Overall, there still remain unanswered questions pertaining as to whether DNMT inhibitors may potentiate chemoradiotherapy in the curative-intent setting in select patients with HPV-positive or HPV-negative HNSCC, and whether a neoadjuvant approach, particularly in combination with immunotherapeutic interventions, may increase remission rates in the curative intent setting. Here, DNMT1 is linked to head and neck squamous cell carcinoma.