Reviewer’s report
Title: 
Outcomes of HPV type-specific serostatus do not associate with oral or
genital HPV-carriage in non-vaccinated women followed for three years
Version: 
0 
Date: 
08 Dec 2021
Reviewer's report:
In this study the authors evaluated potential effects that serum antibodies had on
the persistence or clearance of HPV DNA. The data set itself is troubling because
there is a large increase in the percentage of DNA positive women between
months two and six, with the percentage of positive women increasing from 13%
to 47% for type 16 with similar increases seen for the other types. The
percentage of positive women was even higher at month 24 (57% for type 16).
There is not a similar increase in the detection of HPV DNA in oral samples.
Since these women had recently given birth it is unreasonable to expect that they
acquired infections from new partners (authors might have information of
number of new partners to explain this). Perhaps it could be speculated that
changes in their hormonal status permitted an increase in HPV replication but if
that were the case a similar increase would be expected in the oral mucosa.
These anomalous data are not discussed. If the high proportion of DNA positives
is the result of misclassification significant differences between groups based on
serostatus could have been negated. This is a weakness of this study and should
at minimum be discussed. 
Page 9 line28. The authors conclude that being HPV16 seronegative was
associated with an increased likelihood of testing HPV16-DNA positive at visits
24 and 36. I don't see that:
At enrollment there are 134 women who are DNA negative and consistently
seronegative. At month 24 there are only 65 DNA negative women who are
consistently seronegative, thus ~ 50% had acquired DNA (it appears there was
some lost to follow-up). Among the 34 women who were DNA negative and
consistently seropositive at enrollment, at month 24 there are 21 who are still
DNA negative, or about 55% acquired DNA, not different than the seronegative
women. 
Page9 Line 55. "Our previous analysis …". I don't understand didn't all the
women who seroconverted, seroconvert to at least one type? 
Page10 line 44: "Unfortunately, we were unable to elaborate such data for
HPV18 because of the small number of HPV18-infected women". It appears
there were 132 HPV-18 DNA positive women from a total of 233 (55%). The
study showing that high HPV18 antibodies were protective found 293 HPV18
positive women among 11,582 participants (2.9% positive). I'm not sure that the
failure to find a protective effect can be blamed on too few DNA positive
samples but rather that the DNA assay was not specific enough. 
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