A subset of highly expressed HOXD genes was investigated further by functional knockdown studies and POU2F1 is identified as a transcriptional regulator of both HOXD10 and D11. Detailed examination of a cohort of patient biopsies (n=120) highlights HOXD10 as a potential prognostic biomarker in HNSCC. This evidence concerns the gene HOXD10 and head and neck squamous cell carcinoma.