The Use of Fluorescent Markers to Detect and Delineate Head and Neck Cancer: A Scoping Review

Objectives: The aim of surgery for head and neck squamous cell carcinoma (HNSCC) is to achieve clear resection margins, whilst preserving function and cosmesis. Fluorescent markers have demonstrated potential in the intraoperative visualisation and delineation of tumours, such as glioma, with consequent improvements in resection. The purpose of this scoping review was to identify and compare the fluorescent markers that have been used to detect and delineate HNSCC to date.

Methods: A literature search was performed using the Ovid MEDLINE, Ovid Embase, Cochrane CENTRAL, ClinicalTrials.gov and ICTRP databases. Primary human studies published through September 2023 demonstrating the use of fluorescent markers to visualise HNSCC were selected and reviewed independently by two authors.

Results: The search strategy identified 5776 records. Two hundred and forty-four full texts were reviewed, and sixty-five eligible reports were included. The most used fluorescent markers in the included studies were indocyanine green (ICG) (n = 14), toluidine blue (n = 11), antibodies labelled with IRDye800CW (n = 10) and 5-aminolevulinic acid (5-ALA) (n = 8). Toluidine blue and ICG both have limited specificity, although novel targeted options derived from ICG may be more effective. 5-ALA has been demonstrated as a topical marker and, recently, via enteral administration but it is associated with photosensitivity reactions. The fluorescently labelled antibodies cetuximab-IRDye800CW and panitumumab-IRDye800CW are promising options being investigated by ongoing trials.

Conclusion: Multiple safe fluorescent markers have emerged which may aid the surgical resection of HNSCC. Further research in larger cohorts is required to identify which marker should be considered gold standard.