A comprehensive multi-omic analysis in SCCHN may shed light on finding the missing link between NOTCH1 and AKT, and an animal model with an inducible knockout of NOTCH1 is needed to serve as a more authentic platform for the exploration of the role of NOTCH1 in various stages of precancerous lesions to SCCHN. Here, AKT1 is linked to head and neck squamous cell carcinoma.