CXCL12 and Oral leukoplakia: While the expression of CXCL12 (SDF-1α) and CXCR4 progressively increased from oral leukoplakia (OLK) to dysplasia to frank malignancy [147], hyperactivation of this axis in HNSCC is associated with aggressive tumors, regional and distant metastasis, and lower DFS [148].