Vaginal microbiota diversity and paucity of Lactobacillus species are associated with persistent hrHPV infection in HIV negative but not in HIV positive women

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.

Sociodemographic factors and uncomplicated pyelonephritis in women aged 15-50 years: a nationwide Swedish cohort register study (1997-2018)

“…For example, a genetical basis (i.e., innate immune deficiency) linked to pyelonephritis has been found in Sweden (Lundstedt et al, 2007). Furthermore, ethnic differences of the human vaginal microbiome might be an explanation for the increased risk of UTI, as certain vaginal microbiomes associated with UTI (Gupta et al, 1998, Stapleton et al, 2011 and other genitourinary infections (Dareng et al, 2020, Ravel et al, 2011, might be overrepresented in certain ethnic groups of women (Ravel et al, 2011). For example, women of African and Hispanic origin (living in USA) seem to have a higher pH and a lower proportion of the generally considered "healthy" Lactobacillus spp.…”

Cervicovaginal Microbiome Factors in Clearance of Human Papillomavirus Infection

“…Above-mentioned observational studies are only possible to demonstrate association of CVM with HPV infection and CIN diseases rather than causality. Longitudinal data is increasingly applied to explore the causal link ( 7 , 40 , 41 ), which has profound clinical impact to provide effective alternatives for therapeutic strategies of HPV-infected CIN. Six-month follow-up of 211 Nigerian women showed the association of Lactobacillus paucity and high CVM diversity with persistent hrHPV infection ( 40 ).…”

“…Longitudinal data is increasingly applied to explore the causal link ( 7 , 40 , 41 ), which has profound clinical impact to provide effective alternatives for therapeutic strategies of HPV-infected CIN. Six-month follow-up of 211 Nigerian women showed the association of Lactobacillus paucity and high CVM diversity with persistent hrHPV infection ( 40 ). Analysis of serial cervicovaginal specimens obtained over 8-10 years unraveled that high relative abundance of L. crispatus in CVM had the lowest risk of HPV infection compared to other types of CVM, according to 16S V1-V2 rRNA gene amplicon sequencing and HPV DNA testing conducted annually ( 41 ).…”

Gardnerella Vaginalis Alters Cervicovaginal Epithelial Cell Function Through Epithelial Cell-type Specific Immune Responses

“…[8]. Even though a Lactobacillus-de cient CST-IV state may not be associated with a clear pathological phenotype, the presence of CST-IV confers a higher risk of adverse vaginal pathologies such as herpes papillomavirus (HPV), BV, HIV and other Sexually transmitted diseases [22][23][24][25]. Understanding the mechanisms by which Lactobacillus-de cient microbial communities impart an increased risk of adverse reproductive outcomes remains an obstacle to advancing reproductive health.…”