Surveillance HNSCC with promoter hypermethylation in saliva; 1 Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance

Purpose: Hypermethylation of tumor suppressor gene promoters has been found in head and neck squamous carcinoma (HNSCC) and other solid tumors. We evaluated these alterations in pre-treatment salivary rinses from HNSCC patients using real-time quantitative MSP (Q-MSP). Experimental Design: Pre-treatment saliva DNA samples from HNSCC patients were evaluated for patterns of hypermethylation using Q-MSP. Target tumor suppressor gene promoter regions were selected based on a previous study describing a screening panel for HNSCC in a high risk population subjects. The selected genes were: DAPK, DCC, MINT-31, TIMP-3, p16, MGMT, CCNA1. Results: We analyzed the panel in a cohort of 61 HNSCC patients. Thirty-three of the analyzed patients (54.1%) demonstrated methylation of at least one of the selected genes in the saliva DNA. Pre-treatment methylated saliva DNA was not significantly associated with tumor site (p=0.209) nor clinical stage (p=0.299). However, local disease control and overall survival were significantly lower in patients presenting hypermethylation in saliva rinses (p=0.010 and p=0.015, respectively). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (HR=12.2; 95%CI=1.8-80.6; p=0.010) and overall survival (HR=2.8; 95%CI=1.2-6.5; p=0.016). Conclusions: We were able to confirm an elevated rate of promoter hypermethylation in HNSCC patients’ saliva using a panel of gene promoters previously described as methylated specifically in HNSCC. Detection of hypermethylation in pre-treatment saliva DNA appears to be predictive of local recurrence and overall survival. This finding has potential to influence treatment and surveillance of HNSCC patients. Statement of Translational Relevance. This manuscript details a promoter methylation based assay panel that is independently associated with local recurrence and survival in on April 9, 2017. © 2011 American Association for Cancer Research. clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 31, 2011; DOI: 10.1158/1078-0432.CCR-11-0324