The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions

Anita Mitra,Phillip R Bennett,Anna-Barbara Moscicki,Ann Smith,George Ntritsos,Maria Kyrgiou,Julian R Marchesi,David A Macintyre,Konstantinos K Tsilidis

doi:10.1038/s41467-020-15856-y

Abstract

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.

Highlights

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); causal inference remains uncertain
Emerging evidence leads us to conclude that vaginal microbiota (VMB) composition varies in women with high-risk human papillomavirus (hrHPV) infections and high-grade CIN11–15
We previously reported that increased CIN disease severity is associated with decreasing relative abundance of Lactobacillus spp.[14], the cross-sectional nature of these datasets did not permit exploration on the impact that that VMB composition may have on clinical outcome of CIN and HPV infection clearance[11,12,13,14,16,17,18,19,20]

Summary

Introduction

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); causal inference remains uncertain. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies. Recent studies have begun to examine the impact of the VMB, HPV and cellular change on the metabolic profile, which promotes many of the inflammatory and metabolic mechanisms necessary for persistent viral infection and carcinogenesis[21,22] In this prospective longitudinal study of historically collected samples, we investigate the vaginal microbiota composition in a cohort of non-pregnant adolescent and young adult women aged 16–26 years, with histologically proven CIN2 managed conservatively over a 24-month period. Our findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, and in addition may provide rational strategies for the development of targeted prevention and treatment methods

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