DHPS and cancer: In this study, we found an overall upregulation of EIF5A2 mRNA and the transcripts of several key enzyme genes involved in polyamine metabolism, e.g., ODC1, SRM, and SMOX, in HPV− HNSCC, and blocking DHPS/eIF5Ahpu consistently inhibited OSCC cell growth and the expression of genes involved in regulation of epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties both in vitro and in vivo.