Abstract / Summary
Human papillomaviruses of the beta genus (beta-HPV) are ubiquitous components of the cutaneous virome, persistently colonizing the skin of immunocompetent individuals from early infancy. Unlike their alpha counterparts, which drive mucosal carcinogenesis through viral integration and sustained oncoprotein expression, beta-HPVs employ transient, cofactor-dependent mechanisms that operate primarily at the initiation stages of keratinocyte carcinogenesis, a paradigm known as the hit-and-run model. Although their association with cutaneous squamous cell carcinoma is well supported, particularly in immunocompromised individuals, beta-HPV genotypes are being increasingly detected in patients with cervical, head and neck, anal, vulvar, and colorectal carcinomas. This raises the question of whether beta-HPVs play a broader oncogenic role. This review examines the clinical significance of beta-HPV across anatomical sites and evaluates existing and next-generation preventive strategies. Collectively, the evidence suggests that beta-HPVs may act as clinically relevant viral cofactors, although whether their detection at these sites is incidental or causal remains unclear.