Vaginal microbiota and human papillomavirus infection among young Swedish women

Liqin Cheng,Marica Hamsten,Lars Engstrand,Andreas Ährlund-Richter,Ina Schuppe-Koistinen,Johanna Norenhag,Pia Angelidou,Emma Fransson,Nele Brusselaers,Matts Olovsson,Yue O O Hu,Juan Du,Unnur Guðnadóttir,Yinghua Zha

doi:10.1038/s41522-020-00146-8

Abstract

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. To define the HPV-associated microbial community among a high vaccination coverage population, we carried out a cross-sectional study with 345 young Swedish women. The microbial composition and its association with HPV infection, including 27 HPV types, were analyzed. Microbial alpha-diversity was found significantly higher in the HPV-infected group (especially with oncogenic HPV types and multiple HPV types), compared with the HPV negative group. The vaginal microbiota among HPV-infected women was characterized by a larger number of bacterial vaginosis-associated bacteria (BVAB), Sneathia, Prevotella, and Megasphaera. In addition, the correlation analysis demonstrated that twice as many women with non-Lactobacillus-dominant vaginal microbiota were infected with oncogenic HPV types, compared with L. crispatus-dominated vaginal microbiota. The data suggest that HPV infection, especially oncogenic HPV types, is strongly associated with a non-Lactobacillus-dominant vaginal microbiota, regardless of age and vaccination status.

Highlights

Infection with human papillomavirus (HPV) is among the most common sexually transmitted diseases in the world, with the highest prevalence among women below 251,2
bacterial vaginosis-associated bacteria (BVAB) have not been included in the 16S amplicon sequencing-based vaginal microbiota studies related to HPV, probably due to taxonomic information missing from the popular 16S rRNA databases, with most studies on BVAB being based on qPCR sequencing
The HPV vaccine appeared to provide full protection to the participants in the cervical screening, with no one being infected with the HPV types covered in the quadrivalent HPV vaccine (Supplementary Fig. 2a, b)

Summary

Introduction

Infection with human papillomavirus (HPV) is among the most common sexually transmitted diseases in the world, with the highest prevalence among women below 251,2. HPV infection is the main cause of cervical cancer and is related to many other cancers, including head and neck cancer[3]. Depending on their oncogenic potential, mucosal HPV types can be divided into oncogenic HPVs, such as those observed in cancer cases, and nononcogenic HPVs, mainly found in condyloma[4]. The total HPV prevalence caused by HPV types that are not covered by the vaccine is still high, indicating that more interventions to reduce these HPV infections are still needed[7,8]. The sensitivity and specificity for both methods are moderate[19] Molecular diagnosis, such as 16S rRNA gene sequencing, enables the microbiota determination at the species level. BVAB have not been included in the 16S amplicon sequencing-based vaginal microbiota studies related to HPV, probably due to taxonomic information missing from the popular 16S rRNA databases, with most studies on BVAB being based on qPCR sequencing

Methods

Results

Conclusion