BackgroundSquamous cell carcinoma (SCC) is the most common head and neck malignant neoplasm. Despite progress in antineoplastic treatment for SCC, there are still high morbidity and mortality rates. Over the years, several tumor biomarkers have been suggested to predict the prognosis of patients with oral SCC. Studies point to a bidirectional association between the epithelial-mesenchymal transition (EMT) and the expression of PD-L1 with the aggressive biological behavior of the neoplastic cell. Thus, this systematic review aimed to explore the biological roles and mechanisms underlying the interaction between EMT and PD-L1 expression in head and neck SCC-derived cell lines.Material and MethodsAn electronic search was performed in the PubMed/Medline, Web of Science, Science Direct, Scopus, Embase, and Cochrane Collaboration Library databases. Articles evaluating thein vitrorelationship between EMT/PD-L1 interaction and the biological behavior of head and neck SCC cell lines were selected for this systematic review. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.ResultsAfter applying the previously established inclusion/exclusion criteria, 9 articles were included in the qualitative synthesis. The present systematic review suggests the existence of a bidirectional interaction between EMT and PD-L1 expression, which is related to alterations in the cell cycle, proliferation, apoptosis, and cell survival, affecting the migration and invasion ability of tumor cells.ConclusionsCombined targeting of the two pathways may be potentially effective for immunotherapy in head and neck SCC.Key words:Epithelial-mesenchymal transition, EMT, PD-L1, squamous cell carcinoma.