HNSCC includes a variety of malignancies affecting the upper aerodigestive tract, such as oral cavity, oropharynx, hypopharynx and larynx, and most commonly affects male older individuals with heavy tobacco and/or alcohol use history, where the chronic inflammation and the prolonged exposure to carcinogens may result in the accumulation of genetic alterations in key regulatory genes such as TP53, CDKN2A, NOTCH1, CCND1, etc. which increases the risk of HNSCC [85]. Here, NOTCH1 is linked to head and neck squamous cell carcinoma.