Association of high-risk human papillomavirus infection duration and cervical lesions with vaginal microbiota composition

Abstract

Background: Cervical cancer is reportedly caused by the synergistic effects of persistent high-risk human papillomavirus (HPV) infection. Cervical microbiota represent a unique and dynamically changing microecological system that is directly exposed to the vagina. The relationship between HPV and the composition of the cervical microbiome has long been a primary focus of research.Methods: To determine the specific differential florae throughout the process of cervical cancer development, in the present study, 16S rRNA sequencing was combined with KEGG pathway enrichment analysis to analyse five groups of cervical scraping samples with increasing durations of HPV infection and cervical intraepithelial neoplasia pathological classification. Results:The findings revealed that decreasing levels of probiotics, including Shuttleworthia, Prevotella, Lactobacillus, and Sneathia, and increasing levels of pathogenic bacteria, including Dispar, Streptococcus, and Faecalibacterium prausnitzii, could be the direct result of early HPV infection. Other pathogenic bacteria, such as Bifidobacteriaceae, might represent key factors in cancer progression. Additionally, KEGG pathway enrichment analysis indicated that HPV infection directly inhibits multiple pathways, including those of sporulation, porphyrin and chlorophyll metabolism, arginine and proline metabolism, isoquinoline alkaloid biosynthesis, and ansamycin biosynthesis, which may lead to the development of early symptoms of cervical cancer. Biomarkers were predicted based on operational taxonomic unit (OTU) abundance data, and OTU851726 and OTU715913 were undoubtedly the best potential indicators of cervical cancer. Conclusions:The findings of the present study could assist with the development of a guideline for screening new clinical drugs for cervical cancer.

Genital Microbiota of Women From Six Ethnic Groups With and Without Human Papillomavirus Infection in Shangri-La, China

“…Third, excellent local environmental advantages have created healthy reproductive system microbes, which are good for resisting the damage of viruses to human cells, causing a lower incidence rate of CC with a lower infection rate. However, it is speculated that the specific vaginal and cervical microecology might affect HPV infection in the cervical epithelium and the outcome after infection in a specific manner (Liu et al, 2020). Therefore, it is necessary to deeply study local women's reproductive tract microorganisms.…”

“…Due to the physiological structure of the cervix and vagina, imbalance in the vaginal microecosystem directly increases the chance of HPV infection and accelerates the process of cervical precancerous lesions (Kovachev, 2020). Vaginal health is more commonly associated with low microbial diversity (Laniewski et al, 2020;Liu et al, 2020;Nunn et al, 2020), and there are some differences among the population. The reasons for these observed differences among ethnic groups are unknown, but it is tempting to speculate that the species composition of vaginal communities could be governed by genetically determined differences between hosts (Zhou et al, 2007;Zhou et al, 2019).…”

The role of probiotics in vaginal health

“…A study (DI Pierro et al, 2021) demonstrated for the first time that oral Lactobacillus curlicus can change the state of CST and increase HPV clearance. Persistent high-risk HPV infection and changes in cervical microenvironment promote the development of cervical precancerous lesions (Liu et al, 2020). Lactobacillus activates the immune system to inhibit the proliferation of malignant tumors by secreting various a n t i t u m o r m e t a b o l i t e s , in c l u d i n g p h o s p ho r y l a t e d polysaccharides and extracellular polysaccharides.…”

Cervicovaginal microbiota significantly changed for HPV-positive women with high-grade squamous intraepithelial lesion

“…Though HPV infection can orchestrate immune responses and then affect CVM structures, VM-host interactions keep existed before HPV infection and thus impose momentous effect on persistence of stochastic HPV infection via VMmodulated host responses (Anahtar et al, 2015). In consistence, several studies indicated significant CVM differences between women with clearance of HPV infection and those with persistent infection (Di Paola et al, 2017;Berggrund et al, 2020;Liu et al, 2020;Mitra et al, 2020;Usyk et al, 2020). In addition, longitudinal studies indicated the vital impact of CVM on persistence of HPV infection (Mitra et al, 2020;Usyk et al, 2020).…”