Leveraging Autofluorescence for Tumor Detection, Diagnosis, and Accurate Excision with Surgical Margin Assessment in Tumor Excision

<b>Background/Objectives:</b> Oral cancer ranks among the top ten cancers globally, with a five-year survival rate below 50%. This study aimed to evaluate the effectiveness of autofluorescence-guided surgery compared to standard surgical methods in identifying tumor-free margins and ensuring complete excision. <b>Methods:</b> A prospective cohort of 80 patients was randomized into two groups: the control group underwent excision with a 10 mm margin based on clinical judgment, while the experimental group used autofluorescence guidance with a 5 mm margin beyond fluorescence visualization loss. Autofluorescence imaging was performed using the OralID device, which employs a 405 nm excitation laser to detect abnormal tissue. Ethical approval was obtained from the "Spitalul Clinic Municipal de Urgență Timișoara" Ethics Committee (approval number 08/26.02.2021), and the trial was registered at the University of Medicine and Pharmacy Timisoara (trial no. 59/25.11.2021). A double analysis was conducted: a primary analysis of the full cohort and a subgroup analysis focusing on squamous cell carcinoma (control: <i>n</i> = 19; experimental: <i>n</i> = 24). Histopathological analysis was the gold standard for margin evaluation, with margins coded as tumor-free margins (0), close (1), or infiltrated (2). <b>Results:</b> Statistically significant differences were observed in tumor-free margins between the control (73.17%) and experimental (97%) groups (<i>p</i> = 0.003). Subgroup analysis for SCC showed no significant difference (control: 84.21%; experimental: 95.83%; <i>p</i> = 0.306). Tumor location also differed significantly <i>(p</i> = 0.011), while other baseline variables, such as tumor type and patient characteristics, showed no significant differences. <b>Conclusions:</b> Autofluorescence-guided surgery improves the detection of tumor-free margins and may serve as an effective adjunct in oral cancer management. Larger studies are recommended to confirm these findings.