Original Article

Subject Category: Tumor Biology

Journal of Investigative Dermatology (2009) 129, 1026–1034; doi:10.1038/jid.2008.317; published online 16 October 2008

High bold beta-HPV DNA Loads and Strong Seroreactivity Are Present in Epidermodysplasia Verruciformis

Valentina Dell'Oste1, Barbara Azzimonti1, Marco De Andrea1,2, Michele Mondini1,3, Elisa Zavattaro1, Giorgio Leigheb1, Sönke J Weissenborn4, Herbert Pfister4, Kristina M Michael5, Tim Waterboer5, Michael Pawlita5, Ada Amantea6, Santo Landolfo2 and Marisa Gariglio1

  1. 1Department of Clinical and Experimental Medicine, Medical School of Novara, Novara, Italy
  2. 2Department of Public Health and Microbiology, Medical School of Turin, Turin, Italy
  3. 3NoToPharm S.r.l, Bioindustry Park del Canavese, Colleretto Giacosa (TO), Italy
  4. 4Institute of Virology, University of Cologne, Cologne, Germany
  5. 5Infection and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany
  6. 6San Gallicano Dermatological Institute IRCCS, Rome, Italy

Correspondence: Dr Marisa Gariglio, Department of Clinical and Experimental Medicine, Medical School of Novara, Via Solaroli 17, Novara 28100, Italy. E-mail: gariglio@med.unipmn.it

Received 18 March 2008; Revised 4 September 2008; Accepted 7 September 2008; Published online 16 October 2008.

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Abstract

Epidermodysplasia verruciformis (EV) is a rare disease, characterized by cutaneous warts and associated with a strong predisposition to beta-genus human papillomavirus (HPV). Earlier studies reported high copy numbers of HPV-DNA in nearly all skin tumors from EV patients, but neither HPV replication status in non-lesional skin nor anti-HPV seroreactivity in these patients have been reported yet. We therefore performed a comprehensive viral load analysis for the more common beta-HPV types on skin samples and plucked eyebrow hairs from four EV patients treated at our dermatology department. The results clearly demonstrate that they carry a multiplicity (up to eighteen types) of beta-HPV genotypes in both skin sites. Worthy of note, a high intrapatient concordance for specific types between hair bulbs and skin biopsies was observed and the same beta-PV profile was maintained over time. Viral load analysis revealed a load range between less than one HPV-DNA copy per 100 cells to more than 400 HPV-DNA copies per cell in both eyebrow hairs and skin proliferative lesions. Evaluation of seroreactivity to beta-HPV types in the four EV patients revealed that antibodies against the 16 beta-HPV were significantly more prevalent and showed higher titers than in the controls.

Abbreviations:

EV, epidermodysplasia verruciformis; GST, glutathione S-transferase; HPV, human papillomavirus; ISH, in situ hybridization; PV, papillomavirus; Q-PCR, quantitative real-time PCR; SCC, squamous-cell carcinoma

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