###### Abstract  
Intraoral ultrasonography has been widely employed for the preoperative assessment of tumor margins due to its capability to evaluate depth of invasion (DOI) and tumor thickness (TT). Recently, a novel ultrasonographic technique, ultra-high frequency ultrasound (UHFUS) has been increasingly applied to the study of oral lesions. This study evaluates the potential application of intravalt UHFUS to assess DOI and TT parameters of oral squamous cell carcinoma (OSCC) lesions. Patients clinically suspected of OSCC lesions were enrolled and underwent an intraval UHFUS examination preoperatively. The parameters of TT, DOI, echogenicity, and vascularization were assessed. The parameters of TT and DOI as evaluated by means of UHFUS were compared to histology, which was set as the benchmark. Ten patients in total were enrolled. UHFUS-based DOI and TT measurements were found to positively correlate with histology (\(p<0.05\)), although UHFUS provided a slight overestimation of DOI. No differences were found in terms of echogenicity or vascularization depending on the site of the lesion. According to these preliminary results, UHFUS could support the preoperative assessment of TT and DOI, potentially enhancing the clinical evaluation of OSCC. Keywords:oral neoplasms; neoplasm invasiveness; neoplasm staging; squamous cell carcinoma of head and neck; diagnostic imaging; ultrasonography; ultra-high frequency ultrasound +
Footnote †: journal: Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (F.G.)  
Footnote †: journal: Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N.) Footnote †: journal: Medical and Molecular Pathology Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N.N. ); [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N. ); [EMAIL_ADDRESS] (M.N.N. ); filipSurgery is the treatment of choice, and obtaining clear resection margins (\(\geq\)5 mm for all T stages) is fundamental to achieve the locoregional control of the disease [3; 4]; however, the assessment of the deep margins of the tumor is often difficult due to the infiltrative nature of OSCC [5]. The application of diagnostic imaging techniques, in particular intraoral ultrasonography (US), computed tomography (CT) and magnetic resonance (MR), may support the assessment of tumor dimensions preoperatively. Intraoral US has been reported to show good correlation with histopathology and good accuracy compared to other diagnostic imaging techniques [4; 6; 7]. Specifically, intraoral US has been employed for the evaluation of the parameters tumor thickness (TT) and depth of invasion (DOI). TT is defined as the distance from the surface of the tumor to the point of deepest invasion, while DOI is the distance from the adjacent epithelial surface to the deepest point of invasion of the tumor [5]. Interestingly, DOI evaluation has been introduced in the 8 th American Joint Committee on Cancer- Union for International Cancer Control (AJCC-UICC) TNM staging system in stages 1, 2, and 3 [8]. DOI seems to be a good predictor in terms of prognosis compared to TT, as it may help to discriminate between superficial and deeply invasive tumors [8]. From this perspective, DOI may also be predictive of the presence of regional nodal metastases [9; 10]. Apart from the prognostic usefulness of DOI estimation, the possibility to obtain information on the deeper invasion of the tumor may improve the surgical planning of the resection and give an indication of prophylactic neck dissection in cases of DOI \(\geq\) 4 mm [6; 11].