Of course, we cannot rule out that other oncogenic factors (KRAS), TFs (p53), or epigenetic modifiers (UTX) are also involved in LIF transcription in HNSCC as reported among other biological contexts.[26, 49, 50] In aggregate, we conclude that SOX2 and SMAD3 bind to LIF‐SE to activate LIF transcription and thereby facilitate CSC maintenance and tumor development in HNSCC. Here, TP53 is linked to head and neck squamous cell carcinoma.