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Background: Tongue squamous cell carcinoma (TSCC) represents the most prevalent form of head and neck squamous cell carcinomas, comprising approximately one-third of all oral cancers. Paris polyphylla(PP) exhibit promising anti-tumor properties, yet their underlying mechanisms remain elusive. This study offers novel insights into the molecular mechanisms underlying TSCC treatment with PP and establishes a theoretical basis for their clinical application. Methods: Employing transcriptomics and network pharmacology methodologies, we identified autophagy-related key genes associated with the effects of PP. These genes were subjected to KEGG and GO enrichment analyses to determine their related functions. In vitro, CAL-27 cells were treated with 10, 30, and 60 μg/ml of PP for 24 h to assess tumor cell proliferation, apoptosis, and autophagy-related markers. Key findings. Molecular docking of MAPK3 and PSEN1 with PP revealed stable hydrogen bond interactions, indicating the therapeutic potential of these saponins in TSCC through the autophagy pathway. In vitro experiments demonstrated significant inhibition of proliferative activity in tongue squamous carcinoma CAL-27 cells and promotion of tumor cell apoptosis by PP. Western blot analysis confirmed alterations in the expression of autophagy markers P62, LC3B, and Beclin1 following treatment, suggesting activation of the autophagy pathway. Conclusions: Our results suggest that PP inhibits tumor cells through the autophagy pathway, in which MAPK3 and PSEN1 play a role as potential functional molecules. [ABSTRACT FROM AUTHOR]

Background: Chronic nonspecific cheilitis is a complex condition characterized by persistent lip peeling and discomfort. This case report explores the clinical progression of a patient with history of tongue squamous cell carcinoma and subsequent Tislelizumab treatment, presenting with persistent lip peeling. Case presentation: A patient with a history of tongue squamous cell carcinoma (T2N0M0), treated with chemotherapy, surgery, and Tislelizumab, presented with six months of persistent lip peeling. Clinical examination revealed distinct features of chronic nonspecific cheilitis with infectious angular cheilitis (Oral Candidiasis). A tailored treatment plan, emphasizing oral hygiene practices and local treatments with Sodium Bicarbonate, Tacrolimus ointment, and Chlortetracycline ointment. Follow-up visits demonstrated sustained improvement, highlighting the significance of individualized approaches. Conclusions: This case underscores the importance of recognizing and managing oral manifestations in patients with a history of cancer and immunotherapy. The patient's response to treatment suggests that a multifaceted approach, combining local therapy with lifestyle modifications, can be effective in managing chronic nonspecific cheilitis associated with immunotherapy. Routine follow-up appointments, guided by personalized medicine principles, contribute to sustained patient well-being. [ABSTRACT FROM AUTHOR]

INTRODUCTION The underlying factors of oral squamous cell cancers (OSCC) have been elucidated, but studies have focused little on etiological differences in affected oral cavity sites. The aim of this retrospective study was to clarify the role of carcinogen exposure in OSCC of different oral cavity areas. METHODS A cross-sectional study of patients with primary OSCC was conducted retrospectively, based on patient records from Helsinki University Hospital, Finland, between January 2016 and December 2020. The patients' self-reported history of tobacco smoking and alcohol use was explained by tumor site, age, sex, tumor size, and lymph node status in a logistic regression model. The information on smoking and alcohol use was compiled from a patient background form. RESULTS In 519 patients, tumors occurred most often in the tongue (51%), gingiva (21%), or floor of the mouth (FOM; 15%). FOM had 26-fold greater odds for a history of smoking and alcohol use than other tumor sites (OR=25.78; 95% CI: 8.02-82.95; p<0.001). Gingival and buccal sites were associated significantly less with smoking and alcohol use (OR=0.43, 95% CI: 0.28-0.67; p<0.001 and OR=0.47; 95% CI: 0.25-0.92; p<0.026, respectively). Patients of older age were less likely to have a history of smoking and alcohol use (AOR=0.95; 95% CI: 0.94-0.97; p<0.001) than younger patients. Tumor size (T3-4) and FOM increased the odds for history of smoking and alcohol use (AOR=1.73; 95% CI: 1.15-2.60; p=0.009 and AOR=26.15; 95% CI: 8.01-84.84; p<0.001, respectively). CONCLUSIONS OSCC of oral cavity sites has notable differences in etiology. FOM seems to be related almost exclusively to conventional smoking and heavy alcohol use. [ABSTRACT FROM AUTHOR]

Simple Summary: The United States is suffering from an epidemic associated with infections with the Human Papilloma Virus (HPV) that are responsible for the development of head and neck squamous cell carcinoma (HNSCC). Our study aims to characterize immune profiles, and the oral microbiota in oropharyngeal tumors associated with anti-PD-1 treatment response in a preclinical murine model for HPV+ oropharyngeal cancer. We confirmed 16 immune markers and specific bacteria in the oral cavity that differentiate between treatment responders and non-responders, which may be used as potential biomarkers for PD-1 blockade response. The United States is suffering from an epidemic associated with high-risk strains of the Human Papillomavirus (HPV) predominantly responsible for the development of head and neck squamous cell carcinoma (HNSCC). Treatment with immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand PD-L1 has shown poor efficacy in HNSCC patients, observing only a 20–30% response. Therefore, biological marker identification associated with PD-1 blockade response is important to improve prognosis and define novel therapeutics for HNSCC patients. Therapy response was associated with increased frequencies of activated CD27+T cells, activated CD79a+ B cells, antigen-presenting CD74+ dendritic and B cells, and PD-L1+ and PD-L2+ myeloid-derived suppressor cells (MDSCs). The oral microbiota composition differed significantly in mice bearing tongue tumors and treated with anti-PD-1. A higher abundance of Allobaculum, Blautia, Faecalibacterium, Dorea, or Roseburia was associated with response to the therapy. However, an increase in Enterococcus was attributed to tongue tumor-bearing non-responding mice. Our findings indicate that differences in immune phenotypes, protein expression, and bacterial abundance occur as mice develop tongue tumors and are treated with anti-PD-1. These results may have a clinical impact as specific bacteria and immune phenotype could serve as biomarkers for treatment response in HNSCC. [ABSTRACT FROM AUTHOR]

Background and Aims: Adenoid cystic carcinoma is a rare and slowly progressing cancer that frequently starts in minor salivary glands, often causing no symptoms. Therefore, advanced stage at initial presentation is frequently reported. Case Presentation: We provide a case study of a 33-year-old young woman with pT1 staging adenoid cystic tumour, emphasising the clinical presentation, treatment plan and patient prognosis. Comprehensive examination and imaging tests showed that the patient had a growing mass at the base of her mobile tongue. The diagnosis was supported by histopathological examination. Based on the tumour's small size and minimal invasion, pT1 was assigned as its staging. A comprehensive treatment strategy was used, and during surgery, the tumour was removed with precise margins that preserved both function and appearance. One-year follow-up showed no evidence of recurrence or ongoing problems. Conclusion: This case report emphasises the significance of early diagnosis, thorough treatment planning and attentive follow-up. It also highlights the infrequent presentation of disease. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 51-year-old Caucasian male with advanced oral cavity cancer who underwent neoadjuvant chemotherapy followed by surgery and radiation therapy. The treatment was successful, resulting in tumor regression and improved pain and eating. The article also discusses the importance of surgical factors and the conflicting results regarding the impact of neoadjuvant therapy on outcomes. Perspectives from plastic surgery, pathology, radiation oncology, speech pathology, and a patient's experience are provided. The document concludes by discussing future directions, including the potential use of immunotherapy. [Extracted from the article]

Purpose: Almost 200,000 tongue cancers were diagnosed worldwide in 2020. The aim of this study was to describe occupational risk variation in this malignancy. Methods: The data are based on the Nordic Occupational Cancer (NOCCA) study containing 14.9 million people from the Nordic countries with 9020 tongue cancers diagnosed during 1961–2005. The standardized incidence ratio (SIR) of tongue cancer in each occupational category was calculated using national incidence rates as the reference. Results: Among men, the incidence was statistically significantly elevated in waiters (SIR 4.36, 95% confidence interval (CI) 3.13-–5.92), beverage workers (SIR 3.42, 95% CI 2.02-5.40), cooks and stewards (SIR 2.55, 95% CI 1.82-3.48), seamen (SIR 1.66, 95% CI 1.36-2.00), journalists (SIR 1.85, 95% CI 1.18-2.75), artistic workers (SIR 2.05, 95% CI 1.54-2.66), hairdressers (SIR 2.17, 95% CI 1.39-3.22), and economically inactive persons (SIR 1.57, 95% CI 1.42-1.73). Among women, the SIR was statistically significantly elevated only in waitresses (SIR 1.39, 95% CI 1.05-1.81). Statistically significant SIRs ≤ 0.63 were observed in male farmers, gardeners, forestry workers and teachers, and in female launderers. Conclusions: These findings may be related to consumption of alcohol and tobacco, but the effect of carcinogenic exposure from work cannot be excluded. [ABSTRACT FROM AUTHOR]

Simple Summary: The initiative outlined in this paper emphasises the importance of a collaborative strategy in managing tongue cancer, involving a broad spectrum of healthcare professionals. This multidisciplinary method integrates the expertise of nurses, allied health workers, and various medical specialists to enhance diagnosis, treatment, and recovery processes for patients. By developing and examining a series of online lectures, this study highlights the critical roles played by each discipline in the comprehensive care pathway, from prevention and early detection to the management of advanced stages of the disease. This approach aims not only to address the clinical aspects of tongue cancer but also to support the overall well-being of patients, showcasing the benefits of teamwork in healthcare settings for improving patient outcomes. A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration. [ABSTRACT FROM AUTHOR]

Background: Recent studies have indicated that microRNA (miRNA) expression in tumour tissues has prognostic significance in Tongue squamous cell carcinoma (TSCC) patients. This study explored the possible prognostic value of miRNAs for TSCC based on published research. Methods: A comprehensive literature search of multiple databases was conducted according to predefined eligibility criteria. Data were extracted from the included studies by two researchers, and HR results were determined based on Kaplan‒Meier curves according to the Tierney method. The Newcastle‒Ottawa Scale (NOS) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pro-GDT were applied to assess the quality of all studies. Publication bias was estimated by funnel plot, Egger's rank correlation test and sensitivity analysis. Results: Eleven studies (891patients) were included, of which 6 reported up-regulated miRNAs and 7 mentioned down-regulated miRNAs. The pooled hazard ratio (HR) from the prognostic indicator overall survival (OS) was 1.34 (1.25–1.44), p < 0.00001, indicating a significant difference in miRNA expression between TSCC patients with better or worse prognosis. Conclusion: MiRNAs may have high prognostic value and could be used as prognostic biomarkers of TSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: While males exhibit higher incidence and mortality rates for most non-sex-specific cancers compared to females, the reasons behind these differences remain unclear. By analyzing the male-to-female rate ratios (MF IRRs) of non-sex-specific cancers by race and ethnicity, this research aims to shed light on whether sex-based differences are rooted in intrinsic biological variations or environmental exposures. Similarities of MF IRRs across race and ethnicity may suggest underlying biological variations that drive sex differences, while variations in MF IRRs may point to external factors driving these incidence differences. The results may help us understand the etiology of non-sex-specific cancers and the complex interplay between biology and environment in cancer development. Men have 2–3 times the rate of most non-sex-specific cancers compared to women, but whether this is due to differences in biological or environmental factors remains poorly understood. This study investigated sex differences in cancer incidence by race and ethnicity. Cancer incidence data from the Surveillance, Epidemiology, and End Result (SEER) program (2000–2019) were used to calculate male-to-female incidence rate ratios (MF IRRs) for each cancer site, stratified by race and ethnicity, and age-standardized to the 2000 U.S. population for individuals ages ≥ 20 years. Among 49 cancer sites, 44 showed male predominance (MF IRR > 1), with seven inconsistencies across race and ethnicity, including cancers of the lip, tongue, hypopharynx, retroperitoneum, larynx, pleura cancers, and Kaposi sarcoma. Four cancers exhibited a female predominance (MF IRR < 1), with only gallbladder and anus cancers varying by race and ethnicity. The MF IRRs for cancer of the cranial nerves and other nervous system malignancies showed no sex differences and were consistent (MF IRR = 1) across race and ethnicity. The MF IRRs for most cancers were consistent across race and ethnicity, implying that biological etiologies are driving the observed sex difference. The lack of MF IRR variability by race and ethnicity suggests a minimal impact of environmental exposure on sex differences in cancer incidence. Further research is needed to identify biological drivers of sex differences in cancer etiology. [ABSTRACT FROM AUTHOR]

The article describes the case of a 68-year old man with primary diffuse large B-cell lymphoma of the tongue base with acute airway obstruction. The patient was administered with intravenous injection of dexamethasone followed by nasotracheal intubation and he received a tracheostomy and biopsy of the tongue base mass. Results of laryngoscopy, computed tomography, magnetic resonance imaging and positron emission tomography of the mass are presented. He received steroids and chemotherapy.

Simple Summary: Oral squamous cell carcinoma of the tongue is the most common type of oral cavity cancer. The depth of tumor invasion is an important factor for both treatment planning and prognosis. In this study, we investigated the accuracy of intraoral ultrasound and magnetic resonance imaging (MRI) in assessing the depth of invasion in patients with oral tongue squamous cell carcinoma. Histopathological measurement of DOI was used as a reference standard. We conducted a prospective study including 30 patients planned for surgical treatment of oral tongue squamous cell carcinoma. Statistical analysis showed that intraoral ultrasound was more accurate than MRI for assessing the depth of invasion of oral tongue cancers. Clinical practice and guidelines could implement intraoral ultrasound accordingly. Oral squamous cell carcinoma (OSCC) of the tongue is the most common type of oral cavity cancer, and tumor depth of invasion (DOI) is an important prognostic factor. In this study, we investigated the accuracy of intraoral ultrasound and magnetic resonance imaging (MRI) for assessing DOI in patients with OSCC. Histopathological measurement of DOI was used as a reference standard. We conducted a prospective study including patients planned for surgical treatment of OSCC in the tongue. The DOI was measured in an outpatient setting by intraoral ultrasound and MRI, and was compared to the histopathological DOI measurements. Bland–Altman analysis compared the mean difference and 95% limits of agreement (LOA) for ultrasound and MRI, and the Wilcoxon signed-rank test was used to test for significance. The correlation was evaluated using Pearson's correlation coefficient. We included 30 patients: 26 with T1 or T2 tumors, and 4 with T3 tumors. The mean difference from histopathology DOI was significantly lower for ultrasound compared to MRI (0.95 mm [95% LOA −4.15 mm to 6.06 mm] vs. 1.90 mm [95% LOA −9.02 mm and 12.81 mm], p = 0.023). Ultrasound also led to significantly more correct T-stage classifications in 86.7% (26) of patients compared to 56.7% (17) for MRI, p = 0.015. The Pearson correlation between MRI and histopathology was 0.57 (p < 0.001) and the correlation between ultrasound and histopathology was 0.86 (p < 0.001). This prospective study found that intraoral ultrasound is more accurate than MRI in assessing DOI and for the T-staging of oral tongue cancers. Clinical practice and guidelines should implement intraoral ultrasound accordingly. [ABSTRACT FROM AUTHOR]

Background: Oral potentially malignant disorders (OPMDs) are associated with an increased risk of cancer of the oral cavity including the tongue. The early detection of oral cavity cancers and OPMDs is critical for reducing cancer-specific morbidity and mortality. Recently, there have been studies to apply the rapidly advancing technology of deep learning for diagnosing oral cavity cancer and OPMDs. However, several challenging issues such as class imbalance must be resolved to effectively train a deep learning model for medical imaging classification tasks. The aim of this study is to evaluate a new technique of artificial intelligence to improve the classification performance in an imbalanced tongue lesion dataset. Methods: A total of 1,810 tongue images were used for the classification. The class-imbalanced dataset consisted of 372 instances of cancer, 141 instances of OPMDs, and 1,297 instances of noncancerous lesions. The EfficientNet model was used as the feature extraction model for classification. Mosaic data augmentation, soft labeling, and curriculum learning (CL) were employed to improve the classification performance of the convolutional neural network. Results: Utilizing a mosaic-augmented dataset in conjunction with CL, the final model achieved an accuracy rate of 0.9444, surpassing conventional oversampling and weight balancing methods. The relative precision improvement rate for the minority class OPMD was 21.2%, while the relative F 1 score improvement rate of OPMD was 4.9%. Conclusions: The present study demonstrates that the integration of mosaic-based soft labeling and curriculum learning improves the classification performance of tongue lesions compared to previous methods, establishing a foundation for future research on effectively learning from imbalanced data. [ABSTRACT FROM AUTHOR]

Background: Oral cancer remains one of the most dreadful diseases in developing nations. Currently, there has been a rise in the prevalence of tongue squamous cell carcinoma (SCC), with a poor prognosis. The use of standard treatment approaches against oral cancer patients brings about several side effects. In recent years, nanomedicine has provided a versatile platform for developing new targeted therapeutic modalities. However, safety remains a concern in the synthesis of nanoparticles (NPs). Therefore, the present study aims to synthesize safer phytoconstituent-mediated gold NPs (AuNPs) utilizing leaf extracts of Annona muricata, where the biochemical components of the plant leaf act as the reducing and capping agents in the synthesis of NPs, and to evaluate its anti-cancer activity against SCC. Materials and Methods: In this in vitro experimental study, AuNPs were synthesized through an effective, simple, and ecologically sound green synthesis method. After characterization of these synthesized AuNPs, in vitro assays such as 3-(4, 5-dimethylthiazole2-yl)-2, 5-biphenyl tetrazolium bromide, wound healing, and clonogenic assays were carried out to investigate the anti-cancer potential of green synthesized AuNPs in the human tongue SCC cell line (SCC-15), and the possible mechanism of action was evaluated through gene and protein expression analysis of Bax, Bcl-2, and p53 genes. The results were expressed as mean ± standard deviation using Statistical Package for Social Sciences (SPSS) 20.0 software and Student's t-test was performed for experimental data. P ≤0.05 were considered statistically significant. Results: The in vitro assays demonstrated that the synthesized AuNPs are exhibiting anti-cancer activity by apoptosis of SCC-15 cells in a dose-dependent manner. Further, it also revealed a highly significant decrease in anti-apoptotic Bcl-2 gene expression, whereas pro-apoptotic genes p53 and Bax revealed a highly significant increase, which is statistically significant compared to the control (P < 0.05). Conclusion: Our findings demonstrated that the AuNPs synthesized from A. muricata leaf extract could act as a novel anticancer agent, particularly against SCC, after further scrutiny. [ABSTRACT FROM AUTHOR]

Simple Summary: Alteration of metabolic pathways, including the activation of aerobic glycolysis and increased dependence on glutamine, is characteristic of several human cancer types. Slc38a1 (also known as SNAT1, SAT1, SA2 or ATA1) is a cell membrane transporter highly capable of the net accumulation of cellular glutamine. It has been shown to be upregulated in several human cancers and/or associated with tumor progression. However, the functional role of this protein in the proliferation and differentiation of the oral epithelium, and its expression in human oral tongue squamous cell carcinoma (OTSCC), is not well understood. This study shows the upregulated expression of SLC38A1 in OTSCC indicating a role of SLC38A1 in OTSCC progression. The aerobic glycolytic pathway, boosting lactate formation, and glutamine addiction are two hallmarks of cancer pathophysiology. Consistent with this, several cell membrane glutamine transporters, belonging to different solute carrier (SLC) families, have been shown to be upregulated in a cell-specific manner to furnish the cells with glutamine and glutamine-derived metabolic intermediates. Among them, the system A transporter Slc38a1 has a higher affinity for glutamine compared to other SLC transporters, and it undergoes highly multifaceted regulation at gene and protein levels. The current study aimed to investigate the functional role of Slc38a1 in the proliferation and maturation of the mouse tongue epithelium. Secondly, we aimed to examine the expression of SLC38A1 and its regulation in human tongue oral squamous cell carcinoma (OTSCC). Employing Slc38a1 wild-type and knockout mice, we showed that Slc38a1 was not directly linked to the regulation of the proliferation and differentiation of the mouse tongue epithelium. External transcriptomic datasets and Western blot analyses showed upregulation of SLC38A1 mRNA/protein in human OTSCC and oral cancer cell lines as compared to the corresponding controls. Further, an investigation of external datasets indicated that mechanisms other than the amplification of the SLC38A1 chromosomal locus or hypomethylation of the SLC38A1 promoter region might be important for the upregulation of SLC38A1 in OTSCC. [ABSTRACT FROM AUTHOR]

Background: The increased life expectancy and accompanying comorbidities of elderly patients is in- creasing the need for composite soft tissue defect reconstruction. Since its introduction in 2004, the superficial circumflex iliac artery perforator (SCIP) flap has become popular among reconstructive surgeons for its various advantages. We describe our experience of free SCIP flap reconstruction in geriatric patients and examine its versatility in a literature review. Methods: Between 2018 and 2022, 19 geriatric patients (12 males, 7 females; 65--82 years old) under- went free SCIP flap transfer for reconstruction. The locations of the defects were all over the body area, from the trunk to the extremities. Patient perioperative demographic data are listed, along with surgical outcomes and complications. Results: In our experience, only one of 19 free SCIP flaps failed (total skin flap necrosis), presenting an overall flap survival rate of 94.7%. Partial flap loss was noted in 2 cases, which could be managed by other minor operations. Over at least 6 months of follow-up, all surviving flaps showed good contour and minimal donor site morbidity. Conclusion: The success rate was high and remained stable over time in geriatric patients managed with free SCIP flap reconstruction. The appearance of recipient and donor sites was optimal. With reduced donor site morbidity, we believe that the free SCIP flap will become a popular option for composite soft tissue defect coverage in the elderly. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we demonstrate that DDX5 serves as a tumor suppressor in the specific context of tongue cancer, which is contrary to its documented oncogenic role in a vast array of cancers. The high expression of DDX5 in tongue cancer is correlated with a better prognosis in clinical patients. The knockdown of DDX5 promotes, while the overexpression of DDX5 inhibits, tongue cancer proliferation, development, and cisplatin resistance. Moreover, we found that the expression of DDX5 in tongue cancer is associated with immune cell infiltration in the tumor microenvironment. Specifically, the expression of DDX5 is associated with a reduced infiltration of M2 macrophages and an increased infiltration of T cell clusters, which may contribute to anticancer effects in the tumor microenvironment. Our study establishes DDX5 as a valuable prognostic biomarker and an important tumor suppressor in tongue cancer. DEAD-box polypeptide 5 (DDX5), a DEAD-box RNA helicase, is a multifunctional protein that plays important roles in many physiological and pathological processes. Contrary to its documented oncogenic role in a wide array of cancers, we herein demonstrate that DDX5 serves as a tumor suppressor in tongue cancer. The high expression of DDX5 is correlated with better prognosis for clinical tongue cancer patients. DDX5 downregulates the genes associated with tongue cancer progression. The knockdown of DDX5 promotes, while the overexpression of DDX5 inhibits, tongue cancer proliferation, development, and cisplatin resistance. Furthermore, the expression of DDX5 in tongue cancer is associated with immune cell infiltration in the tumor microenvironment. Specifically, the expression of DDX5 is associated with the reduced infiltration of M2 macrophages and increased infiltration of T cell clusters, which may contribute to anticancer effects in the tumor microenvironment. In this study, we establish DDX5 as a valuable prognostic biomarker and an important tumor suppressor in tongue cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Even if tongue abscesses are rare, they have very heterogeneous clinical, laboratory and radiological findings. In some cases, their presentation can be particularly nuanced, and they can easily be mistaken for a submucosal malignancy, leading to a dangerous delay in diagnosis. The present paper presents a review of the literature on the possible manifestations (including symptoms, clinical and laboratory findings, imaging) and the management of tongue abscesses in relation to the differential diagnosis of oral tumors. Tongue abscesses are rare conditions that usually follow mucosal disruption due to mechanical trauma or foreign body impaction. They typically manifest abruptly as a rapidly growing, hard mass or swelling in the context of tongue muscles; the patient frequently complains of pain, difficulties in swallowing or speaking, and fever. Nonetheless, the features of its presentation, together with accurate clinical evaluation, blood tests, and appropriate imaging tests, are usually sufficient to easily discern a tongue abscess from a malignancy. However, in rare cases, they may occur with slowly progressing and subtle symptoms, nuanced objective and laboratory findings, and inconclusive radiological evidence, leading to difficult differential diagnosis with submucosal malignancy. Herein, we review the literature, available on Pubmed, Embase, and Scopus, on publications reporting tongue abscesses, with atypical presentation suggesting an oral tumor. Our review confirms that tongue abscesses may manifest as a slowly growing and moderately painful swelling without purulent discharge and minimal mucosal inflammation; in this case, they may constitute an actual diagnostic challenge with potentially severe impact on correct management. Atypical tongue abscesses must therefore be considered in the differential diagnosis of tongue malignancy with submucosal extension, even when other diagnostic elements suggest a neoplasia; in this case, a deep biopsy under general anesthesia is essential for differential diagnosis, and simultaneous drainage of the necrotic and abscessual material may resolve the condition. [ABSTRACT FROM AUTHOR]

Simple Summary: Tongue cancer typically has male predominance. However, several studies have documented an increasing number of incidences among the younger population, with female predominance, which is unusual. Current trends in tongue cancer and possible risk factors require more investigation. The global epidemiological trends in tongue cancer have shifted toward more incidences in younger and female groups. Our study confirms the same findings regarding the younger age group. However, in our locality, no significant changes have been noted regarding gender. More multi-institutional studies are recommended to explain such changes and highlight the possible risk factors so that appropriate corrective actions can be taken into consideration. The tongue is the most common site for oral cavity carcinoma. It typically has male predominance. However, several studies have documented an increasing number of incidences among the younger population, with female predominance, which is unusual. In this study, we aimed to determine current trends in tongue cancer regarding age and gender. Data from 197 tongue cancer patients were extracted from The Oncology Center, Mansoura University (OCMU) database from 2006 to 2021. The patients were divided into two time periods: (2006–2013) and (2014–2021). We computed counts and proportions of tongue cancer for demographic and tumor characteristics. The data were analyzed using SPSS. Gender showed no statistically significant difference in both groups, while the percentages of diagnosed females were 52.7% and 52%, respectively. The percentages of males were 47.3% and 48%, p-value = 0.927. There was a statistically significant difference in the number of patients aged 20 to 39 years old and ≥60 years old in both periods. The p-values were 0.039 and 0.011, respectively. Although tongue cancer is typically more common in males, our results showed no significant difference in the gender of diagnosed patients. In addition, our results showed that the number of younger patients significantly increased in the period from 2014 to 2021. However, we encourage further investigations involving larger populations. [ABSTRACT FROM AUTHOR]

The aim of the study was to dosimetrically compare interstitial high-dose-rate (HDR) brachytherapy (BT) and modern external beam radiotherapy modalities, as volumetric modulated arc therapy (VMAT) and stereotactic radiotherapy with Cyberknife (CK) of tumours of the tongue and floor of the mouth in terms of dose to the critical organs. In National Institute of Oncology, Budapest, between March 2013 and August 2022 twenty patients (11 male/9 female) with stage T1–3N0M0 tongue (n = 14) and floor of mouth (n = 6) tumours received postoperative radiotherapy because of close/positive surgical margin and/or lymphovascular and/or perineural invasion. High-dose-rate interstitial brachytherapy applying flexible plastic catheters with a total dose of 15 × 3 Gy was used for treatment. In addition to BT plans VMAT and stereotactic CK plans were also made in all cases, using the same fractionation scheme and dose prescription. As for the organs at risk, the doses to the mandible, the ipsilateral and the contralateral salivary glands were compared. The mean volume of the planning target volume (PTV) was 12.5 cm3, 26.5 cm3 and 17.5 cm3 in BT, VMAT and CK techniques, respectively, due to different safety margin protocols. The dose to the mandible was the most favourable with BT, as for the salivary glands (parotid and submandibular) the CK technique resulted in the lowest dose. The highest dose to the critical organs was observed with the VMAT technique. The mean values of D2cm3 and D0.1cm3 for the critical organs were as follows for BT, VMAT and CK plans: 47.4% and 73.9%, 92.2% and 101.8%, 68.4% and 92.3% for the mandible, 4.8% and 6.7%, 7.3% and 13.8%, 2.3% and 5.1% for the ipsilateral parotid gland, 3.5% and 4.9%, 6.8% and 10.9%, 1.5% and 3.3% for the contralateral parotid gland, 7.3% and 9.4%, 9.0% and 14.3%, 3.6% and 5.6% for the contralateral submandibular gland. The present results confirm that BT, despite being an invasive technique, is dosimetrically clearly beneficial in the treatment of oral cavity tumours and is a modality worth considering when applying radiotherapy, not only as definitive treatment, but also postoperatively. The use of the CK in the head and neck region requires further investigation. [ABSTRACT FROM AUTHOR]

* Context.--Nonsalivary primary adenocarcinomas of the base of the tongue (PABOTs) are extremely rare and worth reporting. Objective.--To study the detailed clinicopathologic features of PABOT. Design.--Cases of PABOT diagnosed on pathology material were retrieved from the archived electronic surgical pathology records. Results.--Six cases in 4 men and 2 women (M:F ratio, 2:1), with an age range of 31 to 76 years, satisfied the criteria. The tumor epicenter was the base of the tongue in all (6 of 6; 100%), with extension to the epiglottis in 50% (3 of 6), nodal metastasis in 66.7% (4 of 6), and distant metastasis in 33.3% (2 of 6). On histology, all but one were pure adenocarcinoma. Five of 6 cases (83.3%) had a gastrointestinal (GI) phenotype, of which 2 (40%) had a colonic/lower-GI--type (small groups of cells floating in mucin, CK20+, SATB2+, and CDX2+) and 3 (60%) had an upper-GI--like adenocarcinoma (UGI-LA; malignant glands with intracellular mucin, CK7+) histology. Cystic structure suggestive of teratomatous origin was identified in 2 of 5 cases (40%), both with UGI-LA phenotype. The non--GItype case had a unique histology with squamous differentiation in addition to adenocarcinoma areas, diffuse nuclear β-catenin on immunohistochemistry, and a corresponding exon 3 CTNNB1 mutation. One patient succumbed to disease, and 4 are alive with disease (follow-up of 1-9 months after completion of therapy). Conclusions.--We suggest using the broad term primary adenocarcinomas of the base of tongue (PABOTs), which can be further subdivided into colonic-type adenocarcinoma of the tongue and oral cavity, UGI-LA, and not otherwise specified categories, and reiterate a need for recognition and distinction of PABOT from salivary gland tumors. A subset originates from teratoid/duplication cysts, necessitating extensive sampling. Multicentric studies are essential to clinically and biologically prognosticate each of these categories. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumour depth of invasion is a well-known histological risk factor in oral cavity squamous cell carcinoma. With the advent of the eighth edition of the American Joint Committee on Cancer in 2017, a consensus has been established on the point from which to measure the depth of tumour invasion. All of this has led to changes in the T category of the TNM classification, leading to an increase in staging and possible adjustments in the management of adjuvant treatments. The main objective of this research is to assess the prognosis, according to the depth of invasion in patients with clinical early stages of oral tongue squamous cell carcinoma, to evaluate the influence of the depth of invasion in the latest TNM classification as well as in the global staging system, and to analyse its relation to other histological risk factors. Background: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. Methods: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan–Meier method. Statistical significance was established for p values below 0.05. Results: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. Conclusions: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade. [ABSTRACT FROM AUTHOR]

Risk factors for squamous cell carcinomas (SCCs) of the head and neck (HN) and oesophagus are similar. As such, synchronous primary tumors in these areas are not entirely uncommon. Definitive chemoradiation (CRT) is standard care for locally advanced HNSCC and is a preferred option for inoperable oesophageal SCC. Simultaneous treatment of both primaries with CRT can present technical challenges. We report a case of synchronous oropharyngeal and oesophageal SCC primary tumors treated simultaneously with definitive chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: The molecular makeup of a head and neck squamous cell carcinoma (HNSCC) could vary as per the geography and corresponding variability in prevalent etiopathological factors. The objective of this study was to analyze the expression pattern of E-cadherin (E-cad), a transmembrane glycoprotein with tumour suppressor function, in a cohort of HNSCC treated at a tertiary care medical centre in the southern part of India. Material and methods: After obtaining the institutional ethics committee's permission, the expression of E-cad in HNSCC was assessed by using immunohistochemistry on retrospectively collected tumour specimens, obtained by a surgical cohort of cases operated between September 2018 and July 2019. The E-cad expression was then correlated with various clinical and pathological characteristics of HNSCC, retrieved via the medical records of corresponding patients. Results: A total of 60 patients of HNSCC were included, most of whom had lesion in the oral cavity, in an advanced stage. The majority had a strong or moderate expression of E-cad on the surface. On analyzing further, oral cavity tumours had significantly less expression of E-cad compared to laryngeal and hypopharyngeal tumours taken together, and primary tumours had less E-cad expression than recurrent cases. Multivariate analysis with proportional odds regression showed the significant associations of low expression of E-cad expression with the moderate/poor differentiation of tumours and with the extranodal extension. Conclusions: Among the HNSCC, the loss of E-cad expression was mostly associated with primary tumours of the oral cavity, moderate/poorly differentiated tumours, and in those HNSCCs that had an extranodal extension. [ABSTRACT FROM AUTHOR]

Hemangioendothelioma is a diverse set of proliferative and neoplastic vascular lesions with biological characteristics that fall halfway between benign hemangioma and malignant angiosarcoma. Hemangioendothelioma of the oral cavity is extremely rare and if present, it is seen on lips, gingiva, tongue, maxilla, and mandible. The following case report is about a lesion on the right ventrolateral border of the tongue of a six-year-old female patient. A Laser excision was done. Histopathology revealed the features of hemangioendothelioma. An immunohistochemical (IHC) study was done to correlate the findings with a histopathological picture and arrived at the final diagnosis of epithelioid hemangioendothelioma (EHE). The patient was followed up for two years and no recurrence was noticed. [ABSTRACT FROM AUTHOR]

Objective: We aimed to develop a 5-year overall survival prediction model for patients with oral tongue squamous cell carcinoma based on machine learning methods. Subjects and methods: The data were obtained from electronic medical records of 224 OTSCC patients at the PLA General Hospital. A five-year overall survival prediction model was constructed using logistic regression, Support Vector Machines, Decision Tree, Random Forest, Extreme Gradient Boosting, and Light Gradient Boosting Machine. Model performance was evaluated according to the area under the curve (AUC) of the receiver operating characteristic curve. The output of the optimal model was explained using the Python package (SHapley Additive exPlanations, SHAP). Results: After passing through the grid search and secondary modeling, the Light Gradient Boosting Machine was the best prediction model (AUC = 0.860). As explained by SHapley Additive exPlanations, N-stage, age, systemic inflammation response index, positive lymph nodes, plasma fibrinogen, lymphocyte-to-monocyte ratio, neutrophil percentage, and T-stage could perform a 5-year overall survival prediction for OTSCC. The 5-year survival rate was 42%. Conclusion: The Light Gradient Boosting Machine prediction model predicted 5-year overall survival in OTSCC patients, and this predictive tool has potential prognostic implications for patients with OTSCC. [ABSTRACT FROM AUTHOR]

Introduction: Opportunistic oral cancer screening during visits to the dentist is a non-invasive and accessible option for detection of pre-malignant lesions and early-stage malignancies. The objective of this study was to investigate the knowledge, practices, and attitudes towards oral cancer screening among dentists. Methods: A 42-item survey was sent to 650 dental professionals affiliated with the University of Toronto. Data regarding training/practice characteristics, knowledge of oral cavity cancer, current screening practices, attitudes towards screening, and remuneration were collected. Results: Ninety-one dentists responded. Most obtained their dental degree from Canada (71.4%) and were practicing in large urban centers (87.9%). Most dentists correctly identified the oral tongue (87.8%) and floor of mouth (80%) as the two of most common sites of oral cavity cancer but only 56% correctly identified the most common presentation. 91% performed intra/extra oral examinations at every patient visit. Only 9.9% of dentists discussed the risk factors of oral cancer and 33% were not familiar with resources for smoking cessation and alcohol abuse. International medical graduates were more likely to discuss risk factor management than Canadian medical graduates (p < 0.01). Over 80% of dentists referred to a specialist when a suspected lesion was found. The greatest barrier for oral cancer screening was lack of time. Almost all dentists (98.8%) reported that their screening practices do not differ depending on the patient's insurance status and 63.8% reported compensation would not influence their decision to perform oral examinations. Conclusion: Most dentists have a good knowledge of the presentation and risk factors associated with oral cavity cancer. Most dentists perform screening with every patient, with no influence from compensation and insurance status. Dentists are therefore an excellent first contact for oral cavity cancer screening for the general public and for high-risk populations. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we developed a generic framework to analyze the Surveillance, Epidemiology, and End Results (SEER) database to generate reliable machine learning (ML) prediction models for cancer recurrence. As a proof-of-concept, using 130,979 oral tongue squamous cell carcinoma patients, we generated ML models to predict 5- and 10-year recurrence with high accuracy, recall, and precision. Thus, we demonstrate an effective framework for guiding future ML efforts in predicting cancer recurrence using the SEER database, with implications for the guidance of patient management and follow-up care. Despite diagnostic advancements, the development of reliable prognostic systems for assessing the risk of cancer recurrence still remains a challenge. In this study, we developed a novel framework to generate highly representative machine-learning prediction models for oral tongue squamous cell carcinoma (OTSCC) cancer recurrence. We identified cases of 5- and 10-year OTSCC recurrence from the SEER database. Four classification models were trained using the H2O ai platform, whose performances were assessed according to their accuracy, recall, precision, and the area under the curve (AUC) of their receiver operating characteristic (ROC) curves. By evaluating Shapley additive explanation contribution plots, feature importance was studied. Of the 130,979 patients studied, 36,042 (27.5%) were female, and the mean (SD) age was 58.2 (13.7) years. The Gradient Boosting Machine model performed the best, achieving 81.8% accuracy and 97.7% precision for 5-year prediction. Moreover, 10-year predictions demonstrated 80.0% accuracy and 94.0% precision. The number of prior tumors, patient age, the site of cancer recurrence, and tumor histology were the most significant predictors. The implementation of our novel SEER framework enabled the successful identification of patients with OTSCC recurrence, with which highly accurate and sensitive prediction models were generated. Thus, we demonstrate our framework's potential for application in various cancers to build generalizable screening tools to predict tumor recurrence. [ABSTRACT FROM AUTHOR]

Background Oral lesions can affect people’s quality of life by interfering with chewing, swallowing, and speech. These lesions may originate from epithelial or mesenchymal tissues. Malignant oral lesions can be life-threatening. Epidemiological data of oral lesions in Iran is limited. Objective This study aims to investigate the frequency of oral lesions in Rasht, Iran. Methods In this cross-sectional study, histopathologic data of oral lesions reported by Razi laboratory in Rasht from 2015 to 2019 were evaluated. The data collected: Patients’ age and sex, histopathologic findings, and location, type and origin of lesions. Non-specific diagnoses and dental and bone lesions were excluded. Results A total of 259 pathologic reports were included. The mean age patients was 52.09±19 years, and 40.2% were male. Oral lesions in patients aged <40 years were mainly benign (64.2%), whereas half of lesions in patients ≥70 years were mostly malignant. Tongue was the most common location of the lesions (34.7%) and the main location for malignant lesions (46.7%). Benign lesions were significantly higher in females whereas malignant lesions were significantly higher in males (P=0.011). Epithelial tissues were the most common site of origin (49%) and salivary glands were the least common site of origin (11.6%) for oral lesions. Conclusion Malignant oral lesions are more common in Iranian men aged >70 years, where the tongue is the most common site of involvement and epithelial tissue is the main site of origin. [ABSTRACT FROM AUTHOR]

Background: Speech disorders are common dysfunctions in patients with tongue squamous cell carcinoma (TSCC) that can diminish their quality of life. There are few studies with multidimensional and longitudinal assessments of speech function in TSCC patients. Methods: This longitudinal observational study was conducted at the Hospital of Stomatology, Sun Yat-sen University, China, from January 2018 to March 2021. A cohort of 92 patients (53 males, age range: 24–77 years) diagnosed with TSCC participated in this study. Speech function was assessed from preoperatively to one year postoperatively using the Speech Handicap Index questionnaire and acoustic parameters. The risk factors for postoperative speech disorder were analyzed by a linear mixed-effects model. A t test or Mann‒Whitney U test was applied to analyze the differences in acoustic parameters under the influence of risk factors to determine the pathophysiological mechanisms of speech disorders in patients with TSCC. Results: The incidence of preoperative speech disorders was 58.7%, which increased up to 91.4% after surgery. Higher T stage (P＜0.001) and larger range of tongue resection (P = 0.002) were risk factors for postoperative speech disorders. Among the acoustic parameters, F2/i/decreased remarkably with higher T stage (P = 0.021) and larger range of tongue resection (P = 0.009), indicating restricted tongue movement in the anterior-posterior direction. The acoustic parameters analysis during the follow-up period showed that F1 and F2 were not significantly different of the patients with subtotal or total glossectomy over time. Conclusions: Speech disorders in TSCC patients is common and persistent. Less residual tongue volume led to worse speech-related QoL, indicating that surgically restoring the length of the tongue and strengthening tongue extension postoperatively may be important. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical therapy for tongue carcinoma is challenging due to the various important functions of the tongue. In order to compensate for loss of tongue tissue and function, flap reconstruction has been firmly established. Interestingly, a large number of early-stage tongue cancer receive flap reconstruction despite minor tissue loss. This study aims to investigate functional and survival differences as well as epidemiologic characteristics in tongue carcinoma patients with or without flap reconstruction. Our retrospective and prospective analyses show no significant survival or functional differences between the groups with or without flap reconstruction. Still, we were able to demonstrate that the possibility of flap reconstruction leads to a more generous tumor resection, less frequent presence of close margin, and subsequently less frequent use of toxic adjuvant therapy regimens. Moreover, for the first time, a significantly higher female ratio could be depicted in the reconstruction group (p = 0.02). These findings suggest that, apart from oncologic and functional factors, proportional aspects should be taken into consideration for future decisions on the optimal reconstruction method. Background: Flap reconstruction is commonly used in advanced tongue carcinoma in order to compensate for the loss of tongue tissue and function. Surprisingly, a large number of reconstructed early-stage tongue cancer can be found. Survival or functional benefits in these cases remain unclear. Methods: A retrospective data analysis of 384 surgically treated tongue carcinoma patients was conducted aiming to find epidemiologic and survival differences between patients with (n = 158) or without flap reconstruction (n = 226). A prospective functional analysis was performed on 55 early-stage tongue cancer patients, 33 without and 22 with radial-forearm flap reconstruction, focusing on post-therapeutic swallowing function as the primary endpoint, speech as the secondary endpoint, xerostomia, quality of life, and mouth opening. Results: Consistent with the current literature, we demonstrated the significantly more frequent use of flap grafts in advanced tongue carcinomas. For the first time, we depicted a higher female ratio in the reconstructed group (p = 0.02). There were no significant differences in survival or functional outcomes between the groups. The none-reconstructed group showed more frequent use of adjuvant C/RT despite presenting fewer N+ stages. Conclusions: The higher female ratio in the reconstruction group is plausible due to the anatomically smaller oral cavity and relatively larger carcinoma in women. A higher presence of close margins in the none-reconstruction group may explain the more frequent use of adjuvant C/RT. Since we found no survival or functional differences between the groups, we propose a critical approach toward flap reconstruction in T1/2 tongue carcinoma. At the same time, proportional aspects and adequate resection margins should be taken into account. [ABSTRACT FROM AUTHOR]

Background: Tongue squamous cell carcinoma (TSCC) is the most common oral cancer with a poor prognosis. At present, there is not any systematic study on autophagy-related long non-coding RNA (lncRNA) to predict the survival of patients with TSCC. Material and methods: In this research, the cohort of TSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analysis showed that ten lncRNAs related to autophagy AC010326.3, AL160006.1, AL122010.1, AC139530.1, AC092747.4, AL139287.1, MIR503HG, AC009318.2, LINC01711, and LINC02560 are significantly correlated with prognosis. Based on these lncRNAs, a prognostic signature was established. This signature has an AUC value of 0.782, which accurately distinguishes patients of TSCC into high-risk and low-risk groups in different clinical hierarchical information (such as gender, age, etc.). Results: The clinical nomogram with autophagy-related lncRNA prognostic characteristics has a concordance index of 0.81, and accurately predicts the survival time at 1-year and 3-year of TSCC patients. Related functional enrichment results indicate that the pathways of the high-risk group are enriched on cancer and autophagy. Conclusions: The autophagy-related lncRNA prognostic signature established in this study could accurately predict the prognosis of TSCC patients and may be a molecular biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

Simple Summary: The present study evaluates the reliability of depapillation surrounding oral tongue squamous cell carcinomas (OTSCC) as a perineural invasion predictor and how it could affect narrow-band imaging performance. Our retrospective study was conducted on seventy-six patients affected by OTSCC submitted to radical surgery. The presence of depapillation, clinicopathological variables and narrow-band imaging vascular patterns were analyzed. Our results report that peritumoral depapillation is a reliable feature for perineural invasion in OTSCC, and narrow-band imaging margin detection is not impaired by depapillation. A recent study reported that the occurrence of depapillated mucosa surrounding oral tongue squamous cell carcinomas (OTSCC) is associated with perineural invasion (PNI). The present study evaluates the reliability of depapillation as a PNI predictor and how it could affect narrow-band imaging (NBI) performance. This is thus a retrospective study on patients affected by OTSCC submitted to radical surgery. The preoperative endoscopy was evaluated to identify the presence of depapillation. Differences in distribution between depapillation and clinicopathological variables were analyzed. NBI vascular patterns were reported, and the impact of depapillation on those was studied. We enrolled seventy-six patients. After evaluation of the preoperative endoscopies, 40 (53%) patients had peritumoral depapillation, while 59 (78%) had a positive NBI pattern. Depapillation was strongly correlated to PNI, 54% vs. 28% (p = 0.022). Regarding the NBI pattern, there was no particular association with depapillation-associated tumors. The presence of depapillation did not affect the intralesional pattern detected by the NBI, while no NBI-positive pattern was found in the depapillation area. Finally, the NBI-guided resection margins were not affected by depapillation. Peritumoral depapillation is a reliable feature for PNI in OTSCC. NBI margin detection is not impaired by depapillation. [ABSTRACT FROM AUTHOR]

Cisplatin plus 5-fluorouracil (PF) is used as the standard neoadjuvant chemotherapy (also called preoperative chemotherapy) in the treatment of tongue squamous cell carcinoma (TSCC). Although PF chemotherapy reduces the distant metastasis of TSCC, the five-year survival rate has not significantly improved. In recent years, components considered in traditional Chinese medicine have been researched as adjuvant drugs for radiotherapy and chemotherapy. Plumbagin (PB) is a quinone component isolated from Plumbago zeylanica L. Notably, PB demonstrates numerous anticancer properties. In order to examine the chemosensitization effect of PB on PF and its associated mechanisms, in vitro experiments using TSCC Cal27 and cisplatin (CDDP)-resistant Cal27/CDDP cells were carried out in the present study, and the results were subsequently verified using nude mice xenografts. Results of the present study demonstrated that PB enhanced the anticancer effects of PF on the proliferation, migration, and invasion of Cal27 and Cal27/CDDP cells. Cell cycle assays demonstrated that both Cal27 and Cal27/CDDP cells were arrested in the S phase following the combined treatment of PF and PB. Moreover, the PF and PB combination group induced higher levels of apoptosis in Cal27 and Cal27/CDDP cells compared with the group treated with PF alone. In addition, the results of the present study demonstrated that combined PB and PF inhibited the PI3K/AKT/mTOR/p70S6K pathway in TSCC cells. Moreover, the weight and volumes of tumors in nude mice were reduced following treatment with a combination of PF and PB. Results of the present study also demonstrated that the expression levels of Ki67 were markedly reduced in the combined treatment group compared with the group treated with PF alone. In summary, the results of the present study demonstrated that PB enhanced the PF sensitivity of TSCC through induction of S-phase arrest and apoptosis via the PI3K/AKT/mTOR/p70S6K pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: This brief review describes cases of oral cancer arising from GVHD in patients who underwent haematopoeitic stem cell transplantation (HSCT) as children. The risk of developing secondary solid malignancies after HSCT is well known, and, of the various cancers, oral squamous cell carcinoma (OSCC) is one of the most common. In the literature, there are no summary studies on this topic in the population of patients who have been transplanted as children. So, here we report all the published data on HSCT pediatric patients, affected by oral GVHD, who have been developed OSCC, with the aim of promoting the prevention of oral cancer in this patient setting. After haematopoietic stem cell transplantation and a history of GVHD, the risk of developing secondary malignancies, including oral cancer, is higher. This risk increases with time post-transplantation; therefore, pediatric patients undergoing HSCT, who have long-term survival chances, are in a high-risk category. The aim of this review is to provide data on HSCT, GVHD, clinical manifestations, histological features and treatment of oral cancer, and outcomes in HSCT pediatric patients, affected by oral GVHD, who have been developed OSCC. Descriptive statistics were used to validate data. Fifteen studies on a total of 33 patients were selected. Data on oral cancer showed that the tongue was the most frequently involved site (13 pts; 39.39%), followed by the floor of the mouth (4 pts; 12.12%), and buccal mucosa (4 pts; 12.12%). Oral squamous cell carcinoma was the histological feature reported. There were 19 (57.58%) deaths occurring between 2 and 46.5 months after OC diagnosis. Eleven patients survived with a median follow-up of 34 months. Considering the high risk of developing oral cancer, a conventional oral examination every 6 months is recommended for HSCT pediatric patients who have developed GVHD. [ABSTRACT FROM AUTHOR]

Background/purpose: Locally advanced tongue or tongue base cancer is recommended to be treated by radical resection that is usually detrimental to physiological functions. This study reports the efficacy and treatment outcome of the patients who had received total glossectomy and laryngeal suspension without lip-split mandibulotomy and free flap reconstruction to preserve laryngopharyngeal function.Methods: From 2010 to 2018, 37 consecutive patients who had received the surgery were retrospectively recruited.Results: The overall five-year survival is 72%. The postoperative dependent rate of feeding tube and tracheostomy largely decreases within 1-year follow-up. Treated by this surgical method, these patients are free from facial disfiguration, donor site morbidity, and destructive mastication and occlusion. It is also feasible to perform this surgical technique in the recurrent cases previously treated by chemoradiation.Conclusion: Total glossectomy with laryngeal suspension can be successfully applied to locally advanced tongue or tongue base cancer, and benefits the patients with improved survival and preserved physiological function. Especially surgeons for free flap reconstruction are understaffed at some regional or district hospitals. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery is the current standard for locally advanced tongue cancer. However, substantial impairment may occur even after treatment. Therefore, more effective and less toxic treatment strategies are needed to avoid a reduction in the patient's quality of life. This study aims to evaluate the efficacy and safety of a novel device that we have developed for retrograde intra-arterial chemotherapy (IACT) in patients with locally advanced tongue cancer. Our study demonstrates that the 3-year overall survival and progression-free survival were 81.6% and 74.2%, respectively. These results are not inferior to those of surgery, and no complications (e.g., cerebral infarction or catheter-related infection) have been associated with IACT were observed. We retrospectively evaluated the safety and effectiveness of an external carotid arterial sheath (ECAS) for intra-arterial chemotherapy (IACT) for locally advanced tongue cancer. Thirty-one patients with the Union for International Cancer Control's 8th TNM stage III–IV tongue cancer underwent IACT using the ECAS combined with RT and systemic chemotherapy with either cisplatin and fluorouracil (FP) or docetaxel, cisplatin, and fluorouracil (TPF) between October 2015 and February 2021. The ECAS was inserted retrogradely via the superficial temporal artery, and the tip was placed in the external carotid artery between the maxillary and facial arteries. A microcatheter was inserted into each tumor-feeding artery through the ECAS under fluoroscopy, wherein cisplatin 50 mg/m2 was administered. IACT was performed weekly with neutralization using sodium thiosulfate. Complete response of the primary lesion was achieved in 28/31 (90%) patients. The median follow-up for all patients was 39 months. The 3-year overall survival, progression-free survival, and local control rates were 81.6%, 74.2%, and 83.4%, respectively. Grade 3 and greater toxicities included oral mucositis (45%), neutropenia (39%), nausea (13%), anemia (10%), thrombocytopenia (10%), dry mouth (10%), and fever (3%). There were no severe complications associated with IACT. In conclusion, the ECAS is feasible and effective for locally advanced tongue cancer. [ABSTRACT FROM AUTHOR]

Background: The correlation between COVID‐19 and RT has not been determined to date and remains a clinical question. The aim of this study was to evaluate coronavirus disease 2019 (COVID‐19) pneumonia before, during, and after radiation therapy (RT) regarding the radiation doses, radiation pneumonitis, and surfactant protein levels. Methods: We evaluated patients diagnosed with COVID‐19 before, during, or after RT for the lung between August 2020 and April 2022. In patients with breast cancer, the RT dose to the ipsilateral lung was determined. In all other patients, bilateral lung RT doses were determined. Patients diagnosed with COVID‐19 after RT were evaluated to determine whether radiation pneumonitis had worsened compared with before RT. The serum levels of the surfactant proteins SP‐A and SP‐D were measured before, during, and after RT. Results: The patients included in the study comprised three men (27.3%) and eight women (72.7%). The primary cancer sites were the breast (n = 7; 63.7%), lung (n = 2; 18.1%), esophagus (n = 1; 9.1%), and tongue (9.1%). COVID‐19 was diagnosed before RT in four patients, during RT in two patients, and after RT in five patients. Six (54.5%) patients developed COVID‐19 pneumonia. Radiation pneumonitis grade ≥2 was not identified in any patient, and radiation pneumonitis did not worsen after RT in any patient. No rapid increases or decreases in SP‐A and SP‐D levels occurred after the diagnosis of COVID‐19 in all patients regardless of RT timing. Conclusions: COVID‐19 did not appear to result in lung toxicity and surfactant protein levels did not change dramatically. [ABSTRACT FROM AUTHOR]

Tongue squamous cell carcinoma (TSCC) is the most widespread and invasive subtype of oral cancer with high recurrence rates. Ailanthone (AIL) is an active ingredient in the plant extracts of Ailanthus altissima (Mill.) Swingle. Here, we showed that AIL inhibited the proliferation of human TSCC, the cell viability of Cal-27 and Tca8113 was significantly decreased after AIL treatment for 24 h. Hoechst 33258 staining demonstrated apoptotic characteristics (such as chromatin aggregation) after AIL treatment. The ratio of early- and late-apoptotic cells in AIL-treated Cal-27 and TCA8113 cells increased remarkably when compared with the control group. Bcl-2/Bax ratio and the levels of PARP1, caspase-9, and caspase-3 decreased after AIL treatment, accompanied by significant increase of cleaved PARP1, cleaved caspase-9, and caspase-3 in Cal-27 and TCA8113 cells. Meanwhile, AIL led to Cal-27 cell cycle arrest at G2/M phase. Western blot implied decreased levels of CDK1 and cyclin B1 after AIL treatment. The level of phospho-PI3K p55 subunit and p-Akt were significantly downregulated by AIL in both Cal-27 and TCA8113 cells. These findings implied the potential applications of AIL in the treatment of human TSCC. [ABSTRACT FROM AUTHOR]

Objectives: Increasing use of tobacco by the younger generation has resulted in an increase in oral cavity tumors. Surgical treatment is radical and results in severe functional morbidity. Using computer-aided designing technology, surgical and rehabilitative planning can be better. We present here our concept of a patient-specific biomechanical 3D model of the tongue and its clinical utility in the management of tongue tumors. Methods: Using fused deposition modeling, the 3D model of the tongue was printed which easily differentiates the tumor and the uninvolved tongue by printing in two different colors. The 3D tongue model was used by the surgical and rehabilitation teams to frame the treatment and plan the rehabilitation taking into account the patient preferences and needs. The model was used in two patients with operable squamous cell carcinoma (SCC) of the tongue, and the utility of the model in margin planning, surgical defect assessment, and its aid in the reconstruction and rehabilitation was assessed. Results: Two patients with Stage III SCC of the tongue underwent the surgery based on the plan evolved from the 3D model. All the surgical margins assessed by the frozen section analysis were clear. The model helped in addressing the discordance between patient expectations and surgical outcomes. We found that the model aided the reconstructive surgeon in planning the flap harvest based on the pre-operative defect assessment, which, in turn, translated into better rehabilitative outcomes. Conclusion: 3D biomechanical tongue model is a novel concept and aids in improving the overall treatment outcomes. The realistic 3D reconstructed image model helps the oncologist in planning the resection, enables the reconstructive surgery to more precisely predict the defect volume, and lastly the rehabilitative team in developing better rehabilitation strategies [ABSTRACT FROM AUTHOR]

Carbon monoxide-releasing molecule-3 (CORM-3) is a water-soluble complex which has the ability to release carbon monoxide (CO). The study is aimed at investigating the epidemiological characters and effects of CORM-3 on tongue squamous cell carcinoma (TSCC) cells and the mechanisms involved. Firstly, CAL27 and SCC4 were treated with CORM-3 or iCORM-3. The proliferation, migration, and invasion of cells were separately evaluated by CCK-8, scratch assay, and transwell assay. We found that the optimal concentration of CORM-3 on the proliferation of CAL27 and SCC4 cells was 400 μM, and CORM-3 was significantly inhibited the proliferation, migration, and invasion of TSCC cells. Meanwhile, CORM-3 increased the protein expression of HO-1 detected by western blot. Short-hairpin RNAs (shRNAs) were constructed to manipulate the expression of HO-1 in CAL27 and SCC4 cells. Then, rescue assays were conducted to explore the reversion effect of shHO-1 on the CORM-3 function. Mechanistically, CORM-3 decreased the protein of Keap1 expression as well as increased Nrf2 expression. Upregulation of E-cadherin was observed, as well as the downregulation of N-cadherin expression significantly. The antitumor effect of CORM-3 was used to xenograft tumor in nude mice for further investigation in vivo, and the result showed that CORM-3 significantly suppressed tumor growth in xenograft nude mice. These data suggest that CORM-3 acts as a tumor suppressor by regulating the Keap1/Nrf2/HO-1 signaling pathway in TSCC, which provides a potential chemotherapeutic strategy for TSCC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the intraoperative frozen section with the surgical margin in the postoperative surgical margins of the postoperative pathology of oral squamous cell carcinomas in order to examine the reliability of the frozen section. Methods: A retrospective analysis was conducted for patients who underwent surgery for oral squamous cell carcinoma in a tertiary hospital between January 2018 and 2019. The intraoperative frozen section examinations, grade of the tumor, number of lymph nodes, number of affected lymph nodes, depth of invasion, perineural invasion, lymphovascular invasion, and extranodal extension were recorded from the pathological records. The concordance between the frozen section examination and postoperative pathology 2 methods was examined using the Cronbach α coefficient. Sensitivity, specificity, positive predictive value, negative predictive value regarding surgical margins, and accuracy were calculated and reported. Results: Overall, 181patients who underwent surgery for oral cavity cancers were included; 118 (65.2%) were males. The mean (± standard deviation) age of the included participants was 57.4 ± 16.1 years. The most common tumour subsite was the tongue (n = 71, 39.2%). There was concordancy between the frozen, positive intraoperative malignancy and the postoperative pathology malignancy. The frozen, negative intraoperative malignancy and postoperative safe surgical margin did not significantly differ. Conclusion: As a result of intraoperative frozen examination, we found conformity between the postoperative pathology results of patients with positive and negative surgical margins. Frozen section examination could be used safely to examine intraoperative surgical margins of oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: The 5-year survival of patients with early-stage oral cancer remains at 80% despite advances in treatment. We have previously shown that the proximity between CD20 B cells and CD4 T cells in the invasive margin acts as an independent prognosticator in OSCC, represented by the so-called CD20 cluster score. However, its exact underlying cellular contexture is unknown. In this study, we demonstrated that the abundance of follicular helper T cells as well as the proximity between these cells and B cells were important hallmarks for patients with a high CD20 cluster score and long survival. In early oral squamous cell carcinoma (OSCC), the occurrence of clusters between CD20 B cells and CD4 T cells in the invasive margin (IM) can be captured by using the CD20 cluster score, and is positively associated with patient survival. However, the exact contribution of different CD4 T cell subsets, as well as B cell subsets toward patient prognosis is largely unknown. To this end, we studied regulatory T cells ((Treg cells) FOXP3 and CD4), T helper-type 1 cells ((Th1 cells) Tbet and CD4), follicular helper T cells ((Tfh cells) Bcl6 and CD4), B cells (CD20), germinal center B cells ((GC B cells) BCL6 and CD20), and follicular dendritic cells ((fDCs) CD21) for their density, location, and interspacing using multiplex in situ immunofluorescence of 75 treatment-naïve, primary OSCC patients. We observed that Treg, Th1-, Tfh-, and GC B cells, but not fDCs, were abundantly present in the stroma as compared with the tumor, and in the IM as compared with in the center of the tumor. Patients with high CD20 cluster scores had a high density of all three CD4 T cell subsets and GC B cells in the stromal IM as compared with patients with low CD20 cluster scores. Notably, enriched abundance of Tfh cells (HR 0.20, p = 0.04), and diminished abundance of Treg cells (HR 0.10, p = 0.03), together with an overall short distance between Tfh and B cells (HR:0.08, p < 0.01), but not between Treg and B cells (HR 0.43, p = 0.28), were significantly associated with overall survival of patients with OSCC. Our study identified the prognostic value of clusters between CD20 B cells and Tfh cells in the stromal IM of OSCC patients, and enabled an improved understanding of the clinical value of a high CD20 cluster score, which requires validation in larger clinical cohorts. [ABSTRACT FROM AUTHOR]

Simple Summary: Transoral Robotic Surgery (TORS) has become widely adopted for the surgical removal of oropharyngeal squamous cell carcinoma (OPSCC). However, it is currently unknown if TORS has equal efficacy and outcomes in patients with tonsillar or base of tongue (BOT) OPSCC. Therefore, we performed a systematic review, including articles describing the surgical management of OPSCC with TORS that compared margin status, complications, and recurrence between tonsil and BOT. BOT OPSCC had a higher rate of positive margins compared to tonsillar OPSCC. However, no differences were seen in the recurrence or postoperative hemorrhage rates of BOT and tonsillar OPSCC. While a higher rate of positive margins was seen in BOT OPSCC when compared to tonsillar OPSCC, this did not translate to a higher recurrence rate in the BOT group. Future research on which subset of patients with BOT is more likely to have positive margins is warranted to improve the utility of TORS further. Transoral Robotic Surgery (TORS) has become widely adopted for the surgical removal of oropharyngeal squamous cell carcinoma (OPSCC), with the most common locations being in the tonsil and base of tongue (BOT). However, it is currently unknown if TORS has equal efficacy and outcomes in patients with tonsillar or BOT OPSCC. Therefore, the aim of this study was to compare the margin status and recurrence rates of tonsillar and BOT OPSCC after TORS. Per PRISMA guidelines, PubMed, Scopus, and CINAHL were systematically searched from inception to 2/28/2022. Articles including the surgical management of OPSCC with TORS that compared margin status, complications, and recurrence between tonsil and BOT were included. Meta-analyses of proportions and odds ratios were performed. A total of 28 studies were included, comprising 1769 patients with tonsillar OPSCC and 1139 patients with BOT OPSCC. HPV positivity was seen in 92.3% of tumors. BOT OPSCC had a higher rate of positive margins compared to tonsillar OPSCC (28.1% [95%CI 15.1–43.3] vs. 7.5% [95%CI 3.3–13.3]). No differences were seen in recurrence between BOT and tonsillar OPSCC (OR 1.1 [95%CI 0.8–1.5], p = 0.480). In addition, no differences in postoperative hemorrhage were seen between tonsillar and BOT OPSCC (10.7% [95%CI 6.1–16.5] vs. 8.8% [95% CI 1.5–21.3]). While a higher rate of positive margins was seen in BOT OPSCC when compared to tonsil OPSCC, this did not translate to a higher recurrence rate in the BOT group. Future research on which subset of patients with BOT is more likely to have positive margins is warranted to improve the utility of TORS further. [ABSTRACT FROM AUTHOR]

Simple Summary: There is still limited knowledge of the critical pathogenic processes by which HPV16 induces oral carcinogenesis. Therefore, we aimed to illuminate the oncogenic role of HPV16 in the context of oral squamous cell carcinomas (OSCCs). Using human tongue keratinocyte cells, we demonstrated that HPV16 E6 promotes LTα1β2 and LTβR expression, thus promoting the lymphotoxin signaling pathway and leading to suppression of the transporter associated with the antigen-processing complex (TAPs; TAP1 and TAP2). Additionally, in vitro, we also demonstrated regulation of the antigenic peptide-loaded machinery in HPV-infected OSCC tissues through analysis of the transcriptomic profiles of the head and neck squamous cell carcinoma (HNSCC) cohort from the TCGA database, which was validated using fresh biopsied specimens. Thus, our study enhances the proposed functional role of HPV16 E6-associated immune-evasive properties in oral epithelial cells, revealing a possible mechanism underlying the development of HPV-mediated OSCCs. Infection by high-risk human papillomaviruses (hrHPVs), including HPV type 16 (HPV16), is a major risk factor for oral squamous cell carcinomas (OSCCs). However, the pathogenic mechanism by which hrHPVs promote oral carcinogenesis remains to be elucidated. Here, we demonstrated that the suppression of a transporter associated with the antigen-processing complex (TAPs; TAP1 and TAP2), which is a key molecule in the transportation of viral antigenic peptides into MHC class-I cells, is affected by the E6 protein of HPV16. Mechanistically, HPV-mediated immune evasion is principally mediated via the signal-transduction network of a lymphotoxin (LT) pathway, in particular LTα1β2 and LTβR. Our analysis of transcriptomic data from an HNSCC cohort from the Cancer Genome Atlas (TCGA) indicated that expression of TAP genes, particularly TAP2, was downregulated in HPV-infected cases. We further demonstrated that LTα1β2 and LTβR were upregulated, which was negatively correlated with TAP1 and TAP2 expression in HPV-positive clinical OSCC samples. Taken together, our findings imply that HPV16 E6 regulates the machinery of the antigenic peptide-loading system and helps to clarify the role of oncogenic viruses in the context of oral carcinoma. [ABSTRACT FROM AUTHOR]

Osteomas are rare benign bony tumors located in the tongue area. In most cases, patients presenting with a lingual osteoma are asymptomatic but may complain of the sensation of having a foreign body. Fewer than 100 cases of lingual osteoma have been reported worldwide. Here, we present 2 cases of tongue base osteoma that were treated with excision under a laryngoscope. [ABSTRACT FROM AUTHOR]

Background: Metastasis of infradiaphragmatic tumors to the left supraclavicular lymph node is reported to be rare. When metastasis is detected in the left supraclavicular node in patients with head and neck carcinoma, locating the primary cancer remains a difficult and time-consuming challenge despite the dramatic development of screening technologies and treatment methods.Case Presentation: We report three cases of malignant infradiaphragmatic tumor diagnosed following an initial finding of left supraclavicular node metastasis after surgery for tongue squamous cell carcinoma (follow-up period, range 18-62 months). In these cases, adenocarcinoma was diagnosed based on left supraclavicular node biopsies, and a second primary tumor was found, in a 78-year-old Japanese woman with a diagnosis of cholangiocarcinoma, a 64-year-old Japanese man with a diagnosis of bladder carcinoma, and a 61-year-old Japanese man with a diagnosis of prostate carcinoma. In the cholangiocarcinoma case, carbohydrate antigen 19-9 and alpha-fetoprotein levels helped to diagnose cholangiocarcinoma. Palliative care only was given, with survival for 11 months after diagnosis of lymph node metastasis. In the bladder carcinoma case, pathological analysis of fine-needle aspiration biopsy specimen of the metastatic cervical lymph node showed atypical cells with slight squamous differentiation. Hematoxylin-eosin staining of the bladder lesion did not identify a clear glandular or squamous component, and we could not make a definitive diagnosis of whether the lesion was poorly differentiated squamous cell carcinoma, adenocarcinoma, or high-grade urothelial carcinoma. GATA3 staining aided in the diagnosis of urothelial bladder cancer with left supraclavicular node metastasis. He survived for 2 months after diagnosis of left supraclavicular lymph node metastasis. In the prostate carcinoma case, 18F-fluorodeoxyglucose uptake was weak. Prostate-specific antigen levels and magnetic resonance imaging findings aided the diagnostic process. This patient underwent bilateral orchiectomy and adjuvant hormonal therapy and survived for 47 months after diagnosis of left supraclavicular node metastasis.Conclusions: Pathological diagnosis on the basis of immunohistochemistry and specific diagnosis methods such as radiological and serological assessments are important for providing rapid diagnosis and appropriate treatment. [ABSTRACT FROM AUTHOR]

Background: Oral tongue squamous cell carcinoma (OTSCC) is a prevalent malignant disease that is characterized by high rates of metastasis and postoperative recurrence. The aim of this study was to establish a nomogram to predict the outcome of OTSCC patients after surgery. Methods: We retrospectively analyzed 169 OTSCC patients who underwent treatments in the Cancer Hospital of Shantou University Medical College from 2008 to 2019. The Cox regression analysis was performed to determine the independent prognostic factors associated with patient's overall survival (OS). A nomogram based on these prognostic factors was established and internally validated using a bootstrap resampling method. Results: Multivariate Cox regression analysis revealed the independent prognostic factors for OS were TNM stage, age, lymphocyte-to-monocyte ratio and immunoglobulin G, all of which were identified to create the nomogram. The Akaike Information Criterion and Bayesian Information Criterion of the nomogram were lower than those of TNM stage (292.222 vs. 305.480; 298.444 vs. 307.036, respectively), indicating a better goodness-of-fit of the nomogram for predicting OS. The bootstrap-corrected of concordance index (C-index) of nomogram was 0.784 (95% CI 0.708–0.860), which was higher than that of TNM stage (0.685, 95% CI 0.603–0.767, P = 0.017). The results of time-dependent C-index for OS also showed that the nomogram had a better discriminative ability than that of TNM stage. The calibration curves of the nomogram showed good consistency between the probabilities and observed values. The decision curve analysis also revealed the potential clinical usefulness of the nomogram. Based on the cutoff value obtained from the nomogram, the proposed high-risk group had poorer OS than low-risk group (P < 0.0001). Conclusions: The nomogram based on clinical characteristics and serological inflammation markers might be useful for outcome prediction of OTSCC patient. [ABSTRACT FROM AUTHOR]