Vaginal Microbiome-Based Bacterial Signatures for Predicting the Severity of Cervical Intraepithelial Neoplasia.

Setu Bazie Tagele,Gi-Ung Kang,Jae-Ho Shin,Huy Quang Pham,Hyung Soo Han,Sajjad Ahmad,Min-Sueng Kim,Gun Oh Chong,Se Young Jeon,Yeong-Jun Park,Yoon Hee Lee,Da-Ryung Jung

doi:10.3390/diagnostics10121013

Abstract

Although emerging evidence revealed that the gut microbiome served as a tool and as biomarkers for predicting and detecting specific cancer or illness, it is yet unknown if vaginal microbiome-derived bacterial markers can be used as a predictive model to predict the severity of CIN. In this study, we sequenced V3 region of 16S rRNA gene on vaginal swab samples from 66 participants (24 CIN 1−, 42 CIN 2+ patients) and investigated the taxonomic composition. The vaginal microbial diversity was not significantly different between the CIN 1− and CIN 2+ groups. However, we observed Lactobacillus amylovorus dominant type (16.7%), which does not belong to conventional community state type (CST). Moreover, a minimal set of 33 bacterial species was identified to maximally differentiate CIN 2+ from CIN 1− in a random forest model, which can distinguish CIN 2+ from CIN 1− (area under the curve (AUC) = 0.952). Among the 33 bacterial species, Lactobacillus iners was selected as the most impactful predictor in our model. This finding suggests that the random forest model is able to predict the severity of CIN and vaginal microbiome may play a role as biomarker.

Highlights

Cervical cancer is common in women worldwide [1], and 95–100% of patients with invasive cervical cancer are infected with human papillomavirus (HPV) [2]
We aimed to develop a panel of vaginal microbiome-derived biomarkers of the severity of cervical intraepithelial neoplasia (CIN) using a machine learning-based random forest classification model
HPV infections were detected in seven patients (29.2%) of the CIN 1− group and in 41 patients (97.6%) of the CIN 2+ group (p < 0.0001)

Summary

Introduction

Cervical cancer is common in women worldwide [1], and 95–100% of patients with invasive cervical cancer are infected with human papillomavirus (HPV) [2]. The recognition that HPV is the causative agent of cervical cancer has changed the perception of cervical cancer screening. Compared to primary screening with Pap cytology, the primary HPV test has superior sensitivity for detecting cervical cancer [3]. HPV infection is necessarily a cause, it is not determinant of the development of cervical cancer. Most HPV infections are eliminated and only a small fraction of infected women progress to cervical intraepithelial neoplasia (CIN) or cervical cancer [4]. There has been evidence that the vaginal microbiome can either protect or stimulate CIN or cervical cancer progression [8]

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Results