Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers

J Natl Cancer Inst. 2008 Mar 19;100(6):407-20. doi: 10.1093/jnci/djn025. Epub 2008 Mar 11.


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 (P(trend) = .01) and with increasing intensity (joints per month, P(trend) = .007), duration (in years, P(trend) = .01), and cumulative joint-years (P(trend) = .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, P(trend) < .001), increasing years of heavy alcohol drinking (> or = 15 years of 14 drinks per week; P(trend) = .03), and increasing number of lost teeth (P(trend) = .001). Compared with subjects who neither smoked tobacco nor drank alcohol, those with heavy use of tobacco (> or = 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alcohol Drinking / adverse effects
  • Alphapapillomavirus / isolation & purification
  • Antibodies, Viral / blood
  • Capsid Proteins / blood
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / virology*
  • Case-Control Studies
  • DNA, Viral / isolation & purification
  • Female
  • Head and Neck Neoplasms / etiology
  • Head and Neck Neoplasms / virology*
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 16 / isolation & purification*
  • Humans
  • Male
  • Marijuana Smoking / adverse effects
  • Middle Aged
  • Odds Ratio
  • Oral Hygiene / adverse effects
  • Risk Assessment
  • Risk Factors
  • Sexual Behavior
  • Smoking / adverse effects
  • Viral Load


  • Antibodies, Viral
  • Capsid Proteins
  • DNA, Viral