1. ^*Cancer Research UK, Skin Tumour Laboratory, Newark Street, London, UK;
2. ^†Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Newark Street, London, UK;
3. ^‡Skin Virus Laboratory, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Ashfield Street, London, UK;
4. ^§Department of Pathology, University of Cambridge, Cambridge, UK

Correspondence: Dr Catherine Anne Harwood, Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 2 Newark Street, London E1 2AT, UK. Email: caharwood@doctors.org.uk

¹These two authors contributed equally to this work.

Received 3 November 2003; Revised 1 November 2004; Accepted 3 November 2004.

Abstract

Epidermodysplasia verruciformis (EV)-type human papillomavirus (HPV) DNA have been detected by PCR in squamous cell carcinomas (SCC) from both organ transplant recipients (OTR) and immunocompetent individuals. Their role in skin cancer remains unclear, and previous studies have not addressed whether the viruses are transcriptionally active. We have used in situ hybridization to investigate the transcriptional activity and DNA localization of HPV. EV-HPV gene transcripts were demonstrated in four of 11 (36%) OTR SCC, one of two (50%) IC SCC, and one of five (20%) OTR warts positive by PCR. Viral DNA co-localized with E2/E4 early region gene transcripts in the middle or upper epidermal layers. Non-EV cutaneous HPV gene transcripts were demonstrated in one of five (20%) OTR SCC and four of 10 (40%) OTR warts. In mixed infections transcripts for both types were detected in two of six (33%) cases. Our results provide evidence of EV-HPV gene expression in SCC; although only a proportion of tumors were positive, the similarly low transcriptional activity in warts suggests this is an underestimate. These observations, together with emerging epidemiological and functional data, provide further reason to focus on the contribution of EV-HPV types to the pathogenesis of cutaneous SCC.