Given that NSD1 and NSD2 have been linked to various aspects of HPV- HNSCC, including epigenetic alterations, immune status of the tumor, and predicting patient outcome at specific subsites [8, 9, 21–26], we investigated the roles of NSD1 and its two paralogs NSD2 and NSD3 in HPV+ HNSCC. Here, NSD3 is linked to head and neck squamous cell carcinoma.