Role of Human Papillomavirus (HPV) in the Development and Progression of Cervical Cancer
Abstract
Cervical cancer remains a major cause of morbidity and mortality, disproportionately affecting women in low- and middle-income countries despite its high preventability. Persistent infection with high-risk human papillomavirus (hrHPV), particularly genotypes 16 and 18, is a necessary causal factor in cervical carcinogenesis. This review synthesizes current evidence on the role of HPV in the initiation and progression of cervical cancer, spanning viral biology, molecular pathogenesis, host determinants, and clinical implications. We summarize HPV structure, classification, transmission, and natural history, highlighting how the E6 and E7 oncoproteins disrupt p53 and pRb pathways, drive genomic instability, and interact with host epigenetic and DNA damage-response machinery. We also examine host genetic susceptibility, hormonal influences, smoking, HIV-associated immunosuppression, cervicovaginal dysbiosis, micronutrient deficiencies, and immune evasion mechanisms that condition progression from transient infection to high-grade lesions and invasive cancer. Finally, we review advances in HPV-based screening, biomarkers, and prophylactic and therapeutic vaccination, and discuss how HPV status and genotype inform prognosis and treatment response. Understanding these viral–host interactions is essential for optimizing implementation of the WHO 90-70-90 strategy and for designing context-appropriate interventions to reduce persistent global inequities in cervical cancer burden. Special emphasis is placed on challenges and opportunities for scaling prevention and care in high-burden, resource-limited settings.
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