Dear Dr. Govindsamy,

Dear authors, as you can see, the reviewers have requested substantial revisions to your manuscript. We are certainly willing to reconsider a revised submission, but please know that this is not preliminary acceptance of your paper. When returning your revised manuscript, please be sure to include a point-by-point summary of the suggestions of the reviewers that specifies how and where in the text you have addressed the suggestions.

Please submit your revised manuscript by Jan 18 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 you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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,

Ricardo Ney Oliveira Cobucci, Ph.D

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

Reviewer #2: Partly

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: No

Reviewer #2: Partly

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: No

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: No

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: This systemic review protocol appears too ambitious in attempting to include all cervical cancer prevention strategies. Cervical cancer prevention encompasses primary prevention: HPV vaccination, and secondary prevention: various screening methods. Attempting to address all these strategies simultaneously within one systemic review could result in a lack of focus and clarity. Suggest narrow down to just one strategy.

It is recommended that the authors adopt the PICO framework to effectively structure this systematic review.

Firstly, the target population needs to be clearly defined. The authors should provide a rationale for selecting women aged 9-25 years, particularly given that screening methods is typically aimed at women aged 25-60.

Regarding the intervention or exposure focus, which is central to this study protocol, it should be clarified whether the primary emphasis is on HPV vaccination as a method of primary prevention or on screening methods. Including both aspects may lead to confusion among readers.

Additionally, the study protocol should specify the comparison or control group more explicitly.

The outcomes outlined in the study protocol are currently unclear and require further elaboration.

Reviewer #2: The authors describe the protocol of their proposed systematic review on the effectiveness of integrating cervical cancer prevention strategies into HIV care programs. This integration is vital for cervical cancer control in this vulnerable population and hence, the systematic review is well-timed.

However, there are certain major and few minor concerns regarding this protocol, as described below:

1. "Adolescent girls and young women (AGYW) face heightened risk of persistent HPV infection, a primary cause of cervical cancer." This statement is factually incorrect.

2. Why is the review being limited to studies reported after 2006. Though I agree that HPV vaccination was not available before 2006, but the review also includes cervical cancer screening and management of precancerous lesions. This restriction of time shall lead to erroneous results in these two areas of cervical cancer prevention.

3. "HPV is estimated to infect approximately 291 million women globally, with a significantly higher prevalence among women under the age of 25 years". Though this statement is correct, the authors should also mention that majority of these HPV infections are known to clear on their own.

4. "There are significant disparities in the prevalence of cervical cancer globally which highlights variations in accessibility..." This paragraph is not required and may be removed.

5. The sections on introduction of HPV vaccine, cervical cancer screening and treatment are very long and unnecessary. These need to be shortened extensively.

6. "According to WHO recommendations, females aged 9-20 years should receive one- or two-dose schedules and females 21 years and older should receive two-doses with a six- month interval". This statement is incorrect and in contradiction to the WHO Position Paper on HPV Vaccine, 2022. The reference provided for this statement is not accessible on the web. The authors need to check this information so that wrong information is not provided to the readers.

7. "Such integration can potentially improve access to cervical cancer screening, early detection, and pre-treatment services for AGYW living with HIV". Even in the WHO Guidelines, cervical cancer screening may begin at 21 years of age in women living with HIV. Hence, limiting this review to studies conducted in adolescent girls and young women would greatly limit the results reported thereof. For instance, the study of Mwanahamuntu et al reported cervical cancer screening in women living with HIV with mean age of 34 years.

8. "Moreover, the search end dates of these reviews are outdated being more than six years old- and do not consider recent recommendations and advancements in the field." Which reviews are being referred to here? No references have been provided.

9. For Objective 2, what is the definition of effectiveness of integrating cervical cancer prevention strategies into HIV care programs? Which parameters would be extracted from the included studies for this outcome?

10. How would knowledge, awareness, and willingness combined in the review? The reporting units of various studies could vary significantly.

11. What would be the comparator for the various parameters related to integration of cervical cancer prevention strategies in HIV care programs?

12. For Outcome 1, what would be the data extracted from the included studies? How would that be assessed in the review?

13. For Outcome 2, there should be a comparator to assess the effectiveness against non-integration. In absence of a comparator, the results and conclusion would be less meaningful.

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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 #1: No

Reviewer #2: 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 . Please note that Supporting Information files do not need this step.

Dear Dr. Govindsamy,

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.

Dear, 

a reviewer has also asked for revisions to the manuscript that are important in order to improve the quality and that the reviewer and the editor can consider publishing in the new revision. Authors should carefully evaluate these suggestions, resolve all of them in the manuscript if they consider it possible, or reply to the reviewer with an acceptable justification as to why they do not agree, or are unable to revise as suggested.

Please submit your revised manuscript by Apr 04 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,

Ricardo Ney Oliveira Cobucci, Ph.D

Academic Editor

PLOS ONE

Journal Requirements:

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.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: Yes

Reviewer #2: Partly

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: Yes

Reviewer #2: No

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: The authors have positively responded to the suggestions and have made significant edits, greatly improving this study protocol. I have no further issues.

Reviewer #2: 1. The rationale of including AGYW living with HIV is still not acceptable. The systematic review protocol aims to include all cervical cancer prevention strategies. When the WHO guidelines advocate cervical cancer screening in WLHIV starting at 25 years of age, how would the data align with the objective of the usefulness of cervical cancer screening in HIV care? The authors need to rethink the age group to be included. It would be better to have two age tiers.

2. The rationale of including studies post-2006 is also not acceptable. On the one hand, the authors claim that their systematic review shall have a global significance and on the other, they state that pre-2006, studies on cytology-based screening methods do not align with the WHO global guidelines. The authors need to revisit the WHO cervical cancer screening guidelines. The guidelines state that primary HPV-based screening is the standard. However, if this is not feasible, standardized cytology-based cervical cancer screening is acceptable. Hence, inclusion of only studies published after 2006 would bias the results highly and is not advocated. Duplication of earlier reviews is never an issue with a new systematic review and studies are not excluded solely on this basis.

3. In order to report on the effectiveness of integration of cervical cancer prevention strategies into HIV care programs, only studies with a before-and-after design should be included. This should be specifically stated.

**********

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 #1: No

Reviewer #2: 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

Effectiveness of integrating cervical cancer prevention strategies into HIV care programmes: A mixed-methods systematic review protocol.

PONE-D-24-24785R2

Dear Dr. Govindsamy,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Ricardo Ney Oliveira Cobucci, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The editor considers that the corrections made by the authors in the protocol were sufficient for the manuscript to be accepted, as recommended by one of the reviewers and after a careful editorial evaluation. 

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #2: Partly

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #2: Yes

**********

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

Reviewer #2: Yes

**********

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #2: I am not convinced about the rationale of restricting this review to AGYW living with HIV. Though this population may be at a higher risk of persistent HPV infection, the review should be more encompassing to justify the aim of utility of integrating cervical cancer prevention strategies with HIV care.

**********

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 #2: No

**********