Journal of the National Cancer Institute Advance Access published online on November 27, 2007
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm233
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ARTICLES |
Lack of Association of Alcohol and Tobacco with HPV16-Associated Head and Neck Cancer
Affiliations of authors: Departments of Environmental Health (KMA, EAE, KTK) and Genetics and Complex Diseases (CSF), Harvard School of Public Health, Boston, MA; Institute for the Environment, University of Brunel, West London, U.K. (AZ); Head and Neck Oncology Program, Dana-Farber Cancer Institute, Boston, MA (MRP); Department of Vaccine Biologics Research, Merck and Co, Inc, West Point, PA (JFS, JB); Epidemiology Program, Louisiana State University Health Sciences School of Public Health, New Orleans, LA (ESP); Department of Environmental Health, Boston University School of Public Health, Boston, MA (MDM); Departments of Community Health and Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, RI (KTK)
Correspondence to: Karl T. Kelsey, MD, Departments of Community Health and Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, RI 02912 (e-mail: karl_kelsey{at}brown.edu).
Background: Human papillomavirus type 16 (HPV16) seropositivity and alcohol and tobacco use have been associated with risk of head and neck squamous cell carcinoma (HNSCC). However, it is less clear whether HPV16 influences HNSCC risk associated with alcohol and tobacco use.
Methods: Incident cases of HNSCC diagnosed between December 1999 and December 2003 were identified from nine medical facilities in Greater Boston, MA. Control subjects were frequency matched to case subjects on age, sex, and town of residence. A total of 485 case subjects and 549 control subjects reported information on lifetime smoking and alcohol consumption and provided sera, which was used to determine presence of HPV16 antibodies. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of HNSCC risk by alcohol consumption (drinks per week: <3, 3 to <8, 8 to <25, 
25) and smoking (pack-years: none, >0 to <20, 20 to <45, 45), adjusting for age, sex, race, education, and HPV16 serology. Polytomous logistic regression was used to estimate odds ratios and 95% confidence intervals for the association of HPV16 serology, alcohol consumption, and tobacco use in site-specific analyses. All statistical tests were two-sided.
Results: The strongest risk factors by tumor site were smoking for laryngeal cancer, alcohol for cancer of the oral cavity, and HPV16 for pharyngeal cancer. For pharyngeal cancer, risk increased with increasing alcohol consumption (OR25 versus <3 drinks per week = 5.1, 95% CI = 2.4 to 11.0) and smoking (OR45 pack-years versus never smoker = 6.9, 95% CI = 3.1 to 15.1) among HPV16-seronegative subjects but not among HPV16-seropositive subjects (Pinteraction, HPV16 serology and alcohol = .002; Pinteraction, HPV16 serology and smoking = .007). Among light drinkers or never smokers, HPV16 seropositivity was associated with a 30-fold increased risk of pharyngeal cancer.
Conclusions: Alcohol or tobacco use does not further increase risk of HPV16-associated pharyngeal cancer. HNSCC risk associated with smoking, alcohol, and HPV16 differs by tumor site.
| CONTEXT AND CAVEATS Prior knowledge It was unclear how infection with human papillomavirus type 16 (HPV16) influences the association between smoking and drinking and the risk of head and neck squamous cell carcinoma. Study design Alcohol consumption and smoking habits among patients who were diagnosed with head and neck squamous cell carcinoma and matched control subjects were ascertained by a questionnaire, and the presence of HPV16 in the blood was determined using antibody tests. Logistic regression was used to examine the relationships between these risk factors. Contribution This study found that smoking and drinking was not associated with the risk of head and neck squamous cell carcinoma among those whose blood tested positive for HPV16. Implications Head and neck squamous cell carcinomas that are associated with viral infection and those associated with smoking and drinking may have different etiologies. Limitations The presence of serum antibodies to the virus may be a poor surrogate for viral infection at the cancer site, and the low participation rate of matched control subjects may have biased risk estimates.
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Manuscript received April 27, 2007; revised September 20, 2007; accepted October 22, 2007.
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J Natl Cancer Inst 2007 99: 1737.