Propofol in Perioperative Management of Head and Neck Cancer: A Narrative Review of Molecular Mechanisms and Clinical Implications.

The potential impact of propofol on head and neck cancer (HNC) progression and clinical outcomes, in relation to both direct effects on tumor biology and indirect effects mediated by perioperative immune and inflammatory responses, remains controversial. Most mechanistic evidence currently available for HNC originates from studies of oral squamous cell carcinoma. Accordingly, mechanistic findings are interpreted primarily as OSCC-derived evidence and should not be generalized to all HNC subsites without further validation. To address this, we critically examined propofol's potential role as a perioperative anesthetic modulator of tumor biology and host responses. Preclinical studies have demonstrated that propofol suppresses proliferation, induces apoptosis, inhibits angiogenesis, and enhances 5-fluorouracil chemosensitivity. Conversely, other studies report enhanced epithelial-mesenchymal transition, migration, and invasion through SNAI1 upregulation, highlighting the context-dependent nature of propofol-mediated effects. The generalizability of these molecular observations to other HNC subsites, including laryngeal, hypopharyngeal, and oropharyngeal cancers, remains unclear. Clinically, propofol-based total intravenous anesthesia has been associated with reduced postoperative pulmonary complications and improved perioperative recovery. However, currently available HNC-specific studies have not demonstrated a consistent improvement in overall or recurrence-free survival. These discrepancies likely reflect tumor heterogeneity, variations in experimental design, perioperative confounding factors, and differences in host immune and inflammatory responses. This narrative review was based on literature identified through PubMed, Scopus, and Google Scholar, and integrates current mechanistic, immunological, and clinical evidence regarding propofol exposure during cancer surgery. Current evidence supports the perioperative benefits of propofol-based anesthesia; however, its long-term oncologic significance in HNC remains inconclusive and warrants further prospective, mechanism-driven, and biomarker-guided investigations.