Widespread cutaneous carcinomas associated with human papillomaviruses 5, 14 and 20 after introduction of methotrexate in two long-term PUVA-treated patients

Background: PUVA treatment for patients with severe psoriasis has been demo nstrated to be highly effective. However, an increased risk of nonmelanoma and melanoma skin cancers has been reported. It is generally accepted that the risk of squamous-cell carcinoma (SCC) is significantly increased in pat ients with long-term PUVA therapy. The role of methotrexate (MTX) and infec tion with oncogenic human papillomaviruses which may act as cocarcinogens i s poorly documented. Case Reports: Two cases of multiple SCCs associated wi th numerous PUVA keratoses and PUVA freckles after long-term PUVA therapy a nd subsequent treatment with MTX are presented. In 1 case, the tumor progre ssed to metastatic SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the presence of oncogenic human papillomavirus (HPV) genotype s. The genotype of HPV-5, -14 and -20 was detected in scrapings and skin tu mors using PCR amplification. Conclusion: These observations support the co ncept that long-term PUVA treatment is carcino-genic and rise questions con cerning an additional influence of MTX in the development and progression o f skin cancer. The risk of metastatic SCC seems to be underestimated in hig h-dose PUVA-treated patients due to longer latency for developing metastase s and the small number of studies with long-term follow-up. Treatment with MTX should be considered cautiously in patients previously exposed to high doses of PUVA. The presence of oncogenic HPVs in carcinomas and psoriatic s kin lesions detected only with the highly sensitive nested PCR method is no t necessarily a proof of their implication in skin carcinogenesis. Copyrigh t (C) 2001 S. Karger AG, Basel.