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 HR-HPV-attributable OPSCC patients, defined by p16(INK4A) 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 HPV-attributable 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-L1-reactivity. 3yr-overall (OS) and disease specific survival (DSS) was higher in patients with HR-HPV-attributable 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.