Integrating Microbiome Insights into Cervical Cancer

Abstract

Cervical cancer is largely preventable, yet it continues to cause substantial morbidity and mortality worldwide, particularly in regions with limited access to human papillomavirus (HPV) vaccination and screening. Persistent infection with high-risk HPV genotypes, especially HPV-16 and HPV-18, represents the primary initiating event in cervical carcinogenesis. However, viral infection alone does not fully explain why only a subset of infected individuals develop high-grade lesions or invasive disease. Recent longitudinal and mechanistic studies indicate that the cervicovaginal microbiome plays an important modulatory role by influencing epithelial barrier integrity, local immune responses, and inflammatory homeostasis. This review synthesizes current evidence from multi-omics and translational studies linking cervicovaginal microbial composition and function to HPV persistence, cervical intraepithelial neoplasia (CIN), and cervical cancer progression. Communities dominated by Lactobacillus crispatus are frequently associated with antiviral conditions and mucosal stability, whereas anaerobe-enriched microbial profiles, commonly referred to as community state type IV (CST IV), are associated with chronic inflammation, metabolic dysregulation, and increased lesion severity. Microbial metabolites and inflammatory mediators may interact with HPV oncogene activity and host epigenetic regulation, supporting a microbiome-metabolome-epigenome axis in cervical carcinogenesis. The review also discusses emerging clinical implications, including microbiome-based biomarkers and microbiota-targeted interventions. While early studies suggest potential benefits of probiotics and postbiotics for HPV clearance and immune modulation, current evidence remains limited. Methodological heterogeneity, low-biomass sampling, and population variability continue to restrict causal inference and clinical translation. Addressing these challenges will be essential for integrating microbiome-informed strategies into cervical cancer prevention and management.