Update on Our Understanding of HPV as a Risk Factor for Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients

Keratinocyte carcinomas are by far the most common malignancies seen in organ transplant recipients (OTR). Life-long immunosuppressive therapy is the most important risk factor for developing squamous cell carcinoma (SCC) in OTR. In the years after transplantation, OTR develop numerous warts and wart-like lesions followed by the development of SCC, which resembles the clinical picture of epidermodysplasia verruciformis patients in which human papillomavirus (HPV) infection was linked with skin cancer for the first time. HPV can be divided into genera and cause several distinct benign and (pre-) malignant diseases.There is evidence linking beta HPV infection with the development of SCC in OTR. However, the role of beta HPV in cutaneous SCC carcinogenesis is still enigmatic. Beta HPV is not integrated in the human cellular DNA and is not necessary for the maintenance of the malignant phenotype of cutaneous SCC. Whether different beta HPV types have different effects on cellular mechanisms and a combination of these HPV types may further increase the risk of cutaneous SCC is unknown. The carcinogenic effect, if present, is subtle and probably exerted early in carcinogenesis.