PONE-D-22-01399Prognostic role of PD-L1 expression in patients with salivary gland carcinoma: a systematic review and meta-analysisPLOS ONE

Dear Dr. Zhang,

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Additional Editor Comments:

The authors perform a meta-analysis of analyzing the association of PD-L1 expression with specific clinicopathological features and prognosis outcomes in salivary gland carcinoma. Please review and address the thoughtful comments from both reviewers.

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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

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

Reviewer #1: Yes

Reviewer #2: 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

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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

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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: The authors have contributed a unique manuscript investigating the prognostic role of PD-L1 expression on patients with salivary gland carcinoma. This manuscript has been registered a priori to PROSPERO, and firmly adheres to PRISMA guidelines. Although there are certain limitations, this paper provides valuable insights into the future management of PD-L1 positive salivary gland carcinomas.

Key limitations include that this review is based on

• Lines 114-117 (Data extraction and quality assessment)

Please clarify if the third reviewer resolved conflicts during the full-text examination ONLY or also for the title/abstract screen. How many authors participated in the full-text assessment? (I assume the prior two, but this should be clearly expressed.)

• Lines 402-406 (Discussion)

The authors repeat this finding from the results in the discussion: “significantly associated with SGC patients' OS and DFS… no significant correlation between PD-L1 expression and DFS or DSS of SGC patients”

First, should the second DFS be PFS? Please ensure the validity/integrity of the data/findings reported prior to resubmission.

What rationale do the authors suggest for these findings? How do the statistically differences between OS/DFS and the nonsignificant differences between PFS/DSS matter clinically?

• Lines 438-446 (Limitations)

This systematic review is based on studies conducted with retrospective data (inferior level of evidence). Please elaborate on this in the limitations section.

• Discussion

Although the authors mention that the heterogeneity between subtypes/treatment limit outcomes in the limitations section, this topic should be further elaborated on.

For instance, significant differences in prognosis exist between subtype (mucoepidermoid carcinoma vs. acinic cell carcinoma), or primary sites (submandibular vs parotid). Further discussion on this is suggested.

Reviewer #2: The authors present a meta-analysis of analyzing the association of PD-L1 expression with specific clinicopathological features and prognosis outcomes in salivary gland carcinoma. They identified 10 independent cohort studies that met their inclusion criteria. The evidence shows a significant association between PD-L1 expression and male gender, older age, T stage, positive N, higher pathological grade, and non- adenoid cystic carcinoma (ACC) subtype. Additionally, they showed a significance between PD-L1 expression and overall survival in the <100 patient subgroup (5 studies) and disease-free survival with pooled hazard ratio data (5 studies).

The study is well written, and the authors used appropriate statistical modeling to account for between study variation.

The study was a literature review, thus no IRB or consent issues

I have two questions/comments for the authors:

1. For the clinicopathological features, how did you define Old or Young. The cutoff values for age listed under table 2 are not clear for what you used to define this criteria.

2. Could you expand further on the meta-regression used for the survival outcomes in your discussion.

Minor points:

1. The 4th and 5th sentences under “Risk of bias in studies” are unclear. 4th sentence makes no sense, and in the 5th sentence do you mean “in-complete follow-up, or evidence of participants missing”?

2. In the first sentence under “Association between PD-L1 expression and OS of SGC patients” do you mean “extracted from seven studies” versus “included research”

3. I am also confused by your use of “with 2 types of research” (line 350) and “which included 18 researches” (Line 360)

4. Space needed between PD-L1 and positive (line 424)

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Reviewer #1: No

Reviewer #2: No

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Prognostic role of PD-L1 expression in patients with salivary gland carcinoma: a systematic review and meta-analysis

PONE-D-22-01399R1

Dear Dr. Zhang,

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.

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Kind regards,

Andrew Birkeland, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have revised their manuscript and responded to the reviewers' comments appropriately.

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 #2: 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 #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 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

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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 #2: 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: The authors have addressed all concerns appropriately. The reviewer would like to thank the authors for their submission!

Reviewer #2: (No Response)

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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 #2: No

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