Considering this, as well as our recently published work12 showing that SMYD3 directly binds to and transcriptionally regulates specific immune-related genes in HPV-negative HNSCC cancer cells, we decided to further focus and dissect the epigenetic function of SMYD3 in HPV-negative HNSCC cancer cells. The gene discussed is SMYD3; the disease is head and neck squamous cell carcinoma.