T2 Oral Squamous Cell Carcinoma Research Articles

When should patients with T1N0 oral squamous cell carcinoma be considered for elective neck dissection?

To identify adverse pathological features (APF) predicting nodal failure in clinically node negative T1 oral squamous cell carcinoma (OSCC). This study evaluated patients with T1N0 (≤5 mm depth of invasion (DOI) and ≤2 cm diameter) oral cancers from a prospectively maintained database between 1988 and 2020. All patients underwent surgical excision of the primary lesion without neck dissection. Patients underwent three monthly clinical surveillance and salvage neck dissection was performed if nodal relapse was diagnosed. Overall, 141 patients were included. Nodal relapse was reported in 16/141 (11.3%) patients. Factors impacting regional recurrence-free survival were DOI ≥3 mm (HR: 2.4, P < 0.001), maximum tumour diameter ≥12 mm (HR: 1.1, P = 0.009), perineural invasion (PNI) (HR 7.5, P = 0.002) and poor differentiation (HR 5.3, P = 0.01). Rates of nodal relapse increased from 2% amongst patients with no APFs to 100% for those with four APFs. Patients with two or more APFs had significantly poorer 5-year regional recurrence-free survival (94.8% vs. 56.3%, P < 0.001). Patients with T1N0 OSCC with two or more APFs (DOI ≥3 mm, diameter ≥12 mm, PNI or poor differentiations) should be considered for elective neck dissection.

Controversies in the treatment of early-stage oral squamous cell carcinoma

The treatment of early-stage oral squamous cell carcinoma (OSCC) is still a controversial issue. Thanks to the 8th edition of TNM by AJCC there is a better distinction between the stages of OSCC. However, Stages I and II still share the same treatment protocol, even if the prognosis is radically different. A retrospective study has been conducted including 70 previously untreated patients with Stage I or II OSCC, treated with tumorectomy and selective neck dissection. The study focuses on the link between pT1/2 and various other factors, particularly histological grading, vascular and perineural invasion, local and cervical recurrence, surgical margins and overall survival. These data reveal significant differences between pT1 and pT2 in histological grade, perineural invasion, cervical recurrence, surgical margins, and overall survival, emphasizing the necessity of different treatment protocols for T1 and T2 OSCC. Distinct strategies should be proposed to treat Stage I and II OSCC, with Stage II patients possibly benefitting from more aggressive treatments: following these data, a wait-and-see strategy should only be considered in Stage I, while certain treatments at the cervical level — such as prophylactic neck dissection and sentinel node biopsy — should always be considered for Stage II tumors.

Prognostic study of sentinel lymph node biopsy in early-stage oral squamous cell carcinoma with computed tomography lymphography

PurposeOccult metastasis is a prognostic factor for early-stage oral squamous cell carcinoma (OSCC). Sentinel lymph node (SLN) biopsy (SLNB) is a promising method to detect such metastases. The present study aimed to evaluate the diagnostic reliability of SLNB with computed tomography lymphography (CTL) for early-stage OSCC and to clarify patient outcomes after SLNB. MethodsThe medical records of 42 patients with T1 or T2 cN0 OSCC who had undergone CTL the day before surgery were retrospectively collected and statistically analyzed. ResultsSLNs were identified on CTL in 41 of 42 OSCC patients (97.6 %). Micrometastases were detected in 10 of 41 cases (24.4 %) and 11 of 65 SLNs (16.9 %) by intraoperative pathological diagnosis. Three cases showed occult metastasis within a year after the primary operation. Specificity and negative predictive value were 76.9 % and 90.3 %, respectively. The cumulative 5-year regional recurrence-free rate was 89.7 % in 31 SLNB-negative patients. Five-year overall and disease-free survival rates were 86.9 % and 70.1 %, respectively, in the 41 cases with identified SLNs. ConclusionCTL offers acceptable results and appears likely to be effective in treating early-stage OSCC patients with low-invasive surgery. Further investigation is necessary to compare radioisotope-based methods.

Diagnostic Accuracy of Up-Front PET/CT and MRI for Detecting Cervical Lymph Node Metastases in T1-T2 Oral Cavity Cancer-A Prospective Cohort Study.

The diagnostic accuracy of up-front 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for detecting cervical lymph node metastases in patients with T1-T2 oral squamous cell carcinoma is reported with large discrepancies across the literature. We investigated the sensitivity, specificity, positive and negative predictive value, and accuracy of up-front PET/CT for detecting cervical lymph node metastases in this patient group and compared the performance to magnetic resonance imaging (MRI). In this prospective cohort study, 76 patients with T1-T2 oral squamous cell carcinoma underwent an up-front PET/CT and MRI at the Odense University Hospital from September 2013 to February 2016. Sentinel node biopsy and elective neck dissection were used for histopathological verification of the imaging modalities. Up-front PET/CT was significantly more sensitive than neck MRI (74% vs. 27%, p = 0.0001), but less specific (60% vs. 88%, p = 0.001). The accuracy of PET/CT and neck MRI was comparable (66% vs. 63%, p = 0.85), the PPV was slightly in favor of neck MRI (56% vs. 62%, p = 0.73), the NPV was slightly in favor of PET/CT (77% vs. 63%, p = 0.16). Neither PET/CT nor neck MRI should stand alone for N-staging T1-T2 oral cavity cancer.

Risk factors associated with disease recurrence in patients with T4 staged Squamous Cell Carcinoma of the Oral Cavity treated with surgery and postoperative radiotherapy.

To determine the association of clinical and pathological parameters on recurrence of treated stage T4squamous cell carcinoma of oral cavity patients managed with surgery followed by concomitant chemo and radiation therapy. The retrospective, cohort study was conducted at Patel Hospital, Karachi, and comprised data of patients diagnosed with oral squamous cell carcinoma and admitted between January 1, 2014, and January 30, 2019. Patients of either gender aged 20-80 years who had a minimum follow-up of one year were included. Data was collected using the Head and Neck Cancer registry form and the medical record files. The subjects were also contacted by telephone when needed. The study end-points were disease-free survival and overall survival. Data was analysed using SPSS 21. Out of the 83 patients, 65(78%) were male. The overall median(range) age was 46(20-80) years, and 43(52%) of them were aged 31-50 years. Overall, 15(18%) patients had positive margins and 48(58%) had proven cervical node metastasis on histopathology. Overall survival was 42.2% with the median(range) follow-up time was 14(9-21) months and 5-year disease-free survival was 45.8% with the median (range) follow-up time was 13(7-19). The factor that affected the final outcome was found to be the increasing nodal ratio (p=0.043). Among T4 oral squamous cell carcinoma patients treated with surgery and adjuvant therapy, the rate of disease recurrence was found to be high. Tumours with a high cervical nodal disease burden and/or margin involved were at substantially higher risk of recurrence.

A Combined Prediction Model for Lymph Node Metastasis Based on a Molecular Panel and Clinicopathological Factors in Oral Squamous Cell Carcinoma

ObjectiveLymph node metastasis is the most important factor influencing the prognosis of oral squamous cell carcinoma (OSCC) patients. However, there is no proper method for predicting lymph node metastasis. This study aimed to construct and validate a preoperative prediction model for lymph node metastasis and guide personalized neck management based on the gene expression profile and clinicopathological parameters of OSCC.MethodsBased on a previous study of related genes in OSCC, the mRNA expression of candidate genes was evaluated by real-time PCR in OSCC specimens. In this retrospective study, the gene expression profile and clinicopathological parameters of 112 OSCC patients were combined to construct the best prediction model for lymph node metastasis of OSCC. The model was validated with 95 OSCC samples in this study. Logistic regression analysis was used. The area under the curve (AUC) ultimately determined the diagnostic value of the prediction model.ResultsThe two genes CDKN2A + PLAU were closely related to lymph node metastasis of oral squamous cell carcinoma. The model with the combination of CDKN2A, PLAU, T stage and pathological grade was the best in predicting lymph node metastasis (AUC = 0.807, 95% CI: 0.713-0.881, P=0.0001). The prediction model had a specificity of 96% and sensitivity of 72.73% for stage T1 and T2 OSCC (AUC = 0.855, 95% CI: 0.697-0.949, P=0.0001).ConclusionsHigh expression of CDKN2A and PLAU was associated with lymph node metastasis in OSCC. The prediction model including CDKN2A, PLAU, T stage and pathological grade can be used as the best diagnostic model for lymph node metastasis in OSCC.

Development of a machine learning model for the prediction of nodal metastasis in early T classification oral squamous cell carcinoma: SEER‐based population study

AbstractBackgroundThis study aimed to develop and compare machine learning (ML) based predictive models for lymph node metastasis (LNM) in early T classification oral squamous cell carcinoma (OSCC).MethodsWe used data from the Surveillance Epidemiology and End Results Database to develop and validate the predictive models for LNM in patients with T1, T2 OSCC. Using simple clinical and histopathological data, we developed six ML algorithms to predict LNM. The predictive performance of models was compared.ResultsThe areas under the receiver operating characteristic curves (AUCs) of the six models ranged from 0.768 to 0.956. The best prediction performance was achieved with a XGBoost (AUC = 0.956). Permutation importance analysis showed that tumor size is the most important feature in predicting metastasis.ConclusionsWe developed a simplified and reproducible ML‐based predictive model for metastasis in early T classification OSCC that could be helpful for the decision of a treatment strategy.

Expression of NANOG and Its Regulation in Oral Squamous Cell Carcinoma.

Background Results of previous studies suggest that NANOG may be an important prognostic biomarker in oral squamous cell carcinoma (OSCC), but there are contradictory results regarding NANOG expression patterns on mRNA and protein levels, and the mechanisms of its regulation are poorly understood. Our aim was to analyze the expression and diagnostic significance of NANOG in OSCC, and the possible mechanisms of its regulation, i.e., protein regulators on mRNA level (OCT4, SOX2, KLF4, AGR2, and NOTCH1), methylation status, copy number variation, and regulatory miRNAs, miR-145, miR-335, miR-150, miR-34a, miR-128, and miR-27a. Methods Our study included 120 patients with OSCC. Expression of NANOG protein and mRNA was analyzed using immunohistochemistry and qPCR. Expression of regulatory factors, miRNAs, and copy number variation was performed using qPCR. Methylation status of NANOG promoter was determined using PCR and Sanger sequencing. Results We detected upregulation of NANOG and OCT4 and downregulation of NOTCH1 and AGR2 mRNA in OSCC with lymph node metastases compared to OSCC without lymph node metastases. We observed a strong positive correlation between mRNAs of NANOG and those of its protein regulators OCT4, SOX2, NOTCH1, AGR2, and KLF4. The expression of NANOG was in positive correlation with the expression of miR-34a. There was also a correlation between T status of OSCC and the expression of miR-335 and miR-150 and a correlation of miR-150 with the N status of T2 OSCC. NANOG promoter methylation and copy number variation were only observed in a small proportion of samples. Conclusions Our findings confirm the diagnostic significance of NANOG in OSCC and provide information on NANOG expression patterns on both mRNA and protein levels. They also suggest that protein regulators and microRNAs might play a crucial role, whereas methylation of its promoter and copy number variation probably have a minor role in the regulation of NANOG expression in OSCC.

Reframing Histological Risk Assessment of Oral Squamous Cell Carcinoma in the Era of UICC 8th Edition TNM Staging

ObjectivesTo assess whether application of the risk model originally proposed by Brandwein-Gensler, influences survival and disease progression in patients treated for oral squamous cell carcinoma (OSCCs)Materials and MethodsTumours from 134 T1 and T2 OSCC resections (7th edition) were scored independently by 3 histopathologists according to worst pattern of invasion (WPOI), lymphocytic host response (LHR) and perineural invasion (PNI) and categorised according to risk score. Local recurrence, locoregional recurrence, disease progression and overall survival were study endpoints. Interobserver variability of pathologist scoring was also assessed.ResultsSeventy-two patients (54%) were classified with low or intermediate risk and 62 (46%) patients were ‘high risk’. The inter-observer agreement was in moderate to strong agreement with the consensus scores (k range = 0.45–0.82). There was statistical significance between distant metastasis and ‘high risk’ tumours. Thirty tumours were upstaged to T3 in the 8th edition TNM staging, of which 83% had high risk scores. Overall risk score and TNM8 T stage has significant correlation with overall survival in comparison to the TNM 7 T stage.Conclusion‘High risk’ tumours were significantly associated with distant metastasis possibly due to the greater likelihood of aggressive features such as WPOI and PNI. Primary tumours are more likely to express high risk features with increasing T stage. None of the patients classified as ‘low risk’ died perhaps suggesting these tumours represent a rare variant of OSCC with excellent prognosis.

The Length of Peri-Neural Spreading in Clinically Mandibular Invaded Oral Cavity Squamous Cell Carcinoma

Background: The objective of surgical management of oral squamous cell carcinoma (OSCC) is adequate resection with a clear margin. However, there is still a debate as to the optimal length for a mandibular resected margin. Objective: To examine the length of peri-neural spreading in T4 mandibular invaded oral cavity squamous cell carcinoma. Materials and Methods: Twenty-eight T4 pathological OSCC specimens that involved mandible and serial slices were studied and the length of tumor spreading along the inferior alveolar nerve (IAN) was determined. Tumor characteristics, risk factors, and survival were analyzed. Results: The incidence of peri-neural invasion was 11.11%, and IAN invasion was found in 14.29% of the tumor-invaded mandibular marrow. The length of tumor spreading along IAN was 3 to 12 mm. Poor prognostic factors of T4 OSCC were it being located on the tongue (HR 14.16), was pathological N2-3 (HR 31.05), and had high-risk features such as peri-neural invasion, lymphovascular invasion, and extra-nodal extension. Conclusion: A mandibular resected margin of at least 18 mm is recommended as a clear surgical margin in cases of T4 mandibular invasion OSCC. Keywords: Oral cancer, Perineural invasion, Inferior alveolar nerve, Squamous cell carcinoma, Mandibulectomy

The Length of Peri-Neural Spreading in Clinically Mandibular Invaded Oral Cavity Squamous Cell Carcinoma

Background: The objective of surgical management of oral squamous cell carcinoma (OSCC) is adequate resection with a clear margin. However, there is still a debate as to the optimal length for a mandibular resected margin. Objective: To examine the length of peri-neural spreading in T4 mandibular invaded oral cavity squamous cell carcinoma. Materials and Methods: Twenty-eight T4 pathological OSCC specimens that involved mandible and serial slices were studied and the length of tumor spreading along the inferior alveolar nerve (IAN) was determined. Tumor characteristics, risk factors, and survival were analyzed. Results: The incidence of peri-neural invasion was 11.11%, and IAN invasion was found in 14.29% of the tumor-invaded mandibular marrow. The length of tumor spreading along IAN was 3 to 12 mm. Poor prognostic factors of T4 OSCC were it being located on the tongue (HR 14.16), was pathological N2-3 (HR 31.05), and had high-risk features such as peri-neural invasion, lymphovascular invasion, and extra-nodal extension. Conclusion: A mandibular resected margin of at least 18 mm is recommended as a clear surgical margin in cases of T4 mandibular invasion OSCC. Keywords: Oral cancer, Perineural invasion, Inferior alveolar nerve, Squamous cell carcinoma, Mandibulectomy

The Length of Peri-Neural Spreading in Clinically Mandibular Invaded Oral Cavity Squamous Cell Carcinoma

Background: The objective of surgical management of oral squamous cell carcinoma (OSCC) is adequate resection with a clear margin. However, there is still a debate as to the optimal length for a mandibular resected margin. Objective: To examine the length of peri-neural spreading in T4 mandibular invaded oral cavity squamous cell carcinoma. Materials and Methods: Twenty-eight T4 pathological OSCC specimens that involved mandible and serial slices were studied and the length of tumor spreading along the inferior alveolar nerve (IAN) was determined. Tumor characteristics, risk factors, and survival were analyzed. Results: The incidence of peri-neural invasion was 11.11%, and IAN invasion was found in 14.29% of the tumor-invaded mandibular marrow. The length of tumor spreading along IAN was 3 to 12 mm. Poor prognostic factors of T4 OSCC were it being located on the tongue (HR 14.16), was pathological N2-3 (HR 31.05), and had high-risk features such as peri-neural invasion, lymphovascular invasion, and extra-nodal extension. Conclusion: A mandibular resected margin of at least 18 mm is recommended as a clear surgical margin in cases of T4 mandibular invasion OSCC. Keywords: Oral cancer, Perineural invasion, Inferior alveolar nerve, Squamous cell carcinoma, Mandibulectomy

ICG-Guided Sentinel Lymph Node Sampling during Robotic Retroauricular Neck Dissection in cN0 Oral Cancer.

In this study, we sought to evaluate the clinical feasibility of indocyanine green (ICG)-guided sentinel lymph node (SLN) sampling during robotic retroauricular neck dissection (RAND) in patients with cN0 oral cancer. Nine adult patients diagnosed with T1 to T2 oral squamous cell carcinoma were consecutively recruited. All of them underwent transoral partial glossectomy and robotic RAND (levels I-III) simultaneously. Twelve hours prior to surgery, ICG was injected into the 4 quadrants around primary tongue tumors. During robotic RAND, intraoperative and ex vivo ICG-stained LNs were identified using the Firefly system and examined for the presence of fluorescence. ICG-stained LNs were identified in all patients. Thirty-one ICG-stained LNs were detected in 313 retrieved LNs (9.9%). Occult metastases were detected among the ICG-stained LNs in 2 patients (22.2%). There was no metastasis identified in the ICG-unstained LNs. Upstaging rates, sensitivity, specificity, and negative predictive value of ICG-guided SLN sampling were 22.2%, 100%, 91.5%, and 100%, respectively.

Neck nodal recurrence and survival of clinical T1-2 N0 oral squamous cell carcinoma in comparison of elective neck dissection versus observation: A meta-analysis.

The clinical management of patients with T1-2 oral squamous cell carcinoma (OSCC) and clinically node-negative neck (cN0) continues to be controversial. We performed a systematic review of the literature to assess the effect of elective neck dissection (END) and neck observation (OBS) on the prognosis of patients with cT1-2 N0 OSCC. PubMed, Embase, and Cochrane Library were searched for studies related to END and OBS in patients with cT1-2 N0 OSCC. The Mantel-Haenszel method was used to pool odds ratios (OR) for neck nodal recurrence and hazard ratios (HR) for survival. END reduced the risk of neck nodal recurrence (OR 0.45; 95% confidence interval 0.32-0.63; P < .00001) in cT1-2 N0 OSCC. The disease-free survival (HR 0.52; 95% CI 0.42-0.63; P < .00001) was significantly higher in patients treated with END. However, END failed to significantly improve overall survival (HR 0.83; 95% CI 0.67-1.04; P=.10) and disease-specific survival (HR 0.87; 95% CI 0.48-1.57; P=.65) compared with management by OBS. A reduction in neck nodal recurrence and an increase in disease-free survival might support the need for END in early-stage OSCC with clinically N0 neck.

Nerve-tumour interaction enhances the aggressiveness of oral squamous cell carcinoma.

Perineural invasion (PNI) is a poor prognostic pathologic feature of oral squamous cell carcinoma (OSCC). The mechanisms of PNI remain poorly understood, and nerve-tumour interactions have been implicated for its pathogenesis. Systematic investigation of nerve-tumour interactions was performed using fresh human peripheral nerve. In vitro and in vivo models were used to determine the ability of human peripheral nerves to enhance OSCC migration/invasion. Retrospective cohort study was also carried out in one medical centre from 2001 to 2009. 314 T1-2 OSCC patients. In the transwell migration/invasion assay, the cells in five representative fields were counted. In the nerve implantation model, tumour size was estimated. PNI quantification by PNI focus number was carried out in the OSCC patients to correlate with cervical lymph node metastasis and oncologic outcomes. The transwell migration/invasion assay demonstrated that human peripheral nerves, compared with subcutaneous soft tissue, significantly enhanced the migration/invasion abilities of OSCC. Moreover, the enhanced migration was dose-dependent with increased length or number of peripheral nerve segments. The nerve implantation model showed that human peripheral nerve also enhanced OSCC growth in vivo. Finally, increased PNI focus number was found dose-dependently associated with increased cervical lymph node metastasis and decreased 5-year disease-specific survival rates. These results clearly indicated the presence of nerve-tumour interaction that involved paracrine influences leading to aggressiveness of OSCC. Further investigations are required to explore key cell types and molecules involved in nerve-tumour interactions for future therapeutic targeting of PNI in OSCC.

Depth of invasion in early oral cancers: Is it an independent prognostic factor?

6058 Background: Depth of invasion (DOI) has been incorporated in the new AJCC TNM staging (8th edition) for oral cancers. We hypothesized that the negative effect of increasing DOI on outcomes was a result of an increased propensity to node metastasis and appropriate neck treatment would negate its detrimental effect on outcomes. Methods: Patients with T1/ T2 oral squamous cell carcinoma, clinically node negative, from a previously reported Randomized Controlled Trial (NCT 00193765) formed the cohort for this study. Patients were restaged according to the new staging system . Overall survival(OS) was estimated by the revised T stage for the entire cohort and separately for those who underwent END and those who did not (TND arm) using Kaplan Meier and log rank test . Multivariate analysis was performed using Cox proportional hazard model making adjustment for neck treatment, T stage, site, prognostic factors and the interaction between revised T stage and neck treatment. Results: Of the 596 patients 577 were evaluable, with a median follow up of 77.57 months. Initial pT staging was pT1, 389(67.4%); pT2, 181(31.4%); pT3, 7(1.2%) and was modified to pT1, 195(33.8%); pT2, 280(48.5%); pT3, 102(17.7%) on restaging . 288 patients underwent END and 289 did not (TND arm). For the entire cohort 5-year OS rates were 79.0% [95 %CI, 73.12-84.88] for pT1, 69.4% [95% CI, 63.91-74.89] for pT2 and 53.0% [95% CI, 43.2 -62.8] for pT3 with significant difference between the 3 groups (p &lt; 0.001). In those without upfront neck treatment( TND ), OS difference was maintained between the pT1 and pT2 groups [81.1% (95%CI, 73.26-88.94) vs 65.0% (95%CI, 56.77-73.23)], p = 0.004. This difference was not apparent in the END arm ,pT1 -76.9% (95 %CI, 68.47-85.33) vs pT2 -73.7% (95%CI, 66.25-81.15), p = 0.73. T3 tumours had uniformly poor survival irrespective of neck treatment. On multivariate analysis of the revised pT1/T2 cohort (n = 475), pT stage, neck treatment and grade were independent prognostic factors impacting OS. There was a significant interaction between the T stage and neck treatment (p = 0.03). Conclusions: When DOI &lt; 10 mm, END supplants the prognostic implication of depth with similar outcomes for T1 and T2 tumours (new AJCC staging). The exact role of DOI on outcomes warrants further research. Clinical trial information: NCT00193765.

Validation of the eighth edition AJCC staging system in early T1 to T2 oral squamous cell carcinoma.

To validate the newly proposed American Joint Committee on Cancer (AJCC) eighth edition staging in early T1 and T2 oral cavity cancers and its effect in predicting tumour control. Retrospective analysis of treatment outcomes of 441 T1 to T2 oral squamous cell carcinoma (OSCC). Overall survival (OS), disease-specific survival (DSS), and tumour control were calculated and compared between the AJCC 7 and 8 staging systems. The 5-year OS was 78% and 61% for T1 and T2 tumours, respetively (P < 0.001) (AJCC 7) vs 87% and 67% (P < 0.001) (AJCC 8). The 5-year DSS was 78% and 61% for T1 and T2, respectively(P < 0.001) (AJCC 7) vs 89% and 71% (P < 0.001) (AJCC 8). For stages I and II tumours the 5-year OS was 81% and 76%, respectively (P < 0.302) (AJCC 7) vs 87% and 73% (P < 0.017) (AJCC 8). The 5-year DSS was 83% and 82% (P < 0.222) vs 89% and 77% (P < 0.016). With the AJCC eighth edition the 5-year local, regional, and distant control rates for T1 vs T2 tumours were 85% vs 74% (P = 0.003), 95% vs 77% (P = 0.001), and 95% vs 80% (P = 0.014), respectively. The AJCC 8th staging system provided for more accurate prediction of OS, DSS, and disease control in early oral cavity cancers.

Long-term quality of life measured by the University of Washington QoL questionnaire (version 4) in patients with oral cancer treated with or without reconstruction with a microvascular free flap

We used the University of Washington Quality of Life (UW-QoL) questionnaire (version 4) to assess the long-term quality of life (QoL) of patients with oral squamous cell carcinoma treated with or without reconstruction with a microvascular free flap, and all patients with T2–T4 oral squamous cell carcinoma (SCC) treated in this way were eligible for the study. A total of 139 patients’ personal details, medical history, and QoL scores were collected and analysed. The mean (SD) overall QoL score was 73.09 (14.8) for patients with T2–T4 oral SCC. The mean (SD) global QoL scores of patients who had had reconstructions was 75.68 (13.85) and of patients who had not 71.00 (15.34) (t=1.864, df=137, p=0.064). Univariate and multivariate analyses indicated that site of tumour, T stage, and the need for postoperative radiotherapy had significant effects on the global QoL scores. Among patients with T2 oral SCC there was no significant difference between patients who did and did not have reconstructions. However, there were significant differences among patients with T3/T4 SCC in scores for appearance, recreation, mood, anxiety, chewing, swallowing, and speech depending on whether they did or did not have reconstructions. There were significant differences in the domains recreation, chewing, speech, and taste, depending on the primary site of the tumour. We conclude that reconstruction with a microvascular free flap had a beneficial effect on the treatment of SCC and improved the QoL of patients with oral SCC.

Tumor budding is an independent prognostic marker in early stage oral squamous cell carcinoma: With special reference to the mode of invasion and worst pattern of invasion

Pathologically proven regional lymph node metastasis affects the prognosis in early stage oral cancer. Therefore we investigated invasive tumor patterns predicting nodal involvement and survival in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma (cT1,2N0M0 OSCC). Ninety-one cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding. The correlations among invasive tumor patterns, regional metastasis, and disease-free survival were analyzed. Of the 91 cases, 22 (24%) had pathologically proven regional metastasis. The mode of invasion (p<0.01) and tumor budding (p<0.01) were associated with regional metastasis as well as lymphovascular invasion (p = 0.04) in univariate analysis. In logistic regression analysis, however, tumor budding was the only independent predictor of regional metastasis (hazard ratio (HR) = 3.05, 95% confidence interval (CI) = 0.29–5.30, p<0.01). All three invasive patterns, the mode of invasion, WPOI, and tumor budding, were found to be significant predictors of 5-year disease-free survival (p<0.01, p = 0.03, and p<0.01, respectively) as well as lymphovascular invasion (p = 0.02) and perineural invasion (p = 0.02). A final model for Cox multivariate analysis identified the prognostic advantage of the intensity of tumor budding (HR = 2.19, 95% CI = 1.51–3.18, p<0.01) compared with the mode of invasion and WPOI in disease-free survival. Our results indicate that the intensity of tumor budding may be a novel diagnostic biomarker, as well as a therapeutic tool, for regional metastasis in patients with cT1,2N0M0 OSCC. If the pancytokeratin-based immunohistochemical features of more than five buds, and a grade 4C or 4D mode of invasion are identified, careful wait-and-see follow-up in a short period with the use of imaging modalities is desirable. If there are more than ten buds, a grade 4D mode of invasion, or WPOI-5 in the same section, wide resection of the primary tumor with elective neck dissection should be recommended.

Loss of ARID1A, a component of the SWI/SNF chromatin remodeling complex, at the invasion front is related to poor outcomes in oral squamous cell carcinoma

This study aimed to investigate the relationship between loss of AT-rich interactive domain-containing protein 1A (ARID1A) expression and the prognosis of patients with oral squamous cell carcinoma (OSCC). Seventy-five OSCC tissue specimens were immunohistochemically stained with a specific antibody to ARID1A. The immunoreactivity of ARID1A was then correlated with clinicopathological factors, including the prognosis of the patients. Non-tumorous oral squamous cells exhibited nuclear ARID1A staining, whereas the invasive OSCC cells showed different degrees of loss of ARID1A immunoreactivity. Little-to-no ARID1A immunoreactivity was found at the cancer invasion front in 20 of the 75 OSCC tissue specimens, with significant association with unfavorable patient outcomes. Notably, downregulation of ARID1A immunoreactivity was also related to lymphovascular involvement and poor outcome in patients with T1 and T2 OSCC without lymph node metastasis. The results suggest that loss of ARID1A expression at the cancer invasion front might be related to tumor progression in many OSCCs.