Impact of Hormonal Contraceptives on HPV Dynamics in Adolescent Girls and Young Women: Insights from a Randomized Controlled Sub-Study in South Africa

ObjectivesHuman papillomavirus (HPV) is causally associated with cervical cancer, with adolescent girls and young women (AGYW) in sub-Saharan Africa bearing a high burden. Hormonal contraceptives may influence HPV acquisition, persistence, and clearance, but evidence remains inconclusive. Here, we evaluated the impact of hormonal contraceptive methods on HPV prevalence and dynamics in AGYW. MethodsNinety-eight AGYW (15-19 years) were randomized to receive norethisterone enanthate (Net-EN), combined oral contraceptive pills (COCPs), or the etonorgestrel/ethinyl estradiol combined contraceptive vaginal ring (CCVR). Cervical samples were collected at baseline and 16 weeks for HPV genotyping. HPV prevalence, acquisition, persistence, and clearance were compared across contraceptive methods. ResultsBaseline HPV prevalence was high (93/98; 94.9%) and did not differ between arms. At 16 weeks, HPV prevalence remained high (87/97; 89.5%), with no significant differences in overall HPV prevalence or genotype distribution by method. Longitudinal analyses of paired samples (n=87) showed no statistically significant differences in HPV acquisition, persistence, or clearance across methods. However, descriptively distinct patterns of high-risk HPV dynamics were observed, with greater proportions of high-risk HPV clearance in the Net-EN and COCP arms and a higher proportion of newly acquired or persistent high-risk HPV genotypes among CCVR users. ConclusionsHormonal contraceptive methods were not associated with significant differences in overall HPV prevalence or genotype distribution in this cohort of AGYW. Nonetheless, non-significant differences in HPV acquisition, persistence, and clearance were observed over 16-weeks, underscoring the need for larger and longer-term studies to clarify the impact of hormonal contraception on HPV dynamics.