Title: Association of female genital schistosomiasis with human papillomavirus and cervical
pre-cancer: a systematic review
Version: 2 Date: 17 Jul 2024
Reviewer:  Tina Bech Olesen
Reviewer's report:
Comments to the authors
Summary
The authors have conducted a systematic review to examine the association between female
genital schistosomiasis and human papillomavirus and cervical pre-cancer. The rationale is that
S. haematobium is considered a carcinogen and associated with other cancer types.
The article is very well-written and the aim of the study is clearly specified. The authors examine
the association between female genital schistosomiasis (FGS) and several outcomes namely the
prevalence, incidence or persistence of cervical HR-HPV and incidence of histology-verified
cervical pre-cancer or cancer. The study protocol is registered at PROSPERO, which is an
advantage. The abstracts were screened using Covidence. The PRISMA guidelines were used
for the reporting of findings.
Only six studies were eligible for inclusion in the study of which five studies were cross-sectional
and one study was prospective.
The authors conclude that few studies have examined the association between female genital
schistosomiasis and human papillomavirus and cervical pre-cancer and the available studies are
of low quality. Therefore, it was not possible to confirm or exclude an association between
female genital schistosomiasis and human papillomavirus and cervical pre-cancer.
Specific comments to the authors
p. 2: I believe “PROSPERO” should be written using capital letters?
p. 2: in the abstract a sentence/ term “work in Madagascar” is used. I would suggest to re-phrase
this to “a study from Madagascar” or similar.
p. 3: in the first paragraph, a sentence on the available HPV vaccines, which HPV types the
vaccines cover and when and in which parts of the world the vaccines were introduced should
be added.
p. 3: I would suggest to re-phrase the following sentence “The high incidence of cervical cancer
in low- and middle-income countries is associated with limited access to HPV vaccination (…)”.
Instead of “associated with”, I would suggest to use “may be caused by” or similar.
p. 3: Perhaps add a sentence stating “other factors may also contribute to the high incidence
of cervical cancer in low and middle-income countries” and then start the sentence introducing
schistosomiasis and female genital schistosomiasis.
p. 3: The inflammatory response is really interesting and may be an important factor in the
development of cervical cancer? Perhaps the authors could elaborate on that?
p. 4: The observation about the lower clearance of HPV is also really interesting.
p. 5: Why is there such a large discrepancy in the prevalence of female genital schistosomiasis
when different detection methods is used? This would then have a large impact on the detected
association between female genital schistosomiasis and human papillomavirus and cervical pre-
cancer. Perhaps the authors could elaborate on that?
p. 6-7: The title of the paragraph is phrased as “Association of FGS and cervical pre-cancer
and cancer”. Perhaps add a sentence stating that “no studies examined the association between
female genital schistosomiasis and cervical cancer”?
p. 7: Important statement that there is “heterogeneity in ascertainment of both the exposure and
the outcome”.
p. 7: Out of curiosity: Are the any initiatives to improve and agree on the diagnosis of female
genital schistosomiasis?
p. 9: Very well-written paragraph on microabrasion and HPV. Perhaps a sentence about
microabrasion, HPV and the role of female genital schistosomiasis could be added to the
introduction also?
p. 10: The conclusion is very long – and perhaps not very specific to this study. I would suggest
to re-write the conclusion so that it aligns with the study objectives.
In conclusion
This article is very well-written and addresses an important and unexplored field of research.
I would suggest to improve the introduction and the conclusion as stated above and put more
emphasis on microabrasion, HPV and female genital schistosomiasis. Other than that, I have
only minor comments as stated in the specific comments above.