Impact of enforced HPV E6 and E7 expression on the cetuximab response of HPV-negative HNSCC cells in vivo. (a and c) Tumor growth following injection of FaDu cells stably expressing HPV16 E6 (a) or HPV16 E7 oncogenes (c) in NOD/SCID mice. After 14 days, tumor-bearing mice received biweekly intraperitoneal injections of cetuximab (1 mg, white triangles) or the control antibody rituximab (black circles). Mean bidimensional tumor sizes (+s.d.) of five mice per group are given. Rapid and sustained tumor shrinkage was observed following cetuximab treatment. In contrast, tumors from rituximab-treated mice continuously progressed. (b and d) Kaplan–Meier plots of survival of NOD/SCID mice bearing FaDu tumors expressing HPV16 E6 (b) or HPV16 E7 (d). Mice were treated with cetuximab (solid line), or the control antibody rituximab (dashed line) as in a and c. Cetuximab-treated mice showed significantly prolonged survival as compared with rituximab-treated mice. Median survival time was not reached for cetuximab-treated FaDu HPV E6 tumour-bearing mice. It was 30 days for mice treated with rituximab (P=0.003, log rank test). In the FaDu HPV E7 model, median survival time for cetuximab-treated mice was not reached, and was 30 days for rituximab-treated mice (P=0.003, log rank test)