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Background: Oral cavity cancer (OCC) represents a significant public health burden in South Asia, ranking as the most prevalent cancer affecting males in Pakistan and contributing considerably to morbidity and mortality. The objective of this study was to evaluate the survival rates in patients diagnosed with OCC in the Pakistani population and identify the factors influencing survival., Methods: This was a retrospective cohort study conducted at the Aga Khan University Hospital Karachi, Pakistan. A total of 2238 cases diagnosed with OCC from May 2011 through December 2020, who met the inclusion criteria, were included. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Adjusted hazard ratios (HR) and their 95% confidence intervals (CIs) were estimated using a Cox regression model to identify the factors significantly influencing survival., Results: Among all cases, 54.0% were diagnosed in individuals 50 years of age and below and 73.0% were tobacco users. Overall survival, 1-year, 3-year, and 5-year survival rates were 54.9%, 88.9%, 81.6%, and 75.9% respectively. After adjustment for all the significant confounding and prognostic factors, age was an important factor showing that adults > 50 years had poorer survival compared to ≤ 50 years (HR = 1.43, 95% CI = 1.11-1.83). Poorly differentiated grade of OCC compared to well-differentiated grade (HR = 2.49, 95% CI = 1.61-3.84) and stage IV compared to earlier stages (HR = 3.56, 95% CI = 2.13-5.94) were also associated with poor survival., Conclusion: Notably, there was a high occurrence of late stage (III and IV) OCC in individuals aged ≤ 50 years, with the buccal mucosa being the most common site involved. Moreover, a large proportion of our patients had a history of tobacco use. Patients with advanced-stage disease and poorly differentiated grade showed poor survival. Therefore, public awareness about tobacco control for OCC prevention and earlier diagnosis of OCC is urgently needed in our Pakistani population., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for this study was obtained from the Ethical Review Committee (ERC) of The Aga Khan University, Karachi, Pakistan (ERC AKU ID #8381). Since this study was based on data retrospectively obtained from the cancer registry, informed consent was not required as all the data were anonymized. Hence, the Ethical Review Committee (ERC) of the Aga Khan University waived the requirement for informed consent for this study. Consent for publication: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To evaluate the efficacy of sentinel lymph node biopsy (SLNB) in cT1/2N0 minor salivary gland cancer (mSGC) located within the oral cavity., Methods: A retrospective analysis was conducted on patients diagnosed with cT1/2N0 oral mSGC, who were categorized into two groups based on neck management approaches. The impact of SLNB versus observation on regional control and overall survival was assessed using a Cox model., Results: A total of 177 patients were included in the study, with 53 cases undergoing SLNB. All patients had at least one sentinel lymph node, with the majority having two sentinel lymph nodes. The sentinel lymph nodes were predominantly situated in level I, followed by level II. Four patients had positive sentinel lymph nodes, all of whom had primary tumors in the tongue or the floor of the mouth, and were classified as cT2 stage. This yielded a sensitivity and specificity of 100%, a false negative rate of 0%, and a negative predictive value of 100% for SLNB in predicting occult metastasis. In terms of regional control, SLNB exhibited a reduced hazard ratio of 0.90 (95% confidence interval: 0.64-0.96) compared to observation. However, SLNB did not confer a superior overall survival benefit compared to observation., Conclusion: In patients with cT1/2N0 oral mSGC, SLNB proved to be both technically feasible and oncologically safe. When contrasted with observation, SLNB was associated with enhanced regional control, particularly recommending its use for cases of cT2 mSGC arising from the tongue or the floor of the mouth., (© 2024. The Author(s).)

Background: The predictive implications of the pretreatment systemic immune-inflammation index (SII) and lymphocyte-to-monocyte ratio (LMR) in oral cavity cancer have been investigated extensively, however, the findings are conflicting., Methods: To assess the predictive importance of SII and LMR in patients with oral cavity cancer, a comprehensive Meta-analysis of the literature was conducted using the databases from PubMed, Embase, and the Cochrane Library. To determine the link between SII and LMR and overall survival (OS) and disease-free survival (DFS), hazard ratio (HR) and 95% confidence interval (CI) were retrieved., Results: The analysis comprised a total of 18 papers, covering 19 trials (SII = 5, LMR = 12, SII + prognostic nutritional index (PNI) = 2). According to pooled data, increased SII predicted poor OS (HR: 1.61, 95% CI: 1.38-1.87, P < .001) and DFS (HR: 1.90, 95% CI: 1.11-3.27, P = .02) while high LMR was linked with improved OS (HR: 0.64, 95% CI: 0.54-0.77, P < .001) and DFS (HR: 0.69, 95% CI: 0.61-0.79, P < .001). In addition, subgroup analysis indicated that high SII and low LMR negatively correlated with OS regardless of country, cutoff value, sample size, or types of Cox regression analysis., Conclusions: High SII and low LMR may predict worse survival in patients with oral cavity cancer. SII and LMR may therefore represent effective indicators of prognosis in oral cavity cancer., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are commonly used prognostic indicators for a variety of cancers. However, their utility in oral cancers is unknown. We systematically examined evidence on the ability of SII and SIRI to predict overall survival (OS) and disease-free survival (DFS) after oral cancers., Material and Methods: Embase, PubMed, Web of Science, and Scopus were searched for oral cancer studies reporting OS or DFS based on SII or SIRI. Articles published up to 25th May 2024 were included., Results: 17 studies were eligible (14 on SII and 3 on SIRI). Pretreatment high SII scores were found to be significantly linked with poor OS (HR: 1.62 95% 1.26, 2.08 I2=88%) and DFS (HR: 1.62 95% 1.25, 2.27 I2=86%) after oral cancer. Similarly, high SIRI was associated with worse OS in oral cancer patients (HR: 1.60 95% 1.31, 1.94 I2=0%). All results were unchanged on sensitivity analysis. Subgroup analysis based on location, cancer type, sample size, treatment, cut-off, methods of determining cut-off, analysis method, and study quality showed mixed results., Conclusions: Acknowledging the limitations of current evidence, it seems that both SII and SIRI can predict the prognosis of oral cancers. High SII and SIRI are both associated with worse OS while high SII also predicts worse DFS.

This systematic review and meta-analysis investigated the impact of salvage surgery on 5-year overall survival (OS) and prognostic factors in recurrent oral cavity cancer (rOCC) patients. Relevant literature before May 2022 was reviewed, including retrospective cohort studies and observational studies comparing salvage surgery to other treatments. Risk-of-bias assessments were conducted using the Newcastle-Ottawa scale. Statistical and subgroup analyses assessed the impact of salvage surgery on 5-year OS and prognostic factors. 3036 documents were initially retrieved, with 14 retrospective cohort studies (2069 participants) included. Meta-analysis of 5-year OS in salvage surgery patients yielded a rate of 43.0%. Subgroup analysis showed higher OS in Asians (49.9% vs. 36.9%, p = 0.003) and late-relapse (63.8% vs. 30.0%, p = 0.004) groups. Prognostic factors revealed hazards associated with nodal recurrence, extranodal extension, and perineural invasion. Salvage surgery is a viable option for rOCC patients, showing favorable 5-year OS outcomes. Low publication bias enhances study reliability, but its single-arm design limits conclusions on salvage surgery superiority over other treatments., (© 2024 Wiley Periodicals LLC.)

Background: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE., Methods: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted., Results: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 - 7000 cGy, n = 1155 versus 6000 - 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578)., Conclusions: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600-7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients., (© 2024. The Author(s).)

Objectives: Numerous studies have investigated the predictive significance of the platelet-to-lymphocyte ratio (PLR) in oral squamous cell carcinoma(OSCC). However, the results of studies on its prognostic value remain controversial. This study aims to evaluate the prognostic significance of the PLR in patients with OSCC., Materials and Methods: We conducted a comprehensive search of PubMed, Embase, the Cochrane Library, and Web of Science databases for all studies investigating the association between PLR and prognosis in OSCC, from the inception of each database up to November 2023. The outcome measures included overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). To identify potential sources of heterogeneity, sensitivity and subgroup analyses were performed, alongside an assessment of publication bias. The analyses in this study were conducted using RevMan and Stata software., Results: According to the inclusion criteria, 20 articles were included, including 5,714 patients.The meta-analysis revealed that an elevated PLR adversely affects OS (HR = 1.58; 95% CI: 1.29-1.94; p < 0.0001), DFS (HR = 1.71; 95% CI: 1.20-2.42; p < 0.003), and DSS (HR = 2.41; 95% CI: 1.79-3.25; p < 0.00001). The results of the subgroup analysis showed that a preoperative high PLR was associated with reduced OS when the PLR threshold was ≤ 150 (HR = 1.49, P = 0.0003).When the PLR threshold was > 150, Preoperative PLR was not significantly associated with the prediction of overall survival (OS) in OSCC. (P > 0.05)., Conclusion: The prognostic significance of PLR in patients with oral cancer is evident in terms of OS, DSS, and DFS. Nonetheless, it is crucial to note that the predictive value of PLR might depend on specific threshold values., (© 2024. The Author(s).)

Despite significant efforts in developing new diagnostic and therapeutic modalities, oral squamous cell carcinomas (OSCCs) still exhibit a high recurrence rate, a low five-year survival rate, and an increasing prevalence. Toll-like receptors (TLRs), which initiate and perpetuate immune mechanisms upon activation, have been linked to immune surveillance and the antitumor immune response. The aim of this study was to investigate the association between the polymorphisms of the TLR7 rs3853839 and TLR9 rs187084 genes and OSCC risk, clinicopathological features, and survival. Genotyping was assessed by real-time polymerase chain reaction (PCR) in 95 HPV negative OSCC patients and 107 age- and sex-matched healthy controls. Patients with lymph node metastases had higher frequencies of the TLR9 rs187084 CC variant genotype compared to the major TT genotype (P = 0.020) and to T-allele carriers (combined TT + CT genotypes, P = 0.015). A higher prevalence of advanced stage III was observed in patients with the TLR9 rs187084 variant CC genotype compared to TT (P = 0.047) and to T-allele carriers (TT + CT, P = 0.037). Kaplan-Meier analysis revealed a lower overall survival (OS) rate in patients with the TLR9 rs187084 variant CC genotype compared to the TT genotype (P = 0.010, log-rank test) and to T-allele carriers (TT + CT genotypes, P = 0.002), though it was not an independent predictor of OS. Both TLR9 rs187084 and TLR7 rs3853839 polymorphisms were associated with high alcohol consumption (P = 0.027 and P = 0.001, respectively). The investigated genetic variations were not associated with OSCC susceptibility. The variant CC genotype of the TLR9 rs187084 polymorphism might be a marker of poor survival and tumor progression in OSCC.

Despite the employment of extensive therapeutic strategies, OSCC recurrence and mortality rates persist at high levels. This underscores the shortcomings of current prognostic models and the urgency for refined biomarkers. This study explores the prognostic significance of tumor-draining lymph nodes (TDLNs) in OSCC, with a special focus on the quantification of T regulatory cells (Tregs) and the expression of immune checkpoints on T cells., Methods: Forty-nine OSCC patients were enrolled. One TDLN per patient was analysed using flow cytometry to profile immune-checkpoint expression (PD-1, CTLA-4, TIGIT, TIM-3, LAG-3) and other markers such as CD69, CXCR5 on CD4+, CD8+, and Tregs. Disease-free survival (DFS) and overall survival (OS) were assessed., Results: According to multivariate analysis, elevated levels of FoxP3+CD4+ and TIGIT+CD8+ cells in TDLNs correlated with significantly worse DFS, while high CXCR5+CD4+ levels were associated with better DFS. Notably, the expression of immune checkpoints on T cells within TDLNs showed significant associations with recurrence status. Patients experiencing recurrence exhibited heightened levels of T regulatory cells, CD4+PD-1+ and CD4+CTLA-4+, cells in TDLNs. Survival multivariate analyses revealed that T status emerged as an independent predictor of OS., Conclusion: The findings highlight the critical role of TDLNs in the immune microenvironment of OSCC and establish immune checkpoint expression on T cells as promising prognostic biomarkers. These insights upgrade the prognostic framework for OSCC and pave the way for individualized therapeutic strategies. The prognostic significance of TDLNs and a high expression of immune checkpoint inhibitors is a compelling argument for the adoption of neoadjuvant immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Piersiala, Hjalmarsson, Lagebro, Farrajota Neves da Silva, Bark, Elliot, Marklund, Margolin, Georén and Cardell.)

Objective: Researchers have shown significant interest in cancer stem cells in recent years. CD44, CD24, CD133, and ALDH serve as indicators of cancer stem cell-like cells in Oral Squamous Cell Carcinoma. However, the prognostic significance of these Cancer Stem Cell markers in Squamous Cell Carcinoma is still debated. This study employed meta-analysis to evaluate the prognostic significance of cancer stem cells about Oral Squamous Cell Carcinoma., Methods: CD44, CD133, CD24, and ALDH markers were analyzed in 19 retrospective studies to determine their relationship with prognosis and clinicopathological parameters. Risk ratios (RRs) and odds ratios (ORs) were calculated for 3-years survival rates and clinicopathological parameters, respectively, using a fixed-effects model., Result: The finding of our study based on extracted survival rates showed that cancer stem cell markers, CD133 expression was related with the poor prognosis (RR= 1.62 ,95% CI = 1.08-2.44, P= 0.02). ALDH expression significantly correlated with lymph node metastasis (OR= 4.13, 95% Cl= 1.88-9.10, P<0.001) and clinical staging (OR= 2.26, 95% CI= 1.05-4.88, P= 0.04)., Conclusion: The findings indicate that CSC markers could be used to predict oral cancer prognosis. Our study contributes to the literature on survival outcomes of Oral Squamous Cell Carcinoma. These findings offer a structure for the advancement of cancer treatments that specifically target cancer stem cells. Conducting additional studies with a broader group of patients will help confirm the role of cancer stem cells as dependable predictors of prognosis.

Background: Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting., Methods: We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival., Results: A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%)., Conclusion: Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JBM: Honoraria: Roche, Pierre Fabre. The remaining authors declare no conflict of interest.

Purpose: Local recurrence remains the main cause of death in stage III-IV nonmetastatic head and neck cancer (HNC), with relapse-prone regions within high 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET)-signal gross tumor volume. We investigated if dose escalation within this subvolume combined with a 3-phase treatment adaptation could increase local (LC) and regional (RC) control at equal or minimized radiation-induced toxicity, by comparing adaptive 18 F-FDG-PET voxel intensity-based dose painting by numbers (A-DPBN) with nonadaptive standard intensity modulated radiation therapy (S-IMRT)., Methods and Materials: This 2-center randomized controlled phase 2 trial assigned (1:1) patients to receive A-DPBN or S-IMRT (+/-chemotherapy). Eligibility: nonmetastatic HNC of oral cavity, oro-/hypopharynx, or larynx, needing radio(chemo)therapy; T1-4N0-3 (exception: T1-2N0 glottic); KPS ≥ 70; ≥18 years; and informed consent., Primary Outcomes: 1-year LC and RC. The dose prescription for A-DPBN was intercurrently adapted in 2 steps to an absolute dose-volume limit (≤1.75 cm 3 can receive >84 Gy and normalized isoeffective dose >96 Gy) as a safety measure during the study course after 4/7 A-DPBN patients developed ≥G3 mucosal ulcers., Results: Ninety-five patients were randomized (A-DPBN, 47; S-IMRT, 48). Median follow-up was 31 months (IQR, 14-48 months); 29 patients died (17 of cancer progression). A-DPBN resulted in superior LC compared with S-IMRT, with 1- and 2-year LC of 91% and 88% versus 78% and 75%, respectively (hazard ratio, 3.13; 95% CI, 1.13-8.71; P = .021). RC and overall survival were comparable between arms, as was overall grade (G) ≥3 late toxicity (36% vs 20%; P = .1). More ≥G3 late mucosal ulcers were observed in active smokers (29% vs 3%; P = .005) and alcohol users (33% vs 13%; P = .02), independent of treatment arm. Similarly, in the A-DPBN arm, significantly more patients who smoked at diagnosis developed ≥G3 (46% vs 12%; P = .005) and ≥G4 (29% vs 8%; P = .048) mucosal ulcers. One arterial blowout occurred after a G5 mucosal toxicity., Conclusions: A-DPBN resulted in superior 1- and 2-year LC for HNC compared with S-IMRT. This supports further exploration in multicenter phase 3 trials. It will, however, be challenging to recruit a substantial patient sample for such trials, as concerns have arisen regarding the association of late mucosal ulcers when escalating the dose in continuing smokers., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To describe the clinicopathologic presentation of buccal squamous cell carcinoma and identify risks factors for recurrence and overall survival., Methods: This is a retrospective case-control study of patients with oral cavity squamous cell carcinoma (OCSCC) treated at a single tertiary care center between 2010 and 2022. All patients with buccal subsite OCSCC treated during this time frame were included and paired with a randomly selected age and gender matched patient with non-buccal OCSCC. Relevant data was collected via chart review., Results: Seventy-seven patients with buccal SCC were matched with 77 non-buccal OCSCC controls. The median follow-up time was 27 months (IQR 14-61). Median age was 67 years (IQR 57-75) and 53% of the cohort was female. Twenty (26%) buccal SCC patients experienced a recurrence versus 19 (25%) in the controls. Age ≥65-years-old increased odds of all-cause mortality in the buccal SCC group, but not in the control group. Perineural invasion and positive margins increased odds of recurrence in the buccal group only. Overall survival and progression-free survival did not differ between the groups, despite a greater number of T2 buccal tumors and T1 non-buccal tumors., Conclusions: Buccal SCC presents at a higher T stage than other oral cavity SCC subsite and may exhibit variance in the pathologic risk factors that predict poor outcomes versus non-buccal OCSCC. Despite these relatively minor differences, however, oncologic outcomes between these groups were similar., (© 2024 Wiley Periodicals LLC.)

Aims: This study addresses the essential need for updated information on the burden of lip and oral cavity cancer (LOC) in China for informed healthcare planning. We aim to estimate the temporal trends and the attributable burdens of selected risk factors of LOC in China (1990-2021), and to predict the possible trends (2022-2031)., Subject and Methods: Analysis was conducted using data from the Global Burden of Disease study (GBD) 2021, encompassing six key metrics: incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Absolute number and age-standardized rates, alongside 95% uncertainty intervals, were computed. Forecasting of disease burden from 2022 to 2031 was performed using an autoregressive integrated moving average (ARIMA) model., Results: Over the observed period (1990-2021), there were notable increases in the number of deaths (142.2%), incidence (283.7%), prevalence (438.0%), DALYs (109.2%), YLDs (341.2%), and YLLs (105.1%). Age-standardized rates demonstrated notable changes, showing decreases and increases of -5.8, 57.3, 143.7, -8.9%, 85.8%, and - 10.7% in the respective metrics. The substantial majority of LOC burden was observed among individuals aged 40-79 years, and LOC may exhibit a higher burden among males in China. From 2022 to 2031, the age-standardized rate of incidence, prevalence, and YLDs of LOC showed upward trends; while mortality, DALYs, and YLLs showed downward trends, and their estimated values were predicted to change to 2.72, 10.47, 1.11, 1.10, 28.52, and 27.43 per 100,000 in 2031, respectively. Notably, tobacco and high alcohol use emerged as predominant risk factors contributing to the burden of LOC., Conclusion: Between 1990 and 2021, the disability burden from LOC in China increased, while the death burden decreased, and projections suggest these trends will persist over the next decade. A significant portion of this disease burden to modifiable risk factors, specifically tobacco use and excessive alcohol consumption, predominantly affecting males and individuals aged 40-79 years. Attention to these areas is essential for implementing targeted interventions and reducing the impact of LOC in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Ma, Xiao, Chen, Wu, He and Cheng.)

Objective: For patients with clinical nodal-negative (cN0) maxillary oral squamous cell carcinoma (MOSCC), neck dissection (ND) and clinical observation are the main two management strategies for the neck. However, the indications corresponding to these two options remain controversial. This study aimed to elucidate the clinical factors affecting ND treatment and to identify clinical characteristics of the population that may benefit from ND based on a retrospective analysis of cN0 MOSCC patient data from the Surveillance, Epidemiology, and End Results (SEER) database., Methods: 8846 MOSCC patients were identified in the SEER database from 2000 to 2020. The Kaplan-Meier method was utilized to examine overall survival (OS) and disease-specific survival (DSS), while the hazard ratio (HR) was estimated using the stepwise multivariate Cox regression model. Furthermore, multi-subgroup analyses of DSS and OS were performed to compare ND and No ND., Results: We included 2,512 cN0 MOSCC patients. Basic survival analysis and Cox regression modeling showed that ND was an independent prognostic factor that promoted DSS and OS. Additional subgroup analyses revealed that the primary site and T-stage might influence the efficacy of ND modality. Moreover, patients with T3/T4 stage of upper gingival squamous cell carcinoma (UGSCC) (DSS p = 0.009, OS p = 0.004), hard palate squamous cell carcinoma (HPSCC) (DSS p = 0.001, OS p < 0.001), and soft palate squamous cell carcinoma (SPSCC) (p = 0.029) showed a better survival benefit with ND in OS and DSS. Nonetheless, no differences were observed in OS and DSS between ND and No ND at the T1/T2 stage of the abovementioned primary tumor sites. Additionally, the DSS outcomes for T1/T2 stage upper lip squamous cell carcinoma (ULSCC) patients were significantly worse in the ND group than in the No ND group (p = 0.018). However, no significant differences were noted in OS (p = 0.140) as well as OS (p = 0.248) and DSS (p = 0.627) for T1/T2 and T3/T4 patients, respectively., Conclusion: Active surveillance might be a feasible strategy for managing all T-staged ULSCC as well as early-stage (T1/T2) UGSCC, SPSCC, and HPSCC, provided regular and meticulous follow-up is performed. Hence, concurrent ND is recommended for patients with intermediate to advanced (T3/T4) stage UGSCC, SPSCC, and HPSCC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Evaluate whether extranodal extension (ENE) extent impacts outcomes in patients with oral cavity squamous cell carcinoma (OCSCC)., Methods: From an institutional database, patients with OCSCC and pathologic ENE who received adjuvant treatment were included. Surgical slides were reviewed to confirm ENE extent. Multivariable Cox regression was used to relate patient/treatment characteristics with disease-free survival (DFS) and overall survival (OS). ENE was analyzed as both a dichotomous and continuous variable., Results: A total of 113 patients were identified. Between major (>2 mm) versus minor ENE (≤2 mm), there was no significant difference in DFS (HR 1.18, 95%CI 0.72-1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70-1.96, p = 0.55). There was no significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87-1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83-1.11, p = 0.58)., Conclusion: No significant relationship was seen between ENE extent and DFS or OS in individuals with OCSCC., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objective: To assess the prognostic importance of margin in resected buccal cancer within a framework of risk factor-driven postoperative adjuvant treatment., Materials and Methods: Consecutive, treatment naïve patients undergoing primary surgical treatment for buccal cancer. Margin was defined as clear (≥5 mm), close (1-4 mm) and involved (<1 mm). Main outcome was association of margin with local recurrence free survival (LRFS). Subgroup analysis of close margin was performed according to receipt or no receipt of adjuvant treatment. A numerical margin cut-off in mm that could independently predict LRFS was sought to be identified., Results: Of the 167 patients included, the frequency of clear, close and involved margins was 50 (30 %), 78 (47 %) and 39 (23 %) respectively, among whom 52 %, 44 % and 98 % received postoperative adjuvant treatment respectively. Clear and close margins had similar 3-year LRFS (89 % and 96 % respectively), while involved margin had worse 3-year LRFS at 65 %. Involved margin was confirmed to be strongly and independently associated with worse LRFS. Within close margin, receipt and no receipt of adjuvant treatment had similar 3-year LRFS (92 % and 100 % respectively). A margin cut-off of 2 mm was identified at or above which LRFS approximated that of clear margin., Conclusions: This single center cohort study of patients with resected buccal cancer suggests that close margin is distinct from and has a better LRFS than involved margin. A subset of close margin, with margin size ≥ 2 mm and no other adverse features, might be spared adjuvant treatment without compromising outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest We declare no competing interests.

A crucial parameter in determining the prognosis of oral cavity cancer is depth of invasion (DOI). This research aimed to correlate pathological DOI at different intra-oral anatomical sites for oral squamous cell carcinoma (OSCC) with the risk of regional lymph node metastasis (LNM). This study also investigated the correlation of 3-year overall survival (OS) and disease-specific survival (DSS) with tumor depth. DOI measurement of the primary tumor at different intra-oral anatomic sites of clinically node negative patients who underwent curative surgery with elective neck dissection (END) was carried out as per AJCC 8th Edition staging guidelines in 3 DOI groups of ≤5 mm(A), >5 to ≤10 mm(B) and >10 mm(C). Association of groupwise DOI values with histopathological parameters including LNM and 3 years survival was evaluated. Univariate and multivariate logistic regression analysis (Odds ratio (OR) = 1.1 95 % CI: 1.0-1.2, p < 0.05) showed DOI to be a significant predictor for sub-clinical nodal metastasis observed in 136/382 OSCC patients. Receiver operating curve suggested that at 5 mm DOI (4 mm for early-stage OSCC), the risk of occult LNM was >20 % for all intra-oral sites combined. DOI <5 mm group demonstrated a superior 3-year OS (OR = 19.8 % CI: 7.8-49.9) and DSS (OR = 14.7 % CI: 5.9-37.0). Thus, DOI is an independent predictor of nodal metastasis and has significant association with LNM, OS and DSS. Our findings suggest that a DOI of ≥4 mm is an accurate cut-off value for performing END in early-stage OSCC and > 5 mm for advanced cases across all evaluated oral anatomic sites., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationships that seemed to influence the work disclosed in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: The aims of our study are to evaluate the diagnostic performance and prognostic value of radiological lymph node (LN) characteristics in pN+ oral cavity squamous carcinoma (OSCC)., Materials and Methods: pN+ OSCC treated between 2012 and 2020 were included. Preoperative imaging was reviewed by a single radiologist blinded to pathologic findings for the following nodal features: imaging-positive LN (iN+), laterality and total number, and image-identified extranodal extension (iENE). The sensitivity of iN+ for pN+ was calculated. The diagnostic performance of other nodal features was evaluated in the iN+ subgroup. The association of radiologic nodal features with overall survival (OS) was evaluated. Inter-rater kappa for radiologic nodal features was assessed in 100 randomly selected cases., Results: Of 406 pN+ OSCC, 288 were iN+. The sensitivity of iN+ for pN+ was 71% overall, and improved to 89% for pN+ LN >1.5 cm. Within iN+, sensitivity/specificity for LN size (>3 cm), total LN number (>4), and ENE were 0.44/0.95, 0.57/0.84, and 0.27/0.96, respectively. Sensitivity of iENE was higher in the subset, with major (>2 mm) versus minor (≤2 mm) pENE (43% vs. 13%, p = 0.001). Reduced OS was observed in iN+ versus iN- (p = 0.006), iENE+ versus iENE- (p = 0.004), LN size >3 versus ≤3 cm (p < 0.001), and higher LN number (p < 0.001). Inter-rater kappa for iN+, laterality, total LN number, and presence of iENE were 0.71, 0.57, 0.78, and 0.69, respectively., Conclusion: Our study shows that despite modest sensitivity of most radiological nodal features, the specificity of image-identified nodal features is high and their prognostic values are retained in pN+ OSCC., Level of Evidence: 3 (retrospective review comparing cases and controls) Laryngoscope, 134:4947-4955, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Oral Squamous Cell Carcinoma is the most prevalent malignancies affecting the oral cavity. Despite progress in studies and treatment options its outlook remains grim with survival prospects greatly affected by demographic and clinical factors. Precisely predicting survival rates and prognosis plays a role in making treatment choices for the best achievable overall health outcomes., Objective: To develop and validate an accelerated failure time model as a predictive model for cause-specific survival and prognosis of Oral Squamous Cell Carcinoma patients and compare its results to the traditional Cox proportional hazard model., Method: We screened Oral cancer patients diagnosed with Squamous Cell Carcinoma from the Surveillance Epidemiology and End Results (SEER) database between 2010 and 2020. An accelerated failure time model using the Type I generalized half logistic distribution was used to determine independent prognostic factors affecting the survival time of patients with oral squamous carcinoma. In addition, accelerated factors were estimated to assess how some variables influence the survival times of the patients. We used the Akaike Information Criterion, Bayesian Information Criterion to evaluate the model fit, the area under the curve for discriminability, Concordance Index (C-index) and Root Mean Square Error and calibration curve for predictability, to compare the type I generalized half logistic survival model to other common classical survival models. All tests are conducted at a 0.05 level of significance., Results: The accelerated failure time models demonstrated superior effectiveness in modeling (fit and predictive accuracy) the cause-specific survival (CSS) of oral squamous cell carcinoma compared to the Cox model. Among the accelerated failure time models considered, the Type I generalized half logistic distribution exhibited the most robust model fit, as evidenced by the lowest Akaike Information Criterion (AIC = 27370) and Bayesian Information Criterion (BIC = 27415) values. This outperformed other parametric models and the Cox Model (AIC = 47019, BIC = 47177). The TIGHLD displayed an AUC of 0.642 for discrimination, surpassing the Cox model (AUC = 0.544). In terms of predictive accuracy, the model achieved the highest concordance index (C-index = 0.780) and the lowest root mean square error (RMSE = 1.209), a notable performance over the Cox model (C-index = 0.336, RMSE = 6.482). All variables under consideration in this study demonstrated significance at the 0.05 level for CSS, except for race and the time span from diagnosis to treatment, in the TIGHLD AFT model. However, differences emerged regarding the significant variations in survival times among subgroups. Finally, the results derived from the model revealed that all significant variables except chemotherapy, all TNM stages and patients with Grade II and III tumor presentations contributed to the deceleration of time to cause-specific deaths., Conclusions: The accelerated failure time model provides a relatively accurate method to predict the prognosis of oral squamous cell carcinoma patients and is recommended over the Cox PH model for its superior predictive capabilities. This study also underscores the importance of using advanced statistical models to improve survival predictions and outcomes for cancer patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Awodutire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Oral cancer is one of the most common cancers in China and seriously threaten life and health of Chinese people. We analysed the trends and disparities of oral cancer mortality rates and the disease burden of oral cancer in China from 2006 to 2021 to provide a reference for its prevention and control., Methods: Annual death data for oral cancer was gleaned from the China Death Surveillance Database. The age-standardized mortality rate (ASMR), annual percentage change (APC), and average APC (AAPC) were used to analyze the trend of mortality. Loss of life expectancy (LLE) and years of life lost (YLL) were adopted to assess disease burden., Results: From 2006 to 2021, the overall ASMR of oral cancer lightly declined (AAPC: - 0.97%; 95% CI: - 1.89%, - 0.04%), and the similar trend was observed among females (AAPC: - 1.22%; 95% CI: - 1.89%, - 0.55%). The ASMR of males was 2.31-3.16 times higher than that of females per year. The median of LLE for overall, males and females caused by oral cancer from 2006 to 2021 were 0.05, 0.06 and 0.03 years, respectively. There was a decrease of standardized YLL rate from 2006 to 2021 for overall (AAPC: - 1.31%, 95% CI: - 2.24% ~  - 0.37%) and for female (AAPC: - 1.63%, 95% CI: - 2.30% ~  - 0.95%). ASMR in urban areas was 1.02-1.28 times higher than that in rural areas from 2006 to2011, but 0.85-0.97 times lower in urban areas than that in rural areas from 2018 to 2021. The disease burden was higher in urban areas than in rural areas in 2006, whereas the reverse was observed in 2021., Conclusions: There are severe health gaps and disparities in trends between sexes and different areas in China. Males and rural populations need to be focused on targeted interventions for the main influencing factors., (© 2024. The Author(s).)

Objective: This study was designed to evaluate the five-year overall survival (OS) rate and postoperative survival time of patients diagnosed with oral squamous cell carcinoma (OSCC), as well as examine the clinical and pathological factors influencing survival outcomes in OSCC patients., Methods: Data were collected from OSCC patients who underwent their first radical surgical intervention in the Department of Maxillofacial Surgery at the First Affiliated Hospital of Chongqing Medical University between April 2014 and December 2016. Follow-up was conducted until March 2022., Results: The study included a total of 162 patients. The observed 5-year OS rate was 59.3%. Approximately 45.7% of OSCC patients experienced postoperative recurrence or metastasis, with a 5-year overall disease-free survival rate of 49.4%. There was no significant difference in the impact of sex, age, smoking, alcohol consumption, primary tumour location, depth of invasion or primary tumour size on the 5-year survival rate (p > 0.05). Univariate analysis revealed that clinical stage (Hazard Ratio = 2.239, p = 0.004), perineural invasion (PNI) (Hazard Ratio = 1.712, p = 0.03), lymph node metastasis (pN) (Hazard Ratio = 2.119, p = 0.002), pathological differentiation (Hazard Ratio = 2.715, p < 0.001), and recurrence or metastasis (Hazard Ratio = 10.02, p < 0.001) were significant factors influencing survival. Multivariate analysis further indicated that pathological differentiation (Hazard Ratio = 2.291, p = 0.001), PNI (Hazard Ratio = 1.765, p = 0.031) and recurrence or metastasis (Hazard Ratio = 9.256, p < 0.001) were independent risk factors of survival. Intriguingly, 11 OSCC patients were diagnosed with oesophageal squamous cell carcinoma (ESCC) within 1-4 years following surgery., Conclusion: The survival prognosis of OSCC patients is significantly associated with clinical stage, PNI, lymph node metastasis, pathological differentiation, and recurrence or metastasis. Pathological differentiation, PNI and recurrence or metastasis are independent risk factors affecting survival. Routine clinical screening for ESCC may be recommended for OSCC patients with a history of alcohol consumption and tobacco use., (© 2024. The Author(s).)

Purpose: To analyze the immune-related core genes differentially expressed in oral squamous cell carcinoma(OSCC) and construct an immune-related prognostic risk model for OSCC patients., Methods: Weighted gene co-expression network analysis of RNA sequencing data from OSCC patients in the Cancer Genome Atlas (TCGA) database was conducted to identify immune-related modules and core genes. Core genes associated with immune prognosis were screened using univariate Cox regression analysis and survival analysis to construct an immune-related prognostic risk model for OSCC. The prognostic risk model's predictive ability was evaluated using Kaplan-Meier analysis, receiver operating characteristic curves, and external datasets from GSE41613. The expression of 8 immune prognostic core genes in tumor samples from OSCC patients was detected by real-time quantitative PCR assay(RT-qPCR), and the correlation between risk score and depth of invasion was assessed by calculating risk scores for OSCC patients. Statistical analysis was performed with SPSS 21.0 software package., Results: Prognostic risk model for OSCC was successfully constructed based on 8 immune prognostic core genes(CSF2RA, CLEC4C, COL5A3, CTSG, EDNRA, GPC4, GUCY1A2, ANGPT2). The prognostic risk model demonstrated perfect predictive value validated using Kaplan-Meier analysis, receiver operating characteristic curve, and the GSE41613 dataset. The risk scores of OSCC patients calculated based on this model were positively correlated with the depth of invasion, indicating that the model have the ability to predict the potential risk of OSCC., Conclusions: An OSCC prognostic risk model is constructed based on the signatures of 8 immune prognostic core genes, which may effectively predict the prognosis of OSCC patients, providing an important reference for immune prevention of OSCC.

Background: While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery., Methods: We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)-matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1-T4b tumors, clinical N0-3 disease, and clinical stage I-IV., Results: In the PS-matched cohort, the 5-year disease-specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5-year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5-year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5-year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2-3, cN1, and c-Stage II disease in the IC + OP group were significantly more likely to achieve pT0-1 status (p < 0.05)., Conclusions: Following PS matching, the IC + OP group generally exhibited similar prognosis to the OP group. However, for pT4a tumors, the OP group showed superior 5-year outcomes. While IC may not universally improve survival, it could be advantageous for patients who respond positively to the treatment., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Exportin 1 (XPO1) is a nuclear export protein that facilitates the transportation of various substances. XPO1 promotes tumor development as a poor prognostic factor in a variety of tumors and is a therapeutic target for screening inhibitors. However, the role of XPO1 in oral squamous cell carcinoma (OSCC) has yet to be determined., Methods: The expression patterns of XPO1 mRNA in OSCC were investigated using bioinformatics tools, and the expression levels of XPO1 protein in OSCC specimens were confirmed by immunohistochemical assays. Survival analysis was conducted to evaluate the impact of XPO1 on prognosis. GO and KEGG enrichment analyses were utilized to uncover the signaling pathways mediated by XPO1. Additionally, we examined the association between XPO1 and AKT/MAPK/TGFBR1 and immune infiltration., Results: XPO1 mRNA and protein expression levels were significantly enhanced in OSCC and associated with OSCC severity. Enhanced XPO1 expression was indicative of poor survival. Functional analysis showed that XPO1 mediated pathways associated with cell cycle and DNA replication and reduced immune infiltration in OSCC. Additionally, XPO1 mRNA and protein expression levels had significant positive relationships with AKT/MAPK/TGFBR1., Conclusions: XPO1, as a marker of poor prognosis in OSCC, can promote OSCC through AKT/MAPK/TGFBR1., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Aims/introduction: Diabetes has been related to an increased risk of oral cancer. Nevertheless, the impact of diabetes on the outcome of individuals with oral and oropharyngeal cancer is not clear. In this study, a meta-analysis was carried out to assess the link between diabetes and the survival of individuals with oral and oropharyngeal cancer., Materials and Methods: Relevant cohort studies for the meta-analysis objective were obtained through searching electronic databases, such as PubMed, Web of Science and Embase. The data were combined using a random effects model that accounted for differences between studies., Results: A total of 10 cohorts involving 21,871 patients with oral and oropharyngeal cancer were included. Pooled results suggest that compared with those with normoglycemia, oral and oropharyngeal cancer patients with diabetes were associated with a poor overall survival (hazard ratio 1.69, 95% confidence interval 1.29-2.22, P < 0.001; I 2  = 69%). Subgroup analysis suggested a stronger association between diabetes and poor overall survival in patients aged ≥52 years as compared with those aged <52 years (hazard ratio 2.08 vs 1.34, P = 0.03). Other study characteristics, such as study country, tumor stage or follow-up duration, did not seem to significantly affect the association (P for subgroup difference all >0.05). In addition, diabetes was also associated with a poor progression-free survival of patients with oral and oropharyngeal cancer (hazard ratio 1.61, 95% confidence interval 1.30-1.99, P < 0.001; I 2  = 9%)., Conclusions: Patients with oral and oropharyngeal cancer might have a poor survival if they have pre-existing diabetes., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The role of mast cell (MC), a common myeloid-derived immune cell, in the development of oral squamous cell carcinoma (OSCC) is unclear. The aim of this study was to investigate MC infiltration in oral precancer and oral cancer. The evaluation of immune cell infiltration and its association with prognosis in OSCC used RNA sequencing and multiple public datasets. Multiplex immunofluorescence was used to explore the infiltration of MC in the microenvironment of OSCC and oral precancer and the interaction with CD8+ cells. The role of MC in OSCC progression was verified by in vivo experiments. The resting MC infiltration was mainly present in oral precancer, whereas activated MC infiltration was significantly higher in OSCC. Activated MC was associated with malignant transformation of oral precancer and poor prognosis of OSCC. In vivo studies showed that MC promoted the growth of OSCC. The infiltration of activated MC was negatively correlated with the infiltration of CD8+ T cells. The subtype of MC containing tryptase without chymase (MCT) was significantly higher in OSCC compared with oral precancer and was associated with poor survival. Furthermore, spatial distance analysis revealed a greater distance between MCT and CD8+ cells, which was also linked to poor prognosis in OSCC. Cox regression analysis showed that MCT could be a potential diagnostic and prognostic biomarker. This study provides new insights into the role of MC in the immune microenvironment of OSCC. It might enhance the immunotherapeutic efficacy of OSCC by developing targeted therapies against MC., Significance: In this study, we investigated the role of mast cells (MC) in oral precancer and oral cancer and demonstrated that MCs are involved in oral cancer progression and may serve as a potential diagnostic and prognostic marker. It might improve the immunotherapeutic efficacy through developing targeted therapies against MCs., (©2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: Oral cancer poses a significant burden on public health in India, with higher incidence and mortality rates. Despite advancements in treatment modalities, prognosis remains poor due to factors such as localized recurrence and lymph node metastasis, potentially influenced by cancer stem cells. Among signaling pathways implicated in CSC regulation, the Hedgehog pathway plays a crucial role in oral squamous cell carcinoma (OSCC)., Material & Methods: 97 OSCC patients' tissue samples were collected and subjected to RNA isolation, cDNA synthesis and quantitative real-time PCR to analyze PTCH1 and SMO expression. Protein expression was assessed through immunohistochemistry. Clinicopathological parameters were correlated with gene and protein expression. Statistical analysis included Pearson chi-square tests, co-relation co-efficient tests, Kaplan-Meier survival analysis and ROC curve analysis., Results: PTCH1 expression correlated with lymphatic permeation (p = 0.002) and tumor stage (p = 0.002), while SMO expression correlated with lymph node status (p = 0.034) and tumor stage (p = 0.021). PTCH1 gene expression correlated with lymph node status (p = 0.024). High PTCH1 gene expression was associated with shorter survival in tongue cancer patients. ROC curve analysis indicated diagnostic potential for PTCH1 and SMO gene and cytoplasmic SMO expression in distinguishing malignant tissues from adjacent normal tissues., Conclusion: PTCH1 and SMO play a crucial role in oral cancer progression, correlating with tumor stages and metastatic potential. Despite not directly influencing overall survival, PTCH1 expression at specific anatomical sites hints at its prognostic implications. PTCH1 and SMO exhibit diagnostic potential, suggesting their utility as molecular markers in oral cancer management and therapeutic strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Lymph node metastases are associated with poor prognosis in oral cavity squamous cell carcinoma (OCSCC). In other cancers, clinical guidelines on the number of lymph nodes removed during primary surgery, lymph node yield (LNY), exist. Here, we evaluated the prognostic capacity of LNY on regional failure, locoregional recurrence, and disease-free survival (DFS) in patients with OCSCC treated by primary neck surgery., Methods: This retrospective cohort study took place at Sunnybrook Health Sciences Centre in Toronto, Canada and involved a chart review of all adult patients with treatment-naive OCSCC undergoing primary neck dissection. For each outcome, we first used the maximally selected rank statistics and an optimism-corrected concordance to identify an optimal threshold of LNY. We then used a multivariable Cox proportional hazards model to assess the association between high LNY (>threshold) and each outcome., Results: Among the 579 patients with OCSCC receiving primary neck dissection, 61.7% (n = 357) were male with a mean age of 62.9 years (standard deviation: 13.1) at cancer diagnosis. When adjusting for sociodemographic and clinical factors, LNY >15 was significantly associated with improved DFS (adjusted HR [aHR]: 0.73, 95% CI: 0.54-0.98), locoregional recurrence (aHR: 0.68, 95% CI: 0.49-0.95), and regional failure (aHR: 0.61, 95% CI: 0.39-0.93)., Conclusions: Our study findings suggested high LNY to be a strong independent predictor of various patient-level quality of surgical care metrics. The optimal LNY we found (15) was lower than the conventionally recommended (18), which calls for further research to establish validity in practice., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a crucial enzyme in the glycolysis pathway, possessing both kinase and phosphatase capabilities. Although it has emerged as an important oncogene in various cancer types, its function in oral squamous cell carcinoma (OSCC) is still not well understood. In our research, PFKFB4 expression was assessed via immunohistochemical (IHC) staining of tissue microarrays and OSCC patient specimens. The transcriptional expression of PFKFB4 in OSCC was analyzed by utilizing The Cancer Genome Atlas (TCGA) dataset. Correlation between PFKFB4 expression and clinicopathological features was examined using the χ2 test. Prognostic investigation of PFKFB4 was conducted via Kaplan-Meier and Cox analyses. PFKFB4 levels were notably elevated in OSCC samples in comparison to adjacent normal tissues (P < 0.001). Elevated PFKFB4 expression was associated with higher histologic grade (P = 0.0438), higher T stage (P = 0.031), and more advanced clinical stage (P = 0.0063). The ROC curve demonstrated the diagnostic potential of PFKFB4 (AUC = 0.827). Increased levels of PFKFB4 were linked to decreased overall survival (OS) (P = 0.04), poorer disease-specific survival (DSS) (P = 0.04), and shorter progression-free interval (PFI) (P < 0.001). PFKFB4 expression was identified as an independent risk factor for OS based on Cox regression analysis [hazard ratio (HR) = 1.517, P = 0.044)]. An OS nomogram was constructed with a concordance index of 0.690. Our findings reveal that upregulated PFKFB4 expression in OSCC tissues could serve as a potential prognostic biomarker.

The objective of our study was to map county differences in incidence and mortality by cancers and examine their changes over time. Based on the database of National Cancer Registry and Central Statistical Office, age-standardized incidence and mortality rates per 100,000 person-years were calculated for each county for 15 cancer types and 3 time periods. East-West divide was apparent in incidence and mortality of lung cancer, with larger weight in East (Borsod-Abaúj-Zemplén, Heves, Jász-Nagykun-Szolnok, Békés counties). Concentration of lip and oral cavity malignancies was identified in the northeastern periphery (Borsod-Abaúj-Zemplén, Szabolcs-Szatmár-Bereg counties). Breast cancer incidence was the highest in Budapest. As a conclusion, changes in cancer incidence and mortality over time were similar to developed countries; however, values were higher. Differences in spatial distribution follow territorial pattern of social deprivation, which correspond to higher prevalence of health risk factors. Our study contributes to planning of public health programs by pinpointing regional inequalities in different cancer types.

Selective neck dissection (SND) is the treatment of choice in patients with oral squamous cell carcinomas (OSCCs) and clinically node-negative necks (cN0). The treatment of patients with positive-staged necks (cN+) includes SND as well as comprehensive neck dissection (CND). The clear benefit of one or the other remains under debate. We aim to address this lack of clarity by analysing patients with OSCC staged with clinically node-positive necks, treated with either CND or SND using a level-by-level approach. This retrospective study included patients diagnosed with OSCC with clinically (cN+) and pathologically (pN+) positive cervical lymph nodes (LNs) with clear neck level categorization during the years 2010-2019. In total, 74 patients were analysed. Cox regression analysis found no significance for the type of ND being an independent risk factor, neither for overall survival (OS) nor for disease-free survival (DFS). Regional recurrence of CND cases (5.77%) was comparable to SND cases (9.09%). For OS, extracapsular spread (ECS) and male sex were identified as independent risk factors with poorer outcome. pT-stage and ECS were found to be independent risk factors for DFS. The results of this study suggest that both CND and SND may be viable treatment options for certain patients with OSCC pN+., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Jan Oliver Voss et al.)

Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers in the world. OSCC is a highly invasive lesion frequently having soaring morbidity as well as substantial mortality, attributed to resistance to therapy, metastasis, and recurrence driven by specific populations of cancer stem cells (CSC). The evidence of the association of expression of stem cell biomarker CD44 and metastatic potential of the tumor is inconclusive in OSCC and hence needs further evaluation., Objectives: To determine the immunohistochemical expression of CD44 in OSCC and to find its association with lymph node metastasis and TNM staging., Materials and Methods: One hundred and five histologically proven cases of OSCC were studied. Histopathological parameters like depth of invasion, presence of lymph node metastasis, grading, and TNM staging were done according to the new AJCC staging criteria. Both intensity and proportion of CD44 expression were recorded., Results: The mean age observed in this study was 52.59 years with a male: female ratio of 1:3.76. Forty-nine cases (46.6%) showed a depth of invasion of more than 10 mm. Fifty-two out of one hundred and five cases (49%) had nodal involvement. TNM staging was 5.7%, 7.6%, 44.7%, and 42% for stages I, II, III, and IV, respectively. The majority of the cases (87.5%) showed CD44 expression in the tumor. There was a significant association between the CD44 expression and lymph node metastases (P < 0.001). Higher CD44 expression was seen in stages III and IV (P < 0.001)., Conclusion: CD44, a stem cell biomarker is significantly associated with higher TNM stage and lymph node metastases. This may be useful in predicting the tumor behavior in the small biopsy., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Background: An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC., Methods: PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact., Results: Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis., Conclusion: The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The present study aimed to calculate the burden of oral cavity cancer (OCC) including incidence, mortality rate, survival rate, and influence of predictive factors such as clinicopathological, demographic findings, and treatment modalities., Materials and Methods: Data in this retrospective study were collected from India's population-based cancer registry (PBCR) from 2010 to 2016. A total of 1051 cases of OCC were noted. Incidence and mortality rates were calculated. The cumulative survival outcome was calculated using Kaplan-Meier (KM) method. Prognostic factors were estimated using the Cox proportional hazard regression model., Results: The age-standardized incidence rates (ASR), and mortality rate (ASMR), of overall OCC cases were 10.1 and 8.4 per 100 thousand population, respectively. Five-year overall survival (OS) was 32.3%. Survival outcome was significantly associated with the given treatment (Chi-square value = 58.17, P = 0.0001) and anatomical site (Chi-square value = 26.70, P = 0.0001). 17.6% of cases in males were <39-year age group. The hazard ratio (HR) in the age group of >50 years was 2.065 (95% CI 1.34-3.18, P = 0.001). Combination therapy had an HR of 2.630 (95% CI 1.91-3.63, P value 0.000). Tonsillar carcinoma (C09) (95% CI 1.04-3.12) had 1.8 times more chances of death than lip carcinoma (C00)., Conclusion: OCC cases are increasing in the younger population, and overall, cases show higher mortality rates with reduced survival outcomes. Prognostic factors such as age >50 years, single modality treatment, and alveolar and tonsillar malignancy are associated with poor survival. OCC robust screening by a trained health professional can improve early detection and increases awareness and lower mortality of the disease., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Objective: To analyze the impact of clinico-pathological prognostic factors on survival in patients with GBC OSCC. To evaluate the association between various clino-pathological and treatment factors influencing the 3-year and 5-year Overall survival (OS), and Disease specific survival (DSS) in patients with lower GBC OSCC., Patients & Methods: An Institutional Ethical Committee (IEC) approved retrospective chart audit was performed. Biopsy proven squamous cell cancer of gingivobuccal complex (GBC OSCC) patients from 2010 to 2019 who were treated primarily with surgery with or without adjuvant therapy having complete clinicopathological and follow up data were included. Survival outcomes including 2-year, 3-year & 5-year OS, and DSS were calculated and analyzed. A multivariate analysis was performed to identify significant predictor for the survival outcomes. A p-value < 0.05 was considered significant., Results: 183 patients with primary OSCC were identified out of which 83 patients comprised of OSCC of lower GBC. Age (p < 0.001), tumor grade (p = 0.009), pN status (p = 0.002), PNI (p < 0.001), lymph node metastasis (p = 0.002), treatment given (p = 0.02) and adjuvant therapy (p = 0.02) were found as a significant prognostic factor in univariate analysis., Conclusion: The OS & DSS of the patients with lower GBC SCC is 78.3%. The 2-year, 3-year, and 5-year OS of the study population was reported to be 95.2%, 87.9%, and 78.8% respectively. PNI & lymph node metastasis were significant prognostic factor for OS with an adjusted hazard ratio 4.91 and 7.75 respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Oral lichen planus (OLP) is a chronic inflammatory disorder involving epithelia with squamous differentiation. Although described as a potential malignant precursor, the characteristics of malignancies arising among these patients are not widely described. Our goal was to describe the patterns of disease recurrence of patients with oral cavity squamous cell carcinoma (OSCC) arising on the background of OLP., Methods: A retrospective analysis of all surgically treated patients with OSCC at a university-affiliated tertiary care center between 2000 and 2020., Results: Two hundred seventy-nine patients with OSCC treated surgically were included. Forty (14.3%) had OLP. The mean age of patients with OLP was 70.9 years compared with 64.3 years for non-OLP patients (p = 0.03). OLP patients had a significantly higher rate of disease recurrence, persistence, or multiple primary disease (70% vs. 33.9%, p < 0.001). The mean number of sequential oncologic events for each patient with recurrence was also significantly higher among OLP patients (1.86 vs. 1.36, p = 0.03), a difference explained by a higher rate of multiple primary presentations (0.71 vs. 0.28, p = 0.008). A significant difference in disease-free survival (DFS) was demonstrated between the groups as patients with OLP had a lower 5-year DFS (34.7% vs. 61.3%, log-rank p value <0.001). On multivariate analysis, OLP was significantly associated with multiple primary events (p < 0.001, Odds ratio = 7.42, 95% confidence interval 2.9-19)., Conclusions: OSCC patients with OLP background demand close clinical follow-up, as multiple primary disease is significantly more common and the DFS is significantly lower among these patients. A thorough clinical evaluation for all oral cavity subsites is mandatory., Level of Evidence: 3 Laryngoscope, 134:3146-3151, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

We explored the impact of stromal tumor-infiltrating lymphocytes (sTILs) on the prognostic value of an early death model for advanced buccal cancer. We assessed 121 patients with advanced buccal cancer who underwent primary tumor resection at a medical center. Predictors of early death and 5-year overall survival (OS) were analyzed using Cox regression models. Performance of models was evaluated with the Harrell C and Akaike information criterion. The net reclassification improvement of the early death model was also calculated relative to the 5-year OS model for one-year all-cause mortality. A total of 121 patients with advanced buccal cancer were recruited. Mean age was 56.1 ± 9.8 years; 117 (96.7%) patients were male. sTILs ≤30%, clinical nodal disease, pathological nodal disease, poor differentiation, lymphovascular invasion, perineural invasion, WPOI 5, and no adjuvant radiotherapy were risk factors for early death in univariate analysis. In multivariate analysis, clinical TNM, sTILs, clinical nodal disease, poor differentiation, lymphovascular invasion, and no adjuvant RT were independent factors for early death. sTILs, pathological nodal disease, poor differentiation, lymphovascular invasion, and no adjuvant RT were independent factors for early death in the multivariate model with pathological TNM. The discriminatory ability was better for early death model for 1-year all-cause mortality. Finally, incorporation of sTILs into the early death model increased net reclassification by 21% for the clinical TNM model and 28% for the pathological TNM model. Addition of sTILs improved the early death model, which may help physicians to identify high-risk patients for more intensive treatment and follow-up., Competing Interests: Declaration of competing interest No potential compering interest relevant to this article are reported., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective(s): To assess the influence of treatment package time (TPT) on overall survival (OS) and event free survival (EFS) in oral cavity cancer (OCC) patients treated with surgery and adjuvant radiation therapy (RT) with or without concurrent chemotherapy (CHT)., Materials/methods: 354 adult OCC patients treated at a single, high-volume center between 2012-2022 with various pathologic risk features were included. TPT was defined as days from surgery to RT completion. Kaplan-Meier estimates, log-rank p-values, univariable (UVA) and multivariable (MVA) Cox regression analyses were performed to determine the impact of TPT on OS and EFS, and the optimal TPT cutoff., Results: The optimal TPT cutoff was 105 days. TPT < 105 days was significantly associated with improved OS and EFS (p = 0.002 and p = 0.027, respectively) compared to TPT ≥ 105 days. On UVA, factors significantly associated with OS were TPT < 105 days, former/current smoker status, pathologic stage IV, positive perineural invasion (PNI), and extranodal extension (ENE) (all p < 0.05). On MVA for OS, TPT < 105 days, former/current smoker status, pathologic stage IV, and positive PNI (all p < 0.05) remained significant. Factors significantly associated with EFS on UVA were TPT < 105 days, former/current smoker status, pathologic stage IV, positive PNI or ENE, and concurrent CHT (all p < 0.05). On MVA, TPT < 105 days, pathologic stage IV, and positive PNI (all p < 0.05) remained significant., Conclusions: In a large, homogenous cohort of OCCs, optimal TPT was <105 days, with TPT ≥ 105 days significantly associated with worse OS and EFS. Multidisciplinary coordination should analyze factors potentially contributing to treatment delay., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: To assess the influence of diagnosis and referral provided by specialists in oral diagnosis on disease-free survival and overall survival of patients with oral cancer., Methods: A cohort of 282 patients with oral cancer treated at a regional cancer hospital from 1998 to 2016 was analyzed retrospectively. The referral register of the patients was analyzed and assigned to two groups: (1) those referred by oral diagnosis specialists (n = 129), or (2) those referred by nonspecialized professionals (n = 153). The cancer treatment evolution was assessed from the patients' records, and the outcome was registered concerning cancer recurrence and death. Sociodemographic and clinicopathological variables were explored as predictors of disease-free survival and overall survival., Results: Group 1 exhibited lower T stages and a reduced incidence of regional and distant metastases. Surgery was performed in 75.2% of cases in Group 1, while in Group 2, the rate was 60.8%. Advanced T stages and regional metastases reduced the feasibility of surgery. Higher TNM stages and tumor recurrence were associated with decreased disease-free survival, while surgical intervention was a protective factor. Higher TNM stage had a negative impact on the overall survival., Conclusion: Specialized oral diagnosis did not directly impact disease-free survival and overall survival and did not influence the indication of surgery in oral cancer; however, it was associated with the diagnosis of early tumors and better prognosis., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Disparities in oral cavity and pharyngeal cancer based on race/ethnicity and socioeconomic status have been reported, but the impact of living within areas that are persistently poor at the time of diagnosis and outcome is unknown. This study aimed to investigate whether the incidence, 5-year relative survival, stage at diagnosis, and mortality among patients with oral cavity and pharyngeal cancers varied by persistent poverty., Methods: Data were drawn from the SEER database (2006-2017) and included individuals diagnosed with oral cavity and pharyngeal cancers. Persistent poverty (at census tract) is defined as areas where ≥ 20% of the population has lived below the poverty level for ~ 30 years. Age-adjusted incidence and 5-year survival rates were calculated. Multivariable logistic regression was used to estimate the association between persistent poverty and advanced stage cancer. Cumulative incidence and multivariable subdistribution hazard models were used to evaluate mortality risk. In addition, results were stratified by cancer primary site, sex, race/ethnicity, and rurality., Results: Of the 90,631 patients included in the analysis (61.7% < 65 years old, 71.6% males), 8.8% lived in persistent poverty. Compared to non-persistent poverty, patients in persistent poverty had higher incidence and lower 5-year survival rates. Throughout 10 years, the cumulative incidence of cancer death was greater in patients from persistent poverty and were more likely to present with advanced-stage cancer and higher mortality risk. In the stratified analysis by primary site, patients in persistent poverty with oropharyngeal, oral cavity, and nasopharyngeal cancers had an increased risk of mortality compared to the patients in non-persistent poverty., Conclusion: This study found an association between oral cavity and pharyngeal cancer outcomes among patients in persistent poverty indicating a multidimensional strategy to improve survival., (© 2024. The Author(s).)

Background: Serum selenium (Se) concentration has been reported to be associated with the incidence of oral cancer. The association between serum Se and long-term survival in oral cancer patients is still unclear., Purpose: The purpose of this study is to measure the association between serum Se and disease-specific survival (DSS)., Study Design, Setting, and Sample: This was a single-center, prospective cohort study conducted at the First Affiliated Hospital of Fujian Medical University (Fujian Province, China) from September 2011 to December 2018. The inclusion criteria were patients with newly diagnosed primary oral cancer confirmed by histology. The exclusion criteria were patients with recurrent oral cancer or metastatic cancer., Predictor Variable: The predictor variable is the preoperative serum Se concentration measured using inductively coupled plasma-mass spectrometry., Main Outcome Variable(s): The primary outcome variable is DSS calculated from the date of diagnosis to the date of death due to oral cancer or the end of follow-up, whichever occurred first., Covariates: The covariates were age, sex, occupation, education level, body mass index, surgery therapy, adjuvant therapy, tumor node metastasis stage, and pathological grading., Analyses: Kaplan-Meier survival analysis, Cox proportional hazards regression, and restricted cubic spline regression were utilized. P value < .05 was significant., Results: The sample was composed of 235 subjects with a median age of 59 years (ranged from 20 to 80 years) and 142 (60.43%) were male. The median follow-up was 54.90 months (interquartile range: 35.47). Se levels were associated with DSS (unadjusted hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.54-0.91) suggesting that higher levels of Se are associated with longer or improved DSS. After adjustment of age, sex, occupation, education level, residence, tumor node metastasis stage, pathological grading, surgery therapy, radiotherapy, and chemotherapy, patients with higher serum Se had a better DSS (aHR = 0.67; 95% CI: 0.49-0.92). Of note, we found that the association between serum Se and DSS was observed only in patients with radiotherapy (aHR = 0.49; 95% CI: 0.33-0.73). And the protective effect of radiotherapy on survival was only observed in patients with higher Se concentrations (aHR = 0.36; 95% CI: 0.20-0.63). Additionally, there was a multiplicative interaction between Se and radiotherapy on the prognosis of oral cancer patients (P interaction <0.01)., Conclusion and Relevance: Our findings suggest that a high Se concentration might contribute to better DSS among oral cancer patients, and the effect may partly depend on radiotherapy treatment. Given these findings, additional research should focus on the role of Se in DSS among oral cancer patients and the interaction with radiotherapy., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Primary objective was to evaluate the correlation between immune marker expression in baseline tumor biopsies and their respective surgical specimens in squamous cell carcinoma of the oral cavity (OCSCC). Secondary objective was to assess the impact of these markers on overall (OS) and disease-free survival (DFS)., Materials and Methods: Patients with a histological diagnosis of oral squamous cell carcinoma treated surgically between 2012 and 2020 were included in this retrospective, translational monocentric study. The expression of PD-L1, T-cells markers and an OCSCC-adapted immunoscore were evaluated by multiplex immunohistochemistry., Results: One hundred and four patients (mean: 58 years) were included. Seventy patients had paired samples available. Poor correlation was highlighted for PD-L1-positive surface expression (r = 0.29) and combined positive score (CPS). For CPS ≥ 20 and CPS ≥ 1, correlation coefficient r was 0.24 and 0.46 respectively. T-cells density showed also poor correlation with a r of 0.57 and 0.31 for CD3 and CD8 T-cells, respectively. Univariate survival analyses showed significant better OS and DFS (P < 0.05) for patients with stage III-IV OCSCC with a high compared to a low immunoscore, based on surgical samples only., Conclusion: Our study showed poor correlation in PD-L1 expression, CPS, T-cells density and immunoscore between baseline tumor biopsies and surgical resection specimens. In addition, the immunoscore may emerge as a potential prognostic factor in advanced squamous cell carcinoma of the oral cavity. If surgical specimens are available, they may be of interest for clinical practice decision., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JPM reports grants from Boehringer-Ingelheim, Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boehringer, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX oncology, iTEOS, eTheRNA, NEKTAR, F-star, Seagen, Genmab, Astellas, CureVac, MSD, Gilead, and Sanofi outside the submitted work. No disclosures were reported by the other authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cancer utilizes immunosuppressive mechanisms to create a tumor microenvironment favorable for its progression. The purpose of this study is to histologically characterize the immunological properties of the tumor microenvironment of oral squamous cell carcinoma (OSCC) and identify key molecules involved in the immunological microenvironment and patient prognosis., Methods: First, overlapping differentially expressed genes (DEGs) were screened from OSCC transcriptome data in public databases. Correlation analysis of DEGs with known immune-related genes identified genes involved in the immune microenvironment of OSCC. Next, stromal patterns of tumor were classified and immunohistochemical staining was performed for immune cell markers (CD3, CD4, Foxp3, CD8, CD20, CD68, and CD163), programmed death-ligand 1 (PD-L1), and guanylate binding protein 5 (GBP5) in resected specimens obtained from 110 patients with OSCC who underwent resection. Correlations between each factor and their prognostic impact were analyzed., Results: Among the novel OSCC-specific immune-related genes screened (including ADAMDEC1, CXCL9, CXCL13, DPT, GBP5, IDO1, and PLA2G7), GBP5 was selected as the target gene. Histopathologic analysis showed that multiple T-cell subsets and CD20-positive cells were less common in the advanced stages, whereas CD163-positive cells were more common in advanced stages. The immature type in the stromal pattern category was associated with less immune cell infiltration, lower expression of PD-L1 in immune cells, lower expression of GBP5 in the stroma, and shorter overall survival and recurrence-free survival. Expression of GBP5 in the tumor and stroma correlated with immune cell infiltration of tumors and PD-L1 expression in tumor and immune cells. Patients with low tumor GBP5 expression and high stromal expression had significantly longer overall survival and recurrence-free survival., Conclusions: The stromal pattern category may reflect both invasive and immunomodulatory potentials of cancer-associated fibroblasts in OSCC. GBP5 has been suggested as a potential biomarker to predict the prognosis and therapeutic efficacy of immune checkpoint inhibitors., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignant tumors in head and neck. However, few studies have focused on the postoperative prognosis of elderly OSCC patients undergoing surgical resection and reconstruction., Methods: We conducted a retrospective study of 349 patients diagnosed OSCC in the Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University from January 2016 to December 2022. Demographic and clinicopathological characteristics were recorded. Kaplan-Meier analysis was performed to identify the impact of age and reconstruction types on the prognosis of OSCC patients. Univariable regression analysis and multivariable Cox analysis were conducted to find independent prognostic factors of the younger and elderly OSCC patients., Results: Among 349 OSCC patients included in this retrospective study, 241 (69.1 %) were elderly patients and 108 (30.9 %) were younger patients. The two groups were comparable according to the demographic records. The elderly group presented a better recurrence-specific prognosis than that of the younger group (RFS: p = 0.0324). There are no remarkable differences on the prognosis of different reconstructive types. Gender, current address, life habit, invasion patterns, and TNM stage were identified as independent prognostic factors of the younger and elderly OSCC patients., Conclusion: Elderly OSCC patients achieve a better recurrence-free survival than that of the younger patients. Meanwhile, the recurrence of OSCC patients is independent of their demographic and clinicopathological features. Elderly OSCC patients will benefit from aggressive surgical treatment as the younger patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage., Methods: Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced)., Results: CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients., Conclusions: TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients., (© 2024. The Author(s).)