Abstract
Human papillomavirus (HPV) integration is recognized as a hallmark event in cervical carcinogenesis. However, it does not represent a routine phase of the viral life cycle but rather a stochastic occurrence, often constituting a dead-end pathway for the virus. High-risk human papillomavirus (hr-HPV) exhibits a greater propensity for integration. The progression from initial infection to genomic integration constitutes a dynamic multi-step oncogenic process in the development of cervical cancer (CC). This process involves viral entry, immune evasion, persistent infection, and ultimately integration. This article innovatively provides a comprehensive overview of this multi-stage mechanism: HPV, via the L1/L2 proteins, mediates internalization and establishes infection. Subsequently, under the influence of factors such as the host's genetic background, vaginal microbiota imbalance, and immune evasion, the host's DNA damage response (DDR) pathways are activated. Viral DNA integrates into host genome vulnerable sites (e.g., 3q28 and 8q24) through microhomology-mediated end joining (MMEJ) or other alternative pathways. Following integration, the expression of viral oncogenes persists, triggering host genomic rearrangements, aberrant epigenetic modifications, and immune microenvironment remodeling, all of which collectively drive cervical cancer progression. The study further reveals the clinical potential of HPV integration as a highly specific molecular biomarker, offering new perspectives for precision screening and targeted therapy. This dynamic model deepens our understanding of the HPV carcinogenic mechanism and provides a theoretical basis for intervention strategies.