Recurrent Oral Squamous Cell Carcinoma Research Articles

The effect of m6A methyltransferase METTL3 mediated TMEM30A regulation on tumor energy metabolism and cisplatin anti-tumor activity in oral squamous cell carcinoma

AimsCisplatin (CDDP) is still one of the most commonly used first-line treatments for advanced and recurrent oral squamous cell carcinoma (OSCC) patients in clinical practice. However, the decrease in tumor sensitivity to CDDP weakens its therapeutic effect. There is still limited research on the effect of METTL3-mediated methylation of m6A on CDDP sensitivity in OSCC. TMEM30A widely exists in biomembranes and regulates the lipid asymmetry of the membrane, but there is no report on its function in OSCC. This study aims to explore the specific mechanism by which METTL3 regulates m6A methylation of TMEM30A and affects the occurrence and development of OSCC, and further investigate the effects of METTL3 and TMEM30A on the anti-tumor activity of CDDP. Key findingsIn OSCC, METTL3 plays a pro-cancer role and weakens the anti-tumor efficacy of CDDP; METTL3 positively regulates the expression of TMEM30A by m6A methylation modification and binding to TMEM30A; The abnormally high expression of TMEM30A in OSCC not only weakens CDDP sensitivity, but also enhances the malignant evolution of cancer cells, regulates the metabolic balance of ATP and lactate in cells, and is a potential oncogenic gene. SignificanceTMEM30A promotes malignant progression of tumors through METTL3 mediated m6A methylation modification, participates in maintaining the balance of tumor ATP and lactate metabolism, and reduces the anti-tumor activity of CDDP. TMEM30A is a potential gene target for CDDP anti-tumor activity in OSCC.

Role of Imaging and Histopathology for Predicting Neck Node Involvement in Recurrent/Second Primary Squamous Cell Carcinoma (pN-ROC Study).

After improvement in the treatment of oral cancers over the years we now see more patients with recurrent oral squamous cell carcinoma (OSCC) and second primary. Recommendations for addressing the neck (ipsilateral and/or contralateral) in these patients are still unclear and debatable. In this retrospective study we included patients with recurrent and second primary OSCC who underwent surgery between January 2016 and December 2021. We analysed to identify factors and better imaging modality that help predict a pathologically N + neck in these patients. In our cohort of 219 patients treated for recurrent/second primary OSCC, 131 patients underwent a neck dissection along with surgery for primary, out of which 59 patients had pN + neck. Factors that predicted ipsilateral pN + status were the clinical stage (advanced) p = 0.009, 2.724(1.291-5.750), subsite (Tongue + floor of mouth) p = 0.01, 3.105(1.305-7.386), previous treatment received (surgery alone) p = 0.0472.148(1.011-4.562) and histopathology [poorly differentiated squamous cell carcinoma (PDSCC)] p = 0.014, 3.070(1.253-7.519). PET-CECT had the best agreement (p < 0.001, kappa = 0.742) to predict nodal metastasis. There were no factors that could predict contralateral nodal metastasis. Patients with advanced clinical stage, Tongue + floor of mouth subsite, only surgery done previously, and histopathology (PDSCC) had a higher incidence of ipsilateral nodal metastasis in our cohort. The online version contains supplementary material available at 10.1007/s12663-024-02272-8.

Recurrence of oral squamous cell carcinoma in surgically treated patients at Khartoum Teaching Dental Hospital retrospective cross-sectional study

BackgroundIn terms of survival rate, recurrent oral squamous cell carcinoma (OSCC) after primary surgery is considered as a poor prognostic indicator.ObjectiveThis study aims to determine the incidence of OSCC recurrence among patients treated at Khartoum Teaching Dental Hospital (KTDH) and possible risk factors associated with it.MethodsRecords of 303 patients with a history of radical surgery were retrieved from the hospital’s archives, and the histopathological records were retrieved from the archival specimens of Professor Ahmed Suleiman Oral Pathology Laboratory, Faculty of Dentistry, and University of Khartoum.ResultsAdvanced stages of OSCC (III, IV) were associated with higher recurrence rates, and the poorly differentiated OSCC was the commonest recurrent type.ConclusionThe condition of the surgical margin is a significant predictor of OSCC recurrence and tumor stage. The tumor site, the type of surgical resection, and the tumor differentiation were also identified as significant factors influencing the recurrence of OSCC.

Circ_0004771 regulates malignant biological behaviors and has clinical significance in oral squamous cell carcinoma.

The incidence of oral squamous cell carcinoma (OSCC) is increasing, and more effective treatment protocols must rapidly be developed to prevent the death of patients and ensure favorable outcomes. CircRNAs are a unique class of noncoding ribonucleic acid (RNA) molecules unaffected by RNA exonucleases. CircRNAs have more stable expression than linear RNAs and are not readily degraded; therefore, they are the newest focus of RNA research. Here, we analyze the mechanism of hsa_circ_0004771 (circ_0004771) in OSCC to provide a clinical reference. Circ_0004771 expression was measured in peripheral blood, cancerous tissues and adjacent tissues of OSCC patients. Patients were followed up for 3 years. The diagnostic value of circ_0004771 for OSCC occurrence, prognosis, recurrence and survival was analyzed with receiver operating characteristic (ROC) curves. OSCC cells were lentivirally transduced with a circ_0004771-silencing or an empty vector to evaluate alterations in cell growth, invasion, and apoptosis. Apoptosis-related and epithelial-mesenchymal transition (EMT)-related protein expression was quantified. BALB/c nude mice were used for tumorigenesis experiments to evaluate tumor growth in vivo after silencing circ_0004771. Circ_0004771 expression was higher in peripheral blood and cancerous tissue of OSCC patients than in control peripheral blood and paracancerous tissue, respectively, exhibiting excellent predictive value for OSCC occurrence, prognosis, recurrence and survival. Silencing circ_0004771 decreased the growth, invasiveness, and EMT capacity and increased the apoptosis of OCC cells. In mice implanted with OSCC cells transduced with the circ_0004771-silencing lentiviral vector, the tumor growth capacity was obviously decreased. Silencing circ_0004771 inhibits the malignant growth of OSCC.

First‑line programmed cell death 1 inhibitor plus chemotherapy vs. standard treatment in patients with recurrent or metastatic oral squamous cell carcinoma: A retrospective cohort study.

Programmed cell death 1 (PD-1) inhibitor revives the killing effect of immune cells to prevent tumor progression. The present study aimed to evaluate the efficacy and safety of first-line PD-1 inhibitor + chemotherapy vs. standard treatment in recurrent or metastatic (R/M) oral squamous cell carcinoma (OSCC). A total of 51 patients with R/M OSCC were reviewed and divided into the PD-1 inhibitor + chemotherapy (n=21) and standard treatment (n=30) groups based on their actual treatments. The results of the present study demonstrated that the objective response rate (52.4 vs. 36.7%, P=0.265) and disease control rate (81.0 vs. 70.0%, P=0.377) were numerically elevated in the PD-1 inhibitor + chemotherapy group compared with those in the standard treatment group; however, the results did not reach statistical significance. The progression-free survival (PFS) was numerically increased (without statistical significance) in the PD-1 inhibitor + chemotherapy group compared with that of the standard treatment group (P=0.057). Specifically, the PD-1 inhibitor + chemotherapy group and the standard treatment group exhibited a median [95% confidence interval (CI)] PFS duration of 6.7 (1.6-11.8) and 5.2 (3.4-7.0) months, respectively. In addition, the PD-1 inhibitor + chemotherapy group demonstrated increased overall survival (OS) compared with that of the standard treatment group (P=0.032). Specifically, the PD-1 inhibitor + chemotherapy group and the standard treatment group exhibited a median (95% CI) OS duration of 18.3 (11.9-24.7) and 10.3 (7.9-12.7) months, respectively. Furthermore, multivariate Cox regression analysis indicated that PD-1 inhibitor + chemotherapy was independently associated with improved PFS [hazard ratio (HR)=0.308, P=0.002] and OS (HR=0.252, P=0.003). In addition, the incidence of grade 3-5 adverse events (AEs) was relatively low in both groups and the incidence of any grade of each AE was not significantly different between groups (all P>0.050). In conclusion, the first-line PD-1 inhibitor + chemotherapy group had improved efficacy and comparable safety compared with those of the standard treatment in patients with R/M OSCC.

Beyond margins: TIME-infused insights into recurrence in surgically treated oral squamous cell carcinoma (OSCC).

e18036 Background: Surgical margins are considered negative if the tumor is 3-5mm away from margins. At times patients with clear margins report back with a recurrence. There are factors beyond the margins that needs to be analyzed. The tumor immune microenvironment (TIME) plays a critical role in cancer development, progression, &amp; control. Aim: To assess the TIME at different surgical margins and derive scoring criteria for the prognostication of recurrence in OSCC. Objective: 1) Derive a TIME score that prognosticates the recurrence-free survival (RFS) and overall survival (OS) of the patients 2) Determine the most significant margin at which TIME score can be estimated. Methods: A retrospective cohort study between 2016 to 2023. Slides of the OSCC patients who had local recurrence were evaluated for TIME parameters: a) Tumor infiltrating lymphocytes (TILS)-(CD3, CD4, CD8, FOXP3, CD57) b) Tumor associated macrophages (TAMS)-(CD68, CD163) c) Programmed death Ligand(PDL-1) d) P53 and d) Desmoplasia at - Interphase, 1mm, 3mm, 5mm, &amp; periphery of the surgical specimen. 30 patients were included. Logistic Regression Equation (LRE) was derived for all the variables of TIME at 5 different margins. Significant margin and average RFS &amp; OS obtained. TIME score was derived. A standard equation for RFS &amp; OS was obtained using the TIME score. Results: Total = 30 patients. 19 were 40-60 years. Tongue was common site(36.66%). The predicted RFS = 23+/- 7 Months (M). OS = 47+/-8M. Regression model with the highest accuracy was found at 3mm margins (83.33%) for all the variables. LRE were fitted for all the variables to find the RFS &amp; OS. LRE for RFS for each parameter at 3mm: TILS:12.4211-0.0190*CD3-0.1222*CD4-0.0979*CD8-0.0744*FXOP3-0.1809*CD57 TAMS: -0.6635+0.0768*CD68 +0.0241*CD163 PDL1: -0.4055+0.5878*PDL1+TC +2.1972*PDL1+2.1972*PDL1 DESMOPLASIA: 0.4055+0.4418* DESMOPLASIA GRADE P53: 0.4700+0.4055*P53 LRE for OS for each parameter at 3mm: TILS:0.5784+0.0262*CD3-0.0233*CD4-0.0132*CD8-0.0233*FXOP3-0.0036*CD57 TAMS: -2.8158+0.1307*CD68 + 0.0451*CD163 PDL-1: -1.3860+1.9460*PDL1 + 1.0990*PDL1 + 0.4700*PDL1 DESMOPLASIA: -0.4055* DESMOPLASIA P53: -0.8109+0.9287*P53 Value (V) From the above equations substituted in : Probability=1/1+exp(-V)), &gt;0.5 the score is 0 : RFS (&lt; 23+/-7 M), OS (&lt;47+/-8 M) &lt;0.5 the score is 1 : RFS (&gt;23+/-7 M), OS (&gt;47+/-8 M) Summing the score from each equation= TIME score (Max. score =5) RFS = 15.621+3.030*TIME score (p Value significant) OS = 11.481+10.699*TIME score(p Value significant) Conclusions: The TIME score can be the real-time estimator of the recurrence in surgically treated OSCC. 3mm margins have best accuracy in evaluating the RFS and OS. Average RFS &amp; OS are 23+/-6 &amp; 47+/-8 M respectively.

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

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. To correlate Brandwein-Gensler criteria and depth of invasion of OSCC with three-year survival. In the study, This study will include 80 random histopathologically-diagnosed cases of OSCC. hematoxylin-eosin (HE)-stained section slides will be used to evaluate, Brandwein and Gensler criteria by three histopathologists in a blinded manner. The depth of invasion assessment will be done from the basement-membrane (BM), in regions where the BM has been lost, as well as from an illustrative line connecting the BM from the neighbouring epithelium to the point of deepest tumour invasion in the connective-tissue stroma with the help of a research microscope (Leica-DMLB2) in resected tissue specimens of OSCC cases. 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 an increased depth of invasion in resected tissues. 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.

Radiation-induced exosomes promote oral squamous cell carcinoma progression via enhancing SLC1A5-glutamine metabolism.

Radiotherapy (RT) can drive cancer cells to enter a state of cellular senescence in which cells can secrete senescence-associated secretory phenotype (SASP) and produce small extracellular vesicles (sEVs) to interact with cells in the tumor microenvironment (TME). Tumor-derived sEVs that are taken up by recipient cells contribute to cancer cell metabolic plasticity, resistance to anticancer therapy, and adaptation to the TME. However, how radiation-induced sEVs support oral squamous cell carcinoma (OSCC) progression remains unclear. Beta-galactosidase staining and SASP mRNA expression analysis were used to evaluate the senescence-associated activity of OSCC cells after irradiation. Nanoparticle tracking analysis was performed to identify radiation-induced sEVs. Liquid chromatography-tandem mass spectrometry (LC-MS) was used to explore changes in the levels of proteins in radiation-induced sEVs. Cell Counting Kit-8 and colony formation assays were performed to investigate the function of radiation-induced SASP and sEVs in vitro. A xenograft tumor model was established to investigate the functions of radiation-induced sEVs and V-9302 in vivo as well as the underlying mechanisms. Bioinformatics analysis was performed to determine the relationship between glutamine metabolism and OSCC recurrence. We determined that the radiation-induced SASP triggered OSCC cell proliferation. Additionally, radiation-induced sEVs exacerbated OSCC cell malignancy. LC-MS/MS and bioinformatics analyses revealed that SLC1A5, which is a cellular receptor that participates in glutamine uptake, was significantly enriched in radiation-induced sEVs. In vitro and in vivo, inhibiting SLC1A5 could block the oncogenic effects of radiation-induced sEVs in OSCC. Radiation-induced sEVs might promote the proliferation of unirradiated cancer cells by enhancing glutamine metabolism; this might be a novel molecular mechanism underlying radiation resistance in OSCC patients.

Correlation of Prognostic Nutritional Index and Systemic Immune-Inflammation Index with the Recurrence and Prognosis in Oral Squamous Cell Carcinoma with the Stage of III/IV.

This study aimed to explore the correlation of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) with the recurrence and prognosis in patients with advanced oral squamous cell carcinoma (OSCC). A total of 298 OSCC patients with the stage of III/IV were finally included in the study. SII = neutrophil count (109/L) × platelet count (109/L)/lymphocyte count (109/L). PNI = serum albumin (g/L) + 5 × total lymphocyte count (109/L). High preoperative SII and low preoperative PNI were independent risk factors for tumor recurrence in OSCC patients of the stage of III/IV. The area under the curves (AUC) for SII was 0.69 (0.63 to 0.76), for PNI was 0.72 (0.67 to 0.78), and for joint model was 0.81 (0.76 to 0.85). Patients with low level of joint model had significantly higher overall survival rate for 5 years follow-up than those with high level. Both preoperative SII and PNI are valuable independent tumor recurrence prediction index in patients with advanced OSCC. Meanwhile, the combination of preoperative SII and PNI is also valuable on OSCC recurrence and prognosis prediction.

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

This study aimed to determine the oncologic outcomes and identify prognostic factors in patients undergoing salvage glossectomy for recurrent oral tongue squamous cell carcinoma (OTSCC). A retrospective chart review was conducted encompassing all patients who underwent salvage oral glossectomy out of 259 individuals undergoing oral glossectomy at a tertiary academic center. Inclusion criteria comprised patients who met the following conditions: 1) biopsy-proven oral tongue recurrence, 2) salvage glossectomy performed with curative intent, 3) availability of imaging records, and 4) comprehensive documentation. Cases involving base of tongue tumors and second primaries were excluded from the analysis. Categorical data were expressed as proportions, and continuous data as medians/quartiles. Univariate analysis used Fisher's exact test for categorical variables and Student's t-test for continuous ones. Survival analysis employed Kaplan-Meier estimates and the log-rank test. High-risk histopathological risk factors were significantly more common with recurrence compared to initial presentation. The mean locoregional disease-free interval was 35 months.Kaplan-Meier estimates for one- and three-year disease-free survival (DFS) were 62.7% and 33.4%, while disease-specific survival (DSS) rates were 73% and 38.9%, respectively.Recurrent T-stage was a predictor for DFS, while margin status was a strong predictor for both LR control (p = 0.024) and DSS (p = 0.030), as was perineural invasion (p = 0.001 and p = 0.030). Alcohol use was associated with worse overall survival (p = 0.024).In contrast to other reports, nodal status was not a predictor in this series. Upon recurrence, histopathological analysis unveils detrimental changes in tumor biology, which significantly influence disease control. Notably, consistent with findings from other studies, factors, such as recurrent T-stage, presence of perineural invasion, and, most importantly, margin status, play pivotal roles in determining oncologic outcomes. Consequently, the imperative for aggressive salvage surgery becomes evident in achieving sufficient disease control. This underscores the necessity for proactive management strategies aimed at addressing these factors to enhance patient outcomes.

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.

Risk Factors of Oral Squamous Cell Carcinoma with Special Emphasis on Areca Nut Usage and Its Association with Clinicopathological Parameters and Recurrence.

Oral squamous cell carcinoma (OSCC) is the most prevalent type of head and neck cancer and is associated with high mortality, particularly in Southeast Asian countries. Areca nut usage, smoking, and alcohol consumption are the most common risk factors for OSCC. Areca nut chewing is highly prevalent in Pakistan and has been attributed to an increase in OSCC cases. This study aimed to determine the association between areca nut usage and various clinicopathological features of OSCC and further evaluate the association of clinicopathological parameters of OSCC with tumor recurrence. The study was conducted using the data of 228 patients with OSCC resected at Liaquat National Hospital, Karachi, Pakistan, over 5 years between 2018 and 2022. Clinicopathological data were collected from hospital archives, and associations between various risk factors and clinicopathological parameters were determined. Males were more commonly affected (77.2%), and the most common age group was <50 years (54.4%). Areca nut usage was reported in 59.6% of cases, and the buccal mucosa was the most common site (62.7%). Areca nut usage was significantly associated with male gender, greater tumor size, greater depth of invasion (DOI), higher tumor stage, nodal stage, presence of perineural invasion (PNI), and recurrence. In addition, multivariate analysis revealed that OSCC recurrence was significantly associated with older age, larger tumor size and DOI, nodal metastasis, and areca nut usage. Areca nut-related OSCCs were associated with poor prognosis and recurrence in our study population. Furthermore, OSCC recurrence was associated with various clinicopathological parameters, such as larger tumor size, a higher DOI, and nodal metastasis.

Incidence of Contralateral Neck Nodal Metastasis in Recurrent Oral Cavity Squamous Cell Carcinoma

Aim: The aim of the study was to evaluate the incidence of contralateral neck nodal metastasis in recurrent oral cavity squamous cell carcinoma (OCSCC) with ipsilateral neck addressed during previous surgery. Methodology: A retrospective analysis of prospectively collected data of 2870 patients treated at Kailash Cancer Hospital and Research Center, Goraj, from January 2018 to December 2022 was done. Ninety patients with ipsilateral local recurrences with lesions not crossing or reaching midline were evaluated for contralateral neck nodal metastasis. All patients had undergone ipsilateral neck dissection during the previous surgery. Results: Contralateral nodal metastasis was found in 16 patients (17.77%), of which 13 patients (14.44%) had extranodal extension (ENE) and 7 patients (7.77%) had occult metastasis. In 35 patients, ipsilateral completion neck dissection was performed, of which 5 patients (14.28%) were node positive with ENE and 8.33% had bilateral node positivity with ENE. The factors influencing contralateral nodal metastasis after surgery for recurrence were the depth of invasion and ipsilateral neck nodal positivity and factors influencing contralateral node positivity from the previous surgery were nodal status and margins. Conclusion: In patients with local recurrence of oral cavity squamous cell carcinoma, with ipsilateral neck addressed previously, the lymphatic patterns alter. Hence, the predictable echelons are modified and no longer reliable. Hence, along with the excision of the primary lesion, completion of the ipsilateral neck and addressing the contralateral neck becomes mandatory, even if the patient is clinically node negative.

Exploring the Role of Circulating Tumor Cells in Contralateral Neck Metastasis

Background: The management of neck nodes in oral cavity cancers discernibly depends on the approach adopted for the primary tumor. There are abundant literature and consensus guidelines established for ipsilateral neck metastasis in small lateralized oral cavity cancers. However, the literature on the mechanism of contralateral neck metastasis and their management in recurrent settings is sparse. The current analysis aims at elucidating the role of circulating tumor cells (CTCs) in contralateral neck metastasis and the incidence of the same. Materials and Methods: We performed a retrospective cohort study to include all the patients with recurrent ipsilateral oral cavity squamous cell carcinoma who underwent treatment between January 2016 and October 2021. Various parameters were analyzed, and the data were curated to arrive at a conclusion. Results: The analysis of several parameters, including demographics of the patient, tumor site, individual tumor, lymph node, metastasis (TNM) category, depth of invasion (DOI), extra-nodal extension (ENE) status, CTCs, adjuvant treatment received after first surgery followed by TNM category, DOI, worst pattern of invasion, ENE, type of neck dissection, histological grading of tumor, perineural invasion, lymphovascular invasion, nodal yield, and number of nodes positive in the contralateral neck were studied in detail. Conclusion: The study showed a significant correlation between contralateral neck metastasis and CTCs.

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.