Abstract
The vaginal microbiota is thought to play a role in modulating risk of high-risk human papillomavirus (hrHPV) infection. We examined the relationship between the vaginal microbiota and persistent hrHPV infection in HIV-negative and HIV-positive women. We used 16S-rRNA sequencing to characterize the vaginal microbiota of two serial samples taken six months apart from 211 Nigerian women (67%, 142/211 HIV-positive and 33%, 69/211 HIV-negative) and evaluated the association between the vaginal microbiota and persistent hrHPV infection using generalized estimating equation logistic regression models and linear discriminant analysis effect size (LEfSe) algorithm to identify phylotypic biomarkers of persistent hrHPV infection. The high diversity microbiota, Community State Type IV-B, was the most prevalent in both HIV-negative (38% at baseline, 30% at the follow-up visit) and HIV-positive (27% at baseline, 35% at the follow-up visit) women. The relationship between the vaginal microbiota and persistent hrHPV was modified by HIV status. In HIV-negative women, women with Lactobacillus dominant microbiota had lower odds (OR: 0.35, 95% CI 0.14–0.89, p = 0.03) of persistent hrHPV compared to women with Lactobacillus deficient microbiota. While among HIV-positive women, the odds of being persistently infected with hrHPV was higher in women with Lactobacillus dominant microbiota (OR: 1.25, 95% CI 0.73–2.14 p = 0.41). This difference in effect estimates by HIV was statistically significant (p = 0.02). A high diversity vaginal microbial community with paucity of Lactobacillus species was associated with persistent hrHPV infection in HIV-negative women but not in HIV-positive women.
Highlights
Cervical cancer is the third commonest cancer among women globally, with 570,000 new cases and 311,400 deaths estimated to have occurred globally in 2 0181
We found that in HIV-negative women, women with persistent high-risk human papillomavirus (hrHPV) infection had significant over-representation of Leptotrichia species in their vaginal microbiota compared to HIV-negative women without persistent hrHPV infection (Fig. 6) there was significant overrepresentation of Veillonella species in HIV-negative women who were persistently hrHPV negative compared to HIV negative women with persistent hrHPV infection (Fig. 6)
In HIV-positive women, we did not identify any discriminative features between the vaginal microbiota of women with persistent hrHPV infection and women who were persistently HPV negative. In this nested case control study of the vaginal microbiota and persistent hrHPV infection in HIV-negative and HIV-positive women, we found that a high relative abundance of Lactobacillus species was associated with reduced odds of persistent hrHPV infection in HIV-negative women but not in HIV-positive women
Summary
Cervical cancer is the third commonest cancer among women globally, with 570,000 new cases and 311,400 deaths estimated to have occurred globally in 2 0181. Persistence of HPV infection leads to the accumulation of mutations in the somatic cellular genome which increases the risk of CIN and cervical c ancer. Disruptions in these defence mechanisms, as could occur with high diversity vaginal microbiota, may modulate risk of viral infections such as H IV12 and H PV13. Most 16S rRNA sequencing studies of the vaginal microbiota and hrHPV infection to date have focused on prevalent hrHPV infection and vaginal microbiome patterns6,13,16,18–22 These studies showed increased risk of prevalent HPV infection in women with high diversity vaginal microbiota or with decreased relative abundance of Lactobacillus species. We examine the relationship between the vaginal microbiota measured at two different time points and persistent hrHPV infection in a nested case control study of HIV-negative and HIVpositive Nigerian women
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