From HPV Genetic Diversity to Precision Therapeutics: Viral-Host Interactions and Emerging Strategies for Cervical Cancer Prevention and Treatment

Cervical cancer is a major global health challenge, especially in low- and middle-income countries, despite the availability of effective prophylactic human papillomavirus (HPV) vaccines, screening methods and established treatments. Cervical cancer is primarily caused by persistent infection with high-risk HPV, but persistent infection is necessary, but not sufficient, for the development of cancer. Advances in understanding HPV genetic diversity, viral persistence, and virus-host molecular interactions are creating new opportunities to improve precision in HPV prevention and treatment. HPV genotype distribution and differences in oncogenic potential inform vaccine development and screening strategies. The viral oncoproteins E6 and E7 disrupt host tumor-suppressor pathways, driving cellular immortalization and genomic instability. Molecular events such as viral insertion, epigenetic modifications, APOBEC-associated mutations, and immune escape contribute to disease progression. These discoveries have revealed molecular vulnerabilities that can be targeted therapeutically. Immune checkpoint inhibitors and antibody-drug conjugates are used clinically in specific contexts of cervical cancer presentation and treatment. At the same time, therapeutic vaccines, adoptive cellular immunotherapies, RNA interference, and genome editing are being investigated as complementary strategies to target HPV-associated cervical cancer. With advances in next-generation sequencing, molecular biomarkers, and artificial intelligence, these tools could further refine risk stratification and therapy selection. This review explores the current understanding of HPV genetic variation and virus-host interactions driving a shift from traditional prevention and treatment strategies to precision prevention and targeted therapeutics, and critically assesses remaining challenges.