Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort

Abstract

Background: In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. Methods: The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. Results: HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs.

The impact of the female genital tract microbiome in women health and reproduction: a review

“…As a brief remark, several studies have exhibited high diversity of species within cervical microbiome, along with specific genera (for instance, Gardnerella spp. ), to be associated with human papillomavirus (HPV) risk in women [41,42]. Such results underline the link among cervical microbiome and different gynaecological issues.…”

Contribution of Lactobacillus iners to Vaginal Health and Diseases: A Systematic Review

“…The vaginal microbiome plays an important role in determining human vaginal health. Using high-throughput metagenomic and 16S rRNA sequencing, over 250 bacterial species have been identified in the human vagina ( Fredricks et al., 2005 ; Chen et al., 2020 ). Among them, Lactobacillus is the most frequently detected microorganism in the healthy vagina, and this includes Lactobacillus crispatus , Lactobacillus iners , Lactobacillus jensenii , and Lactobacillus gasseri ( Alonzo Martinez et al., 2021 ).…”

Bacterial vaginosis and other infections in pregnant women in Senegal

“…BV is also associated with a higher risk of sexually transmitted infections (STI) as Herpes Simplex Virus type 2 [ 5 ], Human Immunodeficiency Virus (HIV) [ 6 – 9 ], Trichomonas vaginalis, Chlamydia trachomatis , Neisseria gonorrhea [ 10 ] and Human Papilloma Virus (HPV) [ 11 ]. Bacterial vaginosis and low lactobacilli vaginal flora are associated with a delayed clearance of HPV and thus with increased risk of cervical intraepithelial neoplasia [ 12 – 15 ].…”