Table 1.

CSC markers in HNCs. Different markers for the identification and characterization of CSCs in HNCs, including HNSCC, ACC, MEC, and oral melanoma are listed.

Types of CSC markers	Name of marker	Associated properties and functions
Cell surface markers	CD44	Tumor initiation [9]. Enhancement of proliferation and migration, and apoptosis inhibition in HNC [106, 115]. • Overexpression is associated with regional lymph node metastasis, perineural invasion, increased loco-regional recurrence, increased resistance to radiotherapy, and decreased overall survival [31, 32, 35, 116].
	CD133	• Tumor sphere formation, tumorigenicity, and chemoresistance in HNSCC [42]. • Acceleration of angiogenesis, clonogenic and tumorigenic abilities in melanoma [117–119]. • Positive correlation with poor overall survival in HNSCC patients [44, 120].
	CD10	Associated with tumor size, histological grade of malignancy, local recurrence, and therapeutic resistance in HNSCC [36, 37].
	ABCB5	• Promotes melanoma metastasis by activating the NF-κB cascade [121]. • Self-renewal and tumor initiation [122].
Metabolic marker	ALDH1	• Tumorigenic phenotype, self-renewal and stemness properties, and resistance to radiotherapy and chemotherapy in HNSCC [49]. • Sphere-forming, tumorigenic, and metastatic abilities in ACC [123]. • Colocalization with Snail and MMP-9 and induction of EMT-related genes in HNSCC [49, 52]. • Strong correlation with nodal metastasis and cisplatin resistance [124, 125].
Pluripotency markers	BMI1	• Self-renewal, colony formation, migration, and invasion in HNSCC [126]. • Associated with overexpression of the EMT-related transcription factors Snail and Slug in ACC [127]. • Strong correlation with advanced stages, aggressive clinicopathological behaviors, stem cell-like properties, drug resistance, and poor prognosis in HNSCC [82, 128].
	SOX2	• Known to complex with OCT4 and control downstream embryonic genes including NANOG [73]. • Involved in cell proliferation, migration, invasion, stemness, tumorigenesis and anti-apoptosis, and chemoresistance in HNSCC [68]. • Associated with surviving expression in ACC patients [129]. • Correlate positively with radiochemoresistance and poor prognosis in HNSCC patients [68, 71].
	OCT4	• Role in the regulation of epithelial–mesenchymal transition through increasing expression of N-cadherin and Slug [77]. • Observed in metastatic lymph nodes and recurrent tumors from OSCC patients [10]. • Correlated with poor survival and considered as an independent prognostic marker of HNSCC progression [58, 65].
	NANOG	• Overexpressed in HNSCC CSCs [130]. • Associated with tumor transformation, tumorigenicity, and metastasis in HNSCC [58]. • Correlated with histopathological features of MEC including perineural invasion and desmoplasia [131]. • Correlated with poor differentiation status, chemoresistance, and poor prognosis [77, 132].
Self-renewal pathways	SHH	• Promote tumor growth and angiogenesis in HNSCC [89]. • Correlated with the expression of Snail and MMP9 [89]. • Correlated with recurrence, lymph node metastasis, and the worst prognosis in HNSCC patients [89, 95].
	NOTCH	• Involved in cell proliferation, differentiation, survival, self-renewal, and tumorigenesis [98, 99]. • Correlated with increased resistance to cisplatin and poor prognosis in HNSCC patients [100].
	EGFR	• Involved in cell proliferation, migration, cisplatin resistance, and apoptosis inhibition in HNSCC cells [106, 133]. • Promotes the stemness and progression of oral cancer [107, 108]. • Stabilizes and induces Snail-dependent EMT in ACC [134]. • Associated with resistance to treatment and poor clinical outcomes with HNSCC patients [105].
	WNT	Involved in CSC proliferation, sphere formation, and cisplatin resistance in HNSCC [113, 114].