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

Monica Di Paola,Maria Gabriella Torcia,Damariz Rivero,Ann Maria Clemente,Cristina Sani,Carlotta De Filippo,Federico Cozzolino,Michele Tanturli,Duccio Cavalieri,Giuseppe Castronovo,Francesca Carozzi,Eloisa Perissi,Anna Iossa

doi:10.1038/s41598-017-09842-6

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.

Highlights

Cervical cancer (CC) is one of the most common cancer in women, with an estimated incidence of 485 000 new cases and 236 000 deaths in 20131, causing 6.9 million disability-adjusted life-years (DALYs)
Cervico-vaginal samples were collected in the contest of a pilot study aimed to evaluate the efficacy of human papillomavirus (HPV) test in a primary screening program involving 1029 women aged between 26–64 years old
We reported Cervical Intraepithelial Neoplasia grade 1 (CIN1) and/or condiloma in 6 out of 28 (21.4%) and CIN grade 2 (CIN2) in 2 out of 28 (7.14%), as shown in Supplementary Table S1

Summary

Introduction

Cervical cancer (CC) is one of the most common cancer in women, with an estimated incidence of 485 000 new cases and 236 000 deaths in 20131, causing 6.9 million disability-adjusted life-years (DALYs). The factors responsible of persistence, as well those that promote and initiate the carcinogenesis process, need to be fully elucidated. Many other factors such as immunodeficiency, age, smoking, oral contraceptives and Chlamydia trachomatis infection are related with higher persistence rates[5, 6]. In the majority of human body sites, highly diverse microbial communities are generally considered a signature of health[8, 9]. In the vaginal environment, health is commonly associated with low microbial diversity and prevalence of only a few species of Lactobacillus[10,11,12,13]. Five major community-state types (CSTs) discriminate vaginal microbiota in healthy women[11]. Anaerobic bacterial species of Gardnerella, Prevotella, Peptostreptococcus genera and/or aerobic bacteria of Enterobacteriacee family usually populate vaginal environment depleted of Lactobacillus species[18,19,20]

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Results

Conclusion