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Additional Editor Comments (if provided):

Dear Author,

Based on the reviewers’ feedback, the manuscript has received suggestions for both minor and major revisions. My assessment indicates that a major revision is required.

I have reviewed the manuscript and identified several relevant articles that could strengthen your work. I have provided the links to these articles

https://www.pvj.com.pk/pdf-files/25-421.htm

https://www.pvj.com.pk/pdf-files/24-538.pdf

https://www.pvj.com.pk/pdf-files/25-040.pdf

https://doi.org/10.47278/journal.abr/2024.004

https://doi.org/10.47278/journal.abr/2025.008

DOI : 10.9775/kvfd.2024.32444

please review them carefully and cite them appropriately where applicable.

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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: Partly

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: 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: Yes

Reviewer #3: Yes

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Reviewer #1: Title: Systematic analysis of non-melanoma skin cancer burden: a comparative study

between China and the world from 1990 to 2021 and prediction to 2036.

I. Overall

1. Abbreviations should be defined at first mention and used consistently thereafter (eg. UV, etc.).

II. Abstract

2. Objective: Kindly enunciate the objective through the use of an action verb.

3. Keywords:

a) Kindly replace "Non-melanoma skin cancer" with "Skin cancer."

b) Although "Bayesian age-period-cohort model" and "Joinpoint regression model" are not directly listed in MeSH, terms like "Bayesian Analysis" and "Regression Analysis" can be suitable alternatives.

c) Kindly replace "Burden of Disease" with "Global Burden of Disease."

III. Introduction

1. Lines 30-32 ► “According to GLOBOCAN […] 8% of all cancer deaths”: This declaration is not substantiated by the cited source. It is important to review the statistics you provided to ensure they are supported by a reference.

2. Lines 35-36 ► “The age-standardized incidence […] to 784 (/100,000) in 2019 [5]”: This declaration is not substantiated by the cited source. You need to adopt a more meticulous approach when presenting statements and statistics.

3. Lines 36-39 ► “Moreover, […] in most countries [6]”: I think you can find a more recent reference.

4. Lines 40-41 ► “At present, […] clinical treatment [7, 8]”: Regarding the main assertion of this passage, I was convinced that the references you mentioned would be systematic reviews or meta-analyses demonstrating that there are very few epidemiological studies on NMSC conducted in China, which is not the case. The two references you wisely cited fail to support this fundamental claim.

5. Lines 42-42 ► “Epidemiological evidence […] interventions”: Isn’t it paradoxical to compare the epidemiological data on NMSC between China and the rest of the world, considering you mentioned in the previous paragraph that there is a lack of data on this type of cancer in China?

6. I believe it would be wise to delve deeper into the epidemiological context of NMSC in China.

IV. Materials and methods

1. To ensure the reproducibility of the data analysis, please indicate whether model non-identifiability was addressed and specify the evaluation criteria.

2. Please provide a reference for the formula you used for the breakpoint regression model.

V. Results

1. Wouldn’t it be wise to isolate age and gender in Figures 1, 3, and 5?

VI. Discussion

1. When the acronym "DALY" is used as a quantifiable measure, it should be employed in the plural form (DALYs).

2. Lines 175-178 ► “Although the level of NMSC […] than that of the world”: This passage must be revised to ensure a balance between precision and fluidity, while also eliminating redundancy and fixing the spelling of the acronym "DLAY."

3. Lines 178-181 ► “There were significant gender […] faster in women”: To enhance the clarity of this text, it would be appropriate to split it into two distinct sentences, highlighting the parallelism between the incidence comparisons and those of mortality/DALYs, while incorporating a smoother transition between the two sentences.

4. Lines 204-205 ► “These factors […] from 5th in 1990 to 4th today”: This sentence does not accurately reflect the cited source [20]. It actually outlined the changes in the most common types of cancer and the main causes of cancer-related mortality during the period from 2018 to 2020, rather than from 1990 to 2025, which is implied by your use of the word "today."

5. Lines 211-213 ► “Second, China’s medical […] developed coastal areas”:

a. The logical connector "Second" that you used is not appropriate;

b. It is imperative to cite one or more references.

6. Lines 216-219 ► “According to […] in men than women [22]”: This passage does not match the indicated reference. The mention of the "American Cancer Society" is inappropriate, as the study was conducted by authors who are individuals. The use of expressions like "twice, three times" to quantify proportions makes it difficult to validate and align with the cited data.

7. Lines 224-228 ► “Firstly, […] of developing cancer”: The use of the past tense in writing this passage deceives the reader; it is phrased in a way that makes it seem like a conclusion, while it actually represents aspects of the discussion.

8. Lines 237-240 ► “Between […] by 6.4% per year”:

a. Firstly, this passage does not match the indicated reference [26];

b. Secondly, if it turns out that this passage is supported by a reference, I believe that is misplaced, particularly as it comes after a discussion on the Chinese context, even though it emphasizes the American context.

VII. References

1. Reference [20] has been incorrectly cited in the final list of references.

2. It is clear that the references need to be verified, especially since the year of publication is often repeated in the entries.

3. It would also be wise to include the DOI when possible.

Reviewer #2: in conclusion sections we need to be more specific and get specific recommendations for specific geographic area , there is need to get a specific location inside China with high pervelance of malenoma

Reviewer #3: General comments:

The study is generally well-structured with time trend and prediction components. However, there are a few important statistical limitations and opportunities for enhancement.

While BAPC is an appropriate choice, the manuscript does not clearly communicate whether posterior distributions, credible intervals, or model diagnostics (e.g., DIC, convergence checks) were evaluated to assess forecast reliability.

The use of national-level aggregates may mask important subnational variations. The authors could consider a Bayesian hierarchical model or spatiotemporal modeling approach (e.g., INLA, STAN) in future work to more precisely estimate and compare disease burden patterns across regions, especially within China. The projections assume the continuation of historical patterns. Incorporating scenario-based forecasts (e.g., demographic shifts, UV index changes, intervention uptake) would make predictions more policy-relevant.

Although this is not a meta-analysis in the strict sense, the paper would benefit from methods used in systematic reviews, such as sensitivity analyses, effect size estimations, and heterogeneity testing, especially when comparing China to global averages.

Detailed comments:

Abstract

A comprehensive grammar and style revision is recommended. The section reads as a rough translation and would benefit from professional language editing or rewriting with better fluency.

“The increase rates (707.31%, 16.00%, and 10.04%) and upward trends -” The wording is unclear and needs to be clarified as to what these percentages refer to. A language and grammar check throughout the abstract is needed to improve readability and academic tone.

The abstract mentions using the Joinpoint regression model and the Bayesian age-period-cohort model. Still, it does not specify how the data were handled, what population demographics were considered, or how the models were validated. A sentence on the scope of data (like population, age range) and model assumptions would improve transparency

In the results, are the percentages the total increase over the period or annual averages? How do the values compare between China and the global average? It is recommended to focus on a few key figures and interpret them succinctly in context.

Introduction

Use the full term first with abbreviation (e.g., "disability-adjusted life years (DALYs)") and remain consistent in using “DALYs” instead of alternating between singular and plural forms.

Line 32: You mention "8% of all cancer deaths," but this conflicts with the relatively low mortality usually associated with NMSC. Double-check this figure.

Line 40: The statement “relatively few epidemiological studies on NMSC in China” is vague. You should briefly cite existing national-level epidemiological sources (if any) to support the claim, or clarify whether the lack is due to underreporting, registry limitations, or low research focus.

Materials and Methods

What ICD codes were used to define NMSC in the GBD dataset? (e.g., ICD-10 C44 for NMSC?) Were age-standardized rates obtained directly from GBD or calculated independently? Clarify the age-standardization process (e.g., using which standard population). What age groups were included in the study? How were male and female data handled? Were trends analyzed separately by sex for each metric? Cite the methods chosen by the previous literature and mention/quote your selection criteria for a specific test.

The model should be described more formally: Did you use the National Cancer Institute’s Joinpoint Regression Program? Specify the full name and source for software: “Joinpoint Regression Program (version 5.0.2) developed by the U.S. National Cancer Institute.”

What significance level was used to identify joinpoints? Were there any constraints on the number of joinpoints? Was model selection based on a permutation test?

In the Bayesian age-period cohort model, what R package was used? What were the prior assumptions, time intervals, or model parameters? How was model fit assessed?

This section is incomplete without including BAPC modeling details, which are critical for prediction validity.

Results

Lines 99-103: The last part about age groups is confusing and partially contradictory. You say: “the lowest was 85+ years old,” then shortly after, say “highest in the world was 85+ years.” Also, 20–54 years is described as the lowest age-specific incidence, but that contradicts earlier groupings. Clarify this.

Lines 141-148: While the data is informative, there’s little attempt to interpret or explain what these DALY trends might mean (e.g., differences in disability impact, treatment access, demographic effects).

Discussion

The discussion blends a summary of results, external context, and policy implications without clear thematic organization. It begins with a generic overview and then jumps to specific issues like tanning, ozone depletion, and tourism without adequate linkage. There’s a lack of focused structure.

The key finding that China has a lower incidence but faster increases and relatively high DALY/mortality burdens deserves deeper analysis. Is this due to late diagnosis, limited access to dermatologic care, or underreporting of non-lethal cases? Why are DALYs and deaths rising faster than globally, despite lower baseline rates?

Statements like “this may be related to…” or “it has been shown that…” are too vague. Citations [14] to [17] are not explained or integrated. It is unclear what study [14] found and how it aligns or differs from your own results. Clearly describe each cited study and explicitly link it to your findings.

Consider gender-specific behaviors (e.g., tanning practices, occupational exposures, cosmetic trends), and whether care-seeking or diagnosis patterns differ. Expand discussion beyond UV exposure. Consider biological factors (e.g., hormone-related differences in immune response), or differences in early detection and healthcare access. Consider referencing recent studies on sex-specific tumor behavior, if available, or national screening trends. Use established concepts like cumulative UV exposure, immunosenescence, or actinic damage to describe the mechanisms more accurately. Please see Sarwar Z., Nomi Z.A., Awais M., Shahbakht R.M., et al. (2025) for a broader discussion on the impact of climate change on disease patterns, including environmental triggers such as increased UV exposure that may contribute to the rising burden of skin-related diseases. Effect of Climate Change on Transmission of Livestock Diseases. Agrobiological Records, 19, 1–11. https://doi.org/10.47278/journal.abr/2025.001

Include mention of improved early detection, increased awareness, and treatment advances (as you briefly touch on with the melanoma example). Clarify whether such progress applies to NMSC specifically. The example about melanoma treatments (e.g., checkpoint inhibitors) may not apply unless explicitly linked. For integrating plant-based compounds into zoonotic disease control strategies, particularly for their potential anthelmintic and immunomodulatory effects, please see Alsayeqh, A.F. (2025). Botanicals: A Promising Control Strategy Against Highly Zoonotic Foodborne Trichinosis. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 31(2), 129–136. https://doi.org/10.9775/kvfd.2023.32154

Include one or two concrete examples of relevant NMSC-related actions under the policy, or state the lack thereof. The section contains meaningful points but needs a more precise, evidence-backed explanation of observed trends, especially regarding aging, gender, and future burden. It should also clarify distinctions between NMSC and melanoma, and better integrate policy and prevention contexts.

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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: Yes:  Hicham EL MOUADDIB, PhD

Reviewer #2: No

Reviewer #3: No

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Systematic analysis of non-melanoma skin cancer burden: a comparative study between China and the world from 1990 to 2021 and prediction to 2036

PONE-D-25-28458R1

Dear Dr. Cao,

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,

Muhammad Ahmad

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewer #1:

Reviewer #2:

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

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

**********

Reviewer #1: Dear authors,

Thank you for the effort you put into improving the manuscript for this revision.

At the end of this second review, I retained only two remarks. The first concerns the first formula you provided. Apparently, due to a font or formatting issue (Line 80), this was not properly edited. Moreover, you should provide a reference for that. The second remark concerns reference [8], for which you should provide an internet link.

Regards,

Reviewer #2: (No Response)

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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

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