Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck

N Engl J Med. 2001 Apr 12;344(15):1125-31. doi: 10.1056/NEJM200104123441503.


Background: Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV-16), cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck.

Methods: To examine the relation between head and neck cancers and HPVs, we performed a nested case-control study within a joint Nordic cohort in which serum samples were collected from almost 900,000 subjects. Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma of the head and neck developed, on average, 9.4 years after enrollment and from 1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels as a marker of smoking habits. Polymerase-chain-reaction (PCR) analyses for HPV DNA were performed in tumor tissue from 160 of the study patients with cancer.

Results: After adjustment for cotinine levels, the odds ratio for squamous-cell carcinoma of the head and neck in subjects who were seropositive for HPV-16 was 2.2 (95 percent confidence interval, 1.4 to 3.4). No increased risk was observed for other HPV types. Fifty percent of oropharyngeal and 14 percent of tongue cancers contained HPV-16 DNA, according to PCR analysis.

Conclusions: HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood*
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / virology*
  • Case-Control Studies
  • Cohort Studies
  • Cotinine / blood
  • Female
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / virology*
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Papillomaviridae* / classification
  • Papillomaviridae* / immunology
  • Papillomavirus Infections / complications*
  • Risk Factors
  • Tumor Virus Infections / complications*


  • Antibodies, Viral
  • Cotinine