Human papillomavirus infection and skin cancer risk in organ transplant recipients

Abstract

Warts and squamous cell carcinomas are important cutaneous complications in organ transplant recipients. The role of infection with human papillomaviruses (HPV) in the development of cutaneous squamous cell carcinoma is still unclear. An extremely diverse group of HPV types, mainly consisting of epidermodysplasia-verruciformis (EV)-associated HPV types, can be detected in benign, premalignant, and malignant skin lesions of organ transplant recipients. Frequently, there are multiple HPV types present in single skin biopsies. Typically, the prevalence of viral warts rises steadily after transplantation and a strong association exists between the number of HPV-induced warts and the development of skin cancer. The interval between the transplantation to the development of warts is clearly shorter than the interval from transplantation to the diagnosis of the first skin cancer. A comparison of transplant recipients with and without skin cancer, however, showed an equally high prevalence of EV-HPV DNA in keratotic skin lesions in both groups of patients and the detection rate and spectrum of HPV infection in hyperkeratotic papillomas, actinic keratoses, and squamous cell carcinomas was also similar. HPV DNA can frequently be detected in patients with hyperproliferative disorders like psoriasis and antibodies against HPV in patients with regenerating skin (e.g., after extensive second degree burns). Latent infection with EV-HPV seems to be widespread. The hair follicle region might be the reservoir of EV-HPV. The E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV-light induced damage. It is therefore conceivable that individuals who are infected by EV-HPV are at an increased risk of developing actinic keratoses and squamous cell carcinomas, possibly by chronically preventing UV-light induced apoptosis.