Risk Factors for False-Negative Results in Sentinel Lymph Node Biopsy for Early-Stage Oral Cavity Cancer: A Scoping Review

Background and objectives: Sentinel lymph node biopsy (SLNB) has become the standard approach for cervical staging in patients with early-stage oral cavity squamous cell carcinoma (OCSCC). Although it demonstrates diagnostic accuracy exceeding 90% in referral centres, the occurrence of false-negative (FN) results undermines oncological safety and adversely impacts patient prognosis. This scoping review aims to synthesise and evaluate the scientific evidence regarding the risk factors and technical errors that underpin FN incidence. Methods: A systematic search was conducted across MEDLINE (PubMed), Scopus and Web of Science for studies published between 2000 and 2025, adhering to PRISMA-ScR guidelines. Primary clinical and observational studies specifically addressing the variables and aetiology of diagnostic failure in SLNB for early-stage OCSCC (cT1-T2 N0) were included. Results: Twenty-seven studies were included in the final qualitative synthesis. Four critical domains characterising FN risk were elucidated, facilitating risk-stratified selection and surveillance strategies: (1) Clinical and tumour factors: Depth of invasion >4–5 mm, T3–T4 tumour size, and prior cervical anatomical disruption. (2) Surgical factors: Insufficient sentinel lymph node (SLN) harvest (≤2 SLNs), lack of exhaustive lymphatic basin exploration, the initial learning curve, and the exclusive use of non-isotopic tracers. (3) Anatomical factors: Floor of the mouth tumours and the radioactive shine-through effect. (4) Histopathological protocol: Suboptimal ultrastaging, insufficient frozen section biopsy, and limitations in rapid molecular techniques. Overall, studies using standardised protocols report a false-negative rate between 5% and 15%. Conclusions: FN events in SLNB are multifactorial and predictable phenomena, arising from cumulative vulnerabilities along the diagnostic continuum. The technique achieves an optimal diagnostic yield in cT1–T2 N0 cases without prior cervical treatment when applied under optimal conditions. However, methodological heterogeneity in the literature limits the interpretation of the results and partially constrains their clinical application.