Microbiome-driven resistance in cervical cancer therapy: from mechanistic dissection to clinical translation.

Cervical cancer remains a major global health burden. Despite standard-of-care therapies, 30-50% of locally advanced-stage patients develop treatment resistance, leading to recurrence and mortality. While tumour-intrinsic mechanisms (e.g., DNA methylation, cancer-associated fibroblasts) explain only partial resistance heterogeneity, emerging evidence identifies the microbiome as a critical modulator of therapeutic efficacy. This review synthesizes recent advances demonstrating that vaginal microbial dysbiosis, characterized by enrichment and depletion, drives resistance through lactate-mediated metabolic rewiring, immune checkpoint stabilization and drug metabolism alteration. Longitudinal studies reveal dynamic microbiome trajectories during therapy, with geographic variations (notably HIV co-infection in sub-Saharan Africa) further modulating treatment responses. We critically evaluate microbiome-based interventions, from probiotics to engineered bacteria, including synthetic biology-driven precision microbiome therapies, and establishing standardized multi-centre trial protocols. Bridging mechanistic insights with clinical application represents a paradigm shift towards microbiome-informed cervical cancer management.