To the best of our knowledge, we are the first to explore; the correlation of CIMP characteristics with genetic (polymorphisms of GSTM1, GSTT1, CYP1A1, XRCC1 and XRCC2 genes) and environmental factors (smoking, betel quid and tobacco chewing) and also with HPV and survival status of HNSCC patients. Here, XRCC1 is linked to head and neck squamous cell carcinoma.