PONE-D-21-15964Addition of digital VIA to conventional naked-eye examination for triage of HPV-positive women: A study conducted in a low-resource settingPLOS ONE

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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: I Don't Know

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: 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: Addition of digital VIA to conventional naked-eye examination for triage of HPV-positive women: A study conducted in a low-resource setting

Thank you for the opportunity to review this paper. It describes a study conducted in West Cameroon to evaluate the improvement in diagnostic performance when supplementing naked-eyed VIA/VILI with digital VIA/VILI using a low-cost smartphone camera. This low cost technology is exciting as it could potentially improve test-see-treat programs in low-resource settings by providing an inexpensive and readily accessible tool that may improve the sensitivity of VIA/VILI for triage of high-risk HPV positive patients. I have a couple of comments/suggestions for the authors:

1) Table 2 lists the VIA/VILI and D-VIA/D-VILI results of each of the 26 patients with CIN2+, stratified by CIN grade. The table is detailed in providing data at the participant level. However, it would be helpful to summarize the data for the reader. Would it be possible to present CIN grade- stratified 2x2 tables, indicating the number (%) within each cell? This would additionally provide the benefit of readily showing the concordance of naked VIA and D-VIA.

<cin2

VIA vs. D-VIA 2x2

CIN2

VIA vs. D-VIA 2x2

CIN3

VIA vs D-VIA 2x2

Cancer

VIA vs D-VIA 2x2

2) Is there any reason why data for patients with low grade CIN aren’t provided? Following the format suggested above, it would be helpful to have a 2x2 table for patients with <cin2.

3) Consort diagram and lines 210-213 on page 13. The authors indicate that 1 patient had a D-VIA with insufficient quality for assessment. However, the next sentence indicates that 188/188 patients with CIN2+ had D-VIA results, while 186 had VIA results.

4) It may be worth reporting on statistically significant differences in negative predictive value—one of the values of good screening/triage tests is providing reassurance to patients with negative triage tests that they can return in one year without fearing that they were mistakenly under-managed. While I didn’t do the math, it seems like a jump from 90.6% NPV to 94.7% is a significant improvement in the reassurance rate.

5) As the target sample size was understandably not attained due to COVID-19, it would be worth mentioning the power of the study given the actual sample size.

6) A few minor editorial comments:

a. Page 6, Procedure—“Midwives independently performed a naked-eye cervical evaluation (native, after acetic acid and Lugol’s iodine). Can you use i.e., after you use the word native to define what that means?

b. Page 4, Introduction, Line 74-76: “Advances in technology for ….. are adapted to the context.” It is unclear what is meant by “adapted to the context” (i.e., are contextual adaptations based on capacity and availability of resources/infrastructure?)</cin2.

</cin2

Reviewer #2: Summary: This study tested how well digital-VIA with a smartphone aided in diagnosis of cervical dysplasia when added to naked-eye VIA. These tests were compared to histological diagnosis of CIN2. The study had to be cut short because of COVID but provided some interesting data that suggests that D-VIA helped in diagnosis and same-day treatment of cervical dysplasia.

Major comments:

1. The idea of using a smartphone with digital images of the cervix to aid in diagnosis has the potential for a low cost and innovative improvement to traditional VIA.

2. The manuscript should be reviewed by a native-English speaker and editor as there are numerous sentences that could be written more clearly and spelling/grammatical mistakes could be corrected.

3. Who reviewed the VIA and D-VIA to determine if they needed treatment? Were these midwives? What if there was a difference of opinion between providers?

4. The methods section in regards to procedures needs to be expanded significantly: specifically, what were the questionnaires asking participants? When was biopsy and ECC being performed? Was this before or after VIA? Did everyone get VIA and VILI? How many images were taken? How were these stored or disposed of securely?

5. Table 1 only includes those who are HPV positive (188) but I think this really should be the total women recruited of 1081 and their characteristics.

6. Are the WHO recommendations for treating dysplasia only if CIN2+? Of those who were not treated as VIA and D-VIA missed dysplasia, how many were called back and successfully treated?

7. I would try and provide some more structure to the introduction: what is known about cervical cancer and its screening and treatment; what is not known; and then what you are hoping to accomplish. Some of the details of VIA and D-VIA could be included in the methods as your ‘intervention’.

8. Was regular VIA also completed prior to digital VIA? I imagine there could be some bias if digital VIA was done before naked-eye VIA.

Minor comments:

1. VIA is visual inspection with acetic acid and VILI is visual inspection with Lugol’s iodine. VILI has different test characteristics than VIA and so technically VIA should just include discussion of acetic acid and not also VILI.

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Reviewer #1: No

Reviewer #2: No

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Addition of digital VIA to conventional naked-eye examination for triage of HPV-positive women: A study conducted in a low-resource setting

PONE-D-21-15964R1

Dear Dr. Dufeil,

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,

Michael Scheurer, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #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 #2: Yes

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

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 #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 #2: Yes

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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 #2: The authors have done a very nice job in addressing the reviewer comments. I just have a few minor comments but otherwise feel this manuscript should be accepted.

Minor comments:

1. In abstract, would not switch between presenting raw numbers or percentages first. I would pick one and use it continuously through the manuscript.

2. Second paragraph of introduction, first sentence could read for better clarity: “Cervical cancer screening allows for the detection and prevention of disease a precancerous stage…”

3. In discussion, the main limitation sentence should read: “The main limitation of the study…which required a temporary shut down of the screening unit, and as a consequence, to terminate the study prematurely.”

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If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #2: No