Recent advances in fluorescent probes for guided surgery of head and neck carcinomas.

Head and neck squamous cell carcinoma (HNSCC) rank as the sixth most common cancer worldwide. Traditional treatments include surgery, radiation, and chemotherapy, with surgery being the primary option for early-stage disease. However, achieving clear surgical margins is a major challenge, as incomplete removal of tumor cells increases the risk of recurrence and metastasis, negatively affecting patient survival. This often requires extensive tissue removal, leading to complications such as swallowing and speech difficulties. However, it is difficult for surgeons to accurately distinguish the tumor tissue and its boundary with the naked eye. Consequently, fluorescence-guided surgery (FGS) has attracted increasing attention in recent years. FGS presents a promising solution by providing high sensitivity, real-time visualization of tumor margins, allowing for more precise and less invasive procedures, thereby preserving patient function and improving quality of life. This review presents a structured overview of recent fluorescent probe development for HNSCC surgery, with additional context on foundational advances and recent clinical applications. Across the reviewed studies, EGFR-targeted probes achieved reported tumor-to-background ratios (TBRs) of up to 7.1, PARP-targeted probes up to 10.3, FAP-targeted probes approximately 5.9, GLUT1-targeted probes approximately 2.1, and Hsp70-targeted probes approximately 2.6. Among these approaches, EGFR-targeted probes currently represent the most clinically advanced class, with agents such as panitumumab-IRDye800CW and cetuximab-IRDye800CW already evaluated in clinical studies. In contrast, activatable probes and dual-modality imaging agents represent emerging strategies with the potential to further improve tumor specificity and intraoperative contrast.