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 demonstrated 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 patients with long-term PUVA therapy. The role of methotrexate (MTX) and infection with oncogenic human papillomaviruses which may act as cocarcinogens is poorly documented.


METHODS
Two cases of multiple SCCs associated with numerous PUVA keratoses and PUVA freckles after long-term PUVA therapy and subsequent treatment with MTX are presented. In 1 case, the tumor progressed to metastatic SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the presence of oncogenic human papillomavirus (HPV) genotypes. The genotype of HPV-5, -14 and -20 was detected in scrapings and skin tumors using PCR amplification.


CONCLUSIONS
These observations support the concept that long-term PUVA treatment is carcinogenic and rise questions concerning an additional influence of MTX in the development and progression of skin cancer. The risk of metastatic SCC seems to be underestimated in high-dose PUVA-treated patients due to longer latency for developing metastases 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 skin lesions detected only with the highly sensitive nested PCR method is not necessarily a proof of their implication in skin carcinogenesis.
Zumtobel
U
U
Department of Dermatology, Hôpital St-André, Bordeaux, France.
Schwarze
H P
HP
Favre
M
M
Taïeb
A
A
Delaunay
M
M
D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000821:virology; D003043:Cocarcinogenesis; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007642:Keratosis / Q000209:etiology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000209:etiology*; D011701:PUVA Therapy / Q000009:adverse effects*; D027383:Papillomaviridae / Q000302:isolation & purification*; D011565:Psoriasis / Q000188:drug therapy; D012867:Skin / Q000821:virology; D012878:Skin Neoplasms / Q000209:etiology* / Q000821:virology
D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D008727:Methotrexate