Human Papillomavirus Infection as a Risk Factor for Squamous-Cell Carcinoma of the Head and Neck
Jon Mork, M.D., A. Kathrine Lie, M.D., Eystein Glattre, M.D., Sarah Clark, D.Phil., Goran Hallmans, M.D., Egil Jellum, Ph.D., Pentti Koskela, Ph.D., Bjorn Moller, M.Sc., Eero Pukkala, Ph.D., John T. Schiller, Ph.D., Zhaohui Wang, M.D., Linda Youngman, Ph.D., Matti Lehtinen, M.D., and Joakim Dillner, M.D.
Background Oncogenic human papillomaviruses (HPVs), especiallyHPV type 16 (HPV-16), cause anogenital epithelial cancers andare suspected of causing epithelial cancers of the head andneck.
Methods To examine the relation between head and neck cancersand HPVs, we performed a nested case–control study withina joint Nordic cohort in which serum samples were collectedfrom almost 900,000 subjects. Samples collected at enrollmentfrom 292 persons in whom squamous-cell carcinoma of the headand neck developed, on average, 9.4 years after enrollment andfrom 1568 matched controls were analyzed for antibodies againstHPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels asa marker of smoking habits. Polymerase-chain-reaction (PCR)analyses for HPV DNA were performed in tumor tissue from 160of the study patients with cancer.
Results After adjustment for cotinine levels, the odds ratiofor squamous-cell carcinoma of the head and neck in subjectswho were seropositive for HPV-16 was 2.2 (95 percent confidenceinterval, 1.4 to 3.4). No increased risk was observed for otherHPV types. Fifty percent of oropharyngeal and 14 percent oftongue cancers contained HPV-16 DNA, according to PCR analysis.
Conclusions HPV-16 infection may be a risk factor for squamous-cellcarcinoma of the head and neck.
Source Information
From the Cancer Registry of Norway, Oslo (J.M., E.G., B.M.); the Department of Otolaryngology, National Hospital, Oslo, Norway (J.M.); the Department of Pathology, Norwegian Radium Hospital, Oslo (A.K.L.); the Northern Sweden Health and Disease Study, Umeå, Sweden (G.H.); the Janus Committee, Norwegian Cancer Society, Oslo, Norway (E.J.); the National Public Health Institute, Oulu, Finland (P.K.); the Finnish Cancer Registry, Helsinki, Finland (E.P.); the Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Md. (J.T.S.); the Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom (L.Y.); the National Public Health Institute, Helsinki, Finland (M.L., J.D.); and the Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden (J.D.).
Address reprint requests to Dr. Mork at the Department of Otolaryngology, National Hospital, N-0027 Oslo, Norway, or at jon.mork{at}ioks.uio.no.
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