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Genus β human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study

BMJ 2010; 341 doi: (Published 08 July 2010) Cite this as: BMJ 2010;341:c2986
  1. Margaret R Karagas, professor1,
  2. Tim Waterboer, post doctoral fellow 2,
  3. Zhongze Li, statistical analyst 1,
  4. Heather H Nelson, associate professor 3,
  5. Kristina M Michael, post doctoral fellow 2,
  6. Jan Nico Bouwes Bavinck, professor 4,
  7. Ann E Perry, associate professor 1,
  8. Steven K Spencer, professor 1,
  9. Janet Daling, professor emeritus 5,
  10. Adele C Green, professor 6,
  11. Michael Pawlita, scientist 2
  12. for the New Hampshire Skin Cancer Study Group
  1. 1Section of Biostatistics and Epidemiology, Department of Community and Family Medicine and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH, 03756, USA
  2. 2German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  3. 3Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA
  4. 4Leiden University Medical Center, 2300 RC Leiden, Netherlands
  5. 5University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA
  6. 6Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Qld 4029, Australia
  1. Correspondence to: M Karagas margaret.karagas{at}
  • Accepted 25 March 2010


Objective To investigate the association between genus β human papillomaviruses and the incidence of non-melanocytic skin cancer in the general population.

Design Population based case-control study.

Setting New Hampshire, USA.

Participants 2366 skin cancer cases and controls from the general population aged 25 to 74 years (663 squamous cell carcinoma, 898 basal cell carcinoma, 805 controls), with plasma samples tested for L1 antibodies to 16 genus β human papillomaviruses by multiplex serology.

Main outcome measures Odds ratios for squamous cell carcinoma and basal cell carcinoma associated with seropositivity to β human papillomaviruses.

Results Squamous cell carcinoma, but not basal cell carcinoma, cases had a higher prevalence of each of the individual β human papillomaviruses assayed compared with controls. The odds ratios for squamous cell carcinoma increased with the number of β types positive (odds ratio for one type positive 0.99 (95% confidence interval 0.74 to 1.33); two to three types positive 1.44 (1.03 to 2.01); four to eight types positive 1.51 (1.03 to 2.20); more than eight types positive 1.71 (1.12 to 2.62); P for trend (categorical)<0.001; P for trend (continuous)=0.003). With limited statistical power, the association was stronger among long term users of systemic glucocorticoids (odds ratio 3.21, 1.22 to 8.44) than among non-users (1.23, 0.97 to 1.55).

Conclusions These findings support a relation between genus β human papillomavirus infection and the incidence of squamous cell carcinoma of the skin in the general population, as well as potential enhancement of risk by immunosuppression.


  • We thank G Orth, E M de Villiers, and W Lancaster for the gift of human papillomavirus plasmids. We thank the study investigators and staff of the New Hampshire Health Study. The following physicians are members of the New Hampshire Skin Cancer Study Group: Duane R Anderson, Robert W Averill, Anthony J Aversa, Stephen Brady, Bruce A Bairstow, Richard D Baughman, Lawrence G Blasik, James Campbell, Carolyn Carroll, M Shane Chapman, William E Clendenning, Daniel W Collison, Jorge L Crespo, Frederick W Danby, Stephen M Del Guidice, Robert L Dimond, James G H Dinulos, Wilmot S Draper, Jeremy P Finkle, Judith Fisher, Jacqueline Fournier, William E Frank, John L Fromer, Norman C Goldberg, David Goldminz, Robert Gordon, David S Greenstein, Thomas P Habif, Charles Hammer, Tom Hokanson, Steve A Joselow, George Lewis, Michael D Lichter, Maritza O Liranzo, Lynette Margesson, Michael A Mittleman, Jose Peraza, Robert B Posnick, Warren M Pringle, Mark Quitadamo, Pauline B Reohr, N Chester Reynolds, Anna Ryan, Peter Sands, Mitchell E Schwartz, Gregory Seymour, Lisa D Sherman, Joan A Sisto, Steven K Spencer, James C Starke, Margaret I Stewart, Susan Sullivan, N Hakan Thyresson, Andrew P Truhan, Mauray J Tye, John Watson, K William Waterson, Robert Willer, and Kathryn Zug.

  • Contributors: MRK, MP, HHN, and ACG were responsible for the study concept and design. MRK, TW, HHN, and MP acquired the data. All authors contributed to the analysis and interpretation of data; MRK and ZL did the statistical analyses. MRK drafted the manuscript. MRK, TW, HHN, KMM, JNBB, AEP, SKS, JD, ACG, and MP critically reviewed the manuscript for important intellectual content. MRK, MP, and HHN obtained funding. TW, HHN, KMM, JNBB, AEP, SKS, ACG, and MP provided administrative, technical, or material support. MRK, MP, and HHN supervised the study. MRK is the guarantor.

  • Funding: The study was funded in part by grants CA118443 and CA57494 of the US National Institutes of Health, National Cancer Institute and grant QLK2-CT-2002-01179 of the European Community. The NCI and the EC were not involved in the design and conduct of the study or the collection, management, analysis, and interpretation of the data. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NCI or the EC.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare (1) no support from any company for the submitted work; (2) no relationships with any companies that might have an interest in the submitted work in the previous 3 years; (3) their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (4) no non-financial interests that may be relevant to the submitted work.

  • Ethical approval: The Committee for the Protection of Human Subjects (CPHS) at Dartmouth College approved the study, and all participants provided informed consent in accordance with CPHS guidelines.

  • Data sharing: No additional data available.

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