Molecular concepts of virus infections causing skin cancer in organ transplant recipients

Globally approximately 15% of all malignant tumors are caused by viruses and even a higher percentage is observed in organ transplant recipients (OTR). Here, nonmelanoma skin cancer (NMSC) is the most frequent malignancy, which correlates with cutaneous human papilloma virus (HPV) infection. In the present review, we reflect on some recent general concepts how tumor viruses can either act as direct or indirect carcinogens in the multistep process of carcinogenesis. Immunosuppressive drugs in OTR, which reduce the risk of organ rejection, could be critical in increasing the activation of persisting viral infections, thereby enhancing the probability to develop skin tumors. We discuss virus-induced transformation with special emphasis on the function of HPV as an indirect and HHV-8 as direct carcinogen in the development of NMSC and Kaposi sarcoma (KS), respectively. Moreover, we describe a rodent model system useful to examine future strategies in preventing skin tumor formation in immunosuppressed OTR.