Current systemic cancer treatment in head and neck squamous cell carcinoma (HNSCC) is moving toward more personalized approaches such as de-escalation protocols human-papilloma-virus dependent HNSCC or application of checkpoint inhibitors. However, these treatments have been challenged by cancer stem cells (CSC), a small population within the bulk tumor, which are leading to treatment failure, tumor recurrence, or metastases. This review will give an overview of the characteristics of HNSCC-CSC. Specifically, the mechanisms by which HNSCC-CSC induce tumor initiation, progression, recurrence, or metastasis will be discussed. Although evidence-based treatment options targeting HNSCC-CSC specifically are still being sought for, they warrant a promise for additional and sustainable treatment options where for HNSCC patients where others have failed.
Keywords: Aldehyde dehydrogenase I; CSC-directed therapeutic; Cancer stem cell (CSC); Epidermal growth factor receptor (EGFR); Epithelial-to-mesenchymal transition (EMT); Head and neck squamous cell carcinoma (HNSCC); Immune evasion; Immune response; Immunotherapy; Mesenchymal-to-epithelial transition (MET); PD-1; PD-L1; Tumor microenvironment.