PONE-D-24-38433Clinical efficacy analysis of the Chinese medicine Paiteling applied to human papillomavirus infection: a retrospective studyPLOS ONE

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Additional Editor Comments:

Dear Authors,

Thank you very much for your submission to PLOS ONE. As both reviewers noted, the manuscript is intriguing. I recommend that you revise the manuscript in accordance with their comments.

I look forward to receiving your revised version.

Sincerely,

Kazunori Nagasaka

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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?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

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?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Both in the interferon group and in the paiteling group, the complications related to use should be mentioned in more detail.

Especially the place of interferon therapy today is controversial.

Viral clearance occurs in 90% of these patients within 2 years. In this case, the effectiveness of treatment is questionable.

It would have been more effective if the authors had conducted this study in symptomatic HPV infection cases.

It is debatable how accurate it is only in HPV-DNA+ cases.

Nevertheless, it should be evaluated because it is an original study.

The authors can add the study below as a reference to increase the value of manuscript.

Sarier M, Usta SS, Turgut H, et al. Prognostic value of HPV DNA in Urothelial Carcinoma of the Bladder: A Preliminary Report of 2-Year Follow-up Results. Urol J. 2021;19(1):45-49. doi:10.22037/uj.v18i.6429

Reviewer #2: 1. Data completeness: the article states that no datasets were generated or analysed, which could mean that the study results were based solely on existing medical records without additional data collection to validate those records.

2. Sample size: Although the study included 575 patients with HPV infection, this number may still not be large enough for some subgroups to be analysed, especially when multiple HPV subtypes are considered.

3. Confounding factors: studies may not adequately consider or control for all the confounding factors that may affect the results, such as the patient's age, lifestyle, and allergies to the drug's ingredients。

4. Failure to mention the control group: The article did not mention whether there was a control group using placebo or other treatments, which is crucial for assessing the efficacy of Patulin.

5. Reporting of side effects: The article mentions that some patients in the PATLIN group experienced mild side effects, but these were mostly tolerable and may have disappeared on their own at the end of treatment. However, the reporting of side effects may not be comprehensive enough, as only serious or persistent side effects are more likely to be reported.

6. Statistical analysis: Although statistical software was used to analyse the data, the article does not detail whether the statistical tests used were best suited to the type of data or whether they were adjusted for all possible confounders.

7. Standardisation of treatment: The study mentions the treatment modalities of Patulin and Interferon, but does not detail whether the treatment was administered in exactly the same way in all patients, which may have affected the consistency of the results.

8. Failure to discuss economic costs: The article did not discuss the economic costs of the treatment with PATRIN, which is important for assessing its feasibility in the real world.

Reviewer #3: The study by He et al., titled “Clinical Efficacy Analysis of the Chinese Medicine Paiteling Applied to Human Papillomavirus Infection: A Retrospective Study,” evaluates the effectiveness of Paiteling in treating HPV infections on a population level. This retrospective study included 575 HPV-infected patients from the First People’s Hospital of Jingzhou Gynecology Outpatient Clinic, covering the period from October 2020 to December 2023. The patients were divided into two groups: 319 received Paiteling, while 256 were treated with interferon.

A key strength of this study is the large sample size in both treatment groups. However, a significant limitation is the absence of a clearly defined or sufficiently long post-treatment follow-up period to assess the efficacy of Paiteling compared to interferon. Although the study appears to combine both retrospective (HPV infection) and prospective (treatment and efficacy evaluation) elements, it is classified as a retrospective study. Furthermore, the authors did not clearly explain how this study differs from previous similar studies conducted in China, nor did they adequately compare their findings with earlier research, leading to a somewhat brief discussion.

Major and general comments:

-The authors did not evaluate factors influencing the effectiveness of Paiteling treatment, such as age, baseline viral load, HPV type, single versus multiple HPV infections, immunological and nutritional status, obesity, and other comorbidities.

-Additionally, details on the duration and number of post-treatment follow-ups, as well as the number of patients lost to follow-up, are missing.

-The discussion section is superficial and could benefit from comparisons with previous studies on the clinical efficacy of Paiteling treatment for cervical cancer and the clearance of persistent HPV infections. It is important to determine whether the current findings align with or differ from existing evidence on the effectiveness of Paiteling treatment, to highlight the significance of this study.

-The strengths and limitations of the study should also be addressed. Although the sample size is relatively large, the subcluster analysis of treatment outcomes by HPV types in the two intervention groups is limited by small sample sizes and lacks statistical power. Except for HPV types 16, 18, 52, and 58, the sample sizes for other high and low-risk HPV types are extremely low, which is a common limitation of retrospective study designs in clinical research.

Minor and specific comments:

-Line 90-91: What does the term “information” mean? It might refer to detailed patient information, including demographics, medical history, and clinical outcomes. If this was the case, of course, it was, the authors should delete information in “Information and Methods” and Replace “1.1 General Information” with “1.1 Study Subjects”.

-Line 96: The phrase “those who met the indications for colonoscopy” is unclear. It likely means patients who had medical reasons or criteria that warranted a colonoscopy. You could rephrase it to: “patients who had medical indications for undergoing a colonoscopy.”

-Line 98-99: This sentence “Five hundred and seventy-five patients who met the inclusion and exclusion criteria were screened …” appears incorrect. If the 575 subjects were enrolled because they met the inclusion criteria, you should delete “and exclusion”. The revised sentence would be: “Five hundred and seventy-five patients who met the inclusion criteria were screened.”

-Line 115: “1.3 Methods of Administration” appeared to me unclear. If it refers to how drugs were administered, you should specify this. You could rephrase it to: “1.3 Methods of Drug Administration”. Also, since this section was written as a proposal or protocol, and needs to be rewritten in the past tense. For example: “The drugs were administered according to the following methods…”

-Line 144: Including a figure that demonstrates the flow of participants through the study is a great idea. A figure titled “A flow chart illustrating the number of participants enrolled in different intervention groups, dropouts, and the number of individuals who cleared the virus versus those who did not” needs to be provided in the methods or result section for clarity of the manuscript.

-Line 177: Replace “see Table 2 for details” with “(Table 2)”.

-Line 209: The section on adverse reactions should be more detailed. I suggest generating a table that summarises the findings on adverse reactions. The table provides figures on the number of study participants who developed adverse reactions in the two intervention groups, along with the most commonly observed adverse reactions.

-Line 247: The term “scholars” is vague. It could be referring to researchers or experts. You might want to clarify this based on the context.

-Lines 263-264: The sentence “reduce the patient’s psychological and economic burden, it is worth to promote the clinical” seems incomplete. You could rephrase it to: “ ..reduce the patient’s psychological and economic, and thus, promoting the clinical application of these findings is highly recommended.”

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Reviewer #1: No

Reviewer #2: Yes: Shuguang Zhou

Reviewer #3: Yes: Tesfaye Gelanew

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Clinical efficacy analysis of the Chinese medicine Paiteling applied to human papillomavirus infection: a retrospective study

PONE-D-24-38433R1

Dear Dr. Yi,

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,

Kazunori Nagasaka

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Authors,

Thank you for submitting your manuscript to Plos One.

Our reviewers have recommended that the manuscript is ready for publication. Congratulations on your work! We look forward to receiving your future studies.

Sincerely,

Kazunori Nagasaka

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #3: Yes

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Comments are addressed this paper is ready to publish

Reviewer #3: I have no more comments! However, authors need to meticulously revise to minimize grammatical errors here and there. They need to expand and discuss the limitations of the study, given it has several limitations.

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7. PLOS authors have the option to publish the peer review history of their article (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 #3: Yes: Tesfaye Gelanew

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