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.Conclusions: This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.

The feature of cervical microbiota associated with the progression of cervical cancer among reproductive females

“…Hydrogen peroxide and bacteriocins produced by Lactobacillus hindering the proliferation of other microorganisms too [6]. Even in the CA group of our study, Lactobacillus was still the most abundant genus, although less than 50% [18]. Therefore, a large number of Lactobacillus existing might lead to the small variety of bacteria.…”

Insights into the role of vaginal microbiome in women's health

“…CST-IV doubled in women who had low-grade squamous intraepithelial neoplasia (LSIL), increased threefold in women with high-grade squamous intraepithelial neoplasia (HSIL), and fourfold in women with invasive disease. Women with HSIL exhibited higher abundance of Peptostreptococcus anaerobius and Anaerococcus tetradius, and depletion in L. crispatus as opposed to women with LSIL [70,72].…”

“…External carcinogenic factors like contraceptive use and cigarette smoking that are found to be causes of cancer have also been associated with BV. Dysbiosis of the vaginal microbiome with a depleted Lactobacillus population can support HPV infection [72,73]. Additionally, an acute inflammation caused by BV may play a role in cervical cancer by the influence of the antimicrobial proteins and immune cell populations in the vagina [74].…”

The Tumor Microbiome Is Implicated in Breast Cancer Prognosis

“…The promotion of in ammation and remodeling of the ECM results in mutagenesis that may promote the onset and progression of cancer [53]. Studies have shown that Anaerococcus is involved in progression of cervical intraepithelial neoplasia [54,55] and bladder cancer [56]. Therefore, the increase of Anaerococcus may be related to progression of breast cancer.…”