PREVALENCE OF HUMAN PAPILLOMAVIRUS DNA IN CUTANEOUS NEOPLASMS FROM RENAL-ALLOGRAFT RECIPIENTS SUPPORTS A POSSIBLE VIRAL ROLE IN TUMOR PROMOTION

It is well established that renal allograpft recipients (RARs) have an increased incidence of viral warts and premalignant and malignant cut aneous lesions, and the risk of their development increases in proport ion to duration of graft survival. It has been postulated that, in add ition to the effects of prolonged immunosuppression and previous sun e xposure, human papillomaviruses (HPV) may also contribute to the carci nogenic process. In this study, the prevalence of HPV DNA was examined in a range of premalignant and malignant cutaneous tumours from 50 im munosuppressed patients (47 renal allograft recipients plus three card iac allograft recipients) and 56 immunocompetent patients using Southe rn hybridisation as a low-stringency screening method and type-specifi c polymerase chain reaction (PCR) assays for eight HPV types. The comb ined results for renal allograft recipients show that HPV DNA was dete ctable in 79% of viral warts, 42% of premalignant keratoses, 33% of in traepidermal carcinomas, 43% of invasive squamous cell carcinomas and 16% of uninvolved skin specimens (squamous cell carcinomas/renal allog raft recipients significantly different at P <0.05 from uninvolved ski n specimens/renal allograft recipients). In immunocompetent patients t he pattern of HPV DNA prevalence was 100% for viral warts; 25% for ker atoses, 23% for intraepidermal carcinomas, 22% for squamous cell carci nomas and 8% for uninvolved skin. No single HPV type predominated in t umour specimens from either group. More tumours were found to contain HPV DNA by Southern hybridisation analysis than PCR, indicating the pr esence of HPV types other than HPV 1, 2, 5, 6, 8, 11, 16 and 18 in som e tumours. However, 'low cancer risk' HPV types 1, 2 and 6 as well as 'high cancer risk' HPV types 5 and 16 were specifically detected by PC R in a small number of neoplasms. These data suggest that multiple HPV types may contribute to cutaneous neoplasia in RARs and that they app ear to act early in the process of carcinogenesis, perhaps by function ing as tumour promoters via stimulation of cell proliferation.