Recurrent Oral Squamous Cell Carcinoma Research Articles

Oncologic Outcomes of Salvage Surgery in Recurrent Oral Tongue Squamous Cell Carcinoma

Oncologic Outcomes of Salvage Surgery in Recurrent Oral Tongue Squamous Cell Carcinoma

Comparison of mutation landscapes of pretreatment versus recurrent squamous cell carcinoma of the oral cavity: The possible mechanism of resistance to standard treatment.

A high recurrent rate of oral squamous cell carcinoma (OSCC) is a major concern in head and neck cancer treatment. The study of the genetic mutation landscape in recurrent OSCC may provide information on certain mutations associated with the pathobiology and treatment response of the OSCC. We investigated the mutation landscape of matched pretreatment and recurrent tumors to understand the influence of genetic mutations on the pathobiology and clinical outcomes in OSCC. We sequenced 33 formalin-fixed paraffin-embedded (FFPE) recurrent tumors, primary tumors, and primary tumors before recurrence that matched the recurrent tumors collected from Rajavithi Hospital during 2019-2021. We identified recurrent mutations from these samples by the Oncomine Ion Torrent-based next-generation sequencing on the 517 cancer-associated gene panel. From the results, we found that the most commonly mutated gene in the cohort is a histone methyltransferase KMT2D (54.55%), implicating that aberrance in epigenetic regulation may play a role in oral cancer tumorigenesis. Functional protein association network analysis of the gene frequently mutated in the recurrent tumors showed enrichment of genes that regulate the cancer cell cycle, that is, MRE11A, CDKN2A, and CYLD. This finding was confirmed in the primary-recurring matched pair. We found that recurrent tumors possess a small but recurring group of genes, with presumably the subclonal mutations driving the recurrence of the tumor, suggesting that the recurrent disease originated from a small fraction of the cancer cell that survives standard treatment. These genes were absent in the primary tumor with a good response to the standard treatment. On the other hand, we found an enrichment of DNA repair genes, namely ATR, BRCA1, BRCA2, RAD50, and MUTYH, in nonrecurrent tumors suggesting that the mutations in the DNA repair pathway may at least partially explain the different response to the standard treatment. Our pilot study identified pathways of carcinogenesis in oral cancer and specific gene sets that indicate treatment responses and prognoses in this group of patients.

Genomic alterations in oral multiple primary cancers

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n = 202) and oral MPCs (n = 34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs. Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Occult metastasis is no burden factor in oral squamous cell carcinoma patients when adhering to a standardized approach in neck dissection

ObjectivesManagement of the neck in patients with oral squamous cell carcinoma (OSCC) is pivotal to oncologic control and survival. However, there is controversy regarding necessity of neck dissection (ND) in patients with clinically node-negative neck. We aimed to assess risk factors for occult metastasis and to explore whether the presence of occult lymph node metastases (LNMs) has an impact on recurrence and survival.Material and methodsA retrospective cohort study was performed including patients with primary OSCC who underwent radical tumor resection and ND in a high-volume center adhering to the prevailing German guideline. The ND was performed according to a standardized approach.ResultsFour hundred twenty-one patients with primary surgically treated OSCC were included. The incidence of occult metastasis was 14.49%. A pathological T stage > 1 (multivariate analysis, odds ratio (OR) 3.958, p = 0.042) and the presence of extranodal extension in LNMs (multivariate analysis, OR 0.287, p = 0.020) were identified as independent risk factors for occult metastasis. When comparing patients with and without occult metastasis, there were no significant differences in terms of progression-free survival (log-rank, p = 0.297) and overall survival (log-rank, p = 0.320). There were no cases of ipsilateral neck recurrence. One patient developed contralateral neck metastasis; however, he initially presented with a unilateral pT1 pN0 tumor.ConclusionsOverall, our findings suggest that conducting a standardized approach in ND should be applied in terms of management of the neck in order to maintain survival rates and to prevent neck recurrence in OSCC patients.Clinical relevance.None of the risk factors for occult metastasis can be reliably assessed preoperatively. Although elective ND does not guarantee the complete prevention of neck recurrence, it increases the likelihood of either timely removal of micrometastases or strengthens the justification for adjuvant therapy. Consequently, this approach leads to improvements in clinical outcomes.

Tislelizumab plus nimotuzumab is effective against recurrent or metastatic oral squamous cell carcinoma among patients with a performance status score ≥ 2: a retrospective study.

The efficacy of treatments targeting recurrent or metastatic head and neck squamous cell carcinoma are unsatisfactory in practice for patients with a ECOG PS score ≥ 2. Thus, this study retrospectively evaluated the safety and efficacy of a programmed cell death 1 inhibitor (tislelizumab) combined with an epidermal growth factor receptor inhibitor (nimotuzumab) in treating patients with a PS score ≥ 2 who suffer from recurrent or metastatic oral squamous cell carcinoma (OSCC). Fifteen patients were treated with tislelizumab (200 mg IV Q3W) and nimotuzumab (200 mg IV Q3W). Programmed cell death-ligand 1 (PD-L1) expression in tumor biopsies was assessed with immunohistochemistry. Whole-exome sequencing was used to evaluate treatment efficacy based on PD-L1 expression and gene mutation. At a median follow-up of 9.6 months, median overall survival was 10.1 months, and median progression-free survival was 4.0 months. Overall response rate was 40%, with 6/15 patients achieving partial response. Eight patients exhibited nine adverse events, eight out of nine being grade 2 and the remaining being grade 3. Whole-exome sequencing showed that DYNC1I2, THSD7A, and FAT1 mutations were associated with patient prognosis. Combination therapy involving tislelizumab plus nimotuzumab is a promising, low-toxicity treatment for recurrent or metastatic OSCC in patients with a PS score ≥ 2.

Feasibility and diagnostic performance of sentinel node biopsy for staging cN0 oral squamous cell carcinoma in a previously treated neck

AbstractObjectivesStaging of the cN0 neck with sentinel node biopsy (SNB) in early‐stage oral squamous cell carcinoma (OSCC) is validated in patients with a previously untreated neck. We aimed to investigate the feasibility and diagnostic accuracy of SNB and unexpected drainage patterns in patients with cT1‐T2N0 OSCC and a history of previous head and neck cancer comprising treatment of the neck, that is, surgery, radiotherapy, or both.MethodsFifty patients with a previously treated neck diagnosed with a new primary or recurrent cN0 OSCC between 2014 and 2021 were included and retrospectively analyzed. Feasibility was assessed by the rate of successfully performed SNB neck staging procedures. Based on follow‐up data, the diagnostic performance of SNB was evaluated by calculation of negative predictive value (NPV) and false omission rate (FOR).ResultsA SNB staging procedure was successfully performed in 76% (38/50) of the patients. Technical failures were due to the lack of drainage preoperatively or failure in intraoperative SN detection. In patients successfully staged with SNB, the rate of a positive SN was 13% (5/38). In the SNB‐negative group, no patients were diagnosed with a regional node recurrence during follow‐up, and the NPV and FOR were 100% and 0%, respectively. Unexpected lymphatic drainage occurred in 32% (12/38) of the patients.ConclusionSNB is technically feasible in cT1‐2N0 OSCC patients with a previously treated neck with a high diagnostic accuracy. Importantly, SNB enables the detection of individual and unexpected lymphatic drainage patterns.

SALIVARY IL-6 AND IL-8 AS POTENTIAL BIOMARKERS FOR ORAL SQUAMOUS CELL CARCINOMA

Introduction: Early identification of oral squamous cell carcinoma (OSCC) is a crucial factor influencing the disease's prognosis. The elevated levels of IL-6 and IL-8 in saliva are a result of their overproduction in the cancer microenvironment. The production of salivary cytokines, particularly IL-6 and IL-8, has a role in cancer development. These cytokines may also be used as biomarkers. The use of saliva as a biomarker is quite interesting because it is in direct contact with cancer cells, easy to access, non-invasive, and cost-effective. Aim: The aim of this literature review was to assess the potential of salivary IL-6 and IL-8 as biomarkers for OSCC early diagnosis. Review: The initiation of carcinogenesis in the oral cavity is actively repressed by inflammation and cell-mediated immunity. IL-6 and IL-8 are two important molecules involved in stromal-to-cancer cell communication. These cytokines play a major part in the growth, progression, metastasis, and recurrence of OSCC. Several studies have found that OSCC patients have higher levels of salivary IL-6 and IL-8 than healthy people and patients with an oral potentially malignant disorder (OPMD). Conclusion: Salivary IL-6 and IL-8 are very promising potential biomarkers for the early diagnosis of OSCC. Further research is still needed to validate and use these biomarkers clinically.

Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study

Background: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy. Methods: 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse. Results: Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse. Conclusions: Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment.

Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma.

The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors.

Role of Lymphovascular Invasion in Oral Cavity Squamous Cell Carcinoma Regional Metastasis and Prognosis.

The overall 5-year survival for oral squamous cell carcinoma (OSCC) has not changed in the last 20 years despite advances in treatment. Lymphovascular invasion (LVI) has been shown to be a negative prognostic factor in other cancers, however its role in the prognosis of OSCC remains unclear. This study aims to determine if LVI is a predictor of cervical lymph node metastasis and/or recurrence in OSCC. We conducted a retrospective cohort review of patients from our institutional cancer registry who were treated for OSCC between 2004 and 2018. Patient demographics, surgical pathology results, and clinical outcome data were collected. A multivariable logistic regression analysis was performed to determine if LVI was an independent predictor of cervical lymph node metastasis and/or recurrence. 442 patients were included, 32.8% were female and median age at time of diagnosis was 61.2 years. LVI was present in 32.8% of patients. When controlled for age, sex, t-classification, perineural invasion, depth of invasion (DOI), and margin status, LVI was a significant predictor of the presence of cervical node metastasis (OR: 3.42, CI: 2.17-5.39, P < .001). There was no significant association found between LVI and local recurrence (OR: 1.03, CI: 0.57-1.84, P = .92), regional recurrence (OR: 1.10, CI: 0.57-2.11, P = .78), or distant recurrence (OR: 1.59, CI: 0.87-2.94, P = .13). The results of this study suggest that LVI is a significant predictor of the presence of cervical lymph node metastasis at presentation independent of other known prognostic factors. LVI, however, was not found to be a significant independent predictor of locoregional or distant recurrence.Level of Evidence: Level III.

Multimodal Prediction of Cervical Lymph Node Metastasis and Recurrence in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignancy in the head/neck region, and cervical lymph node (CLN) metastasis is a strong poor-prognosis factor. In addition, many patients with OSCC experience recurrence despite multidisciplinary treatment. We sought to identify factors associated with CLN metastasis and recurrence in patients with OSCC. We evaluated a total of 45 patients and 233 target CLNs. The longest diameter of the target CLN, the shortest diameter of the target CLN (LS), the area of the target CLN, and the relative computed tomography (CT) values of the target CLNs calculated based on the CT values of the internal jugular vein (LCT) were obtained from preoperative CT images, and the maximum standardized uptake values of the primary tumor (pSUV) and target CLN (nSUV) were obtained from preoperative 18F-fluorodeoxyglucose-positron emission tomography/CT images. We performed immunohistochemical staining for cytokeratin 13 (CK13) and 17 (CK17) on neck dissection tissues. A discrimination equation was used that can predict CLN metastasis with a 92.2% discrimination rate using LS, LCT, pSUV, and nSUV. The CLNs were divided into discrimination and non-discrimination groups based on discriminant equations and CK13 and CK17 were used as the objective variables. A significantly higher recurrence rate was observed in the non-discrimination group (CK13: 5-year recurrence rate 28.6% vs. 64.3%, p<0.01; CK17: 5-year recurrence rate 28.0% vs. 76.0%, p<0.01). CLN metastases in OSCC can be assessed by combining preoperative imaging. The combined use of CK13 and CK17 expression with imaging findings offers an integrated approach to predict OSCC recurrence.

Impact of Salvage Surgery on Health-Related Quality of Life in Oral Squamous Cell Carcinoma: A Prospective Multi-Center Study.

Patients with recurrent oral squamous cell carcinoma (OSCC) have limited treatment options. Salvage surgery offers potential curative therapy. The need for extensive ablative surgery together with microvascular reconstruction implies invasive and painful treatment with questionable functional outcome. To address the impact of salvage surgery on the health-related quality of life (HRQoL) of patients suffering from recurrent OSCC, a multi-center prospective analysis was initiated. Patients with recurrent OSCC from 2015 to 2022 at two German cancer centers were included. Interdisciplinary tumor board decisions determined surgery as the only curative treatment modality. HRQoL, was assessed via a EORTC questionnaire (European Organization for Research and Treatment of Cancer-EORTC: QLQ-C30 and QLQ-H&N35) in dependence of the recurrent tumor stage. Patients completed the questionnaires once before surgery (baseline) and then every 3 months during follow-up or up to the end of treatment. In total, 55 patients were included. The mean follow-up period was 26.7 ± 19.3 months. Global health status showed superior mean scores after 12 months (60.83 ± 22.58) compared to baseline (53.33 ± 26.41) in stage 1 and 2 recurrent tumors. In advanced recurrent tumors' mean scores for global health showed only minor positive differences after 12 months (55.13 ± 22.7) compared to baseline (53.2 ± 25.58). In terms of the mouth pain, mean scores were lower after salvage surgery in small recurrent tumors after 12 months (20.37 ± 17.73) compared to baseline (41.67 ± 33.07; Wilcoxon two-sample signed-rank test p = 0.028). In advanced recurrent tumors, a significant reduction in mean scores was detected 3 months after salvage surgery (29.7 ± 22.94) compared to baseline (47.76 ± 25.77; Wilcoxon two-sample signed-rank test p = 0.003). Up to 12 months, swallowing function was evaluated inferior compared to baseline independent of tumor stage (Mean score recurrent stage I/II: 12-months 48.15 ± 27.57, baseline 28.7 ± 22.87; stage III/IV: 12-months 49.36.42 ± 27.53; baseline 30.13 ± 26.25). Improved HRQoL could be obtained in advanced recurrent OSCC after salvage surgery despite reduced swallowing function. In small recurrent tumors, overall, HRQoL was superior to baseline. Salvage surgery positively affected pain burden. For advanced recurrent tumors, important pain relieve could be observed as soon as 3 months after surgery.

Protocol for correlation of histological risk assessment/scoring system with a depth of invasion in oral squamous cell carcinoma

Introduction: The commonest type of cancer in the head and neck region is oral squamous cell carcinoma (OSCC) due to its high rates of occurrence and mortality. The early diagnosis of oral cancer gives better prognosis. Brandwein-Gensler criteria predict the early stage of OSCC cases with a high risk of locoregional recurrence. Objectives: To correlate Brandwein-Gensler criteria and depth of invasion of OSCC with three-year survival. Methodology:  In the study, hematoxylin-eosin (HE)-stained section slides will be used to evaluate Brandwein and Gensler criteria and depth of invasion in resected tissue specimens of OSCC cases. Expected results: The present study will find the correlation between Brandwein-Gensler criteria and depth of invasion in OSCC in order to evaluate the locoregional recurrence in OSCC cases. In high-risk OSCC cases, there may be increased depth of invasion in resected tissues.   Conclusions: We hypothesized that the correlation between Brandwein-Gensler criteria and depth of invasion can be used as an independent predictor for locoregional recurrence in OSCC.

Identification of a serum-based microRNA signature that detects recurrent oral squamous cell carcinoma before it is clinically evident

BackgroundSurvival rates for oral squamous cell carcinoma (OSCC) have remained poor for decades, a fact largely attributable to late-stage diagnoses and high recurrence rates. We report analysis of serum miRNA expression in samples from patients with high-risk oral lesions (HRL, including OSCC/carcinoma in situ lesions) and healthy non-cancer controls, with the aim of non-invasively detecting primary or recurrent disease before it is clinically evident.MethodsDiscovery, test, and validation sets were defined from a total of 468 serum samples (305 HRL and 163 control samples). Samples were analysed using multiple qRT-PCR platforms.ResultsA two-miRNA classifier comprised of miR-125b-5p and miR-342-3p was defined following discovery and test analyses. Analysis in an independent validation cohort reported sensitivity and specificity of ~74% for this classifier. Significantly, when this classifier was applied to serial serum samples taken from patients both before treatment and during post-treatment surveillance, it identified recurrence an average of 15 months prior to clinical presentation.ConclusionsThese results indicate this serum miRNA classifier is effective as a simple, non-invasive monitoring tool for earlier detection of recurrent disease when lesions are typically smaller and amenable to a wider array of treatment options to improve survival.

An Oral Microbial Biomarker for Early Detection of Recurrence of Oral Squamous Cell Carcinoma.

Changes in the oral microbiome are associated with oral squamous cell carcinoma (OSCC). Oral microbe-derived signatures have been utilized as markers of OSCC. However, the structure of the oral microbiome during OSCC recurrence and biomarkers for the prediction of OSCC recurrence remains unknown. To identify OSCC recurrence-associated microbial biomarkers for the prediction of OSCC recurrence, we performed 16S rRNA amplicon sequencing on 54 oral swab samples from OSCC patients. Differences in bacterial compositions were observed in patients with vs without recurrence. We found that Granulicatella, Peptostreptococcus, Campylobacter, Porphyromonas, Oribacterium, Actinomyces, Corynebacterium, Capnocytophaga, and Dialister were enriched in OSCC recurrence. Functional analysis of the oral microbiome showed altered functions associated with OSCC recurrence compared with nonrecurrence. A random forest prediction model was constructed with five microbial signatures including Leptotrichia trevisanii, Capnocytophaga sputigena, Capnocytophaga, Cardiobacterium, and Olsenella to discriminate OSCC recurrence from original OSCC (accuracy = 0.963). Moreover, we validated the prediction model in another independent cohort (46 OSCC patients), achieving an accuracy of 0.761. We compared the accuracy of the prediction of OSCC recurrence between the five microbial signatures and two clinicopathological parameters, including resection margin and lymph node counts. The results predicted by the model with five microbial signatures showed a higher accuracy than those based on the clinical outcomes from the two clinicopathological parameters. This study demonstrated the validity of using recurrence-related microbial biomarkers, a noninvasive and effective method for the prediction of OSCC recurrence. Our findings may contribute to the prognosis and treatment of OSCC recurrence.

The ability of the eighth edition of the TNM staging system plus minor invasion criteria to predict the biological behaviour of oral cavity carcinomas.

Oral squamous cell carcinoma (OSCC) treatment is based largely on the TNM stage. The eighth edition includes important new prognostic parameters (extranodal extension and depth of invasion), while it does not consider tumour molecular characteristics or minor invasion criteria (perineural and lymphovascular invasion, grading and resection margins). This study evaluated how well the TNM eighth edition predicts the biological behaviour of OSCC, considering survival and risk of locoregional recurrence. Data from 217 patients treated for OSCC were analysed, including epidemiologic characteristics, histological features and treatment. No significant correlations with overall survival or tumour recurrence were found for pT stages and the type of treatment, while different pN stages had significant differences in recurrence, but not in overall survival. We found significant correlations between overall survival and tumour grade and lymphovascular and perineural invasion and a significant correlation between tumour resection margins and the risk of recurrence. The current TNM staging system is a necessary but not sufficient tool for predicting the overall survival and risk of recurrence of OSCC. It could be improved by considering other factors, such as minor invasion criteria and biological markers.

Sentinel lymph node biopsy in recurrent or secondary oral squamous cell carcinoma after previous neck dissection

ObjectivesThe aim of this retrospective study was to evaluate the potential of sentinel lymph node biopsy (SLNB) in patients with recurrent or a secondary oral squamous cell carcinoma (OSCC) without clinical signs of lymph node metastases (cN0), who were previously treated with a surgical approach. Patients and MethodsRetrospective analysis of all patients with cN0 recurrent or secondary OSCC, who were treated using SLNB after previous neck dissection. Endpoints were sentinel lymph node (SLN) detection rate, negative predictive value (NPV) and sensitivity. ResultsA total of 17 patients with a mean age of 68.6 years were included. SLN were detected in 15 of 17 cases (detection rate: 88.2%). In seven patients (41.2%), a bilateral or contralateral lymph drainage of a unilateral carcinoma was found. Two patients (11.8%) demonstrated a positive SLN upon pathohistological analysis, which led to an upstaging. In one case, a non-SLN was positive, which is considered a false-negative result. The mean follow-up for all patients with histologically negative SLN including the patients without a detected SLN was 11.8 months (range: 0-31 months). Of these, one patient developed (isolated) neck recurrence after 12 months resulting in an overall NPV of 86.7% and a sensitivity of 50.0% for the SLNB as a neck staging procedure. ConclusionSLNB can improve the staging of patients with recurrent or secondary OSCC, who present with a history of a previous neck dissection. Further studies are required to demonstrate the oncological benefit of SLNB in this patient cohort.

Salvage Mandibulectomy in an Octogenarian with Recurrent Oral Cavity Squamous Cell Carcinoma: A Case Report

Salvage Mandibulectomy in an Octogenarian with Recurrent Oral Cavity Squamous Cell Carcinoma: A Case Report

Increased levels of PD1 and glycolysis in CD4+ T cells are positively associated with lymph node metastasis in OSCC

BackgroundCervical lymph node metastasis is one of the poorest prognostic factors in oral squamous cell carcinoma (OSCC). Activated immune cells generally have metabolic abnormalities in the tumour microenvironment. However, it is unknown whether abnormal glycolysis in T cells could facilitate metastatic lymph nodes in OSCC patients. The aim of this study was to investigate the effects of immune checkpoints in metastatic lymph nodes and determine the correlation between glycolysis and immune checkpoint expression in CD4+ T cells.MethodsFlow cytometry and immunofluorescence staining were used to analyse the differences in CD4+ PD1+ T cells between metastatic lymph nodes (LN+) and negative lymph nodes (LN−). RT‒PCR was performed to detail the expression of immune checkpoints and glycolysis-related enzymes in LN+ and LN−.ResultsThe frequency of CD4+ T cells decreased in LN+ patients (p = 0.0019). The PD1 expression of LN+ increased markedly compared to that of LN− (p = 0.0205). Similarly, the PD1 of CD4+ T cells in LN+ increased significantly compared to that of LN−. Additionally, glycolysis-related enzyme levels in CD4+ T cells from LN+ patients were dramatically higher than those in LN− patients. PD1 and Hk2 expression in CD4+ T cells was also increased in LN+ OSCC patients with prior surgical treatment compared to those without.ConclusionsThese findings suggest that lymph node metastasis and recurrence in OSCC are associated with increases in PD1 and glycolysis in CD4+ T cells; this response may serve as a potential regulator of OSCC progression.

Prognostic impact of the loss of E-cadherin and de novo expression of N-cadherin at the invasive front of primary and recurrent oral squamous cell carcinoma.

The epithelial-mesenchymal transition (EMT) is a biological mechanism in multiple pathophysiological diseases. Related alterations in cadherin expression play a crucial role in carcinogenesis, progression, angiogenesis, and immune response. EMT cells exhibit a transition from an epithelial to a mesenchymal phenotype (cadherin-switch). This process is characterized by the de novo development of N-cadherin (N-CAD), which replaces E-cadherin (E-CAD) and signifies an increased migratory capacity and malignant transformation. The cadherin switch is a hallmark of EMT and has been studied in various cancer entities. We predicted that the cadherin switch in the primary and recurrent oral squamous cell carcinoma (re-OSCC) tissues is an inherent characteristic of the tumor, affects the biologic behavior, and further reflects the post-recurrence survival outcome of these patients. Survival outcome was analyzed by calculating the post-recurrence survival of the high-risk group and correlating the standardized h-score-based IHC expression of both cadherin types with the clinical follow-up. 94 patients with re-OSCC were observed within the cohort. Tissue samples from both primary and recurring tumors were collected. There was a significant association between loss of E-CAD expression and both oral cancer-specific and overall survival, (HR=2.72, CI:1.50-4.95, p=0.001) and (HR=3.84, CI:1.93-7.63, p=0.001), respectively, for expression loss higher than 60%. There was no statistically significant correlation between N-CAD de novo expression and Overall, oral cancer-specific and disease-free post-recurrence survival. The current study clearly shows that cadherin-switch, identified as E-CAD loss and N-CAD de novo expression in the invasion front of a re-OSCC, appears to be an inherent histological hallmark that does not change from primary manifestation to recurrence within the same tumor, regardless of the form of adjuvant therapy used for the primary tumor. The loss of E-CAD expression in re-OSCC is an independent risk factor for poor survival, and may be used to stratify therapy and de/escalate the multimodal treatment.