Journal of the European Academy of Dennatology and Venereology ELSEVIER 8(1997)130-136 Keratoacanthomas: human papillomavirus and herpes simplex virus associated? R. Strumia^*, C. Roveggio^ A. Rotola", P. Monini*', E. Cassai^ Dermatologica. Universiia deuli Siudi. 44100 Ferrara. Italy di Microbiotogia, Via Borsari 46. 44100 Ferrara. Italy Abstract Background A viral cause for keratoacanthoma has been postulated by many investigators. Recently, some investigators reported the identification of genital high risk human papilloma virus types 16 and 18 in keratoa- canthomas from transplant recipients. Observations We analysed by polymerase chain reaction biopsies of six multiple keratoacanthomas and four solitary keratoacanthoma biopsies for the presence of the most common genital papilloma viruses. All keratoa- canthomas included in the study had developed in skin areas exposed to sunlight. In addition, we analysed 16 normal skin tissue biopsies. Six of these control tissue biopsies were from sun-exposed skin areas, while 10 were from skin areas not exposed to sunlight. None of the patients enrolled in the study had clinical evidence of immunosuppression. As herpes simplex virus is associated to a variety of skin diseases and might co-operate with human papilloma virus in cervical cancer, the presence of this virus in bioptic specimens was also addressed. Results DNA sequences from oncogenic papilioma viruses type 16 and 18 were disclosed in two of four solitary keratoacanthomas, three of six multiple keratoacanthomas and four of six biopsies from sun-exposed normal skin. Non-oncogenic papilloma viruses (type 6 or 11) were detected only in one biopsy from a multiple keratoacanthoma, and herpes simplex virus DNA was disclosed in one solitary keratoacanthoma. one multiple keratoacanthoma and one tissue biopsy from sun-exposed skin. All specimens positive for herpes simplex virus were co-infected with human papilloma virus type 16, but this association was not statistically significant (Fisher's exact test; P - 0.14). None of the tissue biopsies from sun-protected normal skin was positive for these viruses. The difference of viral prevalence in sun-exposed and non- exposed skin was statistically sig- nificant {P= 1.5 X 10"-^). Conclusions In this study, human papilloma virus type 16 was detected with a high prevalence in keratoa- canthomas and normal skin from immunocompetent individuals. The different prevalence of viral DNA in sun- exposed and non-exposed skin suggests that sunlight may favour viral infection. The comparable prevalence of viral DNA in neoplastic and normal tissue from skin areas exposed to sunlight would indicate that human papilloma virus infection occurred after the onset of neoplastic proliferation. In turn, the rapid growth of keratoacanthomas and the high viral prevalence (50%) would imply a high overall rate of infection {and/or re-infection). The role of herpes simplex virus in this cutaneous pathology in unclear. © 1997 Elsevier Science Ireland B.V. Keywords: Keratoacanthoma; Papilloma virus; Herpes simplex virus; Polyniera.se chain reaction * Correspondinj; author. Tel.: +39 532 205825; fax: +39 532 206791. 0926-9959/97/$ 17,0() © 1997 Elsevier Science IrelamJ B.V. All rights reserved PI! S0926-9959(96)00575-2