Human papillomavirus and cutaneous squamous cell carcinoma: A review

Human papillomavirus (HPV) comprises a diverse group of more than 220 reference genotypes classified into 5 genera, with beta (b)-HPV predominating in cutaneous tissues.While the oncogenic role of alpha (a)-HPV in cervical and anogenital cancers is well-established, emerging evidence implicates b-HPV in the development of cutaneous squamous cell carcinoma (SCC), particularly among immunosuppressed individuals.This clinical review synthesizes current knowledge on the biology, epidemiology, and immunology of HPV, with a specific focus on b-HPV and its association with cutaneous SCC.Epidemiological findings from both immunocompetent and immunosuppressed cohorts are discussed, with emphasis on the high prevalence and persistence of b-HPV infection in organ transplant recipients (OTRs).The review evaluates immunological responses and the functional roles of T cells in HPV infection control and SCC risk.Additionally, advances in b-HPV vaccine development and the potential for future immunotherapeutic strategies are explored.Overall, this review underscores the need for a deeper understanding of the precise role of HPV in cutaneous SCC pathogenesis and highlights the importance of developing targeted therapeutic interventions, particularly in the context of the increasing immunosuppressed population.( JAAD Reviews 2026;7:61-9.)