Association between human papillomavirus (HPV) status with serum cytokine and angiogenic factor (CAF) profile after induction chemotherapy in head and neck squamous cell carcinoma (HNSCC)

Abstract

6081 Background: Human papillomavirus has been implicated in the development of head and neck squamous cell carcinoma and is associated with a more favorable clinical outcome. Previously, we identified a serum hypoxia signature associated with HNSCC progression (Byers et al, Proc ASCO. 2008). We investigated the association between HPV status, serum biomarkers, and clinical outcome in patients treated with induction chemotherapy. Methods: 47 previously untreated patients with locally advanced nodal disease (T0–4, N2b/c/3, M0) received 6 weekly cycles of paclitaxel (135 mg/m2), carboplatin (AUC 2), and cetuximab (400 mg/m2 week 1; 250 mg/m2 weeks 2–6) followed by definitive local therapy. 46 (98%) patients had a complete or partial response to induction chemotherapy (Kies et al, Proc ASCO. 2006), and 6 have had tumor progression (PD) after a minimum follow-up of two years. Formalin fixed biopsies were available for HPV testing by in situ hybridization with non-radioisotopic chromogen for 25 patients (including 5/6 with PD). 38 CAFs were measured by multiplex bead assay before and during treatment. Results: 12/25 patients were HPV-positive, all male and six were never smokers; of the 13 HPV-negative patients, four were male and three were never smokers. Among those with available data, all 5 patients with PD were HPV-negative (p = 0.02). There were four study deaths, all in the HPV-negative group. Overall survival was superior in HPV-positive patients (p = 0.04). There was no significant association between HPV status and serum CAF markers. However, among HPV-negative patients, PD was associated with the CAF hypoxia signature (5/8 patients with the hypoxia signature progressed versus 0/5 signature-negative). Of the individual CAFs, osteopontin was significantly elevated in all HPV-negative patients with PD. Conclusions: HPV positivity was associated with a longer progression-free survival and overall survival. Among HPV-negative patients, only those with a serum hypoxia signature had disease progression. These data suggest that the combination of HPV status and CAF profiling may identify patients at risk for relapse after sequential therapy. No significant financial relationships to disclose.