MGMT Promoter Hypermethylation is a Common Event in Head and Neck Squamous Cell Carcinoma

Abstract

Promoter hypermethylation of the DNA repair O6-methylguanine-DNA methyltransferase (MGMT) gene is an independent predictor of response to chemoradiotherapy and survival in gliomas and lymphomas. We used pyrosequencing to determine the rate of MGMT promoter hypermethylation (MGMT-HM) in head and neck squamous cell carcinoma (HNSCC). Pre-treatment tumor blocks from 153 primary HNSCC patients with a median age of 61 years (range 32-90) diagnosed between the years 1993 and 2015 were identified for MGMT pyrosequencing using a commercially available kit. Seventy-three percent of patients were male and 27% female. Seventy-eight percent were tobacco users. Human Papilloma Virus (HPV) infection status was independently ascertained by p16 immunohistochemistry. After IRB approval, clinicopathological characteristics were extracted from patient’s charts, including age, gender, site of disease, and tobacco history. Overall, MGMT-HM was identified in 36% of the patients. In the 64, 79, and 10 patients with oral cavity, oropharynx, and larynx/hypopharynx primaries, MGMT-HM was seen in 36%, 33%, and 60%, respectively. Overall, HPV positivity was seen in 51% of the patients. In the patients with oropharynx, oral cavity, and larynx/hypopharynx primaries, HPV positivity was seen in 28%, 73%, and 20%, respectively. Among all HPV positive and negative patients, 31% and 41% had MGMT-HM, respectively. Among all tobacco users and non-users, 33% and 45% had MGMT-HM, respectively. Among oral cavity HPV positive and HPV negative patients, 28% and 39% had MGMT-HM, respectively. Among oral cavity tobacco users and non-users, 29% and 53% had MGMT-HM, respectively. Among oropharynx HPV positive and negative patients, 31% and 38% had MGMT-HM, respectively. Among oropharynx tobacco users and non-users, 32% and 36% had MGMT-HM, respectively. MGMT-HM is a common event in HNSCC and seems to be unrelated to tumor sub-site or HPV status. The frequency of MGMT-HM was observed to be higher in patients who did not use tobacco. It remains to be seen if MGMT-HM plays a role in the differential response to chemoradiotherapy along with HPV status in HNSCC.