Towards a sequential microbiome therapy for HPV-associated cervicovaginal dysbiosis

Abstract Persistent high-risk human papillomavirus (hrHPV) infections are the principal cause of cervical cancer, and are increasingly associated with ecological instability of the cervicovaginal microbiome. Multiomics studies indicate that hrHPV persistence is linked to reduced Lactobacillus dominance, increased anaerobic taxa, and metabolic alterations that may compromise epithelial integrity and antiviral immunity. In this Perspective article, we introduce a sequential microbiome therapy (SMT) framework designed to restore cervicovaginal ecological balance and support viral clearance. SMT is a two-phase, strain-resolved strategy. The first phase targets dysbiotic communities using antimicrobials, biofilm-disrupting or microbiota-modulating approaches to create a window for ecological reset. The second phase introduces health-associated Lactobacillus species selected for their acidification capacity, competitive fitness, and ability to stabilize the mucosal environment. We outline the ecological principles underpinning SMT and discuss its development as a potentially scalable microbiome-directed strategy for restoring cervicovaginal health and managing hrHPV-associated disease within existing cervical cancer prevention frameworks.