Abstract 1742: Evaluating the prognostic value of EGFR by p16/HPV status in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiation

Abstract

Abstract Background: Overexpression of the epidermal growth factor receptor (EGFR) has been correlated with a worse prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN), however the prognostic value of EGFR has not been fully evaluated in the context of human papillomavirus (HPV) status. Methods: Records from 91 consecutive SCCHN patients treated with concurrent chemoradiation at the Tom Baker Cancer Centre between August 2000 and March 2005 were reviewed. Triplicate 0.6 mm cores from available pre-treatment formalin-fixed paraffin-embedded (FFPE) biopsies were assembled into a tissue microarray. Immunofluorescence combined with automated quantitative analysis (AQUA™) was used to evaluate EGFR and p16 protein expression. Phosphorylated EGFR (pEGFR) was assessed by proximity ligation assay. HPV infection status was determined by colorimetric in-situ hybridization using the INFORM HPV Family 16 Probe (CISH). PCR was used to detect HPV DNA. EGFR and pEGFR were correlated with clinical outcomes according to p16-status and HPV-status. Results: FFPE biopsies were available from 49 patients (54%). Patient characteristics were as follows: mean age 55 years, 82% male, 49% oropharyngeal primaries. The complete response rate was 88%. With a median follow-up of 42 months (range 3 to 60), the 5 year overall survival (OS) was 54%. EGFR and pEGFR protein expression were classified as high in 14 (29%) and 13 (27%) tumours respectively. 27 tumours were p16 positive; 30 were HPV positive by either PCR or CISH. p16 was strongly correlated with HPV status (Spearman r=0.80). In univariate analyses, tumours with high EGFR, low p16, and HPV negative were associated with significant 3-, 7-, and 5-fold increases, respectively, in locoregional recurrence, recurrence at any site, disease-specific mortality and worse OS. pEGFR did not predict outcome. Neither EGFR nor pEGFR predicted response. After adjusting for age, smoking status, T- and N-stage, p16, and HPV there was no relationship between EGFR and outcome. p16 and EGFR were inversely related (Spearman r=-0.3). Conclusions: In our small cohort of patients, EGFR did not have prognostic value after correction for p16 / HPV status. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1742.