Cervicovaginal dysbiosis and microenvironment disruption are associated with cervical carcinogenesis

Cervical cancer poses a serious threat to women's health. Emerging evidence indicates that changes in the cervicovaginal microbiota (CVM) and vaginal microenvironment may play a crucial role in cervical carcinogenesis. In this study, we examined CVM and vaginal microenvironment profiles in 510 participants with varying stages of cervical lesions using 16S rRNA sequencing, vaginal pH and H2O2 measurements, and cleanness assessment. A co-occurrence network and generalized multifactor dimensionality reduction model were employed to analyze the correlation and interaction between microbial taxa and microenvironment profile. Our results demonstrated that CVM disorder and abnormal vaginal microenvironment were associated with cervical lesions. As cervical cancerization progressed, the abundance of Lactobacillus gradually decreased with thriving anaerobe levels in the deteriorating vaginal microenvironment. This interaction was characterized by high vaginal pH, a non-Lactobacillus-dominant microbiota, and high CVM diversity (Shannon index ≥ 0.81). Co-occurrence network analysis revealed that abnormal pH and H2O2 levels correlated with Lactobacillus depletion and had a positively co-occurring relationship with anaerobes in precancerous cervical lesions. CVM function significantly varied with changes in the vaginal microenvironment across different stages of cervical lesions. Our findings suggest that CVM dysbiosis, particularly when combined with an abnormal vaginal microenvironment, may promote the progression of cervical lesions. This highlights the importance of addressing vaginal microecology to prevent cervical carcinogenesis.IMPORTANCECervicovaginal microbiota (CVM) and vaginal microenvironment in human papillomavirus infection are associated with the progression of cervical carcinogenesis. CVM dysbiosis, particularly the decrease in Lactobacillus and the increase in anaerobes, is crucial in promoting the malignant progression of cervical lesions. As cervical carcinogenesis progresses, the relative abundance of anaerobes increases in the deteriorating vaginal microenvironment. We systematically analyzed the relationship between CVM and the vaginal microenvironment in cervical lesions, aiming to reveal the contribution of CVM with specific vaginal microenvironmental features and its functional changes in the progression of cervical carcinogenesis. Our results may provide new insights into the etiology and pathogenesis of cervical cancer from the perspective of vaginal microecology.