As previously shown above, treatment of three HPV-negative HNSCC cell lines with the enzymatic SUV420H1 inhibitor A-196 lead to an approximately 50–80% reduction in the global levels of H4K20me3 (Fig. 2D), supporting that SUV420H1 is a major regulator of H4K20me3 in HPV-negative HNSCC cells. This evidence concerns the gene KMT5B and head and neck squamous cell carcinoma.