Evaluation of type-specific antibodies to high risk- human papillomavirus (HPV) proteins in patients with oropharyngeal cancer

Objectives: High risk human papillomavirus (HR-HPV) infection leads to a subgroup of oropharyngeal cancer (OPSCC) characterized by improved treatment response. However an universally accepted definition of an HR-HPV-attributable cancer is lacking. Methods: Detailed, type-specific HPV antibody responses were analyzed by multiplex serology in HRHPV-attributable OPSCC patients, defined by p16INK4A overexpression and HR-HPV DNA detection by PCR amplification and sequencing. Results: Fifty patients were prospectively enrolled. 26/50 (52%) tumor samples were positive for both p16(INK4A) expression and HR-HPV DNA (22 HPV16, 4 HPV33). Seropositivity was present in 26/26 HPVattributable OPSCC and one p16(INK4A)-positive/HPV DNA-negative case. The sensitivity and specificity to diagnose an HR-HPV-attributable tumor was 100% and 96%, respectively for anti-E6 reactivity, 82% and 100%, respectively for anti-E2 reactivity, and clearly lower for anti-E7, anti-E1, anti-E4 and anti-L1reactivity. 3 yr-overall (OS) and disease specific survival (DSS) was higher in patients with HR-HPVattributable tumors (OS 88% vs 64%, p = 0.02; DSS 90% vs 80%, p = 0.07) and seropositive patients (OS 88% vs 62%, p = 0.01; DSS 92% vs 78%, p = 0.05) than HR-HPV-negative or seronegative patients. Conclusions: Detection of HR-HPV type-specific antibodies highly correlated with HPV-attributable OPSCC and was associated with better survival. HR-HPV antibodies are promising diagnostic, prognostic and potentially screening markers in HR-HPV-attributable OPSCC. (C) 2017 Elsevier Ltd. All rights reserved.