Abstract

The aim of this study was to investigate the associations between cervical microbiota and different human papillomavirus (HPV) infection statuses in cytologically normal women. The cervical microbiota of HPV-positive or -negative women with a normal cytologic diagnosis was characterized and compared using 16S rDNA-based high-throughput sequencing, and the differences in cervical microbiota associated with new acquisition, persistence, and clearances of HPV genotypes were analyzed via one-year follow-up. The results showed that the cervical microbial richness of HPV-positive women was lower than for HPV-negative women, and the difference was more significant in the postmenopausal group relative to the premenopausal group. Ureaplasma parvum and related taxa were associated with baseline HPV positivity, while Brochothrix, Diplorickettsia, Ezakiella, Faecalibacterium, and Fusobacterium genera and their related taxa and Pseudomonas aeruginosa were associated with baseline HPV negativity. For HPV-positive women, the baseline abundance of Actinomyces was negatively associated with new HPV infection, Alloprevotella tannerae, Prevotella nigrescens, and Prevotella oulorum; and Dialister invisus were positively associated with new HPV-type infection within the year of follow-up. Lactobacillus delbrueckii was found to be negatively associated with persistent HPV infection and 9 taxa belonging to Prevotella, Dialister, and Lachnospiraceae were found to be positively associated with persistence, and/or negatively associated with clearance of HPV types. We also observed 10 novel taxa associated with the clearance/persistence of HPV that had not been reported elsewhere. Those taxa associated with different infection statuses of HPV could be used as a biomarker to help predict the risk of developing persistent HPV infection.

Highlights

  • Cervical cancer is one of the most common cancers among women worldwide, and persistent infection with high-risk human papillomavirus (HPV) types has been confirmed to be the necessary factor for developingNote: Supplementary data for this article are available at Cancer Prevention Research Online.W

  • 90 were HPV positive and 43 were HPV negative at baseline; 55 women who were positive at baseline became HPV negative after 1 year, and 1 woman who was HPV negative at baseline became positive at the follow-up visit

  • We investigated the association between cervical microbiota and variables that included HPV positivity and other risk factors in women with a negative cytologic screening diagnosis

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Summary

Introduction

Cervical cancer is one of the most common cancers among women worldwide, and persistent infection with high-risk human papillomavirus (HPV) types has been confirmed to be the necessary factor for developingNote: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).W. Cervical cancer is one of the most common cancers among women worldwide, and persistent infection with high-risk human papillomavirus (HPV) types has been confirmed to be the necessary factor for developing. Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/). It is known that HPV infection is very common in sexually active women, and the infecting HPVs can usually be spontaneously eliminated from individuals within 6 to 18 months. A small proportion of infected women retain the virus, and this could lead to the development of cervical intraepithelial neoplasia (CIN) and cervical carcinoma [2]. The mechanism by which some individuals develop a persistent HPV infection that goes on to develop into clinically significant disease, remains largely unclear

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