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Published in: Medical Microbiology and Immunology 2/2012

01-05-2012 | Original Investigation

Beta-papillomavirus DNA loads in hair follicles of immunocompetent people and organ transplant recipients

Authors: Sönke Weissenborn, Rachel E. Neale, Tim Waterboer, Damiano Abeni, Jan Nico Bouwes Bavinck, Adele C. Green, Catherine A. Harwood, Sylvie Euvrard, Mariet C. W. Feltkamp, Maurits N. C. de Koning, Luigi Naldi, Wim G. V. Quint, Gianpaolo Tessari, Charlotte M. Proby, Ulrike Wieland, Herbert Pfister, EPI-HPV-UV-CA group

Published in: Medical Microbiology and Immunology | Issue 2/2012

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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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Literature
1.
go back to reference Green AC, Hughes MC, Ibiebele TI, Williams GM, van der Pols JC, Ortonne JP (2008) Antioxidant supplementation and risk of skin cancers. J Nutr 138:978; author reply 979 Green AC, Hughes MC, Ibiebele TI, Williams GM, van der Pols JC, Ortonne JP (2008) Antioxidant supplementation and risk of skin cancers. J Nutr 138:978; author reply 979
2.
go back to reference De Hertog SA, Wensveen CA, Bastiaens MT, Kielich CJ, Berkhout MJ, Westendorp RG, Vermeer BJ, Bouwes Bavinck JN (2001) Relation between smoking and skin cancer. J Clin Oncol 19:231–238PubMed De Hertog SA, Wensveen CA, Bastiaens MT, Kielich CJ, Berkhout MJ, Westendorp RG, Vermeer BJ, Bouwes Bavinck JN (2001) Relation between smoking and skin cancer. J Clin Oncol 19:231–238PubMed
3.
go back to reference Majewski S, Jablonska S (1995) Epidermodysplasia verruciformis as a model of human papillomavirus-induced genetic cancer of the skin. Arch Dermatol 131:1312–1318PubMedCrossRef Majewski S, Jablonska S (1995) Epidermodysplasia verruciformis as a model of human papillomavirus-induced genetic cancer of the skin. Arch Dermatol 131:1312–1318PubMedCrossRef
4.
go back to reference Feltkamp MC, Broer R, di Summa FM, Struijk L, van der Meijden E, Verlaan BP, Westendorp RG, ter Schegget J, Spaan WJ, Bouwes Bavinck JN (2003) Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer. Cancer Res 63:2695–2700PubMed Feltkamp MC, Broer R, di Summa FM, Struijk L, van der Meijden E, Verlaan BP, Westendorp RG, ter Schegget J, Spaan WJ, Bouwes Bavinck JN (2003) Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer. Cancer Res 63:2695–2700PubMed
5.
go back to reference Karagas MR, Waterboer T, Li Z, Nelson HH, Michael KM, Bavinck JN, Perry AE, Spencer SK, Daling J, Green AC, Pawlita M (2010) Genus beta human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study. BMJ 341:c2986PubMedCrossRef Karagas MR, Waterboer T, Li Z, Nelson HH, Michael KM, Bavinck JN, Perry AE, Spencer SK, Daling J, Green AC, Pawlita M (2010) Genus beta human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study. BMJ 341:c2986PubMedCrossRef
6.
go back to reference Masini C, Fuchs PG, Gabrielli F, Stark S, Sera F, Ploner M, Melchi CF, Primavera G, Pirchio G, Picconi O, Petasecca P, Cattaruzza MS, Pfister HJ, Abeni D (2003) Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals. Arch Dermatol 139:890–894PubMedCrossRef Masini C, Fuchs PG, Gabrielli F, Stark S, Sera F, Ploner M, Melchi CF, Primavera G, Pirchio G, Picconi O, Petasecca P, Cattaruzza MS, Pfister HJ, Abeni D (2003) Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals. Arch Dermatol 139:890–894PubMedCrossRef
7.
go back to reference Struijk L, Bouwes Bavinck JN, Wanningen P, van der Meijden E, Westendorp RG, Ter Schegget J, Feltkamp MC (2003) Presence of human papillomavirus DNA in plucked eyebrow hairs is associated with a history of cutaneous squamous cell carcinoma. J Invest Dermatol 121:1531–1535PubMedCrossRef Struijk L, Bouwes Bavinck JN, Wanningen P, van der Meijden E, Westendorp RG, Ter Schegget J, Feltkamp MC (2003) Presence of human papillomavirus DNA in plucked eyebrow hairs is associated with a history of cutaneous squamous cell carcinoma. J Invest Dermatol 121:1531–1535PubMedCrossRef
8.
go back to reference Struijk L, Hall L, van der Meijden E, Wanningen P, Bavinck JN, Neale R, Green AC, Ter Schegget J, Feltkamp MC (2006) Markers of cutaneous human papillomavirus infection in individuals with tumor-free skin, actinic keratoses, and squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 15:529–535PubMedCrossRef Struijk L, Hall L, van der Meijden E, Wanningen P, Bavinck JN, Neale R, Green AC, Ter Schegget J, Feltkamp MC (2006) Markers of cutaneous human papillomavirus infection in individuals with tumor-free skin, actinic keratoses, and squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 15:529–535PubMedCrossRef
9.
go back to reference Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V (2009) A review of human carcinogens–Part B: biological agents. Lancet Oncol 10:321–322PubMedCrossRef Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V (2009) A review of human carcinogens–Part B: biological agents. Lancet Oncol 10:321–322PubMedCrossRef
10.
go back to reference Boxman IL, Berkhout RJ, Mulder LH, Wolkers MC, Bouwes Bavinck JN, Vermeer BJ, ter Schegget J (1997) Detection of human papillomavirus DNA in plucked hairs from renal transplant recipients and healthy volunteers. J Invest Dermatol 108:712–715PubMedCrossRef Boxman IL, Berkhout RJ, Mulder LH, Wolkers MC, Bouwes Bavinck JN, Vermeer BJ, ter Schegget J (1997) Detection of human papillomavirus DNA in plucked hairs from renal transplant recipients and healthy volunteers. J Invest Dermatol 108:712–715PubMedCrossRef
11.
go back to reference Boxman IL, Russell A, Mulder LH, Bavinck JN, ter Schegget J, Green A (2001) Association between epidermodysplasia verruciformis-associated human papillomavirus DNA in plucked eyebrow hair and solar keratoses. J Invest Dermatol 117:1108–1112PubMedCrossRef Boxman IL, Russell A, Mulder LH, Bavinck JN, ter Schegget J, Green A (2001) Association between epidermodysplasia verruciformis-associated human papillomavirus DNA in plucked eyebrow hair and solar keratoses. J Invest Dermatol 117:1108–1112PubMedCrossRef
12.
go back to reference de Koning MN, Weissenborn SJ, Abeni D, Bouwes Bavinck JN, Euvrard S, Green AC, Harwood CA, Naldi L, Neale R, Nindl I, Proby CM, Quint WG, Sampogna F, ter Schegget J, Struijk L, Wieland U, Pfister HJ, Feltkamp MC (2009) Prevalence and associated factors of betapapillomavirus infections in individuals without cutaneous squamous cell carcinoma. J Gen Virol 90:1611–1621PubMedCrossRef de Koning MN, Weissenborn SJ, Abeni D, Bouwes Bavinck JN, Euvrard S, Green AC, Harwood CA, Naldi L, Neale R, Nindl I, Proby CM, Quint WG, Sampogna F, ter Schegget J, Struijk L, Wieland U, Pfister HJ, Feltkamp MC (2009) Prevalence and associated factors of betapapillomavirus infections in individuals without cutaneous squamous cell carcinoma. J Gen Virol 90:1611–1621PubMedCrossRef
13.
go back to reference Plasmeijer EI, Neale RE, Buettner PG, de Koning MN, Ter Schegget J, Quint WG, Green AC, Feltkamp MC (2010) Betapapillomavirus infection profiles in tissue sets from cutaneous squamous cell-carcinoma patients. Int J Cancer 126:2614–2621PubMed Plasmeijer EI, Neale RE, Buettner PG, de Koning MN, Ter Schegget J, Quint WG, Green AC, Feltkamp MC (2010) Betapapillomavirus infection profiles in tissue sets from cutaneous squamous cell-carcinoma patients. Int J Cancer 126:2614–2621PubMed
14.
go back to reference Kohler A, Forschner T, Meyer T, Ulrich C, Gottschling M, Stockfleth E, Nindl I (2007) Multifocal distribution of cutaneous human papillomavirus types in hairs from different skin areas. Br J Dermatol 156:1078–1080PubMedCrossRef Kohler A, Forschner T, Meyer T, Ulrich C, Gottschling M, Stockfleth E, Nindl I (2007) Multifocal distribution of cutaneous human papillomavirus types in hairs from different skin areas. Br J Dermatol 156:1078–1080PubMedCrossRef
15.
go back to reference Hazard K, Karlsson A, Andersson K, Ekberg H, Dillner J, Forslund O (2007) Cutaneous human papillomaviruses persist on healthy skin. J Invest Dermatol 127:116–119PubMedCrossRef Hazard K, Karlsson A, Andersson K, Ekberg H, Dillner J, Forslund O (2007) Cutaneous human papillomaviruses persist on healthy skin. J Invest Dermatol 127:116–119PubMedCrossRef
16.
go back to reference de Koning MN, Struijk L, Bavinck JN, Kleter B, ter Schegget J, Quint WG, Feltkamp MC (2007) Betapapillomaviruses frequently persist in the skin of healthy individuals. J Gen Virol 88:1489–1495PubMedCrossRef de Koning MN, Struijk L, Bavinck JN, Kleter B, ter Schegget J, Quint WG, Feltkamp MC (2007) Betapapillomaviruses frequently persist in the skin of healthy individuals. J Gen Virol 88:1489–1495PubMedCrossRef
17.
go back to reference Weissenborn SJ, De Koning MN, Wieland U, Quint WG, Pfister HJ (2009) Intrafamilial transmission and family-specific spectra of cutaneous betapapillomaviruses. J Virol 83:811–816PubMedCrossRef Weissenborn SJ, De Koning MN, Wieland U, Quint WG, Pfister HJ (2009) Intrafamilial transmission and family-specific spectra of cutaneous betapapillomaviruses. J Virol 83:811–816PubMedCrossRef
18.
go back to reference Weissenborn SJ, Neale R, de Koning MN, Waterboer T, Abeni D, Bouwes Bavinck JN, Wieland U, Pfister HJ (2009) Prevalence and multiplicity of cutaneous beta papilloma viruses in plucked hairs depend on cellular DNA input. J Virol Methods 161:280–283PubMedCrossRef Weissenborn SJ, Neale R, de Koning MN, Waterboer T, Abeni D, Bouwes Bavinck JN, Wieland U, Pfister HJ (2009) Prevalence and multiplicity of cutaneous beta papilloma viruses in plucked hairs depend on cellular DNA input. J Virol Methods 161:280–283PubMedCrossRef
19.
go back to reference Weissenborn SJ, Wieland U, Junk M, Pfister H (2010) Quantification of beta-human papillomavirus DNA by real-time PCR. Nat Protoc 5:1–13PubMedCrossRef Weissenborn SJ, Wieland U, Junk M, Pfister H (2010) Quantification of beta-human papillomavirus DNA by real-time PCR. Nat Protoc 5:1–13PubMedCrossRef
20.
go back to reference Weissenborn SJ, Nindl I, Purdie K, Harwood C, Proby C, Breuer J, Majewski S, Pfister H, Wieland U (2005) Human papillomavirus-DNA loads in actinic keratoses exceed those in non-melanoma skin cancers. J Invest Dermatol 125:93–97PubMedCrossRef Weissenborn SJ, Nindl I, Purdie K, Harwood C, Proby C, Breuer J, Majewski S, Pfister H, Wieland U (2005) Human papillomavirus-DNA loads in actinic keratoses exceed those in non-melanoma skin cancers. J Invest Dermatol 125:93–97PubMedCrossRef
21.
go back to reference Dell’Oste V, Azzimonti B, De Andrea M, Mondini M, Zavattaro E, Leigheb G, Weissenborn SJ, Pfister H, Michael KM, Waterboer T, Pawlita M, Amantea A, Landolfo S, Gariglio M (2009) High beta-HPV DNA loads and strong seroreactivity are present in epidermodysplasia verruciformis. J Invest Dermatol 129:1026–1034PubMedCrossRef Dell’Oste V, Azzimonti B, De Andrea M, Mondini M, Zavattaro E, Leigheb G, Weissenborn SJ, Pfister H, Michael KM, Waterboer T, Pawlita M, Amantea A, Landolfo S, Gariglio M (2009) High beta-HPV DNA loads and strong seroreactivity are present in epidermodysplasia verruciformis. J Invest Dermatol 129:1026–1034PubMedCrossRef
22.
go back to reference Bouwes Bavinck JN, Euvrad S, Naldi L, Proby C, Neale RE, Abeni D, Tessari G, Feltkamp MCW, Claudy A, Stockfleth E, Harwood C, E-H-U-C group (2007) Keratotic skin lesions and other risk factors are associated with skin cancer in organ-transplant recipients: a case-control study in The Netherlands, United Kingdom, Germany, France and Italy. J Invest Dermatol 127:1647–1656PubMed Bouwes Bavinck JN, Euvrad S, Naldi L, Proby C, Neale RE, Abeni D, Tessari G, Feltkamp MCW, Claudy A, Stockfleth E, Harwood C, E-H-U-C group (2007) Keratotic skin lesions and other risk factors are associated with skin cancer in organ-transplant recipients: a case-control study in The Netherlands, United Kingdom, Germany, France and Italy. J Invest Dermatol 127:1647–1656PubMed
23.
go back to reference Boom R, Sol CJ, Salimans MM, Jansen CL, Wertheim-van Dillen PM, van der Noordaa J (1990) Rapid and simple method for purification of nucleic acids. J Clin Microbiol 28:495–503PubMed Boom R, Sol CJ, Salimans MM, Jansen CL, Wertheim-van Dillen PM, van der Noordaa J (1990) Rapid and simple method for purification of nucleic acids. J Clin Microbiol 28:495–503PubMed
24.
go back to reference de Koning M, Quint W, Struijk L, Kleter B, Wanningen P, van Doorn LJ, Weissenborn SJ, Feltkamp M, ter Schegget J (2006) Evaluation of a novel highly sensitive, broad-spectrum PCR-reverse hybridization assay for detection and identification of beta-papillomavirus DNA. J Clin Microbiol 44:1792–1800PubMedCrossRef de Koning M, Quint W, Struijk L, Kleter B, Wanningen P, van Doorn LJ, Weissenborn SJ, Feltkamp M, ter Schegget J (2006) Evaluation of a novel highly sensitive, broad-spectrum PCR-reverse hybridization assay for detection and identification of beta-papillomavirus DNA. J Clin Microbiol 44:1792–1800PubMedCrossRef
25.
go back to reference Antonsson A, Karanfilovska S, Lindqvist PG, Hansson BG (2003) General acquisition of human papillomavirus infections of skin occurs in early infancy. J Clin Microbiol 41:2509–2514PubMedCrossRef Antonsson A, Karanfilovska S, Lindqvist PG, Hansson BG (2003) General acquisition of human papillomavirus infections of skin occurs in early infancy. J Clin Microbiol 41:2509–2514PubMedCrossRef
26.
go back to reference Antonsson A, Forslund O, Ekberg H, Sterner G, Hansson BG (2000) The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses. J Virol 74:11636–11641PubMedCrossRef Antonsson A, Forslund O, Ekberg H, Sterner G, Hansson BG (2000) The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses. J Virol 74:11636–11641PubMedCrossRef
27.
go back to reference Moberg M, Gustavsson I, Wilander E, Gyllensten U (2005) High viral loads of human papillomavirus predict risk of invasive cervical carcinoma. Br J Cancer 92:891–894PubMedCrossRef Moberg M, Gustavsson I, Wilander E, Gyllensten U (2005) High viral loads of human papillomavirus predict risk of invasive cervical carcinoma. Br J Cancer 92:891–894PubMedCrossRef
28.
go back to reference Weissenborn SJ, Funke AM, Hellmich M, Mallmann P, Fuchs PG, Pfister HJ, Wieland U (2003) Oncogenic human papillomavirus DNA loads in human immunodeficiency virus-positive women with high-grade cervical lesions are strongly elevated. J Clin Microbiol 41:2763–2767PubMedCrossRef Weissenborn SJ, Funke AM, Hellmich M, Mallmann P, Fuchs PG, Pfister HJ, Wieland U (2003) Oncogenic human papillomavirus DNA loads in human immunodeficiency virus-positive women with high-grade cervical lesions are strongly elevated. J Clin Microbiol 41:2763–2767PubMedCrossRef
29.
go back to reference Pawelec G, Larbi A (2008) Immunity and ageing in man: annual review 2006/2007. Exp Gerontol 43:34–38PubMed Pawelec G, Larbi A (2008) Immunity and ageing in man: annual review 2006/2007. Exp Gerontol 43:34–38PubMed
30.
go back to reference Zur Hausen H (2009) The search for infectious causes of human cancers: where and why. Virology 392:1–10PubMedCrossRef Zur Hausen H (2009) The search for infectious causes of human cancers: where and why. Virology 392:1–10PubMedCrossRef
31.
go back to reference Pfister H (2003) Chapter 8: Human papillomavirus and skin cancer. J Natl Cancer Inst Monogr (31) 52-56 Pfister H (2003) Chapter 8: Human papillomavirus and skin cancer. J Natl Cancer Inst Monogr (31) 52-56
32.
go back to reference Nindl I, Gottschling M, Stockfleth E (2007) Human papillomaviruses and non-melanoma skin cancer: basic virology and clinical manifestations. Dis Markers 23:247–259PubMed Nindl I, Gottschling M, Stockfleth E (2007) Human papillomaviruses and non-melanoma skin cancer: basic virology and clinical manifestations. Dis Markers 23:247–259PubMed
33.
go back to reference Pfefferle R, Marcuzzi GP, Akgül B, Kasper HU, Schulze F, Haase I, Wickenhauser C, Pfister H (2008) The human papillomavirus type 8 E2 protein induces skin tumors in transgenic mice. J Invest Dermatol 128:2310–2315PubMedCrossRef Pfefferle R, Marcuzzi GP, Akgül B, Kasper HU, Schulze F, Haase I, Wickenhauser C, Pfister H (2008) The human papillomavirus type 8 E2 protein induces skin tumors in transgenic mice. J Invest Dermatol 128:2310–2315PubMedCrossRef
34.
go back to reference Hufbauer M, Lazic D, Akgül B, Brandsma JL, Pfister H, Weissenborn SJ (2010) Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice. Virology 403:128–136PubMedCrossRef Hufbauer M, Lazic D, Akgül B, Brandsma JL, Pfister H, Weissenborn SJ (2010) Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice. Virology 403:128–136PubMedCrossRef
Metadata
Title
Beta-papillomavirus DNA loads in hair follicles of immunocompetent people and organ transplant recipients
Authors
Sönke Weissenborn
Rachel E. Neale
Tim Waterboer
Damiano Abeni
Jan Nico Bouwes Bavinck
Adele C. Green
Catherine A. Harwood
Sylvie Euvrard
Mariet C. W. Feltkamp
Maurits N. C. de Koning
Luigi Naldi
Wim G. V. Quint
Gianpaolo Tessari
Charlotte M. Proby
Ulrike Wieland
Herbert Pfister
EPI-HPV-UV-CA group
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Medical Microbiology and Immunology / Issue 2/2012
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI
https://doi.org/10.1007/s00430-011-0212-3

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