Abstract 3625: An analysis of human papilloma virus (HPV) E6 antibodies and risk of head and neck cancer: two large European studies.
Authors: Brennan Paul , Johannson Mattias , Anantharaman Devasena , Pawlita Michael , Kreimer Aimee ,   on behalf of the EPIC and ARCAGE study groups
Published: August 2014

Abstract
Background. Human papillomavirus (HPV) infection, in particular HPV16, is causing an increasing number of oropharyngeal cancers in Europe and the United States. HPV16 E6 antibodies are a marker of tumour integration and would be expected to be present among cases with a HPV related tumour but absent or very low in individuals without a HPV related cancer. We investigated the presence of HPV16 E6 antibodies in two large European studies - (i) a retrospective case-control study of 1219 cases (366 oral cavity, 324 oropharynx and 529 hypopharynx/larynx) and 1425 controls with blood samples collected at the time of diagnosis among the cases (the ARCAGE study), and (ii) a nested case-cnotrol study of 638 incident head and neck cancers (including 180 oral, 135 oropharynx, and 247 hypopharynx/larynx), and 1599 comparable controls from the EPIC cohort study, with blood samples collected between 1 and 14 years before diagnosis among the cases.
Methods. Plasma from all cases and controls was analyzed for antibodies against multiple proteins of HPV16, with a particular focus on HPV16 E6. Odds ratios (OR) of cancer and 95% confidence intervals (CI) were calculated adjusting for potential confounders. All-cause mortality was evaluated among cases using Cox proportional hazards regression.
Findings. Within ARCAGE, HPV16 E6 seropositivity was present in 0.8% (11/1425) of controls and 30.2% (97/324) of oropharynx cases (OR=132.0, 95% CI 65-266). A much weaker association was also seen for larynx cancer (8/529 cases positive; OR=4.2 95%CI 1.5-11.3). No association was seen for oral cancer (4/366 cases positive; OR=1.9 95% CI 0.6-6.2). Within the EPIC nested case-control study 34.8% of oropharyngeal cancer cases and 0.6% of controls were HPV16 E6 positive (OR= 274, 95% CI 110 to 681), although no association was seen with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis.
Interpretation. Our results indicate that (i) HPV16 E6 antibodies are rare in controls, and less than 1%, (ii) about 30% of oropharynx cancer cases are positive for HPV16, with blood samples taken at the time of diagnosis, and (iii) HPV16 E6 seropositivity is present more than 10 years prior to diagnosis of oropharyngeal cancers. Further, because of its near absence in controls, it may potentially be useful as a biomarker for early detection of oropharyngeal cancer that is presumably HPV-positive.
Citation Format: Paul Brennan, Mattias Johannson, Devasena Anantharaman, Michael Pawlita, Aimee Kreimer, on behalf of the EPIC and ARCAGE study groups. An analysis of human papilloma virus (HPV) E6 antibodies and risk of head and neck cancer: two large European studies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3625. doi:10.1158/1538-7445.AM2013-3625