Abstract 4497: Biomarkers of HPV in head and neck squamous cell carcinoma

Abstract

Abstract Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC) and patients with HPV-associated disease have a favorable prognosis. Currently there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV. We measured DNA-based and serological markers in a single population-based study to assess their associations with disease outcome and to determine the most relevant biomarker for clinical use. HPV16 serology was determined using an immunoassay for the capsid protein L1, and multiplex serology based on the capsid protein L1 and the early oncoproteins E6/E7 for 488 patients. Immunohistochemical detection of p16 expression in tumors was performed in a subset of 233 cases, and we used two different methods to assess the presence of HPV16 DNA in a subset of 179 cases’ tumors. Seropositivity for the E6 and E7 proteins (individually) was significantly associated with enhanced survival (HRE6 or HRE7=0.3, 95%CI=0.2-0.5). Neither the presence of HPV16 DNA or p16 overexpression was associated with significant enhanced overall survival (HRDNA=0.8, 95%CI=0.5-1.3; HRp16=0.8, 95%CI=0.5-1.4). However the combination of HPV positive DNA and E6/E7 serology was associated with similarly enhanced overall survival (HRDNA+/E6+/E7+=0.1, 95%CI=0.01-0.6), while E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HRDNA+/E6-/E7-=1.2, 95%CI = 0.7-2.2). Further, the combination of p16 staining and early gene seropositivity showed a favorable survival (HRp16+/E6+/E7+=0.3, 95%CI=0.1-0.9), while those who were p16 positive and early gene seronegative had significantly increased hazard of death (HRp16+/E6-/E7-=2.1, 95%CI=1.1-4.2). Determination of only HPV16 DNA status or p16 immunostaining is not an effective prognostic biomarker for HNSCC. However the combination of measurement of HPV16 DNA and p16 immunostaining with E6/E7 antibodies has high predictive clinical value, strongly suggesting that a combined biomarker approach is necessary for the assessment of the prognosis of HNSCC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4497. doi:1538-7445.AM2012-4497