The Impact of vaginal microbiota on human Papillomavirus infection.
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Background: Cervical human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) in sub-Saharan African women of reproductive age. While most women clear HPV infection, persistent infection with high-risk HPV is the most common nonsystem biological risk factor for cervical cancer development. Increased levels of proinflammatory cytokines and overgrowth of diverse microbial communities have been implicated in undermining the clearance of the infection and promoting oncogenesis. Here we aimed to evaluate the role of vaginal microbiota composition in the persistence and clearance of HPV infections in women. Methods: This study included the assessment of 56 women who participated in the CAPRISA 083 cohort. The CAPRISA 083 study evaluated point of care STI testing immediate treatment and expedited partner therapy. Sexually transmitted infections (STIs) and BV were screened using the GeneXpert system or OSOM Trichomonas rapid test and Nugent score, respectively. Vaginal swabs and SoftCup genital secretions were collected at enrolment, 6 weeks, and 13 weeks posttreatment. The Roche Linear Array was used for HPV genotyping, and the vaginal microbiome was characterized using 16S rRNA sequencing. Results: The study demonstrated a 36/56 (64 %), 28/56 (50 %), and 36/56 (64 %) prevalent of HPV at baseline, 6 weeks and 13 weeks, respectively. The prevalence of high-risk HPV infection at baseline was 58%, 61% at 6 weeks, and 45% at 13 weeks. HPV 16, 45, 58, and 59 were the most dominant high-risk genotypes in all visits, while HPV 6 was the least common. Overall, 46% (26/56) of participants cleared any HPV genotype, while 45% (25/56) acquired and 38% (21/56) had persisted any HPV genotype at follow-up visits. Alpha diversity of the vaginal microbiome of women with HPV (p value= 0.57) and high-risk HPV (p value= 0.6) infection did not differ significantly to that in vaginal microbiome from uninfected women. LEfSe analysis identified Lactobacillus spp. (particularly L. iners) as potential biomarkers for HPV clearance between visits, whereas HPV persistence was associated with enrichment of Sneathia amnii and other BVassociated bacteria. Conclusion: While our data do not indicate the causal link between the diverse genital microbiome and HPV clearance or persistent, L. iners and Sneathia abundance were associated with HPV clearance and persistent, respectively. These data suggest the need for longitudinal investigation to confirm a biological mechanism for this relationship, which will likely benefit cervical cancer management.