We found that Kmt2d-HT mice showed significantly increased tumor lesion areas, SCC numbers, SCC areas, and tumor invasion grades as well as Ki-67 positive tumor cell numbers compared with Kmt2d-WT mice (Fig. 1j–l and Supplementary Fig. 1g), indicating that heterozygous deletion of Kmt2d could accelerate HNSCC progression. Here, KMT2D is linked to head and neck squamous cell carcinoma.