Development of a β-HPV vaccine: Updates on an emerging frontier of skin cancer prevention

Human papillomaviruses (HPVs) are small, non-enveloped, doublestranded DNA viruses. Over 200 subtypes of HPV have been identified, organized into five major genera. beta-HPVs are a group of approximately 50 HPV subtypes that preferentially infect cutaneous sites. While alpha-HPVs are primarily responsible for genital lesions and mucosal cancers, growing evidence has established an association between beta-HPVs and the development of cutaneous squamous cell carcinomas. Given this association, the development of a vaccine against beta-HPVs has become an important topic of research; however, currently licensed vaccines only provide coverage for genital HPVs, leaving beta-HPV infections and their associated skin cancers unaddressed. In this review, we summarize the current advances in beta-HPV vaccine development, including progress made in preclinical testing and limited clinical data. We also discuss novel findings in the viral pathomechanisms involved in beta-HPV cutaneous tumorigenesis that may play a large role in future vaccine development. We hope that synthesizing the available data and advances surrounding beta-HPV vaccine development will not only lead to increased dedication to vaccine development, but also heightened awareness of a future vaccine among clinicians and the public.