Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection

Abstract

Changes in cervico-vaginal microbiota with Lactobacillus depletion and increased microbial diversity facilitate human papillomavirus (HPV) infection and might be involved in viral persistence and cancer development. To define the microbial Community State Types (CSTs) associated with high-risk HPV−persistence, we analysed 55 cervico-vaginal samples from HPV positive (HPV+) women out of 1029 screened women and performed pyrosequencing of 16S rDNA. A total of 17 samples from age-matched HPV negative (HPV−) women were used as control. Clearance or Persistence groups were defined by recalling women after one year for HPV screening and genotyping. A CST IV subgroup, with bacterial genera such as Gardnerella, Prevotella, Megasphoera, Atopobium, frequently associated with anaerobic consortium in bacterial vaginosis (BV), was present at baseline sampling in 43% of women in Persistence group, and only in 7.4% of women in Clearance group. Atopobium genus was significantly enriched in Persistence group compared to the other groups. Sialidase-encoding gene from Gardnerella vaginalis, involved in biofilm formation, was significantly more represented in Persistence group compared to the other groups. Based on these data, we consider the CST IV-BV as a risk factor for HPV persistence and we propose Atopobium spp and sialidase gene from G. vaginalis as microbial markers of HPV−persistence.

Cervicovaginal microbiome and natural history of HPV in a longitudinal study

“…Previous cross-sectional studies analyzing the association between the cervicovaginal microbiome and HPV infection outcomes have consistently identified Gardnerella as a key biomarker associated with CIN2+. This has been reported in studies that utilized both nextgeneration sequencing [39,41] and other methods of microbiome analyses [52,43]. We present data that Gardnerella is in fact associated with CIN2+ lesions, but rather than directly causing the CIN2+ lesion, appears to induce a higher diversity CVM over time as measured at V2,…”

Evaluation of the Associations Between Cervical Microbiota and HPV Infection, Clearance, and Persistence in Cytologically Normal Women

“…In the comparison of the alpha diversity, it is interesting to note that the richness of the cervical microbiota of HPVpositive women was lower than for HPV-negative women in our study. This result is controversial with respect to previous studies that showed that for the microbiota in the female reproductive tract, low microbial diversity was more closely associated with a healthier condition, and HPV-positive women have a higher species diversity (4,10). A possible explanation for this controversy is that compared with the previous study, only cytologically normal women were included in the HPV-positive group in this study, so as to eliminate the potential impact of the microbiologic changes derived from HPV-related cervical lesions.…”

“…The aforementioned evidence indicates that the cervicovaginal microbiota plays a substantial role in the infection and clearance of HPV virus in the reproductive tract and constitutes a new biomarker reservoir to predict the persistence or regression of HPV. So far, however, only a few longitudinal studies concerning associations between cervicovaginal microbiota and HPV infection/clearance have been conducted, and they were of very limited sample size (9,10).…”

Association of human papillomavirus and bacterial vaginosis with increased risk of high-grade squamous intraepithelial cervical lesions

“…Epidemiological studies have indicated that variations in the cervical-vaginal microbiota followed by Lactobacillus depletion and a rise in the microbial variety leads to bacterial vaginosis, increases the possibility of HPV infection, and may be associated with viral persistence and cancer development 26. Our data reinforce this evidence as co-infections between a single bacterial vaginosis with HPV-DNA, high-risk HPV, and HPV-16 increased the risk for low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions/cervical cancer.…”