**7. Post-operative follow-up**

*Oral Diseases*

Cyclin B-1

Activin A

**Table 1.**

E-cadherin (ECAD) Podoplanin

metastasis and recurrence [31].

Matrix metalloproteinase-7 (MMP-7)

partial epithelial-to-mesenchymal transition

oral cavity and oropharynx [32].

podoplanin expression [34].

was predictive of poor outcome (p = 0.021) [35].

for predicting occult neck metastasis [38].

node metastasis in oral tongue squamous cell carcinoma [36].

Zhang et al. showed that the secreted protein acidic and rich in cysteine (SPARC) has a positive rate in 49.1% of tongue cancer tissues and 0% in normal tissues. The expression of SPARC was positively correlated with occult lymph node

*Predictors and non-predictors of occult lymph node metastases in oral cavity carcinoma.*

Vascular endothelial growth factor-C (VEGF-C)

High mobility group box 1 (HMGB1)

**Predictor Non-predictor**

Secreted protein acidic and rich in cysteine (SPARC)

Huber et al. showed that the differentiation grade and down-regulation of E-cadherin expression significantly correlate with positive lymph node status in univariate and multivariate analyses. Thus, E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the

Huber et al. showed that podoplanin expression correlated significantly with sentinel lymph node metastasis and remained a significant predictor for lymph node status even after controlling for tumor stage [33]. In relation to this, a more recent study revealed the association of podoplanin and SOX2 in the progression of oral squamous cell carcinoma [34]. OX2 is a transcription factor related to the maintenance of stem cells in a pluripotent state. Podoplanin is a type of transmembrane sialoglycoprotein, which plays an important role in tumor progression and metastasis [34]. There was a significant inverse correlation between the expression of SOX2 and podoplanin with the tumor grade, survival analysis showed that a high expression of SOX2 correlated positively with the disease-free survival, and a significant positive association between the pattern of SOX2 and

Mäkinen et al. showed that matrix metalloproteinase-7 (MMP-7) expression was associated with presence of occult metastases (OR 3.67; p = 0.013); increased invasion depth (OR 4.60; p = 0.005); high tumor grade (OR 3.30; p = 0.007). MMP-7

In a study by Kelner et al. in 2015, it was found that high immunohistochemical expression of activin A was significantly associated with presence of occult lymph

Non-predictors of occult lymph node metastases as shown in **Table 1** include vascular endothelial growth factor-C (VEGF-C) and High mobility group box 1 (HMGB1). No statistically significant difference was found between OSCC with and without occult lymph node metastasis in regard to VEGF-C immunoexpression by malignant cells [37]. Isolated VEGF-C expression by malignant cells is not of predictive value for occult lymph node metastasis in early stages of oral squamous cell carcinoma [37]. Likewise, Prediction of occurrence of late neck metastasis in early tongue squamous cell carcinoma by evaluating HMGB1 (high mobility group box 1) expression in the primary lesion showed that immunohistochemistry study of HMGB1 in early tongue squamous cell carcinoma did not appear to be very useful

Most recently, immunohistochemistry quantification of partial epithelial-to-mesenchymal transition (p-EMT) in oral cavity squamous cell carcinoma primary tumors

**136**

Based on the algorithm proposed by Paler et al., follow-up CT scan may be done for N1 disease and PET CT for N2/N3 disease 12 weeks after treatment [40]. CT scan may also be done for N0 neck [1].

The NCCN guidelines follow-up recommendations for oral cavity carcinoma include a complete head and neck examination every 1–3 months for the first post-operative year, every 2–6 months for the second post-operative year, every 4–8 months for years 3–5, and every 12 months beyond 5 years post-operatively. Speech/hearing and swallowing evaluation, nutritional evaluation and rehabilitation, smoking cessation and alcohol counseling, and surveillance for depression are included in the post-operative supportive care recommendations [1].
