NOTCH1 and neoplasm: HNSCC encompasses a diverse group of tumors originating from the squamous epithelium of the oral cavity, pharynx, and larynx.323 Over the past half-century, there has been a decline in the incidence of smoking-related HNSCC, while cases induced by HPV infection have seen a gradual increase.324 Studies focusing on the long tail genes of HNSCC have revealed that 67% of carcinogenic mutations in human HNSCC cases converge on Notch signaling, establishing Notch inactivation as a marker for HNSCC.325–327 This aligns with the recognized role of Notch1 as a tumor suppressor in HNSCC.