Case–Control Study of Human Papillomavirus and Oropharyngeal Cancer
Gypsyamber D'Souza, Ph.D., Aimee R. Kreimer, Ph.D., Raphael Viscidi, M.D., Michael Pawlita, M.D., Carole Fakhry, M.D., M.P.H., Wayne M. Koch, M.D., William H. Westra, M.D., and Maura L. Gillison, M.D., Ph.D.
Background Substantial molecular evidence suggests a role forhuman papillomavirus (HPV) in the pathogenesis of oropharyngealsquamous-cell carcinoma, but epidemiologic data have been inconsistent.
Methods We performed a hospital-based, case–control studyof 100 patients with newly diagnosed oropharyngeal cancer and200 control patients without cancer to evaluate associationsbetween HPV infection and oropharyngeal cancer. Multivariatelogistic-regression models were used for case–controlcomparisons.
Results A high lifetime number of vaginal-sex partners (26 ormore) was associated with oropharyngeal cancer (odds ratio,3.1; 95% confidence interval [CI], 1.5 to 6.5), as was a highlifetime number of oral-sex partners (6 or more) (odds ratio,3.4; 95% CI, 1.3 to 8.8). The degree of association increasedwith the number of vaginal-sex and oral-sex partners (P valuesfor trend, 0.002 and 0.009, respectively). Oropharyngeal cancerwas significantly associated with oral HPV type 16 (HPV-16)infection (odds ratio, 14.6; 95% CI, 6.3 to 36.6), oral infectionwith any of 37 types of HPV (odds ratio, 12.3; 95% CI, 5.4 to26.4), and seropositivity for the HPV-16 L1 capsid protein (oddsratio, 32.2; 95% CI, 14.6 to 71.3). HPV-16 DNA was detectedin 72% (95% CI, 62 to 81) of 100 paraffin-embedded tumor specimens,and 64% of patients with cancer were seropositive for the HPV-16oncoprotein E6, E7, or both. HPV-16 L1 seropositivity was highlyassociated with oropharyngeal cancer among subjects with a historyof heavy tobacco and alcohol use (odds ratio, 19.4; 95% CI,3.3 to 113.9) and among those without such a history (odds ratio,33.6; 95% CI, 13.3 to 84.8). The association was similarly increasedamong subjects with oral HPV-16 infection, regardless of theirtobacco and alcohol use. By contrast, tobacco and alcohol useincreased the association with oropharyngeal cancer primarilyamong subjects without exposure to HPV-16.
Conclusions Oral HPV infection is strongly associated with oropharyngealcancer among subjects with or without the established risk factorsof tobacco and alcohol use.
Source Information
From the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health (G.D.); the Departments of Pediatrics (R.V.), Otolaryngology–Head and Neck Surgery (C.F., W.M.K.), and Pathology (W.H.W.), Johns Hopkins Hospital; and the Division of Viral Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University (M.L.G.) — all in Baltimore; the Division of Cancer Prevention, National Cancer Institute, Bethesda, MD (A.R.K.); and the Infection and Cancer Control Program, German Cancer Research Center, Heidelberg, Germany (M.P.).
Address reprint requests to Dr. Gillison at Johns Hopkins University, Cancer Research Bldg. I, Rm. 3M 54A, 1650 Orleans St., Baltimore, MD 21231, or to gillima{at}jhmi.edu.
Human Papillomavirus and Oropharyngeal Cancer
Ukpo O. C., Moore E. J., Smith D. I., Williams H., Higgins C. D., Crawford D. H., Braakhuis B. J., Snijders P. J., Leemans C. R., Gillison M. L.
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N Engl J Med 2007;
357:1156-1158, Sep 13, 2007.
Correspondence
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