Persistence of human papillomavirus DNA in benign and (pre)malignant skin lesions from renal transplant recipients

An extremely diverse group of human papillomavirus (HPV) types consisting o f epidermodysplasia verruciformis (EV-associated HPV types and other cutane ous HPV types (e.g., HPV types 2 and 3) is associated with nonmelanoma canc ers and benign lesions of the skin. The frequent presence of multiple HPV t ypes in single skin biopsy specimens of renal transplant recipients prompte d us to develop PCR techniques for the detection of distinct (sub)groups of genotypically related cutaneous HPV types, i.e., three subgroups of EV-ass ociated HPV types and two groups (A2 and A4) of other cutaneous HPV types. This approach generally allowed a reliable identification of HPV genotypes by direct sequencing of the PCR products, despite the frequent occurrence o f multiple infections. The targeted spectrum of HPV types comprises 66 cuta neous HPV types including 21 putative novel HPV types. We also detected 17 putative novel HPV subtypes. We demonstrated that the skin of nearly all re nal transplant recipients who developed various benign and (pre)malignant s kin lesions was persistently infected with one or more EV-associated HPV ty pes and/or HPV types belonging to groups A2 and A4. The frequency and distr ibution of EV-associated HPV and HPV types belonging to groups A2 and A4 we re similar in biopsy specimens from hyperkeratotic papillomas (77.5%), squa mous cell carcinomas (77.8%), and actinic keratoses (67.9%) but appeared to be lower in specimens of basal cell carcinomas (35.7%), benign lesions (38 .5%), and clinically normal skin (32.3%). These findings suggest that renal transplant recipients are prone to persistent cutaneous HPV infection. Our data do not support the existence of high-risk cutaneous HPV types.