We identified critical genes such as CALCA, ALX4, BOLL, ZIC1, ADCYAP1, NKX2-6, USP44, HOXD10, EYA4, ZNF577, ZNF781, ZNF154, HOXD9, and HOXD10, underscoring their universal roles as epigenetic markers across various cancers, including HNSC. Here, ALX4 is linked to cancer.