Infection-driven bladder carcinogenesis: Molecular mechanisms of pathogen-urothelial cell interactions

Bladder cancer (BC) is one of the most common malignancies affecting the genitourinary tract. Although infectious agents are recognized as etiological factors in various cancers, their involvement in BC has traditionally been underestimated. Accumulating evidence implicates several pathogens-notably Schistosoma haematobium, Human papillomavirus (HPV), uropathogenic Escherichia coli (UPEC), and BK virus-in the initiation and progression of BC. Schistosoma haematobium promotes squamous cell carcinoma (SCC) through inducible nitric oxide synthase (iNOS)-mediated DNA damage; HPV contributes to oncogenesis via E6-mediated p53 degradation, E7-mediated Rb inactivation, and telomerase activation; and recurrent UPEC infections facilitate carcinogenesis through chronic inflammation, genotoxic damage, and epithelial barrier disruption. However, detailed mechanistic insights remain limited for many pathogens, and host-pathogen bidirectional interactions require further elucidation. This review consolidates current understanding of infection-driven BC pathogenesis and identifies critical gaps for future mechanistic investigations.