Abstract 650: IGSF4 methylation is an independent marker of HPV positive OPSCC.

Abstract

Abstract Human papilloma virus (HPV) is a known causative agent for oropharyngeal squamous cell cancer (OPSCC). The goal of our study was to determine the relationship of HPV type 16 (HPV16) infection and methylation status in an OPSCC cohort. HPV16 was detected using real-time quantitative PCR (qPCR) in a retrospective cohort of 111 primary OPSCC. A 24 tumor suppressor gene candidate panel was assessed for methylation using the methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) assay. Univariate associations with HPV and gene methylation, age, gender, race and smoking were analyzed using Fisher's exact tests and logistic regression. A final multiple logistic regression model, to include patient characteristics and genes significant on univariate analysis, was built using backwards selection of genes. Statistical significance was set at p<0.05 and all analyses were done using SAS 9.2. In univariate analyses, Caucasian American (CA) OPSCC were more likely to be HPV positive as compared to African American (AA) OPSCC (OR=3.01, 95% CI 1.28, 7.07, p=0.011). Also, smoking (never vs current) [OR=3.60 (1.06, 12.24), p=0.04], and TIMP3, DAPK1, ESR1, and IGSF4 were associated with HPV positive status (OR=5.03, p=0.021; OR=3.71, p=0.04; OR=5.03, p=0.021; OR=7.68, p=0.012, respectively). The final model, after controlling for patient characteristics and after backward elimination of genes, indicated IGSF4 methylation is an independent predictor of HPV positive status [OR=7.07 (1.22, 40.79), p=0.029]. HPV infection status is independently associated with methylation of IGSF4, indicating interplay of DNA methylation and HPV in OPSCC pathogenesis. Citation Format: Kang Mei Chen, Josena K. Stephen, Meredith Mahan, Shaleta Havard, George Divine, Glendon Gardner, Vanessa P. Schweitzer, Maria J. Worsham. IGSF4 methylation is an independent marker of HPV positive OPSCC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 650. doi:10.1158/1538-7445.AM2013-650