Distinct Risk Factor Profiles for Human Papillomavirus Type 16–Positive and Human Papillomavirus Type 16–Negative Head and Neck Cancers

• Published in: JNCI : Journal of the National Cancer Institute Vol. 100; no. 6; pp. 407 - 420
• Main Authors: Gillison, Maura L., D'Souza, Gypsyamber, Westra, William, Sugar, Elizabeth, Xiao, Weihong, Begum, Shahnaz, Viscidi, Raphael
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 19.03.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Alcohol Drinking - adverse effects; Alphapapillomavirus - isolation & purification; Antibodies, Viral - blood; Biological and medical sciences; Capsid Proteins - blood; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - virology; Case-Control Studies; DNA, Viral - isolation & purification; Female; Head & neck cancer; Head and Neck Neoplasms - etiology; Head and Neck Neoplasms - virology; Human papillomavirus; Human papillomavirus 16 - genetics; Human papillomavirus 16 - immunology; Human papillomavirus 16 - isolation & purification; Humans; Male; Marijuana Smoking - adverse effects; Medical sciences; Middle Aged; Odds Ratio; Oncology; Oral Hygiene - adverse effects; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Pathology; Risk Assessment; Risk Factors; Sexual Behavior; Smoking - adverse effects; Tumors; Viral Load; United States; North America; America; Tobacco smoking; Papovaviridae; Case control study; Epidemiology; Papillomavirus; Alcoholic beverage; Human papillomavirus 16; Human papillomavirus; Cancerology; ENT disease; Head and neck squamous cell carcinoma; Drug of abuse; Public health; Human; Ethanol; Sexual behavior; Loss; Malignant tumor; Infection; Virus; Viral disease; Risk factor; Head and neck cancer; Marijuana; Tooth; Comparative study; Cancer
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djn025

Background High-risk types of human papillomavirus (HPV), including HPV-16, cause a subgroup of head and neck squamous cell carcinomas (HNSCCs). We examined whether the risk factors for HPV-16–positive HNSCCs are similar to those for HPV-16–negative HNSCCs in a hospital-based case–control study. Methods Case subjects (n = 240) diagnosed with HNSCC at the Johns Hopkins Hospital from 2000 through 2006 were stratified by tumor HPV-16 status as determined by in situ hybridization. Two control subjects (n = 322) without cancer were individually matched by age and sex to each HPV-16–positive and HPV-16–negative case subject. Data on risk behaviors were obtained by use of audio computer-assisted self-interview technology. Multivariable conditional logistic regression models were used to estimate the odds ratios (ORs) for HPV-16–positive HNSCC and HPV-16–negative HNSCC associated with risk factors. All statistical tests were two-sided. Results HPV-16 was detected in 92 of 240 case subjects. HPV-16–positive HNSCC was independently associated with several measures of sexual behavior and exposure to marijuana but not with cumulative measures of tobacco smoking, alcohol drinking, or poor oral hygiene. Associations increased in strength with increasing number of oral sex partners (Ptrend = .01) and with increasing intensity (joints per month, Ptrend = .007), duration (in years, Ptrend = .01), and cumulative joint-years (Ptrend = .003) of marijuana use. By contrast, HPV-16–negative HNSCC was associated with measures of tobacco smoking, alcohol drinking, and poor oral hygiene but not with any measure of sexual behavior or marijuana use. Associations increased in strength with increasing intensity (cigarettes per day), duration, and cumulative pack-years of tobacco smoking (for all, Ptrend < .001), increasing years of heavy alcohol drinking (≥15 years of 14 drinks per week; Ptrend = .03), and increasing number of lost teeth (Ptrend = .001). Compared with subjects who neither smoked tobacco nor drank alcohol, those with heavy use of tobacco (≥20 pack-years) and alcohol had an increased risk of HPV-16–negative HNSCC (OR = 4.8, 95% confidence interval [CI] = 1.8 to 12) but not of HPV-16–positive HNSCC (OR = 0.67, 95% CI = 0.29 to 1.9). Conclusions HPV-16–positive HNSCCs and HPV-16–negative HNSCCs have different risk factor profiles, indicating that they should be considered to be distinct cancers.