The actinic keratosis virome: can we prevent squamous cell carcinoma with a vaccine?

Squamous skin cancer, which is commonly called squamous cell carcinoma (SCC), represents an immunological puzzle. The major skin cancers (SCC, basal cell carcinoma, Merkel cell carcinoma, and melanoma) and actinic keratosis (AK), as a potential precursor lesion of SCC, are common in immune-suppressed patients. The increased risk of a particular cancer in chronically immune-suppressed patients is a feature of those cancers for which a virus contributes to the aetiology. However, amongst the skin cancers mentioned, a causal virus (Merkel polyomavirus) has been identified only for Merkel tumours. It is therefore reasonable to determine whether a virus or viruses contribute to the risk of the development of AK and SCC. This chapter will first consider the limitations of the methodologies available for determining the roles of viruses in the aetiologies of AK and SCC and review current evidence of the contribution of a virus to the risk of developing these diseases. It will then consider why there might be an increased risk of AK in chronically immune-suppressed patients although no relevant virus can be identified.