Association between female genital schistosomiasis and high-risk human papillomavirus among women of reproductive age in Zambia: the Schista study

BackgroundFemale genital schistosomiasis (FGS) is a chronic gynaecological disease caused by the deposition of Schistosoma haematobium eggs in the female genital tract. It is highly prevalent in sub-Saharan Africa (SSA), the region with the highest cervical cancer incidence and mortality rates globally. Persistent infection with high risk (HR-) human papilloma virus (HPV) is necessary for cervical cancer development. We aimed to determine the cross-sectional association between FGS and HR-HPV genotypes in women across three communities in Zambia. MethodsWomen aged 15-50, sexually active, not menstruating or pregnant, were recruited at home by community health workers. Participants provided two cervicovaginal self-swabs, a urine sample, collected HIV and Trichomonas vaginalis self-tests and completed a questionnaire. At clinic follow-up, midwives collected two cervicovaginal swabs and cervical images with point-of-care colposcopy (EVA System, MobileODTiZI). Swabs were analysed for 14 HR-HPV types (GeneXpertiZI) and for Schistosoma DNA (ITS-2 qPCR). Urine samples were analysed for Schistosoma ova by microscopy and for circulating anodic antigen (CAA) to detect active infection. Visual FGS was defined as colposcopic identification of specific genital lesions. Molecular FGS was defined as Schistosoma qPCR positivecervicovaginal swabs. ResultsA total of 2,532 women (median age 28 years [IQR:22-36]) were recruited at home and 67% (1,694/2,532) completed clinic follow-up. Prevalence of visual FGS, molecular FGS, and HR-HPV were 35.2% [595/1,691], 6.5% [165/2,532], and 28.7% [690/2,401], respectively. HIV seropositivity was 17.5% (443/2,530), with 91.2% (406/443) self-reporting the use of antiretroviral therapy (ART). Risk factors crudely associated with HR-HPV infection included younger age, marital status, higher number of pregnancies, molecular FGS positivity, and urinary S. haematobium positivity detected using microscopy. There was evidence of a weak association between molecular FGS and all HR-HPV (adjusted Odds Ratio [aOR]=1.3, 95% Confidence Intervals [CI] 0.9-1.9). Women with molecular FGS were significantly more likely to test positive for HR-HPV 16/18/45 (aOR=1.7, 95%CI 1.0-2.8). No significant association was observed between visual FGS and HR-HPV infection (crude [c] OR = 0.9, 95% CI 0.7-1.1). ConclusionsTo our knowledge, this is the first study to jointly screen for FGS and HR-HPV in Zambia and to report an association between the most oncogenic HR-HPV types and molecular FGS. These findings call for the need for integrating FGS and HR-HPV screening strategies to address the dual burden in SSA.