Background Fifteen longitudinal studies have shown associations between bacterial vaginosis and high risk human papillomavirus (hrHPV) acquisition and/or persistence, and/or cervical dysplasia. However, few studies assessed the vaginal microbiota (VMB) comprehensively, and none controlled the dysplasia association for persistent hrHPV.
Methods 623 women attending HIV outpatient clinics in Johannesburg, South Africa, were examined for hrHPV (InnoLipA HPV Genotyping Extra Assay), cervical dysplasia (histology), and vaginal microbiota (VMB; V3-V4 Illumina HiSeq 2x300bp with Swarm OTU-picking) at baseline and endline, a median of 16 months after baseline. VMB research questions were addressed in two nested case-control designs.
Results Hierarchical clustering resulted in seven VMB types: L. iners-dominated (Li; n=214 samples), Lactobacillus crispatus or L. jensenii-dominated (Lcj; n=68), Bifidobacterium-dominated (BD; n=2), lactobacilli + bacterial vaginosis (BV)-anaerobes (L+A; n=208), BV-like (BV; n=303); BV-anaerobe dominated (AD; n=56); and pathobiont-characterised (PB; n=19). Women with new or persistent hrHPV during follow-up were less likely to have an Lcj VMB type (compared to Li) at endline, and persistent hrHPV was associated with vaginal anaerobic dysbiosis at baseline (decreased lactobacilli, increased BV-anaerobes, and increased Nugent score). Women who developed CIN2+, compared to women with persistent hrHPV but no CIN2+, were more likely to have vaginal anaerobic dysbiosis at endline (decreased lactobacilli, increased BV-anaerobes, and increased diversity), but not at baseline. These associations persisted after controlling for age, hormonal contraception, and CD4+ count; several additional potential confounders (HIV plasma viral load, antiretroviral therapy, sexually transmitted infections, sexual risk-taking, among others) were evaluated.
Conclusion Frequent hrHPV exposure (and/or increased sexual risk-taking) likely causes vaginal dysbiosis, but a bilateral relationship cannot be ruled out. Women with vaginal dysbiosis are not at increased risk of CIN2+ development when hrHPV status is taken into account, but vaginal dysbiosis does develop when CIN2+ lesions develop. These results should be confirmed in even larger longitudinal studies.
Disclosure No significant relationships.
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