High Frequency of Detection of Epidermodysplasia Verruciformis–Associated Human Papillomavirus DNA in Biopsies from Malignant and Premalignant Skin Lesions from Renal Transplant Recipients

Abstract

Based on immunologic and epidemiologic data, it is plausible that skin cancer in renal transplant recipients is associated with human papillomaviruses (HPV). At present, conflicting evidence exists concerning the presence of HPV DNA in these cancers. We recently described a nested polymerase chain reaction method that enables the detection of all previously isolated epidermodysplasia verruciformis (EV)-associated HPVs. We now describe the detection of EV-associated HPV DNA in 49 (80%) of 61 biopsies from squamous cell carcinomas, in four (50%) of eight basal cell carcinomas, in 14 (93%) of 15 actinic keratoses, in two (40%) of five cases of Bowen's disease, and in four (57%) of seven keratoacanthomas. HPV DNA typing revealed that all detected HPV types belonged to the EV-associated HPV types. A wide spectrum of EV-associated HPVs was found, including six putative new HPV types. In a high percentage of the lesions more than one HPV type was detected. We often found the same HPV types in different skin biopsies from both malignant and premalignant lesions from the same patient. The high frequency of detection of EV-associated HPV types in biopsies from malignant and premalignant lesions is in agreement with the hypothesis that EV-associated HPVs are involved in the pathogenesis of skin cancer in renal transplant recipients.

RETRACTED ARTICLE: E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage

“…The cancers in EV individuals predominantly occur at body sites exposed to sunlight, pointing to a role for ultra violet (UV) radiation in the development of the disease (Orth et al, 1979). In addition to EV, a role for HPVs has also been postulated in the development of non-melanoma skin cancers (NMSC) in both immunocompetent and immunocompromised individuals, such as organ transplant recipients (Jablonska, 1990;Purdie et al, 1993;de Jong-Tieben et al, 1995;Shamanin et al, 1996;Hop¯et al, 1997;Surentheran et al, 1998). Interestingly, these individuals also often develop NMSC at UV-exposed sites (reviewed in Proby et al, 1996).…”

“…These patients are exposed to chronic as well as acute UV doses and whose cutaneous lesions, including both warts and cancers, frequently harbour a diverse spectrum of HPV sequences (Shamanin et al, 1994(Shamanin et al, , 1996Berkhout et al, 1995;de Jong-Tieben et al, 1995). Although HPV10 is usually associated with benign proliferations in immunocompetent and immunosuppressed individuals (Favre et al, 1989;Obalek et al, 1992;Shamanin et al, 1994) it has also been found in carcinomas in organ transplant recipients in which the lesions are often multiply infected (Storey et al, 1998).…”

Antibody responses to 26 skin human papillomavirus types in the Netherlands, Italy and Australia

“…In organ-transplant recipients, b-HPV DNA is frequently detected in skin cancer and its precursor lesions, mainly actinic keratoses, suggesting a role for b-HPVs in skin cancer development (Berkhout et al, 2000;de Jong-Tieben et al, 1995;Harwood et al, 2000).…”

Skin Carcinoma Arising From Donor Cells in a Kidney Transplant Recipient

“…In kidney graft recipients, the relative risk of development of skin carcinomas is 10 to 250 times higher than in matched controls (4). UV-induced mutations (5,6), human papillomavirus infections (7,8), and immunodepression have been implicated in the pathogeny of these tumors. Occurrence of carcinomas is also correlated with human leukocyte antigen B mismatching between donor and recipient (9) suggesting the involvement of immunologic phenomena.…”