Objectives: Human papillomavirus (HPV) is the leading cause of cervical cancer, with adolescent girls and young women (AGYW) in subSaharan Africa carrying a disproportionately high burden of infection. Hormonal contraceptives may influence HPV acquisition, persistence, and clearance, but evidence remains inconclusive. This substudy aimed to evaluate the impact of different hormonal contraceptives on HPV prevalence and genotype distribution in AGYW. Methods: Ninety eight HIV-seronegative AGYW aged 15 to 19 years from South Africa were randomized to receive one of three hormonal contraceptive methods: norethisterone enanthate (Net EN) injectable, combined oral contraceptive pills (COCPs), or the etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR). Cervical DNA samples were collected at baseline and after 16 weeks for HPV genotyping using the HPV Direct Flow Chip test. HPV prevalence, persistence, clearance, and acquisition were analyzed across contraceptive methods. Results: At baseline, HPV prevalence was high (94.9%), with no differences among contraceptive arms. After 16 weeks, HPV prevalence remained high (89.5%) across groups. No significant differences were observed in overall HPV prevalence or genotype distribution by contraceptive method. Longitudinal analysis revealed that AGYW using NetEN tended to have a higher cumulative number of high risk HPV (HR HPV) genotypes that cleared whereas those using CCVR acquired more HR HPV types and had greater HR HPV persistence compared to other groups. Conclusions: This study highlights the high burden of HPV among South African AGYW. However, different hormonal contraceptive methods did not significantly influence HR HPV dynamics.

The authors have declared no competing interest.

NCT02404038

This work was funded by the South African Medical Research Council and the US National Institute of Health (R01 HD083040 for this sub-study to [PIs: Heather Jaspan and Jo Ann Passmore], and R01AI094586 for the parent study to Linda Gail Bekker. Merck donated the CCVRs for the study. This HPV sub-study was funded by a grant from the Poliomyelitis Research Foundation to Dr Passmore, and a grant from NRF SARChi Chair to Prof Anna Lise Williamson

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