Abstract 2721: Comparative responses of HPV-positive vs HPV-negative head and neck cancer cells to radiation and/or chemotherapeutic drugs

Abstract

Abstract Purpose: HPV is associated with a growing proportion of head and neck squamous cell carcinomas (HNSCCs), which show improved clinical outcome compared with non-HPV associated HNSCC. Whether this improved outcome reflects enhanced responsiveness to radiation and/or chemotherapy remains unclear. There is little data available regarding the radio- and chemo-sensitivity of HPV-associated HNSCC. We provide detailed analysis of radiation response profiles in verified HPV-positive HNSCC lines. Methods: Degenerate PCR and Southern blot were used to confirm HPV status in HNSCC human tumor cell lines. Clonogenic survival assays were used to assess radiation sensitivity. Proliferation assays were used to assess sensitivity to chemotherapy. Western blot was used to assess EGFR expression, activity, and the effect of EGFR inhibitor treatment. Results: Clonal expansion of existing HPV-positive HNSCC cell lines was performed to confirm the presence of a homogeneous population of cells and HPV-integration status confirmed by Southern Blot. HPV-positive cells were more sensitive to radiation-induced cell death compared to HPV-negative cells using single dose and fractionated radiation exposure regimens. Of the HPV+ cells tested to date, we have seen further radiosensitization with exposure to EGFR inhibitors (e.g., enhancement ratio 1.27 for UM-SCC47 with erlotinib) despite similar response to the EGFR inhibitor alone. HPV+ tumor xenografts have been raised in immunocompromised mice for in vivo radiation and chemotherapy response assessment. Conclusions: Consistent with clinical reports, HPV-associated HNSCC cells exhibit increased sensitivity to radiation. The in vitro sensitivity of HPV-positive HNSCC to chemotherapy is in progress, as is the response evaluation of HPV+ xenografts to radiation and chemotherapy. Underlying molecular mechanisms for altered response profiles in HPV+ HNSCC are considered as they pertain to future clinical trial designs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2721. doi:10.1158/1538-7445.AM2011-2721