The interaction between HA and CD44v3 with Oct4-Sox2-Nanog signaling stimulates the production of miR-302, which subsequently results in the downregulation of AOF1/AOF2/DNMT1. This process enhances the survival and resistance to chemotherapy in tumor cell populations characterized by high levels of CD44v3 and ALDH1. Furthermore, the concurrent use of SM164 and cisplatin leads to increased efficacy in killing cancer cells by specifically targeting cancer stem cells in HNSCC. This evidence concerns the gene POU5F1 and head and neck squamous cell carcinoma.