Abstract

Background: Reports from previous studies suggest that the vaginal microbiota may play a role in cervical HPV pathogenesis. In this study, we examined associations between the vaginal microbiome and persistent high-risk human papillomarvirus (hrHPV) infection among HIV-negative and HIV-positive women. Methods: We used 16S rRNA gene amplicon sequencing to characterize the vaginal microbiota in 2 serial mid-vaginal samples taken approximately 6 months apart in 211 Nigerian women and the SPF10LIPA25 system for HPV detection. We used generalized estimating equation (GEE) logistic regression models with robust variance estimation and the cluster option for repeated measures, to evaluate the association between the vaginal microbiota composition and persistent hrHPV infection (defined as being positive for hrHPV at 2 visits 6 months apart); Linear discriminant analysis effect size (LEfSe) to identify phylotype biomarkers of persistent hrHPV; Markov chain transition probabilities to evaluate transition patterns and hierarchical clustering algorithms for community state (CST) assignments. Results: Some 142 women were HIV-positive and 69 were HIV-negative. Of the 211 participants, 71 were persistently positive for hrHPV. Mean age (SD) of participants was 38 (8) years. Most participants (84%, 175/211) were premenopausal. High diversity, low Lactobacillus spp. bacterial community state types, CST IV (A and B) were the most prevalent community state types (CST) in HIV-negative (57% at baseline and 40% at the follow-up visit) and HIV-positive (73% at baseline and 65% at the follow-up visit) women. There was effect modification by HIV status (P = 0.02). Among HIV-negative women, those who had a high relative abundance of Lactobacillus spp. were less likely to have persistent hrHPV (OR: 0.35, 95% CI: 0.14 to 0.89, P = 0.03) compared to women with low relative abundance of Lactobacillus spp. LEfSe analysis identified Sneathia spp as being differentially more abundant in HIV-negative women with persistent hrHPV. Markov chain transition probabilities showed that most CST transitions were to the highly diverse, low Lactobacillus spp., CST IV. In HIV-positive women, there was no significant association between the relative abundance of Lactobacillus spp and persistent hrHPV. Conclusions: Our results provide evidence to suggest that persistent hrHPV is associated with a lack of Lactobacillus spp in the vaginal microbiota of HIV-negative women.

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