Non-melanoma skin cancer, i.e. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent tumors and their number is still increasing world- wide. Approximately 200000 cases of SCC develop per year, causing about 2000 deaths. Unlike BCCs, which have no known precursor lesions, SCCs can emerge from actinic keratoses. As with BCC, risk for development of SCC is strongly influenced by the nature and dose of UV radiation and genetic backgrounds that regulate that interaction. Mutations in TP53 have been described in actinic keratoses, in situ SCC, and invasive SCC with UV signature lesions common, and a reported mutation rate as high as 45%. As with TP53, UV-induced mutations in HRAS and KRAS have also been characterized in both actinic keratoses and SCC. The reported frequency of RAS mutations in SCCs ranges from approximately 10% to almost 50%. Several recent studies have also reported mutations of p16 in up to 24% of SCCs. In addition to UV, a pathogenic role for human papillomavirus (HPV) in the development of SCC has also been proposed.
