The Role Of Vaginal Microbiota And HPV DNA Methylation In Cervical Lesion Progression

초록

Introduction/Background Persistent high-risk human papillomavirus (hrHPV) infections are a critical factor in cervical cancer progression. Recent research suggests a complex interaction between vaginal microbiota, hrHPV persistence, and lesion development, particularly regarding low-grade squamous intraepithelial lesions (LSIL) and high-grade lesions (HSIL). This study aims to explore the association between vaginal microbiota composition, HPV DNA methylation, and the progression or regression of cervical lesions. Methodology This study included 150 women aged 20-55, all hrHPV-positive with cervical cytology ≥ASCUS. Microbiome profiles were analyzed through 16S rRNA sequencing, focusing on Lactobacillus spp. diversity and abundance. Whole genome sequencing was performed for HPV genotyping and to assess viral integration. Methylation analysis targeted HPV DNA and human CpG sites, with hierarchical clustering to identify methylation patterns associated with lesion status. Results Significant differences in vaginal microbiota were observed between LSIL and HSIL groups. Higher microbial diversity, especially a lower prevalence of Lactobacillus spp., correlated with hrHPV persistence and lesion progression. HSIL samples displayed increased hypermethylation at specific CpG sites compared to LSIL. Additionally, HPV integration frequency was significantly higher in HSIL, often accompanied by shifts in the microbiome composition. Conclusion These findings highlight the potential role of vaginal microbiota and HPV DNA methylation in cervical lesion progression. Targeting microbial communities and epigenetic modifications may offer new avenues for cervical cancer prevention and treatment strategies.