The risk of cutaneous squamous cell carcinoma (SCC) is increased in patients with immunosuppression and associated with beta human papilloma virus (β-HPV). Strickley, Messerschmidt et al. now show that β-HPV infection itself is not causal in SCC development in the context of immunosuppression, but instead it is the loss of β-HPV-mediated T cell immunity that promotes SCC in this context. β-HPV infection has been hypothesized to facilitate the initiation of carcinogen-driven skin cancer. The authors used back-skin infection of mouse papillomavirus type 1 (MmuPV1) in mice to model carcinogen-driven SCC. C57BL/6J mice infected with MmuPVl or sham infected were exposed to a chemical carcinogen protocol 2 months after infection, for 30 weeks. MmuPV1-infected mice developed skin tumours, although onset was delayed and the tumour burden was lower than in sham-infected mice. When immunodeficient Cd4~-/-Cd8~-/-mice were infected with MmuPVl, they developed confluent warts, in contrast to immunocompetent MmuPV1-infected control mice.
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