Table II.

Evaluation of pathological markers on biopsy and postoperative samples in the 6 papers selected.

Author	Study design Time period	Site Stage or TNM teatment	No. patients Biopsy technique	Aim of the study	Markers	Results	Notes
Almangush, 2018 58	Retrospective 1981-2016	Mobile oral tongue Stage I-II = 81% Stage III-IV = 19% Surgery = 100%	100 Incisional biopsy	Analysis of the sensitivity and specificity of BD scores on biopsy and postoperative samples	TB TT BD model score	BD model score preo-op vs post-op - Sensitivity 59.1% - Specificity = 100% - Agreement pre/post op = 83% Depth values (mm) pre-op (mean) = 4.1 (0.5-10 mm) post-op (mean) = 6.3 (0.5-23 mm)	17% = non-representative biopsies (badly fragmented, too superficial, technical artifacts) TB and TT (Tab. I) Budding model score (Tab. II)
Seki, 2016 59	Retrospective 2009-2013	Tongue, floor of the mouth T1 = 43% T2-T4 = 57% Preop CT = 52% Surgery = 48%	91 Not described	Detection of histopathologic parameters predictive for lympho nodal metastases in preoperative biopsy specimens	Histologic Grading TT INF LIV Budding score	Tumour depth: higher in resection specimens than in biopsy samples. It is predictive of lymph node metastases on resection specimens, not on biopsy samples Budding score: good correlation between biopsy and postop specimens BD = > 3 and Tumour depth > 3 mm significantly predictive of lymph node metastases, OS and RFS BD = > 3 and INFa/INFb: predictive of early or late lymph node metastases or late in many cases	TT (Tab. I) INF (Tab. I) Budding score (Tab. IIb) Comparison between TB, TT, and INF status on lymph node metastases was assessed on 33 patients who underwent resection and neck dissection
Seki Soda, 2019 60	Retrospective 2009-2015	Oral cavity Stage not reported Preop CT = 57% Surgery = 43%	248 Incisional biopsy	Evaluation of relashionship between tumour budding score in biopsy and resected specimens and the effect of pre-op chemotherapy on tumour budding	Budding score	Mean budding scores: no significant differences in both groups; but tended to increase in resected patients without preop CT Preoperative CT-S1 treatment is effective for suppressing relapse and lowering the budding scores	Budding score (Tab. II)
Seki, 2017 48	Retrospective 2009-2014	Mobile tongue, buccal mucosa, palate, lip T1-T2 = 76% T3-T4 = 24% Preop CT and resection +/- ND = 53% Resection+/- ND = 47%	209 Incisional biopsy	Evaluation of the relashionship between tumour budding in biopsy specimen and lymphnode metastases	TB INF Tumour grade TT	TB => 3 predictive of Lymphnode metastases and poor prognosis P < 0.01 (mainly T1-T2 cN0) The budding score (high) together with INF and LIV were found to be independent risk factors for lymphnode metastases at multivariate analyses Strong correlation (p < 0.01) between the budding score and tumour grade, tumour depth, INF, and blood vessels invasion TB in early OSCC can be used as a reliable parameter for stratifying patients with different risks of lymph node metastases	Authors describe biopsy technique; Tumour budding can be detected using routine haematoxylin and eosin-stained slides or cytokeratin-stained slides. Results may differ significantly depending on the staining used
Nayanar, 2019 61	Retrospective 2014-2016	Oral cavity (lips, buccal mucosa, tongue, hard palate, retromolar trigone, floor of the mouth) Stage II = 48% Stage III = 20% Stage IV = 32% Wide excision with Neck dissection	160 Incision or wedge biopsy	Identification of clinical and histopathological predictors of lymphnode metastases Development of a predictive scoring system	Shape of rete pegs Pattern of invasion Depth of invasion (TT) Histologic differentiation Site of cancer	Risk score (4-18) Score 4: predictive of N+ = 5% Score 18: predictive of N+ = 91%	The risk score needs to be tested and validated in other patient populations Rete pegs (Tab. I) Risk score (Tab. II)
Sahoo, 2020 49	Retrospective 2014-2016	Oral cavity (GB sulcus, tongue, floor of the mouth, retromolar and maxilla) cT1/T2 Resection and elective neck dissection	150 Excisional biopsy	Comparison of prognostic performance of TT and of DOI (TT2 and TT3) in predicting lymphnode metastases. Predictive potential of PNI and LVI	TT1, TT2, TT3, DOI PNI, LVI	TT2 and LVI correlate with lymph node metastases	TT1, TT2, TT3, DOI (Tab. I)