Title: Association of female genital schistosomiasis with human papillomavirus and cervical
pre-cancer: a systematic review
Version: 2 Date: 15 Jul 2024
Reviewer's report:
This systematic review summarizes the available evidence on the association of female genital
schistosomiasis (FSG) and HPV infection/cervical (pre)cancer. Despite a thorough literature
search the authors identified only six studies. The six studies were highly heterogeneous and
could not be summarized in a meta-analysis. The systematic review covers an important topic
and is well written. I only have a few minor comments/questions:
From the title it is not necessarily clear that both HPV and cervical precancer are the outcomes
of interest. Maybe replacing the first “and” with “with” would help?
Based on the methods section of the abstract, it sounds like the authors only searched for
histology-verified cervical precancer/cancer. The authors state “Outcomes defined with cervical
cytology or visual inspection with acetic acid [VIA] were considered as lower quality evidence”
but it is not clear whether this is a justification for only including histology-verified (pre)cancer,
or whether VIA/cytology-based studies were still included. It would be helpful to clarify this
point in the abstract.
“Visual-FGS was defined as FGS diagnosed by primarily by traditional or hand-held
colposcopy.” The first “by” can be removed.
In the results section, the authors state: “Four studies evaluated the association of FGS and
cervical pre-cancerous lesions (three reported cytology-based outcomes [30, 35, 36] and one
reported VIA [29]).” Did Kjetland 1996 not use histological assessment to determine cervical
disease? (From Kjetland 1996: “Further histological examination of the biopsies showed 1 case
of squamous cell carcinoma (in a woman with FGS) and 2 cases of dysplasia (one woman with
FGS and one without).”)
Make sure to introduce all abbreviations (such as HPV, CVL, SCA)  before they are first used.
“The key differences between the studies in Madagascar [38] and KwaZulu-Natal [37] were
median age (31 [25-37]) vs. 18.2 [standard deviation 1.6]),…” I assume that 18.2 [SD 1.6] is
the mean age and not the median age? If yes, then the column “median age” in Table 1 should
also be adapted accordingly.
Table 1: Generally, the column “location” lists a country. Consider referring to South Africa
instead of KZN.
In the beginning of Supplement B, the authors state that cohort studies were evaluating HPV
persistence and cervical cancer incidence. Later, under A point 4) they mention HP-HPV
prevalence as an outcome of interest. Even if HPV prevalence was assessed in a cohort study, the
outcome is cross-sectional. Shouldn’t the grading for cross-sectional studies be applied here?
Supplement B: I assume that “Under Duration of follow-up Long Enough for Outcomes to Occur
(Cohort Studies only)” the score of 1 under point b should be given for those with more than
6 months and score 0 for those with less than 6 months? Also, 6 months are currently included
in the definition of both score 1 and 0.
Supplement B: In the description of HR-HPV prevalence from the Kjetland 2010 study, the
text sometimes refers to HR-HPV persistence, although HR-HPV persistence is described in
a previous paragraph. It would be helpful if the authors could revise the HR-HPV prevalence
paragraph and make sure that the distinction between HR-HPV prevalence and persistence is
clear.