PONE-D-21-12748

Prevalence of HER2 overexpression and amplification in uterine cervical cancer: a systematic review and a meta-analysis

PLOS ONE

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Additional Editor Comments (if provided):

I appreciate the authors for their nice efforts in planning, conducting, and presenting this systematic review and meta-analysis.

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Article review (Prevalence of HER2 overexpression and amplification in uterine cervical cancer: a systematic review and a meta-analysis, PONE-D-21-12748):

Summary

This is a systematic review and meta-analysis on the prevalence of overexpression or amplification of HER2 in cervical cancer. Overall, this is a well-designed study that provides essential information that could assist in designing clinical trials on targeting HER2 in cervical cancer. This includes an estimate of the prevalence of HER2 alterations and the impact of ASCO/CAP compliant methodology on the HER2 positivity rate.

Comments/Revisions

1. The study is methodologically sound with high-quality data and statistical analysis. There are few grammar and phrasing errors, and professional editing is recommended

2.The term uterine cervical cancer should be replaced by cervical cancer in the title and throughout the manuscript.

3. HER2 targeting has been proven to be an effective therapeutic approach in breast and uterine serous carcinoma. The clinical data in cervical cancer is limited. SUMMIT is a phase II basket trial that included cervical cancer patients and demonstrated evidence of activity. In this preliminary phase of drug development, comparisons to other disease sites that HER2 has an established role are needed. The authors mention heterogeneity in breast and uterine serous cancer, but they should present more specific data on the HER2 expression in breast and uterine serous carcinoma. More information in the ‘Discussion’ is needed to discuss the methodology used and prevalence of overexpression and amplification in these disease sites.

Recommendation

Minor revision

Reviewer #2: Dear Authors:

Thank you for providing so interesting, consolidated data regarding HER2 positivity in such a relevant disease worldwide. I would also like to highlight your cautious and high-quality approach for summarizing observational data by means of systematic review of the literature, for which I have no comments.

I have the following minor comments. I hope they might help for the purpose of your manuscript.

1. Given that PLOSOne public might not be expert on the oncology field, I would consider further contextualization of Cervical Cancer issues in some additional detail. For example:

-What is the disease burden worldwide that makes this study topic relevant?

-What implications would HER2 overexpression detection have either via IHC or FISH? What about diagnostic precision and accessibility in CC?

2. Human Papillomavirus has been clearly related as etiologic risk factor for developing Cervical Cancer. Usual approaches towards controlling or eliminating infection have shown efficacy for preventing CC, but this might have hindered research on other disease mechanisms in the past. Your approach is innovative as it highlights a hypothetical potential prognostic and/or predictive factor in CC, which may contribute as part of multimodal cancer treatment. It would be very interesting if the authors could comment on this relationship so that potential new research could address current knowledge gaps based on your findings (See Conesa-Zamora P et al.Exp Mol Pathol. 2013 Oct;95(2):151-5.)

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Reviewer #1: No

Reviewer #2: Yes: Andres Mauricio Acevedo

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Prevalence of HER2 overexpression and amplification in uterine cervical cancer: a systematic review and a meta-analysis

PONE-D-21-12748R1

Dear Dr. Itkin,

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,

Mona Pathak, PhD

Academic Editor

PLOS ONE