Abstract
There is increasing evidence of an association between human papillomaviruses (HPV) of the beta-genus (beta-PV) and the development of cutaneous squamous cell carcinoma (SCC). The viral DNA load may be an important determinant of pathogenicity, but there are currently no baseline epidemiological data relating to load in people without SCC. We investigated DNA-loads of eight beta-PV types previously associated with risk of SCC. We collected eyebrow hairs from immunocompetent people (ICP) and organ transplant recipients (OTR), determined load by quantitative PCR and obtained demographic, phenotypic, and sun exposure information. Viral loads for ICP from Australia (n = 241) and Italy (n = 223) and OTR from across Europe (n = 318) spanned seven orders of magnitude. The median loads for all types were below one viral DNA copy per 60 cells and were highest for HPV5, HPV8 and HPV20. None of the populations had consistently higher viral loads for all 8 types. However, a higher proportion of OTR were in the top deciles of viral load distributions for six of the eight beta-PV types examined. In a nested analysis of Italian OTR and ICP, this finding was significant for six beta-PV types and cumulative load. Increasing age was significantly associated with higher viral loads in Australia, and there was a weak trend for higher loads with the time elapsed since transplantation in the OTR. We observed a wide distribution of beta-PV loads with OTR significantly more likely to have the highest viral loads. Thus, viral loads may be an important contributor to the higher risk of SCC in OTR.
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Acknowledgments
This study was supported by EC grant QLK-CT-200201179. S.W. is supported by the ‘Deutsche Krebshilfe’, EMBO and the Köln Fortune Programme of the University of Cologne. U.W. was supported by the German Federal Ministry of Education and Research (BMBF), Grant No. 01 KI 0771 (TP7). REN is supported by an NHMRC (Aust) Career Development Award.
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Sönke Weissenborn and Rachel E. Neale contributed equally to the manuscript.
Members of the EPI-HPV-UV-CA group are given in Appendix.
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Appendix
Members of the EPI-HPV-UV-CA group are
Centre for Cutaneous Research, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4, Newark Street, E1 2AT London, United Kingdom: C.A. Harwood, C.M. Proby, J. Breuer, L. Mitchell, K. Purdie, S.R.Lambert, H. Ran.
Department of Dermatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands: J.N. Bouwes Bavinck, P. van der Zwan-Kralt, Y.G.L. de Graaf, L.E. Vos, E.J. Uphoff-Meijerink, R. Willemze.
Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands: M.C.W. Feltkamp, L. Struijk, P. Wanningen, P.Z. van der Meijden, E.I. Plasmeijer.
Department of Medical Statistics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands: R. Wolterbeek.
Department of Dermatology, Hospices Civils de Lyon, 3 Quai des Célestins. 69002 Lyon, France: S. Euvrard, A.C. Butnaru, A. Claudy, J. Kanitakis.
Department of Dermatology and GISED Study Center, Ospedali Riuniti, Largo Barozzi, 1, 24128 Bergamo, Italy: L. Naldi, A. Pizzagalli, F. Sassi.
Department of Biomedical and Surgical Sciences, Section of Dermatology, University of Verona, c/o Ospedale Civile Maggiore, Verona Italy: G. Tessari.
Department of Dermatology, University Hospital Charité, Skin Cancer Center Charité, Charitéplatz 1, 10117 Berlin, Germany: I. Nindl, E. Stockfleth, T. Forschner.
Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56 D-50935 Cologne, Germany: H. Pfister, U. Wieland, S. Weissenborn.
German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany: M. Pawlita, T. Waterboer, P. Sehr, K.M. Michael.
DDL Diagnostic Laboratory, Fonteynenburghlaan 7, 2275 CX Voorburg, The Netherlands: W.G.V. Quint, M.N.C. de Koning*, J. ter Schegget*, B. Kleter, L.J. van Doorn. *Also employed by Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Istituto Dermopatico dell’Immacolata, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy: D. Abeni, F. Sampogna, T.J. Mannooranparampil, N. Melo-Salcedo, S. Simoni, G.P. Petasecca Donati, C. Masini, C. Deppermann Fortes.
Queensland Institute of Medical Research, 300 Herston Rd, 4006 Brisbane Australia: A.C. Green, R. Neale, C. Olsen, P O’Rourke, James Cook University; S. Harrison, P. Buttner.
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Weissenborn, S., Neale, R.E., Waterboer, T. et al. Beta-papillomavirus DNA loads in hair follicles of immunocompetent people and organ transplant recipients. Med Microbiol Immunol 201, 117–125 (2012). https://doi.org/10.1007/s00430-011-0212-3
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DOI: https://doi.org/10.1007/s00430-011-0212-3