Original Article
Subject Categories: Immunology/Infection
Journal of Investigative Dermatology (2005) 125, 93–97; doi:10.1111/j.0022-202X.2005.23733.x
Human Papillomavirus-DNA Loads in Actinic Keratoses Exceed those in Non-Melanoma Skin Cancers
Soenke Jan Weissenborn*, Ingo Nindl†, Karin Purdie‡, Catherine Harwood‡, Charlotte Proby‡, Judy Breuer§, Slawomir Majewski¶, Herbert Pfister* and Ulrike Wieland*
- *Institute of Virology, University of Cologne, Koeln, Germany;
- †Department of Dermatology, Charité, University of Berlin, Berlin, Germany;
- ‡Cancer Research UK Skin Tumour Laboratory, Centre for Cutaneous Research, London, UK;
- §Department of Virology, Barts and the London School of Medicine and Dentistry, London, UK;
- ¶Department of Dermatology and Venereology, Warsaw School of Medicine, Warsaw, Poland
Correspondence: S. J. Weissenborn, PhD, Institute of Virology, University of Cologne, Fuerst-Pueckler-Str. 56, 50935 Koeln, Germany. Email: Soenke.Weissenborn@medizin.uni-koeln.de or ulrike.wieland@uni-koeln.de
Received 7 October 2004; Revised 15 January 2005; Accepted 30 January 2005.
Abstract
Recent studies suggest a role of cutaneous human papillomaviruses (HPV) in non-melanoma skin cancer (NMSC) development. In this study viral DNA loads of six frequent HPV types were determined by quantitative, type-specific real-time-PCR (Q-PCR) in actinic keratoses (AK, n=26), NMSC (n=31), perilesional tissue (n=22), and metastases of squamous cell carcinomas (SCC) (n=8) which were previously shown to be positive for HPV5, 8, 15, 20, 24, or 36. HPV-DNA loads in AK, (partially microdissected) NMSC, and perilesional skin ranged between one HPV-DNA copy per 0.02 and 14,200 cell equivalents (median: 1 HPV-DNA copy per 344 cell equivalents; n=48). In 32 of the 79 HPV-positive skin biopsies and in seven of the eight metastases viral loads were even below the detection limit of Q-PCR. Low viral loads in NMSC were confirmed by in situ-hybridization showing only a few HPV-DNA-positive nuclei per section. Viral loads in SCC, basal cell carcinomas, and perilesional tissue were similar. But, viral loads found in AK were significantly higher than in SCC (p=0.035). Our data suggest that persistence of HPV is not necessary for the maintenance of the malignant phenotype of individual NMSC cells. Although a passenger state cannot be excluded, the data are compatible with a carcinogenic role of HPV in early steps of tumor development.
Keywords:
actinic keratoses, human papillomavirus (HPV), in situ-hybridization (ISH), non-melanoma skin cancer (NMSC), viral load
Abbreviations:
AK, actinic keratoses; BCC, basal cell carcinoma; EV, epidermodysplasia verruciformis; HPV, human papillomavirus; ISH, in situ-hybridization; NMSC, non-melanoma skin cancer; Q-PCR, quantitative real-time PCR; RT, room temperature; SCC, squamous cell carcinoma; TSA, tyramide signal amplification
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