Relationships between epidermal growth factor receptor expression and human papillomavirus status as markers of prognosis in oropharyngeal cancer

Purpose: This study examines the prognostic significance of epidermal growth factor receptor (EGFR) expression in relation to human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (SCC). Materials and methods: Pathological diagnosis of 270 oropharyngeal SCCs was verified by the study pathologist; clinical details were extracted from institutional databases. Recurrence in any form or death from any cause was recorded for a median of 2.5 (range: 0-19.3) years after diagnosis. HPV status was determined by HPV E6-targeted multiplex real-time PCR/p16 immunohistochemistry; EGFR expression was evaluated by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modelled using Cox regression with censoring at dates of last follow-up. Results: Thirty-seven percent of cancers were HPV-positive (91% type 16). HPV was a predictor of loco-regional recurrence, event-free and overall survival after adjustment for clinicopathological variables and EGFR. Patients with EGFR-positive cancers were 5-fold more likely to have loco-regional failure relative to those with EGFR-negative cancers. Patients with HPV-negative/EGFR-positive cancers had an adjusted 13-fold increased risk of having a loco-regional failure, an almost 4-fold increased risk of having an event and more than a 4-fold increased risk of dying of any cause relative to those with HPV-positive/EGFR-negative cancers. There was weak evidence that the effects of EGFR on outcome were limited to patients with HPV-negative cancers. Conclusions: HPV and EGFR are independent prognostic markers in oropharyngeal SCC. Combining testing for HPV and EGFR appears to provide additional prognostic information.