High-risk HPV types and head and neck cancer

Dominique S. Michaud, Scott M. Langevin, Melissa Eliot, Heather H. Nelson, Michael Pawlita, Michael D. McClean, Karl T. Kelsey

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81 Scopus citations


Although HPV16 has been strongly implicated in oropharyngeal carcinogenesis, the role of other high-risk HPV types in the etiology of head and neck cancer remains unclear. To date, few data exist addressing the nature of the association between antibodies to oncogenic proteins of non-HPV16 HPVs in relation to head and neck cancer. We examined the relationship between multiple HPV types (HPV6, 11, 16, 18, 31, 33, 45, 52, 58) and head and neck squamous cell carcinoma (HNSCC) in a large population-based case-control study (1069 cases and 1107 controls). Serological measures for HPV types included antibodies to L1, E6 and/or E7. In a secondary analysis, we excluded HPV16 seropositive subjects to examine independent associations with other high-risk HPVs. All analyses were adjusted for age, race, sex, education, smoking and alcohol consumption. Statistically significant associations were observed for HPV16, 18, 33 and 52 and risk of HNSCC after mutually adjusting for HPV types. Among HPV16 seronegative subjects, elevated risks of HNSCC were observed for HPV18 E6 (OR = 4.19, 95% CI = 1.26-14.0), HPV33 E6 (OR = 7.96, 95% CI = 1.56-40.5) and HPV52 E7 (OR = 3.40, 95% CI = 1.16-9.99). When examined by tumor type, associations with HPV18 and HPV33 remained statistically significant for oropharyngeal cancer, and HPV52 was associated with oral cancer. In addition, magnitude of associations for HNSCC increased markedly with increasing number of seropositive high-risk HPV infections. High-risk HPV types, other than HPV16, are likely to be involved in the etiology of HNSCC. What's New? While human papillomaviruses (HPVs) are suspected to play a role in head and neck squamous cell carcinoma (HNSCC), only the HPV16 subtype has been convincingly associated with risk of the disease. This population-based case-control study shows, however, that HNSCC risk can be influenced by non-HPV16 subtypes, namely HPV18, 33, and 52. Among HPV16 seronegative patients, HPV18 and 33 were most strongly associated with oropharyngeal cancer, while HPV52 was associated with oral cancer.

Original languageEnglish (US)
Pages (from-to)1653-1661
Number of pages9
JournalInternational Journal of Cancer
Issue number7
StatePublished - Oct 1 2014


  • HPV infection
  • head and neck cancer
  • oral cancer
  • oropharyngeal cancer


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