Dear Dr. Paudel,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Dipendra Khatiwada, MD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: No

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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Reviewer #1: The topic of the paper is particularly important for the prevention of HPV infection.

The abstract is well written, as is the introduction.

The methodology is described in detail.

An appropriate statistical analysis was applied.

The results are clearly presented.

In the discussion, the obtained results are compared with data from the literature.

The conclusion is consistent with the aim of the study and its results.

Adequate references were used.

Reviewer #2: This meta-analysis addresses a critical issue concerning HPV infection among Nepalese women. The authors incorporated robust scientific methods and statistical analysis. However, there are several issues regarding the formatting, writing style, and arguments that need to be addressed.

Abstract

Use the full form of ‘human papilloma virus’ for the first instance and use HPV afterward for better clarity (Line: 30)

Rewrite to better clarity (Line: 39)

Introduction

Rewrite “Sexually transmitted infection caused by human papilloma virus (HPV) is common worldwide….” (Line: 43)

Include references before a full stop throughout the manuscript.

“…across various regions of the country” (Line: 51)

Line: 52-53, coverage of both vaccination and HPV screening? Should include statistics for this statement.

Line: 63, use only one ‘strategies’ or ‘policies.’

Use consistency in tense (Line: 62-75). For example, should write “This review further assessed…” in line 72.

Line: 77, “generate recommendations”

Methods

Line: 87, why not 31st December 2024? A justification for the timeline should be included.

Line: 94, use abbreviation only

Line: 101-115, use bullets or numbering for the inclusion and exclusion criteria

“…HPV testing was performed” (Line: 103-104), “…husbands’ migration status” (Line: 107)

On what basis, individuals were labeled as ‘literate’ or ‘illiterate’? (primary education or anything else) Should be more elaborated (Line: 128-129)

Line: 144, mention ‘(CI)’ for use the abbreviation later

Results

Avoid duplications (Line: 171)

Line: 179, use ‘CI’. Also, use three digits from statistics (CI and p-value) for maintaining consistency.

Line: 212-213, what was the p-value?

Line: 219, “…among their wives…”

Rewrite to improve clarity (Line: 221-222)

Correct ‘I2” (Line: 231, 233, 235)

Discussion

Avoid mentioning statistics in the discussion section (Line: 254-257, 262-296)

Line: 260, “…among women….”

Lines: 264-266, discuss comparing with previous findings with reference in a more elaborate way.

Line: 270-271, what are the findings of reviewed articles regarding the importance of vaccination and screening programs? It seems like the authors made assumptions on this, but why did they think so? Please, explain a bit more.

Conclusion

There was no conclusion section in the manuscript. It seems lines 301-308 are conclusive statements, but the strengths of the study are mentioned afterward. Please rewrite and make necessary rearrangements accordingly.

Reviewer #3: This systematic review paper’s stated goal was to “comprehensively analyze the prevalence and distribution of HPV infection among Nepalese women” with the aim of estimating the prevalence, genotype distribution and risk factors for HPV infections among this population. The stated a number of other specific objectives among which were to explore the methods of screening adopted in the studies reviewed and compare findings on prevalence with regional and global figures.

Their review protocol and its methodology were duly registered and the aim was to calculate a pooled prevalence/proportion which will provide insights into the epidemiology of HPV infection among Nepalese women and contribute to improvements in public health actions against these disease. They also hoped to describe the associated factors of HPV infection which will help contextualize preventive efforts.

They were fairly successful in describing the burden of HPV and identifying associated factors from previous literature. They adhered in large parts to the registered methodology and the estimated pooled prevalence was largely reflective of the described methodology.

The authors were able to provide a fairly accurate estimation of the prevalence of HPV infection among Nepal’s women from a systematic review of published literature in the region. This estimate is not very reliable given the high degree of heterogeneity recorded in this manuscript. They have also been able to highlight the major factors associated with HPV infections that have been documented in previous studies and hopefully focus additional research questions on those factors.

They were however not able to demonstrate the significance of these factors on the development of HPV infections among Nepal’s women.

The methodology described was appropriate for the goal of the review

but failed to communicate properly the actual steps taken to execute this methodology. While several steps described are reproducible, they were gaps in the presentation that will leave readers feeling lost and confused. The statistical analysis and results presentation followed a similar pattern with several steps not clear and their descriptions falling short of acceptable standards in reporting. While the estimation of pooled prevalence was fairly straightforwards, the description of the process and the accompany tables were not self explanatory from the write up. Similarly, the statistical excursions into the factors associated with HPV infections appeared unnecessary as the data from the reviewed studies do not support such analysis, rendering the conclusions from these analysis void. With such a significant heterogeneity in the studies, the conclusions from these analysis are not supported by the results. The stated goal to estimate a pooled prevalence is sufficiently weakened by the high degree of heterogeneity. Even though a random effects analysis was done, as stated earlier, the presentation of the analysis was not clear as well as the reporting of the results. A sensitivity analysis was not reported.

The figures and tables lacked sufficient explanatory notes and were not well presented. The quality assessment method used was not clear and the table presenting the findings was also not clear The discussion, while acknowledging the limitations of the review, did not sufficiently demonstrated how the authors have met their main goals and objectives. They did not show how their findings corroborate with established knowledge on the subjects or differs from regional and global findings.The authors also failed to address a number of their specific objectives in both the results and discussion sections. Some of their conclusions were also not supported by the presented analysis and results from this review, especially with respect to risk factors.

A major review of the manuscript is required to provide clarity, focus and valid conclusions.

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what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Dear Dr. Paudel,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Thank you for incorporating previous suggestions. Still, few minor revision are suggested. Also make sure you abide my complete journal formatting rules. 

Please submit your revised manuscript by Sep 06 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Dipendra Khatiwada, MD

Academic Editor

PLOS ONE

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

The manuscript is looking in good shape, complete few minor revision as suggested tp proceed further

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #3: Yes

**********

Reviewer #3:  The authors have made a good attempt at implementing the comments from the previous review. The article is clearer and more concise with better presentation of the methodology. There are improvements in the presentation of results section, with more information provided on the statistical analysis conducted. Overall, the manuscript is acceptable for publication with minor revisions.

The section of the introduction that describes the goals on this review(Lines69 -78) should be revised to capture only those goals archived by the article. For example, the authors stated in their second specific objective(line73-74) their desire to correlate major HPV genotypes with cytological abnormalities of the cervix. This goal was not addressed nor was it achieved. Similarly, the objective to assess the epidemiological study designs for methodological strength and weaknesses was also not addressed in this article. The efforts at determining the quality of studies to be included in the study can not be said to have satisfied this objective.

A major methodological limitation of this article is the number of eligible studies included as well as the type of study design. They also failed to assess the studies for reporting bias. This may have further reduced the number of studies included.

The results section, while better presented, still lacks sufficient clarity and is difficult to follow. It will benefit from a few tables that adequately capture the relevant results of the analysis, and better description of findings. The over-reliance on figures directly exported from statistical software and without appropriate footnotes that explain them undermines the efforts at explaining the results. The reader, if not sufficiently knowledgeable will find it hard to understand this section. The authors should present important findings in tables with explanatory summaries under them to enable the reader appreciate the results being presented. A few figures that supports this important findings and significant negatives may remain to aid this process.

The discussion section presented the findings from the review and efforts was made to highlight similarities between the findings and other published works. It did not sufficiently discuss the importance of the prevalence reported from this review.The focus on the associated factors (such as multiple sexual partners, contraception and smoking) took away from the import of the pooled prevalence, especially given the limitations from the types of studies selected for the review. The literature cited were insufficient and there were implied conclusions that did not exactly correlate with the cited literatures. For example, Line 274 - 278 links the findings on husband multiple sexual partners and increased risk of HPV infection with high prevalence of HPV DNA and type-specific concordance between infected women and their male partners. While this underscores spousal/partner transmission, it does not suggest husbands have multiple sexual partners. It will be helpful to elaborate this and to cite relevant studies that support the findings on multiple sexual partners.This findings on multiple sexual partners was repeated too frequently in the discussion.(lines295-298 repeats this point as well as lines 323-3255. Line 316- being the first to attempt a systematic review is not a strength of the systematic review. There is also no need to summarize the methodology again in this section(line319-323. line 323-325 is a repetition.

The authors should be commended for attempting this systematic review despite the limited number of publications that satisfied the criteria for the review.They have made efforts to compensate for this shortcoming in the various statistical analysis carried out, and have made a fair attempt at presenting and discussing the results.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #3: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org

A meta-analysis of the prevalence, genotype distribution and risk factors for human papillomavirus infection in Nepal

PONE-D-25-00319R2

Dear Dr. Paudel,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Dipendra Khatiwada, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: