PONE-D-19-15806

An observational study comparing HPV prevalence and type distribution between HPV-vaccinated and -unvaccinated girls after introduction of school-based HPV vaccination in Norway

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Reviewer #1: This is an interesting study, which confirms what has previously been seen in Norway with respect to impact of the HPV vaccine programme. Unfortunately, due to the small numbers of the females involved in the study, it is very difficult to see what more such a paper adds to the previously referenced studies from Norway and elsewhere. The utility of using Facebook to recruit women into providing samples and sexual behaviour data is of interest and it is that methodology that I think the authors could focus on more, as a potential for surveillance expansion. However, in its current format, I don't believe the data are particularly novel or representative of a population. The following may help to revise the manuscript.

Questions/comments

1. What has been the uptake of the HPV vaccine in Norway since the programme started? This is not included.

2. Why did Norway move from 4v to 2v? This is not explained and at odds with most countries e.g. UK - the reverse occurred.

3. Please expand on the Facebook recruitment strategy targeting the specific birth cohorts - this is interesting and will be of interest to other countries. Especially if samples are then provided via urine, which has been shown to have similar data with respect to HPV detection, when compared to clinically taken smears.

4. Why are girls vaccinated with bivalent described as unvaccinated? This is not appropriate.

5. Why do the authors change their vaccine status identification from registry to self-reported in the Methods? This is incongruous.

6. Be careful using the term 'rate' with respect to vaccine uptake - they are only rates if a time component is included - otherwise percentage uptake is sufficient and preferable.

7. The authors state that HPV 89 and 90 were most prevalent low-risk types - but no percentages included. Please include.

8. I think it is important to state that while 'vaccine-specific' HPV has reduced, other HR-HPV has not - this suggests a vaccine effect rather than any change in sexual behaviour over time. The authors should develop this.

Reviewer #2: Review Enerly et al.

An observational study comparing HPV prevalence and type distribution between HPV-vaccinated and – unvaccinated girls after a school-based HPV vaccination in Norway

The authors performed a cross sectional study of the HPV prevalence comparing vaccinated and non vaccinated girls in Norway. They used an Evalyn Brush and FLOQSwab device to retrieve material cellular material from the participants from either cervix and oral mucosa. They found a lower prevalence of HPV infections in the vaccinated girls compared to the unvaccinated. The could only ensure at least one vaccination of the participants, which was retrieved from the national epidemiology files.

Major concerns:

The authors present an approved study from the ethics commission and registered the study at the NCT files. However it is doubtful if the participants recruited via facebook are a representative group in this age group. In addition, one must doubt if all participants are able to handle the Evalyn device appropriate. How can the authors ensure that they do observe either false positive or false negative data. To my opinion, controlled studies that are published should ensure that participants see a physician who can ensure that the participant identify herself as the person that take part in the study and that the specimen is taken by an experienced physician under controlled circumstances.

Furthermore, it is to my opinion critical that the authors can only ensure that the girls have received at least only one vaccine shot. Why isn’t it possible that they have all information about the full vaccination program. This is a major setback in the design of the study.

Not surprising the authors have to exclude 210 girls because they did not send back the kit the consent was incomplete. This underscores the major disadvantage of the presented approach the authors have chosen.

Reviewer #3: The sample size is small. But the authors have no commented on this. It is suggested to include justification for the small sample size, in the text. May be it can be included as limitation of the study.

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Reviewer #1: Yes: Kevin Pollock

Reviewer #2: No

Reviewer #3: No

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An observational study comparing HPV prevalence and type distribution between HPV-vaccinated and -unvaccinated girls after introduction of school-based HPV vaccination in Norway

PONE-D-19-15806R1

Dear Dr. Enerly,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Maria Lina Tornesello

Academic Editor

PLOS ONE

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