Human papillomavirus seropositivity and risks of head and neck cancer

Int J Cancer. 2007 Feb 15;120(4):825-32. doi: 10.1002/ijc.22330.


We examined antibody response to VLP HPV-16, HPV-16 E6 and E7 antibodies as potential seromarkers of HPV-related head and neck cancer (HNC). The study included 204 HNC cases and 326 controls evaluated for HPV presence in sera using ELISAs for anti-HPV VLP antibodies and HPV-16 E6 and/or E7 antibodies, and in tumor tissue using PCR and DNA sequencing. Anti-HPV-16 VLP was detected in 33.8% of cases and 22.4% of controls, anti-E6 in 20.6% of cases and 0.9% of controls and anti-E7 in 18.6% of cases and 0.6% of controls. HPV-16 DNA was detected in 26.1% of tumors. The adjusted risk of HNC was elevated among those seropositive for HPV-16 VLP (odds ratio (OR) = 1.7, 1.1-2.5), E6 (OR = 32.8, 9.7-110.8) or E7 (OR = 37.5, 8.7-161.2). Compared to HPV DNA-negative/seronegative cases, tumor HPV-16 cases had increased risk of detection with anti-VLP antibodies (OR = 6.8, 3.1-14.9). The odds were more pronounced among cases seropositive for E6 (OR = 69.0, 19.3-247) or E7 (OR = 50.1, 14.7-171). Antibodies against E6 or E7 were associated with risk of cancer in the oral cavity (OR = 5.1, 1.2-22.4) and oropharynx (OR = 72.8, 16.0-330), and with disease characteristics: stage, grade and nodal status. Anti-E6 and/or E7 antibodies were found in 74% of tumor HPV-16 positive cases but in only 5% of tumor HPV-negative cases (K =0.7, 0.6-0.8) suggesting good correlation between the serologic marker and HPV tumor status. Antibodies to HPV-16 E6 and/or E7 represent a more specific biomarker than anti-HPV-16 VLP of an HPV-related HNC. Because of the survival advantage of HPV-related HNC, HPV-16 E6/E7 detection may be useful in therapy targeted for HPV-related tumors.

Publication types

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

MeSH terms

  • Adenocarcinoma / etiology
  • Alcohol Drinking
  • Antibodies, Viral / blood*
  • Carcinoma, Mucoepidermoid / etiology
  • Case-Control Studies
  • DNA, Viral / analysis
  • DNA-Binding Proteins / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / virology*
  • Humans
  • Male
  • Middle Aged
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae / genetics
  • Papillomaviridae / immunology*
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / blood
  • Papillomavirus Infections / virology*
  • Risk Factors


  • Antibodies, Viral
  • DNA, Viral
  • DNA-Binding Proteins
  • E2 protein, Human papillomavirus type 16
  • E6 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral