Sentinel lymph node biopsy in early-stage oral squamous cell carcinoma: reassessing its role in contemporary practice

Oral cavity squamous cell carcinoma (OSCC) remains a major public-health challenge because of its high incidence and mortality (1). Even in early primary tumors with a clinically negative neck (cT1–T2, cN0), the risk of occult nodal disease commonly approaches 20–30% (2), and nodal involvement is among the strongest adverse prognostic factors for disease-specific survival (3). The traditional standard treatment has been the elective selective neck dissection (SND), which reliably stages the neck but inevitably treats 100% of patients to benefit the 20–30% who are truly affected by metastases (4,5). Within this context, sentinel lymph node biopsy (SLNB) has emerged as a promising staging strategy capable of balancing oncologic safety with reduced surgical morbidity (6).

Building on robust experience first in melanoma and breast cancer, lymphatic mapping with preoperative lymphoscintigraphy and intraoperative gamma-probe guidance when applied to oral cancer, allows targeted removal of first-echelon nodes rather than a systematic clearance of levels I–III, sparing important cervical anatomic structures for unnecessary dissection (7). Multicenter series and guidelines now support SLNB as an accurate staging tool in cT1–T2 cN0 disease, with sensitivity in the 80–90% range and negative predictive values comparable to SND when the technique is performed according to standardized protocols (8,9).

Struckmeier et al. present a single-center cohort evaluating SLNB in early OSCC, treated between January 2020 and October 2024 at the University Medical Center Hamburg-Eppendorf (10). A total of 48 cN0 patients underwent wide local excision of the primary tumor combined with SLNB. The median age was 62.5 years, with a slight predominance of women (55%). Tongue carcinomas accounted for 69% of cases, and most tumors were staged as pT1 (79%), with only 10% crossing the midline. Cervical metastasis was identified in 8% of patients (4% pN1 and 4% pN2b). Adverse histopathological features, including perineural invasion (10%), lymphovascular invasion (8%), and angioinvasion (4%), were relatively infrequent, and all resections achieved clear margins. Adjuvant therapy was required in 17% of patients.

The lymphatic mapping patterns observed are clinically informative. A predominantly ipsilateral drainage pattern was seen in 84% of cases; however, 8% demonstrated contralateral and 8% bilateral sentinel nodes. Floor-of-mouth tumors exhibited higher rates of contralateral drainage (25%), and poorly differentiated tumors showed a similar tendency (33%). Such findings draw attention to a known limitation of conventional SND, which typically samples only ipsilateral levels I–III in early OSCC (11-13). SLNB, by contrast, may detect drainage basins—including contralateral or perifacial nodes—that could otherwise remain ignored in standard dissections (14).

The distribution of sentinel nodes also merits comment. Level IIa was the most frequent drainage site, representing 41% of first sentinel nodes and 48% of second sentinel nodes. Level Ib ranked second for first-echelon drainage (26%), while level III accounted for 39% of second sentinel nodes and 36% of subsequent nodes. Although classical descriptions such as those by Shah (15) position level I as the preferred initial basin of drainage for oral cavity primaries, contemporary analyses suggest a more balanced distribution. Thoenissen et al. (16), in a German cohort undergoing systematic neck dissection, reported nearly identical rates of metastatic involvement in levels I and II with both approximately 39%. This discrepancy between historical and contemporary patterns may stem from differences in population characteristics, tumor subsites, or sample size, but it highlights the value of SLNB in identifying the actual, patient-specific drainage pathways rather than relying solely on traditional anatomic templates.

The survival analysis in the Hamburg cohort offers intriguing insights. Contralateral sentinel node involvement tended to correlate with poorer outcomes, although not reaching statistical significance. More notably, patients in whom more than two sentinel nodes were identified, and particularly those with more than four nodes removed, demonstrated improved recurrence-free survival. At first sight, the number of nodes harvested should not biologically influence prognosis, since patients with positive sentinel nodes invariably proceed to therapeutic neck dissection. However, this association may reflect greater sampling accuracy: a higher sentinel node yield may provide a more reliable representation of the true lymphatic basin, reducing the risk of false-negative staging. This phenomenon parallels the well-documented relationship between lymph node yield and staging reliability in conventional neck dissections (17,18).

An important consideration is the relatively small sample size of 48 patients reported in this cohort, combined with its retrospective design. While the study provides valuable insights into lymphatic drainage patterns and potential prognostic implications of SLNB in early-stage OSCC, the limited number events substantially constrain statistical power, particularly for survival analyses. Consequently, the absence of statistically significant differences—such as the observed trend toward worse recurrence-free survival in patients with contralateral sentinel lymph node drainage—should be interpreted with caution, as these findings may reflect insufficient power rather than true lack of association, increasing the risk of type II error. Similarly, the survival advantages associated with higher numbers of identified sentinel lymph nodes or removed lymph nodes, although statistically significant in this cohort, may be sensitive to sample-driven variability and event distribution. These limitations underscore that the reported survival trends should be viewed as hypothesis-generating rather than definitive, reinforcing the need for validation in larger, ideally prospective, multicenter cohorts. Moreover, the retrospective, single-center design may introduce selection bias and restrict the external validity of the findings. These methodological constraints underscore the need for future studies with larger and more diverse cohorts to validate and expand upon the observations presented.

In summary, this cohort reinforces several clinically relevant considerations regarding the use of SLNB in early OSCC. Although lymphatic drainage was predominantly ipsilateral, the non-negligible rate of contralateral drainage—even in tumors with limited midline extension—supports the role of SLNB as a staging strategy capable of identifying drainage pathways that may be missed by unilateral elective neck dissection, as consistently reported in prospective series and multicenter trials. In addition, the predominance of level II as the most frequent sentinel basin challenges traditional concepts that emphasize level I as the primary site of early nodal spread, aligning with contemporary mapping studies and reinforcing the need for individualized, image-guided neck staging.

From a clinical standpoint, the observed association between a higher sentinel node yield and improved recurrence-free survival underscores the importance of procedural quality and thorough nodal assessment in SLNB. Rather than advocating for more extensive nodal excision, these findings support adherence to standardized SLNB protocols and meticulous intraoperative identification of true sentinel nodes, in line with evidence demonstrating comparable oncologic outcomes and lower morbidity when SLNB is performed in experienced centers. Beyond oncologic considerations, SLNB has also been consistently associated with reduced surgical morbidity and preservation of patient-reported quality-of-life outcomes when compared with elective neck dissection, reinforcing its value in contemporary, patient-centered care. Looking forward, larger multicenter studies should move beyond technical validation and prioritize protocol standardization across institutions, the integration of sentinel node metrics with molecular or pathological risk markers, and the assessment of long-term oncologic endpoints, including disease-specific and overall survival. Collectively, these considerations suggest that SLNB should not be viewed merely as a technical alternative to SND, but as an evidence-based strategy that can meaningfully inform neck management in early OSCC while preserving its minimally invasive intent. Finally, ongoing prospective cooperative group trials are expected to further clarify the role of SLNB relative to elective neck dissection in early-stage oral squamous cell carcinoma, informing future standards of care.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Cancer Research. The article has undergone external peer review.

Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1-2583/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-1-2583/coif). L.L.M. received fee from MSD (Merck Sharp & Dohme) for lectures on HPV vaccines and immunotherapy fields. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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