**2. Histopathological factors**

Various parameters have been investigated to further stratify the risk of subclinical nodal metastases, including tumour thickness and depth of invasion (DOI). Tumour thickness measures the thickness of the tumour from the deepest point of invasion to the top of the granular cell layer, or if ulcerated, the ulcer base serves as the reference point. DOI is measured from the level of the basement membrane to the deepest point of invasion, and in the case of an ulcerated OCSCC, this level is estimated by creating an imaginary line from the adjacent basement membrane [1]. This avoids under-representing an ulcerated tumour or over-representing an exophytic tumour, and has been included in staging for OCSCC in the current 8th edition American Joint Committee on Cancer (AJCC) staging manual [9]. An increased risk of subclinical nodal metastases has been associated with varying tumour thicknesses, between 2 mm to 5 mm, with thicker tumours having a risk of nodal metastases between 44 and 50% [1, 8, 10]. The anatomical sub-site of the OCSCC may also play a role with a lesion thickness > 1.5 mm on the floor of mouth being associated with a risk of nodal metastases of 35% [11]; however, this has not been a consistent finding, with another study demonstrating a 4 mm cut-off associated with an increased risk of nodal metastases regardless of sub-site [5]. This study documented rates of local control, nodal disease, and survival rates of 91%, 8%, and 100%, respectively, for lesions <4 mm thick compared with 84%, 48%, and 74% for those ≥4 mm thick (p < .01). Despite this there are limitations with basing management decisions on the tumour thickness or DOI, as often this may not be assessable on a biopsy alone due to the sparse amount of biopsy material, and if assessable the biopsy may not be representative of the entire tumour [12], resulting in subsequent management decisions based more on clinical assessment.

Histopathological factors predicting for sub-clinical nodal metastases in the setting of sentinel lymph node biopsy (SLNB) have also been investigated with three variables identified including grade (G1 *vs* G2/G3), presence of lymphatic invasion and mode of invasion (cohesive *vs* dissolute) [13]. Interestingly, in this study DOI and tumour thickness were not reliable predictors of nodal metastasis demonstrating the inconsistency and uncertainty in basing management decisions on histopathological factors alone.

### **3. Benefit of elective neck dissection**

Superior outcomes have been published in a prospective randomised controlled trial (RCT) involving patients with early OCSCC (T1/T2 tumours) without clinical evidence of nodal metastases, when they underwent an END compared to observation followed by neck dissection in the setting of nodal relapse [14]. In this study 3 year overall survival was 80% for patients undergoing END compared to 67.5% for patients undergoing delayed therapeutic dissection following relapse (p = 0.01). Subclinical nodal positivity in the END group was 29%, while nodal relapse rates in the observation group was 45% [14].

Of note in the 'true' node negative patients in this study, which included pathological node negative patients in the END group and those who did not relapse in the observation group, *survival was equivalent.* This demonstrates that while patients with subclinical nodal metastases benefit from a neck dissection, the remaining 60–80% of patients without nodal metastases do not experience a survival benefit by undergoing a neck dissection (see **Figure 1**). It is also important to consider that even patients with a pathologically negative neck following END have a rate of regional failure up to 5–10% [3, 15].

This benefit of END has been reported in a previous observational study where patients with early (T1/T2) OCSCC had significantly improved outcomes undergoing END (median survival 12 years) compared to observation (median survival 4.1 years), with the majority (11/12) of recurrences in the observation group

*Sentinel Lymph Node Biopsy for Early Oral Cavity Squamous Cell Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.99410*

**Figure 1.** *Overall survival in 'true node negative' and 'true node positive' patients [14].*

occurring as regional failures [2]. This benefit is selectively achieved in patients undergoing SLNB, as patients with a positive sentinel lymph node (SLN) undergo a completion neck dissection while the morbidity of the neck dissection is avoided when the SLNB is negative.
