomatic 50-year-old male demonstrating the “Corduroy” and “Polka-dot” signs respectively. Sagittal ( C ) and axial ( D ) T1-weighted MRIs of typical VHs are predominately hyperintense with areas of hypo-intensity due to thickening of vertical trabeculae. Sagittal ( E ) and axial ( F ) T2-weighted MRIs of typical VHs also appear as hyperintense lesions with areas of hypo-intensity that may demonstrate the “Corduroy” and “Polka-dot” signs as seen in CT images of typical VHs

Typical VHs tend to appear as hyperintense lesions on T1- and T2-weighted MRI sequences due to predominately fatty overgrowth with penetrating blood vessels [ 31 ] (Fig.  2 ). There are punctate areas of slight hypointensity within the lesion on axial T1-weighted MRI due to thickened vertical trabeculae which resembles the “polka-dot" sign [ 5 ] (Fig.  2 ). These trabeculae appear as linear striations on sagittal/coronal T1- and T2-weighted MRI [ 5 ] (Fig.  2 ). Fluid-sensitive sequences (i.e. short-tau inversion recovery or fat-saturated T2-weighted MRI) appear slightly hyperintense due to the vascular components of the lesion, and T1-weighted MRI with contrast demonstrates heterogenous enhancement of the lesion [ 3 ] (Fig.  3 ).

Contrast-enhanced T1 MRIs of a T8 VH in an asymptomatic fourteen-year-old female ( A ) and L3, L5 VHs in a thirty-one-year-old female with back pain ( B ), illustrating the heterogenous presentation of hemangiomas on post-contrast MRI

Atypical VHs

In contrast to typical VHs, atypical VHs tend to have a higher vascular component-to-fat ratio and may not demonstrate the classical imaging findings such as the “corduroy” and “polka-dot” signs [ 5 ]. This composition gives the lesion an iso- to hypointense appearance on T1-weighted MRI as well as a very high intensity appearance on T2-weighted and fluid-sensitive MRI [ 20 , 31 ] (Fig.  4 ). Atypical VHs often mimic primary bony malignancies or metastases and are more likely to demonstrate aggressive features, often making them difficult to diagnose [ 12 , 13 , 14 , 15 ].

Asymptomatic fifty-six-year-old male with a T9 atypical vertebral hemangioma that appears iso- to hypointense on axial T1 MRI ( A ) and hyperintense on axial T2 MRI ( B ). Atypical vertebral hemangiomas of the L3 and L5 vertebral bodies in a thirty-one-year-old female who presented with backpain. Sagittal T1 ( C ) and T2 ( D ) demonstrate hypo- and hyperintense lesions respectively

Aggressive VHs

Aggressive VHs routinely have atypical features on any imaging modality [ 1 , 5 ]. They may appear radiographically normal or show nonspecific findings such as osteoporosis, pedicle erosion, cortex expansion, vertebral collapse, or irregular vertical trabeculae associated with lytic areas of varying size [ 13 , 15 ] (Fig.  5 ).

Fifty-five-year-old female with an aggressive vertebral hemangioma of the L4 vertebral body with extension into the spinal canal. A Sagittal T1 MRI shows hypo-intensity of the entire vertebral body, although vertebral height is maintained. B Sagittal T2 MRI redemonstrates the lesion but appears hyperintense due to the vascularity of the hemangioma. Axial T1 ( C ) and T2 ( D ) MRI show involvement of the pedicles bilaterally and extension of the lesion into the anterior epidural space

CT findings are often nonspecific, including features such as extraosseous soft tissue expansion, cortical ballooning, or cortical lysis [ 34 , 35 ]. As with atypical VHs, the “corduroy” and “polka-dot” signs may not be readily visualized in aggressive or destructive lesions due to the higher vascular-to-fat ratio common in these hemangiomas [ 5 ]. However, it is important to be mindful of these signs because they can guide to the correct diagnosis. Other CT features that may assist in the diagnosis of inconspicuous VHs include extension of the lesion into the neural arch, involvement of the entire vertebral body, or an irregular honeycomb pattern due to serpentine vascular channels and fatty proliferation within the network of reorganizing bony trabeculae [ 20 ]. Vertebral fractures are rare due to the reinforcement of vertical trabeculae [ 1 ].

The composition of aggressive VHs, with a hypervascular stroma and less fat, results in a hypointense lesion on T1-weighted MRI [ 20 , 31 ] (Fig.  5 ). Again, this may conceal the “corduroy” and “polka-dot” signs which remain amongst the most useful imaging findings in the diagnosis of VHs, particularly in cases where other findings are nonspecific [ 5 ]. These non-specific findings may include hyperintensity on T2-weighted MRI due to the vascular components of the lesion (Fig.  5 ), which is also seen in most neoplastic and inflammatory lesions [ 31 ]. Areas of hyperintensity on fluid-sensitive MRI and the presence of lipid-dense content within the lesion may be seen as well [ 31 , 36 ]. Other features suggestive of an aggressive VH include a maintained vertebral body height, a sharp margin with normal marrow, an intact cortex adjacent to a paraspinal mass, or enlarged paraspinal vessels, however these findings are also nonspecific and relatively uncommon [ 5 , 13 ]. Although highly unusual, there have been cases of aggressive VHs with extensive intraosseous fatty stroma and simultaneous extraosseous extension of the lesion, permitting a straightforward diagnosis [ 36 ].

Even though some aggressive VHs may be diagnosed on CT and MRI, challenging cases may warrant the use of more advanced imaging techniques for accurate diagnosis. Higher fluid content relative to cellular soft tissue gives hemangiomas a bright appearance on diffusion weighted imaging (DWI) with elevated apparent diffusion coefficient (ADC) values, distinguishing them from metastases [ 37 ]. Volume transfer constant (K trans ) and plasma volume, which reflect capillary permeability and vessel density respectively, are quantitative measures derived from dynamic contrast enhanced magnetic resonance imaging (DCE MRI) perfusion imaging that can also be used to differentiate VHs and metastases [ 38 ]. K trans and plasma volume are both low in VHs and elevated in metastatic lesions [ 38 ]. Furthermore, aggressive VHs may show a signal drop when comparing non-contrast T1-weighted MRI with and without fat suppression, as well as microscopic lipid content on chemical shift imaging [ 39 ]. Finally, characteristic findings of aggressive VHs in angiography include vertebral body arteriole dilation, multiple capillary phase blood pools, and complete vertebral body opacification [ 15 ].

Laredo et al. [ 15 ] proposed a six-point scoring system to assist in the diagnosis of aggressive VHs based on the more common features observed in radiographs and CT. One point was given for each of the following findings: a soft tissue mass, thoracic location between T3–T9, involvement of the entire vertebral body, an irregular honeycomb appearance, cortical expansion, and extension into the neural arch [ 15 ]. The authors suggest that aggressive VHs should be suspected when a patient presents with nerve root pain in association with three or more of these features [ 15 ]. However, additional studies are needed to determine the utility of this scoring system as the predictive power has not been determined [ 5 ].

Some VHs are difficult to diagnose because they can have nonspecific findings on radiographs, CT, and MRI, making characteristic findings such as the “corduroy” and “polka-dot” signs, when present, important diagnostic features. VHs may also coexist with other vertebral lesions, further complicating the diagnosis. In these cases, angiography can differentiate a VH from a nonvascular lesion [ 40 ]. Ultimately, a biopsy may be required for accurate diagnosis, especially when there is potential for a malignant lesion such as angiosarcoma or epithelioid hemangioendothelioma.

Clinical features

VHs are often noted incidentally on spinal imaging and are often observed in patients in their fifth to sixth decade of life. Studies have shown that vertebral hemangiomas exhibit a slight female preponderance, with a male-to-female ratio of 1:1.5. [ 6 ]. Clinically, most VHs are asymptomatic and quiescent lesions, which rarely demonstrate active behavior and become symptomatic [ 41 ]. VHs occur most frequently in the thoracic spine [ 42 ], followed by the lumbar spine and cervical spine; sacral involvement is very rare [ 43 ].

When symptomatic, VHs can present with localized back pain or result in neurologic symptoms that are attributable to spinal cord compression, nerve root compression, or both, leading to myelopathy and/or radiculopathy [ 1 ]. At least 4 mechanisms of spinal cord and nerve root compression have been suggested: (1) hypertrophy or ballooning of the posterior cortex of the vertebral body caused by the angioma, (2) extension of the angioma through the cortex into the epidural space, (3) compression fracture of the involved vertebra, and (4) epidural hematoma [ 44 ]. When aggressive and symptomatic with spinal cord compression, VHs tend to occur in the thoracic spine [ 42 ].

Boriani et al. classified VHs into 4 groups based on the presence of symptoms and radiographic findings [ 45 ]. These include: Type I—latent, mild bony destruction with no symptoms; Type II—active, bony destruction with pain; Type III—aggressive, asymptomatic lesion with epidural and/or soft-tissue extension; and Type IV—aggressive, neurologic deficit with epidural and/or soft tissue extension.

Management options

Most VHs are asymptomatic and do not require treatment [ 1 , 21 ]. Treatment is indicated in cases with back pain or neurological symptoms, including myelopathy and/or radiculopathy, often caused by neuronal compression or vertebral fracture [ 1 ]. Previously, surgery was the primary treatment option offered to these patients, which was associated with an increased risk of complications, particularly intraoperative bleeding [ 1 ]. New modalities such as vertebroplasty have since gained traction as adjuncts or alternatives to surgery [ 1 ]. Today, there are several management options available for the treatment of symptomatic VHs, including conservative medical therapy, surgery, percutaneous techniques, radiotherapy, or a combination of these modalities [ 1 , 46 ].

There is no consensus on the best treatment strategy, however recently Teferi et. al. proposed a treatment algorithm for VHs based on their institutional experience and literature review (Fig.  6 ) [ 1 ]. They recommend conservative management for typical, asymptomatic VHs, CT-guided biopsy and metastatic workup with PET-CT for radiographically atypical VHs, surgical intervention with or without adjuvant therapy in cases with epidural spinal cord compression or vertebral compression fracture, and radiotherapy for recurrent, asymptomatic VHs following surgery.

Algorithm for diagnosis and management of VHs proposed by Teferi et al. [ 1 ]

Surgical treatment of VHs is recommended in cases with rapid or progressive neurologic symptoms including compressive myelopathy or radiculopathy [ 47 ]. Baily et al. documented the first case of surgical management for VHs after they successfully resolved a patient’s paraplegia secondary to an aggressive VH [ 48 ]. Prior to the 1960s, the average neurological recovery rate was 73% (range, 43–85%) with a mortality rate of 11.7% [ 49 ]. This is consistent with a series published by Ghormley et al. in 1941 where 5 symptomatic VH patients were treated with decompressive laminectomy and postoperative radiotherapy. Although three patients achieved partial or complete resolution of neurologic deficits, the procedure resulted in the death of the remaining two patients secondary to significant blood loss [ 50 ]. There were very few cases of symptomatic VHs documented prior to the 1960s, with one literature review reporting only 64 instances of VHs with neurologic dysfunction [ 49 ]. More recent studies demonstrate improvement in surgical outcomes with neurological recovery reaching 100% and mortality as low as 0% [ 42 ].

The goal of surgery is to decompress neural elements and stabilize the spine [ 1 ]. Potential options include corpectomy, involving resection of a portion of the vertebral body containing the hemangioma, followed by anterior column reconstruction and/or laminectomy, which offers indirect decompression [ 1 ]. The selected approach depends on the size of the hemangioma and the extent of vertebral body and/or neural arch involvement due to potential weaknesses in the anterior column and the location of the epidural intrusion into the spinal canal [ 1 ]. For example, corpectomy and reconstruction could be performed in cases with ventral spinal cord compression while cases with dorsal compression could be treated with laminectomy [ 1 ].

Corpectomy has an increased risk of substantial intraoperative blood loss, up to 5 L in some cases, due to the hypervascular nature of VHs [ 1 , 51 ]. Acosta et al. reported an average blood loss of 2.1 L in their series of 10 aggressive VHs treated with corpectomy [ 51 ]. Conversely, laminectomy has a lower surgical burden and reduced risk of significant intraoperative blood loss [ 1 ]. Laminectomy blood loss can be further reduced by nearly 50% by performing vertebroplasty before laminectomy [ 8 ]. Preoperative embolization of VHs should also be considered to minimize intraoperative blood loss and reduce mortality [ 1 , 22 ].

Goldstein et al. demonstrated that en bloc resection may not be necessary, as intralesional resection produced equivalent long-term survival and prevention of recurrence in their series of 65 patients [ 47 ]. However, there have not been any large-scale studies comparing outcomes and recurrence rates of indirect decompression versus corpectomy [ 1 ].

The treatment algorithm proposed by Teferi et al. suggests dividing symptomatic VH patients with radiculopathy or neurological deficit into cohorts of epidural spinal cord compression (ESCC) versus vertebral body compression fracture to determine appropriate surgical intervention (Fig.  6 ) [ 1 ]. Patients with ESCC are encouraged to undergo preoperative embolization followed by laminectomy with or without fusion depending on spinal stability, or preoperative embolization followed by corpectomy and fusion if ESCC is accompanied by extensive anterior column compromise [ 1 ]. Conversely, the recommended treatment for symptomatic VHs secondary to vertebral body compression fracture is posterior laminectomy with decompression and fusion [ 1 ].

Whether through corpectomy or laminectomy, surgical management of VHs has a low recurrence rate [ 1 ]. Piper et al. reported complete remission in 84% of VHs treated surgically in their 2020 meta-analysis [ 52 ]. They also reported a severe complication rate, including pathological fracture, significant intraoperative blood loss, wound infection, and cerebrospinal fluid leak, of 3.5% [ 1 , 52 ].

Percutaneous techniques

Percutaneous techniques include vertebroplasty, sclerotherapy, and embolization which have been rising in popularity as treatment options for VHs in isolation or in combination with surgery [ 1 ].

Vertebroplasty is a minimally invasive procedure that improves the structural integrity of a vertebra by injecting an acrylic compound, such as polymethyl methacrylate (PMMA), into a lesion [ 1 ]. It was first utilized in the treatment of VHs by Galibert et al. in 1987 [ 53 ]. PMMA causes thrombosis and irreversible sclerosis of the hemangiomatous venous pool, shrinking the lesion and consolidating trabecular microfractures [ 1 ]. It allows for rapid recovery of mobility, enhances anterior column support, and provides vertebral stabilization, but does not induce new bone formation due to poor biological activity and absorbability [ 54 , 55 ]. Vertebroplasty is particularly effective in alleviating back pain in VH patients with intravertebral fractures by providing an immediate analgesic effect and has previously been recommended as stand-alone first line therapy for VHs with moderate to severe back pain without neurologic compromise [ 1 , 54 ]. It can also be used in combination with surgery to reduce intraoperative blood loss when given as a preoperative adjunct therapy [ 8 ]. The most common complication of vertebroplasty is extravasation of injected compound outside the vertebral body with rates of 20–35% [ 55 , 56 ]. However, some researchers suggest small amounts of extravasation should be considered a stopping point rather than a complication as the vast majority of cases are asymptomatic [ 55 , 56 ]. In a series of 673 vertebroplasty cases, Layton et al. reported extravasation in 25% of patients with only 1% developing clinical symptoms of new onset radiculopathy (5 patients) or symptomatic pulmonary embolism (1 patient) [ 56 ]. Their second most common complication was rib fracture related to lying prone on the fluoroscopy table during the procedure which occurred in 1% of cases (7 patients) [ 56 ].

Alternatively, sclerotherapy involves direct intralesional injection of ethanol under percutaneous CT-guidance which causes thrombosis and destruction of endothelium, resulting in devascularization, shrinkage of the lesion, and, consequently, decompression of the neural elements [ 46 ]. It was first described as a treatment for VHs in 1994 by Heiss et al. and is less common in the treatment of VHs [ 57 ]. CT angiography is a prerequisite to target the most hypervascular subsection of the lesion and ensure patients are candidates for the procedure without leakage of contrast media, which occurred in 25% of patients in a series of 18 cases [ 58 ]. There are reports of intraoperative sclerotherapy as an adjunct to surgery, but the sample sizes are similarly limited [ 59 , 60 ]. Complications of direct ethanol injection include neurologic deterioration (including Brown- Sequard syndrome), pathologic fractures, and VH recurrence [ 46 , 61 ].

The last option for percutaneous intervention is trans-arterial embolization of feeding vessels using particulate agents [ 1 ]. It has been used as a preoperative adjunct therapy with surgery to reduce blood loss as well as a primary treatment for VHs alone or in conjunction with vertebroplasty [ 41 , 62 , 63 , 64 ]. In a series of 26 patients, Premat et al. demonstrated embolization combined with vertebroplasty was safe and effective in treating pain associated with aggressive VHs but was less effective in resolving motor deficits [ 65 ]. The primary role for embolization in the treatment of compressive VHs is preoperative adjunct therapy to reduce the risk of procedural bleeding [ 62 ].

• Radiotherapy

Radiotherapy (XRT) is a noninvasive approach that can obliterate hemangiomas and relieve pain through vascular necrosis and/or anti-inflammatory effects [ 1 ]. It is a suitable option for VH patients with back pain and no neurologic deficits, or as postoperative adjunct therapy after suboptimal surgical decompression. Patients with neural element compromise often require prompt decompression to prevent irreversible injury that is more appropriately managed with surgery rather than the delayed response offered by XRT [ 1 , 21 , 66 ]. Neurological deficits may, in fact, be aggravated by XRT, as demonstrated in 20% of patients with aggressive VHs from a series of 29 cases by Jiang et al. [ 8 ]. Multiple studies have proclaimed a 60–80% success rate in eliminating symptoms from VHs using XRT, which increases to over 90% when including partial symptom relief [ 8 , 67 , 68 ]. This does include neurological deficits in some cases, but the response of these symptoms to XRT continues to vary [ 52 ]. A radiation dose of at least 34 Gy was recommended by Heyd et al. after their multicenter study identified significantly greater symptom relief and recurrence control compared to lower doses [ 67 ].

XRT is gaining popularity as a postoperative adjunct therapy intended to reduce local recurrence, especially in subtotal resections [ 8 , 52 , 67 ]. There is a 50% recurrence rate in partial resections without adjunct XRT [ 8 , 11 ]. The extent to which XRT can reduce recurrence has not been fully elucidated and has been suggested for future study [ 52 ]. However, these potential benefits must be weighed against the known adverse effects including nausea, fatigue, anorexia, ileus, radionecrosis, and specifically in spinal XRT, radiation myelitis [ 1 , 8 , 52 ].

VHs are often asymptomatic, incidental findings on routine spinal imaging that do not require treatment or follow-up imaging unless they become symptomatic. Most can be diagnosed with characteristic CT and MRI findings while atypical lesions may be difficult to differentiate from alternative diagnoses. Some authors suggest the utilization of emerging imaging techniques such as DWI or DCE MRI to differentiate atypical lesions from malignancies, which is a promising solution that requires further research. Other authors suggest observation with regular follow-up may be the best course of management for asymptomatic, atypical lesions while others still recommend biopsy for definitive diagnosis of atypical lesions. Regardless, there is a consensus that symptomatic lesions should be treated. Most authors recommend surgical decompression for treatment in patients with neurological deficits, but there is ongoing debate as to the optimal treatment for back pain alone. There are several treatment options which should be considered case-by-case given the properties of various lesions. Management algorithms have been suggested but additional research is required to identify the optimal treatment for the many different classifications of VHs.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

• Vertebral hemangioma

Computed tomography

Magnetic resonance imaging

Arteriovenous

Positron emission-computed tomography

Technetium 99-methyl diphosphonate

Diffusion weighted imaging

Apparent diffusion coefficient

Volume transfer constant

Dynamic contrast enhanced magnetic resonance imaging

Epidural spinal cord compression

Polymethyl methacrylate

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Kato, K., Teferi, N., Challa, M. et al. Vertebral hemangiomas: a review on diagnosis and management. J Orthop Surg Res 19 , 310 (2024). https://doi.org/10.1186/s13018-024-04799-5

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SYSTEMATIC REVIEW article

Pd-l1 expression as a potential predictor of immune checkpoint inhibitor efficacy and survival in patients with recurrent or metastatic nasopharyngeal cancer: a systematic review and meta-analysis of prospective trials.

• 1 Department of Clinical Oncology, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China
• 2 School of Nursing, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China

Background: The predictive value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal cancer (NPC) patients receiving immune checkpoint inhibitors (ICIs) remains controversial. This study aimed to evaluate the optimal threshold of PD-L1 expression in predicting the efficacy of ICIs in patients with recurrent or metastatic (R/M) NPC.

Methods: A meta-analysis was performed by retrieving relevant literature from PubMed, EMBASE, and Cochrane Library databases. Data on the pooled risk ratio (RR), mean overall survival (OS), progression-free survival (PFS), overall response rate (ORR) with 95% confidence interval, and 1%, 10%, and 25% PD-L1 expression cutoff points were obtained to examine the role of PD-L1 as a biomarker in R/M NPC patients receiving immunotherapy.

Results: In total, 1,312 patients from 14 studies were included. An improvement in PFS was observed in both patients with PD-L1 ≥ 1% (RR = 0.76, 95% CI 0.62–0.92, P = 0.005) and those with PD-L1 < 1% (RR = 0.68, 95% CI: 0.35–1.32, P = 0.26) who received first-line treatment with immunotherapy, with no significant difference between these subgroups. The pooled ORR was significantly higher in patients with PD-L1 ≥ 1% (ORR = 0.37) than in those with PD-L1 < 1% (ORR = 0.22) (P < 0.01) undergoing subsequent-line treatment. However, when we used the PD-L1 cutoff values of 10% and 25%, there was no significant difference between the positive (PD-L1 expression ≥ the cutoff value) and negative (PD-L1 expression < the cutoff value) subgroups. PD-L1 ≥ 1% also tended to be associated with better PFS and OS.

Conclusions: Our meta-analysis suggested that first-line immunotherapy could significantly improve PFS in R/M NPC patients, regardless of the PD-L1 expression levels. Positive PD-L1 expression (≥ 1%) might be a potential predictive biomarker for a better overall response to immunotherapy in R/M NPC patients in subsequent-line setting.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024495841 PROSPERO, identifier CRD42024495841.

1 Introduction

Nasopharyngeal carcinoma (NPC) is a common type of head and neck cancer with a skewed geographical, ethnic, and sex distribution. It is particularly prevalent in east and southeast Asia, where the highest age-standardized rates occur ( 1 ). According to GLOBOCAN 2020 data, approximately 133,354 new cases and 80,008 deaths from NPC were reported worldwide, of which 62,444 cases (46.8%) and 34,810 deaths (43.5%) were registered in China ( 2 ).

In the past decade, the global incidence and mortality rates of NPC have gradually declined ( 3 ), which could be attributable to lifestyle and environmental changes, the use of intensity-modulated radiation therapy, and the increasing application of adjuvant chemotherapy ( 4 , 5 ). However, approximately 15%–30% of patients who develop recurrent or metastatic (R/M) NPC have a median overall survival (OS) of less than 2 years ( 6 ). The main challenges in treating these patients are overcoming chemo-resistance and reducing the risk of adverse events ( 7 ). Currently, immunotherapies, especially immune checkpoint inhibitors (ICIs), represent a promising strategy to resolve these problems and effectively treat R/M NPC patients.

ICIs, particularly anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies, which activate CD8-positive T cells and induce cancer cell mortality, have revolutionized the treatment of advanced cancers. The tumor microenvironment of NPCs, characterized by massive inflammatory and immune cell infiltration, allows NPC patients to fully benefit from ICI therapy. ICIs have emerged as effective treatment options for patients with refractory R/M NPC. More recently, the Food and Drug Administration (FDA) approved toripalimab as a treatment for R/M NPC to be used in combination with first-line chemotherapies or subsequent-line monotherapies ( 8 ). The National Comprehensive Cancer Network (NCCN) Guidelines version 2.2024 refer to cisplatin/gemcitabine combined with ICIs as the first-line treatment in the management of R/M NPC ( 9 ). However, only about 50% of patients respond to treatment, indicating the major challenge of identifying patients who are suitable for immunotherapy ( 6 ).

The level of PD-L1 expression is one of the most commonly explored predictive biomarkers for the success of ICIs. Previous studies have shown that higher PD-L1 expression levels are associated with a higher response rate and better survival in patients with advanced stage melanoma treated with ICIs ( 10 – 13 ). However, the predictive value of PD-L1 expression in NPC patients receiving ICIs remains controversial ( 14 – 16 ). Currently, there is no report of studies exploring the optimal cutoff value of PD-L1 expression to guide the clinical use of ICIs.

In this systematic review (SR), we comprehensively evaluated whether the expression level of PD-L1 influences the efficacy of anti-PD-1/PD-L1 monotherapy or combined therapy in NPC patients. Furthermore, subgroup analyzes were performed to assess and quantify the best cutoff value for PD-L1-positive tumors to guide future clinical practice.

2 Materials and methods

The study was reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyzes (PRISMA) ( 17 ). The protocol for this SR and meta-analysis was registered in PROSPERO (no.: 495841).

2.1 Eligibility criteria

To be eligible for this SR, studies were required to satisfy the following Population, Intervention, Comparison, Outcomes, and Study design (PICOS) criteria. Patients with a pathological diagnosis of R/M NPC who received immunotherapy with/without other systematic treatments were included. The included studies were required to report at least one clinical outcome, namely OS, progression-free survival (PFS), or overall response rate (ORR), based on the PD-L1 expression levels of patients. Randomized control trials (RCTs) and non-RCTs were considered eligible. There was no restriction on the language or publication status of studies. Patients receiving radiotherapy were not eligible for this SR. Review articles, case reports, conference abstracts, protocols, editorials, and commentaries were also excluded.

2.2 Literature search

A comprehensive literature search was performed on PubMed, Embase, and the Cochrane Library to identify potential eligible studies published from January 2013 to December 6, 2023. We also manually searched for eligible studies by checking the reference lists of retrieved studies to minimize the risk of missing relevant information. The detailed search strategy is described in Supplementary File 1 .

2.3 Literature selection

The titles and abstracts of potential studies were screened independently by two authors (C.H.L.W. and S.K.CH.), and then their full texts were assessed for eligibility. If there was any dispute, it was resolved through discussion between the two authors. A third author (C.L.C.) was consulted to settle unresolved disagreements.

A list of studies for inclusion was generated. For duplicate studies, the most recent and comprehensive version of each was selected for inclusion. SRs identified during the search were examined to ensure that no eligible studies were omitted.

2.4 Data extraction

Data were extracted by one author (R.Y.X.) and cross-reviewed by the other two authors (C.H.L.W. and S.K.CH.). Key information, including authors’ details, year of publication, study population, sample size, patient characteristics, follow-up time, intervention, and results of all prespecified outcomes, were extracted from each eligible study using a pre-designed data-extraction table.

2.5 Methodological quality assessment

The methodological quality of all included studies was evaluated by two reviewers (C.H.L.W. and R.Y.X.) independently using the Cochrane’s Risk of Bias in Randomized Trials (RoB 2) tool for RCTs ( 18 ) and the Cochrane’s Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for non-randomized studies ( 19 ). For the included single-arm non-randomized studies, risk of bias was assessed using a modified ROBINS-I approach ( 20 ). The risk of bias was categorized as low, moderate, serious, or critical. Publication bias was assessed using Egger’s regression test and through a visual inspection of funnel plot asymmetry if there were more than 10 studies ( 21 ).

2.6 Data analysis

To examine the role of PD-L1 among R/M NPC patients receiving immunotherapy with/without other systematic treatment, we conducted a pairwise random-effects meta-analysis comparing immunotherapy plus chemotherapy patients with controls in the first-line therapy setting using RevMan version 5.4. We used pooled risk ratios (RRs) with 95% confidence intervals (CIs) to present PFS data.

Single-arm random-effects meta-analyzes were performed to synthesize the effects of immunotherapy with/without other systematic treatments on the clinical outcomes (i.e. OS, PFS, and ORR) in both first-line and subsequent-line settings using R version 4.2.3. The pooled estimated mean OS and PFS, as well as the pooled ORR with 95% CI, are presented.

For both pairwise and single-arm meta-analyzes, subgroup analysis was performed on each clinical outcome by stratifying patients into two groups (1): PD-L1 positive and (2) PD-L1 negative. Three cutoff points for PD-L1 expression level were used: 1%, 10%, and 25%. We also conducted a sensitivity analysis of the impact of treatments on the clinical outcomes by excluding patients who received combined immunotherapies and targeted therapies. We used I 2 values to quantify the level of heterogeneity, with I 2 < 25% indicating a low level of heterogeneity, 25%–50% indicating a moderate level of heterogeneity, and >50% indicating a high level of heterogeneity ( 22 ).

3.1 Literature search and selection

The literature search yielded 488 citations, among which 99 duplicate studies were removed. After screening the titles and abstracts, 116 eligible articles remained. As the full texts of 15 articles were not available, only 101 remaining papers proceeded to full-text assessment. Eighty-nine of these were excluded because (i) no recurrent or metastatic NPC adult patients were included (n = 22); (ii) treatment included radiotherapy or other therapies (n = 38); (iii) PD-L1 outcomes were not reported (n = 22); or (iv) they were retrospective studies (n = 7). With the identification of one additional reference through manual searches of the reference lists of included studies, a total of 14 studies in 13 articles were included in this systematic review. Details of the literature search and study selection are shown in the PRISMA flow diagram ( Figure 1 ) ( 23 ).

Figure 1 Flow diagram of meta-analysis for inclusion/exclusion of studies.

3.2 Characteristics of the included studies

Basic information on the qualified studies analyzed in this meta-analysis is available in Table 1 . One study was an RCT ( 24 ), two were non-randomized studies ( 25 , 29 ), and 11 were single-arm studies reported in 10 articles ( 26 – 28 , 30 – 36 ). All of the included studies were published between 2017 and 2023, with a majority of them conducted on Asian patients ( 24 – 28 , 30 – 36 ). The total sample size of the included studies was 1,434 patients, with six studies having a sample size of more than 100 ( 24 , 25 , 28 , 29 , 31 , 32 ). The follow-up period ranged from 1.0 to 2.5 years. Five studies used combined therapy as the intervention ( 24 , 25 , 33 , 34 , 36 ), while eight studies treated patients with mono-immunotherapy ( 26 – 32 , 35 ). These studies used different PD-L1 measurements, with four of them using 22C3 ( 26 , 29 , 30 , 36 ) (full details are provided in Table 2 ). Among all of these studies, 11 reported ORR ( 26 – 36 ), while 10 reported PFS ( 24 , 25 , 27 , 29 – 34 , 36 ) and five reported OS ( 27 , 29 – 32 ) based on PD-L1 expression. The overall risk of bias of eight studies (61.5%) ( 24 – 27 , 30 , 32 , 35 , 36 ) was considered low, but that of five studies (38.5%) was moderate ( 28 , 29 , 31 , 33 , 34 ), four of which were due to missing data ( Supplementary Table 1 ).

Table 1 Characteristics of the studies included in the meta-analysis.

Table 2 Technical information of PD-L1 measurement in the included studies.

3.3 Results of first-line treatment

Two studies of first-line therapy that included 505 patients reported PD-L1 levels and related PFS outcomes. As depicted in Figure 2A , the pooled results showed that ICIs significantly prolonged PFS (RR = 0.74, 95% CI: 0.60–0.90, P = 0.003). An improvement in PFS was observed in both patients with PD-L1 ≥ 1% (RR = 0.76, 95% CI 0.62–0.92, P = 0.005) and those with PD-L1 < 1% (RR = 0.68, 95% CI: 0.35–1.32, P = 0.26), with no significant difference between these subgroups. When using the PD-L1 cutoff of 10%, which was only used in the “RATIONAL 309” study, there was a tendency toward better PFS in PD-L1-positive patients, with RRs of 0.78 (95% CI: 0.64–0.95, P = 0.01) and 0.87 (95% CI: 0.63–1.19, P = 0.38) for PD-L1 ≥ 10% and PD-L1 < 10%, respectively ( Figure 2B ).

Figure 2 Forest plot of RR of PFS after first-line treatment. (A) 1% cut off; (B) 10% cutoff. PDL1, programmed cell death ligand-1; RR, risk ratio; PFS, progression-free survival.

3.4 Results of subsequent-line treatments

Twelve studies with 929 patients were included in this meta-analysis of first- or subsequent-line treatment. The PD-L1 levels reported in these studies were graded using different standards (PD-L1-positive at > 1% TC/IC (n = 10) ( 26 – 28 , 30 – 36 ), PD-L1-positive at > 10% TC/IC (n = 4) ( 29 , 32 , 34 , 35 ), and PD-L1 positive at > 25% TC/IC (n = 3) ( 28 , 30 , 34 ).

3.4.1 ORR of PD-L1 status after subsequent-line treatment

The forest plots show that the pooled ORR was significantly higher for NPC patients with PD-L1 ≥ 1% (ORR = 0.37, 95% CI: 0.29–0.46) than for those with PD-L1 < 1% (ORR = 0.22, 95% CI: 0.17–0.28) (subgroup difference, P < 0.01) ( Figure 3A ).

Figure 3 Forest plot of pooled results of ORR following subsequent-line treatment. (A) 1% cutoff; (B) 10% cutoff; (C) 25% cutoff.

Using a PD-L1 cutoff value of 10% resulted in a similar pattern ( Figure 3B ) (ORR = 0.43, 95% CI: 0.26–0.61 vs ORR = 0.36, 95% CI: 0.13–0.68). Using the 25% threshold for PD-L1 also revealed similar findings, with an ORR of 0.46 (95% CI: 0.24–0.69) in the PD-L1 ≥ 25% subgroup vs an ORR of 0.34 (95% CI: 0.13–0.64) in the PD-L1 < 25% subgroup ( Figure 3C ). However, as a result of the limited sample sizes and significant heterogeneity, differences between the subgroups were not statistically significant. We also noticed that the ORR appeared to rise with increasing PD-L1 expression level, suggesting that the efficacy of ICIs in NPC patients was correlated with PD-L1 expression levels.

To further elucidate the heterogeneity among these studies, sensitivity analysis was performed by excluding patients who received combined immunotherapy and targeted therapy. The results still showed a better ORR (0.29 vs 0.20) for PD-L1-positive patients who received ICI monotherapy, with significantly reduced heterogeneity (I 2  = 0% in both the groups, subgroup difference P = 0.03) ( Figure 4A ). Additionally, ORR improvement was more pronounced in the PD-L1-positive group vs the PD-L1-negative group for subsequent-line ORR with PD-L1 status of 10% (ORR = 0.34, 95% CI: 0.23–0.47 vs ORR = 0.20, 95% CI: 0.12–0.31, P = 0.07) ( Figure 4B ) and for subsequent-line ORR with PD-L1 status of 25% (ORR = 0.35, 95% CI: 0.20–0.52 vs ORR = 0.20, 95% CI: 0.15–0.26, P = 0.07) ( Figure 4C ).

Figure 4 Forest plot of ORR in sensitivity analysis excluding patients who received combined immunotherapy and targeted therapy as subsequent-line treatments. (A) 1% cutoff; (B) 10% cutoff; (C) 25% cutoff.

3.4.2 PFS and OS association with PD-L1 status after subsequent-line treatment

Eight studies reported the PFS and four reported the OS related to a PD-L1 cutoff of 1%. The PFS and OS results showed similar findings that both mean PFS (4.61 months, 95% CI: 2.60–6.62) and OS (17.56 months, 95% CI: 15.09–20.02) for NPC patients with PD-L1 ≥ 1% were longer than those for patients with PD-L1 < 1% (PFS: 3.39 months, 95%CI: 2.36–4.42; OS: 13.5 months, 95% CI: 6.65–20.35), but there was no significant subgroup difference ( Figures 5 , 6 ).

Figure 5 Forest plot showing pooled results of PFS after subsequent-line treatment (1% cutoff).

Figure 6 Forest plot of pooled results of OS after subsequent-line treatment (1% cutoff).

3.5 Publication bias

Publication bias was assessed with an Egger’s regression plot for 12 articles focusing on subsequent-line therapy. The plot revealed no presence of publication bias (P = 0.13), and no asymmetry was found in the funnel plot ( Figure 7 ).

Figure 7 Funnel plot of publication bias.

4 Discussion

To the best of our understanding, this is the first in-depth analysis of the predictive value of PD-1/PD-L1 status in clinical trials of immunotherapy and combined therapy for patients with advanced metastatic NPC. We comprehensively evaluated the correlation between different expression levels of PD-L1 and the ORR, PFS, and OS of R/M NPC patients, with data retrieved from 14 studies that included 1,434 patients in total. We aimed to determine the predictive value of PD-L1 and to identify an optimal PD-L1 cutoff value for the selection of patients likely to respond effectively to anti-PD-1/PD-L1 treatment.

The NCCN guidelines only recommend to use i) cisplatin/gemcitabine alone, or ii) cisplatin/gemcitabine plus toripalimab, or iii) cisplatin/gemcitabine plus the other PD-1 inhibitors (pembrolizumab or nivolumab) as first-line therapies for R/M NPC ( 9 ). In our analysis of the two included studies in the first-line setting, the use of ICIs could significantly improve PFS, regardless of the PD-L1 expression levels. Various ICI monotherapies (toripalimab, pembrolizumab or nivolumab) are recommended as subsequent-line therapy based on the PD-L1 expression levels in NCCN guidelines ( 9 ). The availability of ample subsequent-line treatment data gave us the opportunity to draw more precise and accurate conclusions. The most compelling finding in our study was that patients with PD‐L1 ≥ 1% who received ICI in the subsequent-line setting had significantly higher ORR than in those with PD-L1 < 1%. Our pooled results showed no significant difference between subgroups in analysis of PFS and ORR for PD-L1 cutoff value of ≥ 10%, and ≥ 25%. However, higher the PD-L1 expression, the higher the probability that the patient was able to achieve clinical benefit from ICIs in the subsequent-line setting.

ICIs, which reactivate immune response in the tumor by preventing immunosuppressive factors from binding to their ligands, have fewer side effects compared to chemotherapy ( 37 ). Side effects of ICIs are usually mild. The most common side effects include fatigue, itchy rash, and diarrhea ( 38 ). In addition, as ICIs may also activate autoreactive T cells, they increase the risk of immune-related adverse events (irAEs). In our included studies, irAEs such as hypothyroidism, aspartate aminotransferase(AST) level increased, and rash, were also frequently reported. The detail information is shown in Table 1 .

PD-L1, the most common immunosuppressive ligand, expressed on the tumor cell membrane combines with the PD-1 of tumor-infiltrating lymphocytes (TIL), contributing to tumor cell evasion from host immune system surveillance ( 39 ). In previous studies, high expression of PD-L1 appeared to adversely affect the survival outcomes of NPC patients. A meta-analysis involving 13 studies showed that PD-L1 over-expression in NPC was associated with a poor OS (hazard ratio = 1.48, 95% CI: 1.00–2.18, P = 0.049) ( 40 ). Another study discovered a significant correlation between high PD-L1 expression and a short PFS/OS ( 41 ). In contrast to previous studies that examined the prognostic value of PD-L1 in patients with NPC, our study evaluated the predictive value of PD-L1 expression for ICI therapy. The results provide evidence that PD-L1-positive patients received more benefit than PD-L1-negative patients at a PD-L1 cutoff value of 1%, which sets a preliminary framework for the R/M NPC patient population suitable for ICI treatment. However, as the cutoff values varied across articles, coupled with the fact that 1% was the most widely used expression-level cutoff for PD-L1 detection, more comprehensive studies on PD-L1 expression levels and ICI treatment efficacy are warranted to accurately validate these results.

Moreover, the PD-L1 expression on ICIs effect shows differences between first-line treatment and subsequent-line treatment, which may be caused by many factors. First, it is known that tumor progression is influenced by the tumor immune microenvironment, one of the important mechanisms is escape from immune surveillance with the selection of poorly immunogenic cells ( 42 , 43 ). When the disease becomes refractory, the tumor microenvironment (TME) becomes more immune-suppressive. As a result, in the first-line setting when TME is still favorable, the immunotherapy-chemotherapy combination would improve survival regardless of PD-L1 expression. However, in subsequent line settings when TME becomes more immunosuppressive, only those with higher PD-L1 expression derived benefit from checkpoint inhibitors.

Second, all first-line trials evaluate the immunotherapy-chemotherapy combination while most later-line studies are using immunotherapy-alone ( 44 ). Chemotherapy could activate the T-cell priming and recruitment and works synergistically with immunotherapy, therefore patients who accept first-line treatment of immunotherapy-chemotherapy combination would respond to the treatment regardless of PD-L1 expression.

Though PD-L1 is the most widely studied biomarker for immunotherapy, additional biomarkers have been evaluated in several studies. For instance, a meta-analysis showed that patients with lower baseline plasma Epstein-Barr virus (EBV) DNA levels had a higher ORR and longer median PFS than those with higher EBV DNA levels, but tumor mutational burden (TMB) was not significantly correlated with clinical prognosis in NPC patients treated with ICIs ( 16 ). Furthermore, a statistical difference in PFS was observed between patients with tumors showing loss of HLA-A and/or HLA-B expression, and patients with tumors expressing both HLA-A and HLA-B in trial NCI-9742 ( 26 ). A single-arm phase II clinical trial indicated that, in R/M NPC patients, a strong suppression of TGFβ1 levels was associated with worse ORR and PFS ( 30 ).

With the development of bioinformatics and biotechnologies, novel forms of biomarkers, such as mutations/chromosomal abnormalities, have been made available that provide new perspectives on precision medicine. A recent clinical trial revealed that 11q13.3 focal amplification and high MRGPRF expression are predictive of poor outcomes following gemcitabine plus apatinib and toripalimab therapy, but in another study (POLARIS-02), the genomic alternations had no statistically significant associations with clinical efficacy ( 28 , 33 ). However, our study of the PD-L1 biomarker has particular clinical relevance. PD-L1 status is readily used in clinical settings, as the technology is well established and inexpensive.

Our meta-analysis has several limitations. First, there was significant variability in the literature with regards to the prevalence and prognostic significance of PD-L1 expression in NPC patients, probably because of differences in the assays and scoring methods used across studies. However, in a cross-correlation study performed using different PD-L1 immunohistochemical assays, the JS311 antibody had similar PD-L1 staining patterns and scores to the antibodies 22C3, 28–8, and SP263 ( 45 ). The predictive utility of PD-L1 expression may also depend on its differential expression in immune cells versus tumor cells. Second, there was a lack of sufficient clinical trials of first-line treatments reporting OS and ORR in patients with different PD-L1 expression levels that could be included in our analysis. Despite the encouraging outcomes, the limited number of articles means we are skeptical of the conclusions, and more clinical trials focusing on ICI treatments are needed for further validation. Third, only three and two studies were included in the analysis of the PFS and OS, respectively, for the PD-L1 10% level. More clinical trials are needed to further enrich and validate our conclusions and better guide the use of clinical PD-L1 levels to maximize the benefits and reduce the side effects of ICIs. Lastly, most of the studies included were conducted in Asian populations, and the regional characteristics of NPC may limit the generalizability of our findings.

5 Conclusions

Our meta-analysis suggested that first-line immunotherapy could significantly improve PFS in R/M NPC patients, regardless of the PD-L1 expression levels. Nonetheless, positive PD-L1 expression (≥ 1%) might be a potential predictive biomarker for a better response to immunotherapy in R/M NPC patients in subsequent-line setting. The higher the PD-L1 expression, the higher the probability that the patient was able to achieve clinical benefit from subsequent-line treatment.

Data availability statement

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

Author contributions

RX: Data curation, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing. CW: Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Writing – review & editing. KC: Investigation, Methodology, Validation, Writing – review & editing. CC: Conceptualization, Funding acquisition, Project administration, Supervision, Writing – review & editing.

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

Acknowledgments

We sincerely thank all authors and study participants for their support in the study. Professional English language editing support provided by AsiaEdit (asiaedit.com).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2024.1386381/full#supplementary-material

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Keywords: nasopharyngeal carcinoma, recurrence or metastasis, PD-L1, immune checkpoint inhibitors, meta-analysis

Citation: Xu R, Wong CHL, Chan KSK and Chiang CL (2024) PD-L1 expression as a potential predictor of immune checkpoint inhibitor efficacy and survival in patients with recurrent or metastatic nasopharyngeal cancer: a systematic review and meta-analysis of prospective trials. Front. Oncol. 14:1386381. doi: 10.3389/fonc.2024.1386381

Received: 15 February 2024; Accepted: 20 May 2024; Published: 03 June 2024.

Reviewed by:

Copyright © 2024 Xu, Wong, Chan and Chiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Chi Leung Chiang, [email protected]

† These authors have contributed equally to this work and share first authorship

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Natural Product Reports

Medicinal plant resin natural products: structural diversity and biological activities †.

* Corresponding authors

a Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China E-mail: [email protected]

Covering: up to the mid of 2023

Plants secrete defense resins rich in small-molecule natural products under abiotic and biotic stresses. This comprehensive review encompasses the literature published up to mid-2023 on medicinal plant resin natural products from six main contributor genera, featuring 275 citations that refer to 1115 structurally diverse compounds. The scope of this review extends to include essential information such as the racemic nature of metabolites found in different species of plant resins, source of resins, and revised structures. Additionally, we carefully analyze the reported biological activities of resins, organizing them based on the their structures. The findings offer important insights into the relationship between their structure and activity. Furthermore, this detailed examination can be valuable for researchers and scientists in the field of medicinal plant resin natural products and will promote continued exploration and progress in this area.

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Ectopic ampulla of vater in D4 with adenosquamous carcinoma: case report and literature review

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Mohammed Abdulmohsen AlSharit, Reem Mohammed Althwanay, Abdullah Saleh AlQattan, Abdulrahman Abdullah AlTamimi, Nabeel Mansi, Ectopic ampulla of vater in D4 with adenosquamous carcinoma: case report and literature review, Journal of Surgical Case Reports , Volume 2024, Issue 6, June 2024, rjae377, https://doi.org/10.1093/jscr/rjae377

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Ampulla of Vater (AOV) is typically located in the second part of the duodenum. There are few reported cases of ectopic AOV over the line extending from the pylorus of the stomach down to the distal part of the duodenum. However, to the best of our knowledge, there are only five cases reported in the English literature of an ectopic AOV in the fourth part of the duodenum, with only one of them having adenocarcinoma of the ampulla. Hereby, we report the first case of ectopic AOV in the fourth part of the duodenum, presenting with obstructive due to adenocarcinoma with focal squamous differentiation. This is the case a 42-year-old lady who had a sleeve gastrectomy for morbid obesity in the past. She presented with right upper quadrant pain for one month associated with subjective fever, unintentional weight loss, pale stool, and dark urine. The physical examination revealed a deeply jaundiced lady with an unremarkable abdominal exam. A computed tomography scan of the abdomen revealed intrahepatic and extrahepatic biliary dilation with ectopic insertion of the distal CBD into the fourth part of the duodenum with no evidence of biliary stones. She underwent pancreaticoduodenectomy after difficult biliary decompression. Histopathological diagnosis was moderately differentiated adenocarcinoma, pancreaticobiliary type with focal squamous differentiation. Ectopic AOV is a very rare entity, especially when it is associated with adenosquamous carcinoma changes.

Congenital anomalies of the gallbladder, biliary tree, and pancreas are rare; they can occur during any of the stages of embryogenesis. These congenital anomalies can present with a variety of symptoms, usually during infancy and childhood; hence, they are usually diagnosed early [ 1 ].

The main AOV, which is the convergence of the common bile duct (CBD) and pancreatic duct (PD), is typically located in the second part of the duodenum. An ectopic opening of the AOV into the third and fourth parts of the duodenum, stomach, and along the pyloric canal is very rare, with an incidence ranging from 5.6% to 23%. We can infer from this wide range that these anomalies can only be detected once symptomatic, explaining the scarcity of reported cases [ 2 ]. Some of these cases were presented as acute cholangitis, while others were discovered incidentally [ 2 , 3 ].

However, to the best of our knowledge, there have been only five cases reported in the English literature of an ectopic AOV in the fourth part of the duodenum, with only one of them having adenocarcinoma of the ampulla. Herein, we report the first case of ectopic AOV in the 4th part of the duodenum, presenting with obstructive jaundice secondary to adenocarcinoma with focal squamous differentiation.

We report a case of a 42-year-old female medically free apart from sleeve gastrectomy in the past. She presented to our clinic complaining of right upper quadrant abdominal pain for 1 month. The pain was moderate, colicky, and associated with subjective fever, pale stool, dark urine, and unintentional weight loss.

On examination, she looked deeply jaundiced. Her abdominal exam was unremarkable. Her laboratory workup showed a picture of obstructive jaundice with elevated tumor markers, namely, CEA and Ca 19.9. An abdominal CT scan was done and showed diffused intrahepatic and extrahepatic biliary dilation with ectopic insertion of the distal CBD into the distal duodenum. However, no distal CBD stones were seen. But the bulging of the periampullary region, specifically at the upper border of the ampulla, nevertheless, no clearly delineated periampullary mass can be appreciated. Magnetic resonance cholangiopancreatography [MRCP] showed the same finding ( Fig. 1 ).

MRI in axial and sagittal views shows the location of the AOV tumor, as pointed out by the arrows.

Endoscopic ultrasound (EUS) was carried out to delineate the anatomy and the location of the ampulla of vater (AOV) and showed an abnormally located AOV in the distal duodenum (D4) with dilated CBD. Endoscopic retrograde cholangiopancreatography [ERCP] was performed in the same setting with difficulties in cannulating the ectopic AOV that was associated with mucosal abnormality. After multiple trials, the cannulated pancreaticogram was unremarkable ( Fig. 2 ). The double-wire technique is used to cannulate CBD. Cholangiogram revealed a short distal filling defect suspicious for stones. Several balloon sweeps were done, but no stones were retrieved. Cytology brushing and fluoroscopically guided intraductal biopsy were done. Also, mucosal ampullary biopsies were taken as well. Then, a CBD stent was inserted. The cytology was inconclusive. However, the ampullary biopsy revealed high-grade dysplasia, and invasive carcinoma could not be excluded. Therefore, she was suspected to have ampullary malignancy.

Endoscopic cannulation and location of the tumor.

She had a CT chest to complete the staging workup, which was negative for metastasis. Eventually, she had a pancreaticoduodenectomy (Whipple procedure) with smooth postoperative recovery. The patient was discharged home on postoperative Day 7. The final histopathology came as moderately differentiated adenocarcinoma, pancreaticobiliary type with focal squamous differentiation (5%), invasion into the muscularis propria of the duodenum, and positive lymphovascular invasion with 1/12 LN positive for tumor deposits ( Figs 3 – 6 ). All surgical margins were tumor-free. After a multidisciplinary meeting, the decision was made with proceed for adjuvant chemotherapy. Currently, she is on adjuvant chemotherapy, which she is tolerating well. Follow-up CT CAP at 3- and 6-month intervals postoperatively showed no evidence of recurrence or distant metastasis.

Positive for immune staining CK7.

Microscopic image with H&E staining shows the tumor cells.

Microscopic image with H&E staining shows a tumor interface with normal liver parenchyma.

Positive immune staining for synaptophysin.

The formation of an ectopic AOV has been correlated to the length of the common channel, i.e. the more distal the location of the papilla, the longer the common channel [ 4 ]. Thus, the formation of an ectopic AOV can be associated with multiple embryonic developmental disorders. Also, the location of the AOV is determined at the 22nd day of gestation, while the union of the pancreaticobiliary duct begins at the fifth week of gestation. Another theory suggests that the association between the anomalous pancreatic duct anatomy (PDA) and the ectopic distal location of the AOV is coupled with the presence of congenital bile duct dilatation (CBD) [ 5 ].

Adenosquamous carcinoma (ASC) of the AOV, which is a malignant tumor that exhibits both elements of the glandular and squamous tissue, has multiple theories of histogenesis; Yang et al. [ 6 ] have described four of them. The four theories are: (i) pluripotent stem cells that can induce the malignant transformation of both cell types, (ii) squamous metaplasia in the intestinal mucosa, (iii) malignant squamous metaplastic transformation of the adenocarcinoma, and (iv) collision of the two malignant tumors.

Hoshimoto et al. [ 7 ] have reported a summary of all the published cases of ACS and AOV in the English literature. Most of the cases presented with the following symptoms: biliary colic, jaundice, and constitutional symptoms [ 8 ]. Moreover, there was no sufficient evidence to establish a gender association. However, multiple case series and case reports have suggested that it is more common in males [ 8–10 ].

The diagnosis of ectopic AOV should be established by identifying the orifice in an anomalous location rather than the posteromedial part of the second duodenum. Multiple studies have reviewed the anomalous location of AOV. But Lee and Fu [ 9 ] summarized the most common locations of ectopic AOV, which were in the third or fourth part of the duodenum.

In a case series of 53 patients with an ectopic opening of AOV into the duodenal bulb done by Disibeyaz et al. [ 8 ], male patients were more common than females, with a ratio of 49:4. The patients were diagnosed with either acute cholangitis or recurrent stone disease. These patients underwent transabdominal ultrasonography as an initial study, followed by computed tomography (CT), and finally upper endoscopy with ERCP. In this study, the endoscopic approach was their primary diagnostic and therapeutic modality, and ERCP was performed successfully in 96% of the cases. However, the remaining 4% were diagnosed by a percutaneous transhepatic cholangiogram (PTC) due to failure of cannulation caused by the deformity of the duodenal bulb [ 8 ].

The management of symptomatic ectopic AOV can vary depending on the patient’s presentation and the underlying etiology. However, these patients can be managed surgically or endoscopically [ 11 ]. Regarding the complications, Balli et al. [ 12 ] presented that the utilization of ERCP in cases of bulbar ectopic AOV carries a statistically significant higher rate of pancreatitis, reaching up to 50% compared to only 16.7% for patients who have a normal location of AOV. Furthermore, the success rate of cannulation was insignificantly lower in cases of ectopic AOV in comparison to patients who have normally located AOV. As for ASC of the AOV, surgery remains the mainstay treatment for ASC of the AOV.

With regard to prognosis, the ASC of the AOV has a poor prognosis, with aggressive behavior and a survival rate reaching half that of pancreatic adenocarcinoma. It is speculated that the percentage of squamous cell differentiation within the tumor is related to its progression and aggressiveness, as demonstrated in animal models. Moreover, it appears that it has a high rate of recurrence, with two reported cases of death within 10 months after surgical intervention. Also, the overall survival, according to the summary of all seven reported cases of ASC and AOV in the English literature, ranged from 6 to 20 months [ 7 ].

The ectopic location of AOV is a very rare entity when it is associated with histopathological changes like ASC. Such patients usually present with jaundice and abdominal pain or other non-specific symptoms or even no symptoms. Biliary decompression is difficult, and preoperative histopathological diagnosis by biopsy is usually undermined. The diagnosis usually targets the staging and the extent of the tumor. The management mainly depends on the stage of the disease and the risk of surgical intervention. But the mainstay treatment is surgical resection of the ASC of the AOV at an early stage. The prognosis of the disease itself is unknown, but early detection and resection are recommended.

Study concept or design: A.S.Q., N.M.

Data collection: R.M.A., A.A.T.

Data interpretation: A.S.Q., M.A.S., N.M.

Literature review: R.M.A., M.A.S., A.S.Q.

Drafting of the paper: N.M., M.A.S.

Editing of the paper: M.A.S., A.S.Q.

None declared.

A written informed consent was obtained from the patient for publication.

Ludwig K , Santoro L , Ingravallo G , et al.  Congenital anomalies of the gastrointestinal tract: the liver, extrahepatic biliary tree and pancreas . Pathologica 2022 ; 114 : 55 – 63 .

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Lee H-L , Fu C-K . Acute cholangitis detected ectopic ampulla of Vater in the antrum incidentally: a case report . World J Clin Cases 2021 ; 9 : 3379 – 84 .

Li L , Yamataka A , Yian-Xia W , et al.  Ectopic distal location of the papilla of Vater in congenital biliary dilatation: implications for pathogenesis . J Pediatr Surg 2001 ; 36 : 1617 – 22 .

Li L , Yamataka A , Wang Y-X , et al.  Anomalous pancreatic duct anatomy, ectopic distal location of the papilla of Vater and congenital biliary dilatation: a new developmental triad? Pediatr Surg Int 2003 ; 19 : 180 – 5 .

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Hoshimoto S , Aiura K , Shito M , et al.  Adenosquamous carcinoma of the ampulla of vater: a case report and literature review . World J Surg Oncol 2015 ; 13 : 287 . https://doi.org/10.1186/s12957-015-0709-0 .

Disibeyaz S , Parlak E , Cicek B , et al.  Anomalous opening of the common bile duct into the duodenal bulb: endoscopic treatment . BMC Gastroenterol 2007 ; 7 : 26 . https://doi.org/10.1186/1471-230X-7-26 .

Lee SS , Kim M-H , Lee S-K , et al.  Ectopic opening of the common bile duct in the duodenal bulb: clinical implications . Gastrointest Endosc 2003 ; 57 : 679 – 82 .

Lee HJ , Ha HK , Kim MH , et al.  ERCP and CT findings of ectopic drainage of the common bile duct into the duodenal bulb . Am J Roentgenol 1997 ; 169 : 517 – 20 .

Alkarboly T , Gharib DT , Salih KM , et al.  Ectopic papilla of vater in the pylorus presenting with cholangitis: a case report with literature review . Int J Surg Case Rep 2022 ; 93 : 106 – 887 .

Balli E , Akay T , Yilmaz S . Comparison of the procedure results of ectopic papillae encountered during ERCP procedure with the procedure results of papillae with normal localization . J Surg Med 2021 ; 5 : 70 – 4 .

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NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Lau F, Kuziemsky C, editors. Handbook of eHealth Evaluation: An Evidence-based Approach [Internet]. Victoria (BC): University of Victoria; 2017 Feb 27.

Handbook of eHealth Evaluation: An Evidence-based Approach [Internet].

Chapter 9 methods for literature reviews.

Guy Paré and Spyros Kitsiou .

9.1. Introduction

Literature reviews play a critical role in scholarship because science remains, first and foremost, a cumulative endeavour ( vom Brocke et al., 2009 ). As in any academic discipline, rigorous knowledge syntheses are becoming indispensable in keeping up with an exponentially growing eHealth literature, assisting practitioners, academics, and graduate students in finding, evaluating, and synthesizing the contents of many empirical and conceptual papers. Among other methods, literature reviews are essential for: (a) identifying what has been written on a subject or topic; (b) determining the extent to which a specific research area reveals any interpretable trends or patterns; (c) aggregating empirical findings related to a narrow research question to support evidence-based practice; (d) generating new frameworks and theories; and (e) identifying topics or questions requiring more investigation ( Paré, Trudel, Jaana, & Kitsiou, 2015 ).

Literature reviews can take two major forms. The most prevalent one is the “literature review” or “background” section within a journal paper or a chapter in a graduate thesis. This section synthesizes the extant literature and usually identifies the gaps in knowledge that the empirical study addresses ( Sylvester, Tate, & Johnstone, 2013 ). It may also provide a theoretical foundation for the proposed study, substantiate the presence of the research problem, justify the research as one that contributes something new to the cumulated knowledge, or validate the methods and approaches for the proposed study ( Hart, 1998 ; Levy & Ellis, 2006 ).

The second form of literature review, which is the focus of this chapter, constitutes an original and valuable work of research in and of itself ( Paré et al., 2015 ). Rather than providing a base for a researcher’s own work, it creates a solid starting point for all members of the community interested in a particular area or topic ( Mulrow, 1987 ). The so-called “review article” is a journal-length paper which has an overarching purpose to synthesize the literature in a field, without collecting or analyzing any primary data ( Green, Johnson, & Adams, 2006 ).

When appropriately conducted, review articles represent powerful information sources for practitioners looking for state-of-the art evidence to guide their decision-making and work practices ( Paré et al., 2015 ). Further, high-quality reviews become frequently cited pieces of work which researchers seek out as a first clear outline of the literature when undertaking empirical studies ( Cooper, 1988 ; Rowe, 2014 ). Scholars who track and gauge the impact of articles have found that review papers are cited and downloaded more often than any other type of published article ( Cronin, Ryan, & Coughlan, 2008 ; Montori, Wilczynski, Morgan, Haynes, & Hedges, 2003 ; Patsopoulos, Analatos, & Ioannidis, 2005 ). The reason for their popularity may be the fact that reading the review enables one to have an overview, if not a detailed knowledge of the area in question, as well as references to the most useful primary sources ( Cronin et al., 2008 ). Although they are not easy to conduct, the commitment to complete a review article provides a tremendous service to one’s academic community ( Paré et al., 2015 ; Petticrew & Roberts, 2006 ). Most, if not all, peer-reviewed journals in the fields of medical informatics publish review articles of some type.

The main objectives of this chapter are fourfold: (a) to provide an overview of the major steps and activities involved in conducting a stand-alone literature review; (b) to describe and contrast the different types of review articles that can contribute to the eHealth knowledge base; (c) to illustrate each review type with one or two examples from the eHealth literature; and (d) to provide a series of recommendations for prospective authors of review articles in this domain.

9.2. Overview of the Literature Review Process and Steps

As explained in Templier and Paré (2015) , there are six generic steps involved in conducting a review article:

• formulating the research question(s) and objective(s),
• searching the extant literature,
• screening for inclusion,
• assessing the quality of primary studies,
• extracting data, and
• analyzing data.

Although these steps are presented here in sequential order, one must keep in mind that the review process can be iterative and that many activities can be initiated during the planning stage and later refined during subsequent phases ( Finfgeld-Connett & Johnson, 2013 ; Kitchenham & Charters, 2007 ).

Formulating the research question(s) and objective(s): As a first step, members of the review team must appropriately justify the need for the review itself ( Petticrew & Roberts, 2006 ), identify the review’s main objective(s) ( Okoli & Schabram, 2010 ), and define the concepts or variables at the heart of their synthesis ( Cooper & Hedges, 2009 ; Webster & Watson, 2002 ). Importantly, they also need to articulate the research question(s) they propose to investigate ( Kitchenham & Charters, 2007 ). In this regard, we concur with Jesson, Matheson, and Lacey (2011) that clearly articulated research questions are key ingredients that guide the entire review methodology; they underscore the type of information that is needed, inform the search for and selection of relevant literature, and guide or orient the subsequent analysis. Searching the extant literature: The next step consists of searching the literature and making decisions about the suitability of material to be considered in the review ( Cooper, 1988 ). There exist three main coverage strategies. First, exhaustive coverage means an effort is made to be as comprehensive as possible in order to ensure that all relevant studies, published and unpublished, are included in the review and, thus, conclusions are based on this all-inclusive knowledge base. The second type of coverage consists of presenting materials that are representative of most other works in a given field or area. Often authors who adopt this strategy will search for relevant articles in a small number of top-tier journals in a field ( Paré et al., 2015 ). In the third strategy, the review team concentrates on prior works that have been central or pivotal to a particular topic. This may include empirical studies or conceptual papers that initiated a line of investigation, changed how problems or questions were framed, introduced new methods or concepts, or engendered important debate ( Cooper, 1988 ). Screening for inclusion: The following step consists of evaluating the applicability of the material identified in the preceding step ( Levy & Ellis, 2006 ; vom Brocke et al., 2009 ). Once a group of potential studies has been identified, members of the review team must screen them to determine their relevance ( Petticrew & Roberts, 2006 ). A set of predetermined rules provides a basis for including or excluding certain studies. This exercise requires a significant investment on the part of researchers, who must ensure enhanced objectivity and avoid biases or mistakes. As discussed later in this chapter, for certain types of reviews there must be at least two independent reviewers involved in the screening process and a procedure to resolve disagreements must also be in place ( Liberati et al., 2009 ; Shea et al., 2009 ). Assessing the quality of primary studies: In addition to screening material for inclusion, members of the review team may need to assess the scientific quality of the selected studies, that is, appraise the rigour of the research design and methods. Such formal assessment, which is usually conducted independently by at least two coders, helps members of the review team refine which studies to include in the final sample, determine whether or not the differences in quality may affect their conclusions, or guide how they analyze the data and interpret the findings ( Petticrew & Roberts, 2006 ). Ascribing quality scores to each primary study or considering through domain-based evaluations which study components have or have not been designed and executed appropriately makes it possible to reflect on the extent to which the selected study addresses possible biases and maximizes validity ( Shea et al., 2009 ). Extracting data: The following step involves gathering or extracting applicable information from each primary study included in the sample and deciding what is relevant to the problem of interest ( Cooper & Hedges, 2009 ). Indeed, the type of data that should be recorded mainly depends on the initial research questions ( Okoli & Schabram, 2010 ). However, important information may also be gathered about how, when, where and by whom the primary study was conducted, the research design and methods, or qualitative/quantitative results ( Cooper & Hedges, 2009 ). Analyzing and synthesizing data : As a final step, members of the review team must collate, summarize, aggregate, organize, and compare the evidence extracted from the included studies. The extracted data must be presented in a meaningful way that suggests a new contribution to the extant literature ( Jesson et al., 2011 ). Webster and Watson (2002) warn researchers that literature reviews should be much more than lists of papers and should provide a coherent lens to make sense of extant knowledge on a given topic. There exist several methods and techniques for synthesizing quantitative (e.g., frequency analysis, meta-analysis) and qualitative (e.g., grounded theory, narrative analysis, meta-ethnography) evidence ( Dixon-Woods, Agarwal, Jones, Young, & Sutton, 2005 ; Thomas & Harden, 2008 ).

9.3. Types of Review Articles and Brief Illustrations

EHealth researchers have at their disposal a number of approaches and methods for making sense out of existing literature, all with the purpose of casting current research findings into historical contexts or explaining contradictions that might exist among a set of primary research studies conducted on a particular topic. Our classification scheme is largely inspired from Paré and colleagues’ (2015) typology. Below we present and illustrate those review types that we feel are central to the growth and development of the eHealth domain.

9.3.1. Narrative Reviews

The narrative review is the “traditional” way of reviewing the extant literature and is skewed towards a qualitative interpretation of prior knowledge ( Sylvester et al., 2013 ). Put simply, a narrative review attempts to summarize or synthesize what has been written on a particular topic but does not seek generalization or cumulative knowledge from what is reviewed ( Davies, 2000 ; Green et al., 2006 ). Instead, the review team often undertakes the task of accumulating and synthesizing the literature to demonstrate the value of a particular point of view ( Baumeister & Leary, 1997 ). As such, reviewers may selectively ignore or limit the attention paid to certain studies in order to make a point. In this rather unsystematic approach, the selection of information from primary articles is subjective, lacks explicit criteria for inclusion and can lead to biased interpretations or inferences ( Green et al., 2006 ). There are several narrative reviews in the particular eHealth domain, as in all fields, which follow such an unstructured approach ( Silva et al., 2015 ; Paul et al., 2015 ).

Despite these criticisms, this type of review can be very useful in gathering together a volume of literature in a specific subject area and synthesizing it. As mentioned above, its primary purpose is to provide the reader with a comprehensive background for understanding current knowledge and highlighting the significance of new research ( Cronin et al., 2008 ). Faculty like to use narrative reviews in the classroom because they are often more up to date than textbooks, provide a single source for students to reference, and expose students to peer-reviewed literature ( Green et al., 2006 ). For researchers, narrative reviews can inspire research ideas by identifying gaps or inconsistencies in a body of knowledge, thus helping researchers to determine research questions or formulate hypotheses. Importantly, narrative reviews can also be used as educational articles to bring practitioners up to date with certain topics of issues ( Green et al., 2006 ).

Recently, there have been several efforts to introduce more rigour in narrative reviews that will elucidate common pitfalls and bring changes into their publication standards. Information systems researchers, among others, have contributed to advancing knowledge on how to structure a “traditional” review. For instance, Levy and Ellis (2006) proposed a generic framework for conducting such reviews. Their model follows the systematic data processing approach comprised of three steps, namely: (a) literature search and screening; (b) data extraction and analysis; and (c) writing the literature review. They provide detailed and very helpful instructions on how to conduct each step of the review process. As another methodological contribution, vom Brocke et al. (2009) offered a series of guidelines for conducting literature reviews, with a particular focus on how to search and extract the relevant body of knowledge. Last, Bandara, Miskon, and Fielt (2011) proposed a structured, predefined and tool-supported method to identify primary studies within a feasible scope, extract relevant content from identified articles, synthesize and analyze the findings, and effectively write and present the results of the literature review. We highly recommend that prospective authors of narrative reviews consult these useful sources before embarking on their work.

Darlow and Wen (2015) provide a good example of a highly structured narrative review in the eHealth field. These authors synthesized published articles that describe the development process of mobile health ( m-health ) interventions for patients’ cancer care self-management. As in most narrative reviews, the scope of the research questions being investigated is broad: (a) how development of these systems are carried out; (b) which methods are used to investigate these systems; and (c) what conclusions can be drawn as a result of the development of these systems. To provide clear answers to these questions, a literature search was conducted on six electronic databases and Google Scholar . The search was performed using several terms and free text words, combining them in an appropriate manner. Four inclusion and three exclusion criteria were utilized during the screening process. Both authors independently reviewed each of the identified articles to determine eligibility and extract study information. A flow diagram shows the number of studies identified, screened, and included or excluded at each stage of study selection. In terms of contributions, this review provides a series of practical recommendations for m-health intervention development.

9.3.2. Descriptive or Mapping Reviews

The primary goal of a descriptive review is to determine the extent to which a body of knowledge in a particular research topic reveals any interpretable pattern or trend with respect to pre-existing propositions, theories, methodologies or findings ( King & He, 2005 ; Paré et al., 2015 ). In contrast with narrative reviews, descriptive reviews follow a systematic and transparent procedure, including searching, screening and classifying studies ( Petersen, Vakkalanka, & Kuzniarz, 2015 ). Indeed, structured search methods are used to form a representative sample of a larger group of published works ( Paré et al., 2015 ). Further, authors of descriptive reviews extract from each study certain characteristics of interest, such as publication year, research methods, data collection techniques, and direction or strength of research outcomes (e.g., positive, negative, or non-significant) in the form of frequency analysis to produce quantitative results ( Sylvester et al., 2013 ). In essence, each study included in a descriptive review is treated as the unit of analysis and the published literature as a whole provides a database from which the authors attempt to identify any interpretable trends or draw overall conclusions about the merits of existing conceptualizations, propositions, methods or findings ( Paré et al., 2015 ). In doing so, a descriptive review may claim that its findings represent the state of the art in a particular domain ( King & He, 2005 ).

In the fields of health sciences and medical informatics, reviews that focus on examining the range, nature and evolution of a topic area are described by Anderson, Allen, Peckham, and Goodwin (2008) as mapping reviews . Like descriptive reviews, the research questions are generic and usually relate to publication patterns and trends. There is no preconceived plan to systematically review all of the literature although this can be done. Instead, researchers often present studies that are representative of most works published in a particular area and they consider a specific time frame to be mapped.

An example of this approach in the eHealth domain is offered by DeShazo, Lavallie, and Wolf (2009). The purpose of this descriptive or mapping review was to characterize publication trends in the medical informatics literature over a 20-year period (1987 to 2006). To achieve this ambitious objective, the authors performed a bibliometric analysis of medical informatics citations indexed in medline using publication trends, journal frequencies, impact factors, Medical Subject Headings (MeSH) term frequencies, and characteristics of citations. Findings revealed that there were over 77,000 medical informatics articles published during the covered period in numerous journals and that the average annual growth rate was 12%. The MeSH term analysis also suggested a strong interdisciplinary trend. Finally, average impact scores increased over time with two notable growth periods. Overall, patterns in research outputs that seem to characterize the historic trends and current components of the field of medical informatics suggest it may be a maturing discipline (DeShazo et al., 2009).

9.3.3. Scoping Reviews

Scoping reviews attempt to provide an initial indication of the potential size and nature of the extant literature on an emergent topic (Arksey & O’Malley, 2005; Daudt, van Mossel, & Scott, 2013 ; Levac, Colquhoun, & O’Brien, 2010). A scoping review may be conducted to examine the extent, range and nature of research activities in a particular area, determine the value of undertaking a full systematic review (discussed next), or identify research gaps in the extant literature ( Paré et al., 2015 ). In line with their main objective, scoping reviews usually conclude with the presentation of a detailed research agenda for future works along with potential implications for both practice and research.

Unlike narrative and descriptive reviews, the whole point of scoping the field is to be as comprehensive as possible, including grey literature (Arksey & O’Malley, 2005). Inclusion and exclusion criteria must be established to help researchers eliminate studies that are not aligned with the research questions. It is also recommended that at least two independent coders review abstracts yielded from the search strategy and then the full articles for study selection ( Daudt et al., 2013 ). The synthesized evidence from content or thematic analysis is relatively easy to present in tabular form (Arksey & O’Malley, 2005; Thomas & Harden, 2008 ).

One of the most highly cited scoping reviews in the eHealth domain was published by Archer, Fevrier-Thomas, Lokker, McKibbon, and Straus (2011) . These authors reviewed the existing literature on personal health record ( phr ) systems including design, functionality, implementation, applications, outcomes, and benefits. Seven databases were searched from 1985 to March 2010. Several search terms relating to phr s were used during this process. Two authors independently screened titles and abstracts to determine inclusion status. A second screen of full-text articles, again by two independent members of the research team, ensured that the studies described phr s. All in all, 130 articles met the criteria and their data were extracted manually into a database. The authors concluded that although there is a large amount of survey, observational, cohort/panel, and anecdotal evidence of phr benefits and satisfaction for patients, more research is needed to evaluate the results of phr implementations. Their in-depth analysis of the literature signalled that there is little solid evidence from randomized controlled trials or other studies through the use of phr s. Hence, they suggested that more research is needed that addresses the current lack of understanding of optimal functionality and usability of these systems, and how they can play a beneficial role in supporting patient self-management ( Archer et al., 2011 ).

9.3.4. Forms of Aggregative Reviews

Healthcare providers, practitioners, and policy-makers are nowadays overwhelmed with large volumes of information, including research-based evidence from numerous clinical trials and evaluation studies, assessing the effectiveness of health information technologies and interventions ( Ammenwerth & de Keizer, 2004 ; Deshazo et al., 2009 ). It is unrealistic to expect that all these disparate actors will have the time, skills, and necessary resources to identify the available evidence in the area of their expertise and consider it when making decisions. Systematic reviews that involve the rigorous application of scientific strategies aimed at limiting subjectivity and bias (i.e., systematic and random errors) can respond to this challenge.

Systematic reviews attempt to aggregate, appraise, and synthesize in a single source all empirical evidence that meet a set of previously specified eligibility criteria in order to answer a clearly formulated and often narrow research question on a particular topic of interest to support evidence-based practice ( Liberati et al., 2009 ). They adhere closely to explicit scientific principles ( Liberati et al., 2009 ) and rigorous methodological guidelines (Higgins & Green, 2008) aimed at reducing random and systematic errors that can lead to deviations from the truth in results or inferences. The use of explicit methods allows systematic reviews to aggregate a large body of research evidence, assess whether effects or relationships are in the same direction and of the same general magnitude, explain possible inconsistencies between study results, and determine the strength of the overall evidence for every outcome of interest based on the quality of included studies and the general consistency among them ( Cook, Mulrow, & Haynes, 1997 ). The main procedures of a systematic review involve:

• Formulating a review question and developing a search strategy based on explicit inclusion criteria for the identification of eligible studies (usually described in the context of a detailed review protocol).
• Searching for eligible studies using multiple databases and information sources, including grey literature sources, without any language restrictions.
• Selecting studies, extracting data, and assessing risk of bias in a duplicate manner using two independent reviewers to avoid random or systematic errors in the process.
• Analyzing data using quantitative or qualitative methods.
• Presenting results in summary of findings tables.
• Interpreting results and drawing conclusions.

Many systematic reviews, but not all, use statistical methods to combine the results of independent studies into a single quantitative estimate or summary effect size. Known as meta-analyses , these reviews use specific data extraction and statistical techniques (e.g., network, frequentist, or Bayesian meta-analyses) to calculate from each study by outcome of interest an effect size along with a confidence interval that reflects the degree of uncertainty behind the point estimate of effect ( Borenstein, Hedges, Higgins, & Rothstein, 2009 ; Deeks, Higgins, & Altman, 2008 ). Subsequently, they use fixed or random-effects analysis models to combine the results of the included studies, assess statistical heterogeneity, and calculate a weighted average of the effect estimates from the different studies, taking into account their sample sizes. The summary effect size is a value that reflects the average magnitude of the intervention effect for a particular outcome of interest or, more generally, the strength of a relationship between two variables across all studies included in the systematic review. By statistically combining data from multiple studies, meta-analyses can create more precise and reliable estimates of intervention effects than those derived from individual studies alone, when these are examined independently as discrete sources of information.

The review by Gurol-Urganci, de Jongh, Vodopivec-Jamsek, Atun, and Car (2013) on the effects of mobile phone messaging reminders for attendance at healthcare appointments is an illustrative example of a high-quality systematic review with meta-analysis. Missed appointments are a major cause of inefficiency in healthcare delivery with substantial monetary costs to health systems. These authors sought to assess whether mobile phone-based appointment reminders delivered through Short Message Service ( sms ) or Multimedia Messaging Service ( mms ) are effective in improving rates of patient attendance and reducing overall costs. To this end, they conducted a comprehensive search on multiple databases using highly sensitive search strategies without language or publication-type restrictions to identify all rct s that are eligible for inclusion. In order to minimize the risk of omitting eligible studies not captured by the original search, they supplemented all electronic searches with manual screening of trial registers and references contained in the included studies. Study selection, data extraction, and risk of bias assessments were performed inde­­pen­dently by two coders using standardized methods to ensure consistency and to eliminate potential errors. Findings from eight rct s involving 6,615 participants were pooled into meta-analyses to calculate the magnitude of effects that mobile text message reminders have on the rate of attendance at healthcare appointments compared to no reminders and phone call reminders.

Meta-analyses are regarded as powerful tools for deriving meaningful conclusions. However, there are situations in which it is neither reasonable nor appropriate to pool studies together using meta-analytic methods simply because there is extensive clinical heterogeneity between the included studies or variation in measurement tools, comparisons, or outcomes of interest. In these cases, systematic reviews can use qualitative synthesis methods such as vote counting, content analysis, classification schemes and tabulations, as an alternative approach to narratively synthesize the results of the independent studies included in the review. This form of review is known as qualitative systematic review.

A rigorous example of one such review in the eHealth domain is presented by Mickan, Atherton, Roberts, Heneghan, and Tilson (2014) on the use of handheld computers by healthcare professionals and their impact on access to information and clinical decision-making. In line with the methodological guide­lines for systematic reviews, these authors: (a) developed and registered with prospero ( www.crd.york.ac.uk/ prospero / ) an a priori review protocol; (b) conducted comprehensive searches for eligible studies using multiple databases and other supplementary strategies (e.g., forward searches); and (c) subsequently carried out study selection, data extraction, and risk of bias assessments in a duplicate manner to eliminate potential errors in the review process. Heterogeneity between the included studies in terms of reported outcomes and measures precluded the use of meta-analytic methods. To this end, the authors resorted to using narrative analysis and synthesis to describe the effectiveness of handheld computers on accessing information for clinical knowledge, adherence to safety and clinical quality guidelines, and diagnostic decision-making.

In recent years, the number of systematic reviews in the field of health informatics has increased considerably. Systematic reviews with discordant findings can cause great confusion and make it difficult for decision-makers to interpret the review-level evidence ( Moher, 2013 ). Therefore, there is a growing need for appraisal and synthesis of prior systematic reviews to ensure that decision-making is constantly informed by the best available accumulated evidence. Umbrella reviews , also known as overviews of systematic reviews, are tertiary types of evidence synthesis that aim to accomplish this; that is, they aim to compare and contrast findings from multiple systematic reviews and meta-analyses ( Becker & Oxman, 2008 ). Umbrella reviews generally adhere to the same principles and rigorous methodological guidelines used in systematic reviews. However, the unit of analysis in umbrella reviews is the systematic review rather than the primary study ( Becker & Oxman, 2008 ). Unlike systematic reviews that have a narrow focus of inquiry, umbrella reviews focus on broader research topics for which there are several potential interventions ( Smith, Devane, Begley, & Clarke, 2011 ). A recent umbrella review on the effects of home telemonitoring interventions for patients with heart failure critically appraised, compared, and synthesized evidence from 15 systematic reviews to investigate which types of home telemonitoring technologies and forms of interventions are more effective in reducing mortality and hospital admissions ( Kitsiou, Paré, & Jaana, 2015 ).

9.3.5. Realist Reviews

Realist reviews are theory-driven interpretative reviews developed to inform, enhance, or supplement conventional systematic reviews by making sense of heterogeneous evidence about complex interventions applied in diverse contexts in a way that informs policy decision-making ( Greenhalgh, Wong, Westhorp, & Pawson, 2011 ). They originated from criticisms of positivist systematic reviews which centre on their “simplistic” underlying assumptions ( Oates, 2011 ). As explained above, systematic reviews seek to identify causation. Such logic is appropriate for fields like medicine and education where findings of randomized controlled trials can be aggregated to see whether a new treatment or intervention does improve outcomes. However, many argue that it is not possible to establish such direct causal links between interventions and outcomes in fields such as social policy, management, and information systems where for any intervention there is unlikely to be a regular or consistent outcome ( Oates, 2011 ; Pawson, 2006 ; Rousseau, Manning, & Denyer, 2008 ).

To circumvent these limitations, Pawson, Greenhalgh, Harvey, and Walshe (2005) have proposed a new approach for synthesizing knowledge that seeks to unpack the mechanism of how “complex interventions” work in particular contexts. The basic research question — what works? — which is usually associated with systematic reviews changes to: what is it about this intervention that works, for whom, in what circumstances, in what respects and why? Realist reviews have no particular preference for either quantitative or qualitative evidence. As a theory-building approach, a realist review usually starts by articulating likely underlying mechanisms and then scrutinizes available evidence to find out whether and where these mechanisms are applicable ( Shepperd et al., 2009 ). Primary studies found in the extant literature are viewed as case studies which can test and modify the initial theories ( Rousseau et al., 2008 ).

The main objective pursued in the realist review conducted by Otte-Trojel, de Bont, Rundall, and van de Klundert (2014) was to examine how patient portals contribute to health service delivery and patient outcomes. The specific goals were to investigate how outcomes are produced and, most importantly, how variations in outcomes can be explained. The research team started with an exploratory review of background documents and research studies to identify ways in which patient portals may contribute to health service delivery and patient outcomes. The authors identified six main ways which represent “educated guesses” to be tested against the data in the evaluation studies. These studies were identified through a formal and systematic search in four databases between 2003 and 2013. Two members of the research team selected the articles using a pre-established list of inclusion and exclusion criteria and following a two-step procedure. The authors then extracted data from the selected articles and created several tables, one for each outcome category. They organized information to bring forward those mechanisms where patient portals contribute to outcomes and the variation in outcomes across different contexts.

9.3.6. Critical Reviews

Lastly, critical reviews aim to provide a critical evaluation and interpretive analysis of existing literature on a particular topic of interest to reveal strengths, weaknesses, contradictions, controversies, inconsistencies, and/or other important issues with respect to theories, hypotheses, research methods or results ( Baumeister & Leary, 1997 ; Kirkevold, 1997 ). Unlike other review types, critical reviews attempt to take a reflective account of the research that has been done in a particular area of interest, and assess its credibility by using appraisal instruments or critical interpretive methods. In this way, critical reviews attempt to constructively inform other scholars about the weaknesses of prior research and strengthen knowledge development by giving focus and direction to studies for further improvement ( Kirkevold, 1997 ).

Kitsiou, Paré, and Jaana (2013) provide an example of a critical review that assessed the methodological quality of prior systematic reviews of home telemonitoring studies for chronic patients. The authors conducted a comprehensive search on multiple databases to identify eligible reviews and subsequently used a validated instrument to conduct an in-depth quality appraisal. Results indicate that the majority of systematic reviews in this particular area suffer from important methodological flaws and biases that impair their internal validity and limit their usefulness for clinical and decision-making purposes. To this end, they provide a number of recommendations to strengthen knowledge development towards improving the design and execution of future reviews on home telemonitoring.

9.4. Summary

Table 9.1 outlines the main types of literature reviews that were described in the previous sub-sections and summarizes the main characteristics that distinguish one review type from another. It also includes key references to methodological guidelines and useful sources that can be used by eHealth scholars and researchers for planning and developing reviews.

Typology of Literature Reviews (adapted from Paré et al., 2015).

As shown in Table 9.1 , each review type addresses different kinds of research questions or objectives, which subsequently define and dictate the methods and approaches that need to be used to achieve the overarching goal(s) of the review. For example, in the case of narrative reviews, there is greater flexibility in searching and synthesizing articles ( Green et al., 2006 ). Researchers are often relatively free to use a diversity of approaches to search, identify, and select relevant scientific articles, describe their operational characteristics, present how the individual studies fit together, and formulate conclusions. On the other hand, systematic reviews are characterized by their high level of systematicity, rigour, and use of explicit methods, based on an “a priori” review plan that aims to minimize bias in the analysis and synthesis process (Higgins & Green, 2008). Some reviews are exploratory in nature (e.g., scoping/mapping reviews), whereas others may be conducted to discover patterns (e.g., descriptive reviews) or involve a synthesis approach that may include the critical analysis of prior research ( Paré et al., 2015 ). Hence, in order to select the most appropriate type of review, it is critical to know before embarking on a review project, why the research synthesis is conducted and what type of methods are best aligned with the pursued goals.

9.5. Concluding Remarks

In light of the increased use of evidence-based practice and research generating stronger evidence ( Grady et al., 2011 ; Lyden et al., 2013 ), review articles have become essential tools for summarizing, synthesizing, integrating or critically appraising prior knowledge in the eHealth field. As mentioned earlier, when rigorously conducted review articles represent powerful information sources for eHealth scholars and practitioners looking for state-of-the-art evidence. The typology of literature reviews we used herein will allow eHealth researchers, graduate students and practitioners to gain a better understanding of the similarities and differences between review types.

We must stress that this classification scheme does not privilege any specific type of review as being of higher quality than another ( Paré et al., 2015 ). As explained above, each type of review has its own strengths and limitations. Having said that, we realize that the methodological rigour of any review — be it qualitative, quantitative or mixed — is a critical aspect that should be considered seriously by prospective authors. In the present context, the notion of rigour refers to the reliability and validity of the review process described in section 9.2. For one thing, reliability is related to the reproducibility of the review process and steps, which is facilitated by a comprehensive documentation of the literature search process, extraction, coding and analysis performed in the review. Whether the search is comprehensive or not, whether it involves a methodical approach for data extraction and synthesis or not, it is important that the review documents in an explicit and transparent manner the steps and approach that were used in the process of its development. Next, validity characterizes the degree to which the review process was conducted appropriately. It goes beyond documentation and reflects decisions related to the selection of the sources, the search terms used, the period of time covered, the articles selected in the search, and the application of backward and forward searches ( vom Brocke et al., 2009 ). In short, the rigour of any review article is reflected by the explicitness of its methods (i.e., transparency) and the soundness of the approach used. We refer those interested in the concepts of rigour and quality to the work of Templier and Paré (2015) which offers a detailed set of methodological guidelines for conducting and evaluating various types of review articles.

To conclude, our main objective in this chapter was to demystify the various types of literature reviews that are central to the continuous development of the eHealth field. It is our hope that our descriptive account will serve as a valuable source for those conducting, evaluating or using reviews in this important and growing domain.

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• Cite this Page Paré G, Kitsiou S. Chapter 9 Methods for Literature Reviews. In: Lau F, Kuziemsky C, editors. Handbook of eHealth Evaluation: An Evidence-based Approach [Internet]. Victoria (BC): University of Victoria; 2017 Feb 27.
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• Introduction
• Overview of the Literature Review Process and Steps
• Types of Review Articles and Brief Illustrations
• Concluding Remarks

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