Analysis of HPV and ERCC1 in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Abstract

6006 Background: We studied the association of human papillomavirus (HPV) and excision repair cross-complementation group 1 (ERCC1) tumor expression with clinical outcomes in patients (pts) with R/M SCCHN. Methods: Archival baseline specimens were obtained from pts on ECOG trials: E1395, phase III trial of cisplatin/paclitaxel (CP) vs. cisplatin/5-FU (CF), and E3301, phase II trial of docetaxel/irinotecan. HPV DNA was detected by in situ hybridization (ISH) with a wide spectrum HPV probe. Tumor p16 status was defined as positive if immunohistochemical staining for p16 was strong and present in >80% of tumor cells. ERCC1 expression was measured (HistoRx PM-2000) and data analyzed using AQUA algorithms, after tissue was stained with ERCC1 ab (1:5000 HPA0297731, Sigma), and a wide-spectrum cytokeratin ab (Dako Z0622) for tumor mask. A prior determined cut point for nuclear staining was utilized. Fisher's exact test and log-rank test were used to compare categorical variables and survival. Stratified logistic regression and Cox regression model were used to estimate odds ratio (OR) and hazard ratio (HR), respectively, adjusting for potential confounding factors. p-values were two-sided. Results: Tissue was evaluable from 65 tumors (T) for HPV, 66 for p16 (E1395 and E3301), and 43 for ERCC1 expression (E1395). 11 T were HPV+ (12 p16+), and 54 were HPV-/p16-. HPV+ tumors were similarly represented in all treatment groups (p=0.58). Objective response rates (RR): 67% for HPV+, 22% for HPV- (p=0.013); 60% p16+, 22% p16- (p=0.05). RR rates were calculated excluding cases with unevaluable/unknown responses. HR for OS was 2.66 (HPV, p=0.02) and 2.27 (p16, p=0.04), favoring HPV+/p16+ pts. 18 T were ERCC1 high (H) and 25 ERCC1 low (L). HR for OS (H vs. L) was 1.96 (p=.11) RR: CF, 58% (L), 29% (H); CP, 33% (L), 56% (H). A test of ERCC1 by treatment interaction (p=0.12) suggested the effect of ERCC1 may be different for taxane vs. non-taxane regimens. Conclusions: This is the first study to show that HPV+/p16+ status is associated with a significant improvement in RR and OS among pts treated for R/M SCCHN. ERCC1 L was associated with a trend towards a better OS.