Human papillomavirus in prostate cancer: examining the evidence for a co-factor role.

The etiological role of human papillomavirus (HPV) in Prostate cancer (PCa) remains unresolved due to stark contradictions between observational associations and molecular detection studies. Traditional models attempting to define HPV as an independent driver of PCa struggle to reconcile these contradictions. This review aims to critically evaluate the conflicting evidence and propose a new framework: HPV may primarily function as a molecular cofactor rather than an independent carcinogenic driver. Within this framework, we systematically explore how HPV infection, through its oncogenic proteins, induces genomic instability, fosters chronic inflammatory microenvironments, and interacts with other pathogens to act as a co-factor that synergistically promotes PCa initiation and progression in individuals with specific genetic backgrounds. This co-factor model not only reconciles existing contradictory data but also provides a novel framework for future research, emphasizing the need to identify HPV-associated PCa subtypes for precision prevention and therapy. We discuss the potential value and applicability of prevention strategies based on this co-factor model. Redefining HPV's role in PCa is crucial for advancing precision risk stratification and targeted prevention.