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Simple Summary: Oral cancer, a malignant neoplasm with invariable poor prognosis in the last 40 years (5-year survival rate of nearly 50%), accounts for a worldwide incidence of 377,713 new cases annually and 177,757 deaths per year. Oral cancer is usually preceded by oral potentially malignant disorders (OPMDs)—such as leukoplakia, oral lichen planus and oral submucous fibrosis—defined by the WHO Collaborating Centre for Oral Cancer as any mucosal abnormality that is associated with a statistical increased risk of developing oral cancer. Unfortunately, there are currently no tools available to accurately predict whether a patient in the early stages of oral carcinogenesis will develop oral cancer, being the presence and severity of epithelial dysplasia the histological marker universally applied for clinical practice. Nevertheless, this system presents relevant limitations related to imprecise and subjective assessments; therefore, emerging molecular biomarkers are under investigation. Among these biomarkers, retinoblastoma protein (pRb) is a well-recognized tumor suppressor in human oncogenesis, with roles linked to evading growth suppressors, a relevant hallmark of cancer. The loss of pRb expression regulates tumor initiation and early progression of neoplasms, and has been hypothesized to exert an oncogenic role during malignant transformation in early stages of oral carcinogenesis. Objective: The aim of this systematic review and meta-analysis was to qualitatively and quantitatively evaluate the current evidence on the significance of the loss of early stages of oral carcinogenesis in lesions diagnosed according to clinical and/or histopathological criteria and their evolution to oral cancer. Materials and Methods: We searched MEDLINE (through PubMed), Embase, Scopus and Web of Science for primary-level studies published before November 2024, designed as prospective or retrospective longitudinal cohorts, and not restricted by language or publication date. The risk of bias was critically assessed using the QUIPS tool. Meta-analyses, heterogeneity exploration, sensitivity and small-study effect analyses were conducted. Results: The inclusion criteria were met by six primary-level studies, which recruited 330 patients with OPMDs with follow-up data. The loss of pRb expression, assessed through immunohistochemistry, was significantly associated with a higher malignant transformation risk of OPMDs (RR = 1.92, 95%CI = 1.25–2.94, p = 0.003). The leukoplakia subgroup retained this significant association (p = 0.006), being the OPMD where the loss of pRb expression showed the best predictive value for malignant transformation (RR = 2.00, 95%CI = 1.22–3.29). Regarding the immunohistochemical technique and scoring methods, better performance and results were achieved by applying a cutoff point > 10% pRb-positive cells with nuclear staining (RR = 2.10, 95%CI = 1.30–3.38, 95%CI = 0.002). Conclussion: The present systematic review and meta-analysis supports that the loss of expression of the tumor suppressor pRb, assessed through immunohistochemistry, is a predictor of the malignant transformation risk of oral leukoplakias. Future studies are needed in other OPMDs following the recommendations provided based on current evidence gaps. [ABSTRACT FROM AUTHOR]

Simple Summary: The microbiota and Fusobacterium nucleatum (Fn) in particular are potential actors in oral oncology. The evidence about the role of Fn and the potential underlying mechanisms are reviewed on the basis of the more robust evidence concerning colorectal cancer. The translational potential of the different scenarios linking Fn to oral squamous cell carcinoma is discussed. Oral squamous cell carcinoma (OSCC) is one the most prevalent head and neck cancers and represents a major cause of morbidity and mortality worldwide. The main established risk factors for OSCC include tobacco and alcohol consumption and betel quid chewing, which may contribute alone or in combination with other environmental factors to carcinogenesis. The oral microbiota is emerging as a key player in the establishment of the molecular and cellular mechanisms that may trigger or promote carcinogenesis, including in the oral cavity. Among the bacterial species found in the oral microbiota, Fusobacterium nucleatum, an anaerobic bacterium commonly found in oral biofilms and a periodontal pathogen, has gained attention due to solid evidence implicating F. nucleatum in colorectal cancer (CRC). F. nucleatum has been shown to induce chronic inflammation, promote cell proliferation and trigger cellular invasion while deploying immune evasion mechanisms. These experimental findings were first obtained in in vitro and in vivo models of CRC and are being confirmed in studies on OSCC. In this review, we summarize the most recent findings on the role of F. nucleatum in OSCC, discuss the clinical implications in terms of prognosis and provide an overview of the key mechanisms involved. Moreover, we identify research questions and aspects that require investigations to clarify the role of F. nucleatum in OSCC. We anticipate that studies in this emerging field may have a significant clinical impact on the diagnosis, prognosis and management of OSCC. [ABSTRACT FROM AUTHOR]

This case study highlights the use of cinematic rendering (CR) in preoperative planning for the excision of a cyst in the oral and maxillofacial region of a 60-year-old man. The patient presented with a firm, non-tender mass in the right cheek, clinically suspected to be an epidermoid cyst. Conventional imaging, including dental magnetic resonance imaging (MRI) protocols, confirmed the lesion's size, location, and benign nature. CR reconstructions, combining advanced algorithms and novel skin presets, allow for the generation of highly realistic, three-dimensional visualizations from conventional imaging datasets. CR provided an enhanced, detailed depiction of the lesion within its anatomical context, significantly improving spatial understanding for surgical planning. The surgical excision was performed without complications, and histological analysis confirmed the diagnosis of a benign epidermoid cyst with no evidence of dysplasia or malignancy. This case demonstrates the potential of CR to refine preoperative planning, especially in complex anatomical regions such as the face and jaw, by offering superior visualization of superficial and deep structures. Thus, the integration of CR into clinical workflows has the potential to lead to improved diagnostic accuracy and better surgical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This study demonstrates that oral cavity squamous cell carcinomas with high levels of tumor-infiltrating B-lymphocytes (TIL-Bs) have a more favorable prognosis, irrespective of the total amount of tumor-infiltrating lymphocytes. Particularly in early-stage disease, the amount of TIL-Bs could be used to stratify patients who do well on standard-of-care therapy and patients who might need treatment intensification. Further research is warranted to unravel the potential cross-talk between and prognostic value of TIL-Bs and T-lymphocytes combined and their relevance in response to immunotherapy treatments, as well as identify the different subpopulations of TIL-Bs with regard to prognosis. Background/Objectives: Most studies on the interaction between the immune system and cancer focus on T-cells, whereas studies on tumor-infiltrating B-lymphocytes (TIL-Bs) are still underrepresented. The aim of this study was to assess the prognostic impact of TIL-Bs in early- and advanced-stage oral cavity squamous cell carcinoma (OCSCC). Methods: In total, 222 OCSCCs were studied. Consecutive sections were stained for CD45 and CD19. OCSCCs were categorized as either "TIL-B-rich" or "TIL-B-poor", and the survival of both groups was analyzed. Similar analyses were performed for CD45+ TILs and the CD19/CD45 ratio. Matched subgroups of twelve TIL-B-rich and TIL-B-poor tumors were stained for CD3 and CD8 to determine differences in T-cell infiltration, and further spatial interaction between T- and B-cells was evaluated in six samples. Results: Five-year OS was 75.0% for TIL-B-rich and 54.2% for TIL-B-poor OCSCCs (p < 0.001). The survival benefit of TIL-B-rich OCSCCs remained significant after correction for the histopathological characteristics (p = 0.033). While for early-stage tumors, TIL-B richness benefited OS independent of demographic-, clinical, or histopathological features, for advanced-stage disease, this was not the case, although a clear benefit of a TIL-B-rich status was observed, specifically up until 36 months after diagnosis. TIL-B-rich tumors contained more CD3+ TILs (p = 0.007), but not CD8+ TILs. Spatial characterization suggested that TIL-Bs mostly co-localized with CD3+CD8− TILs and that this interaction was increased in TIL-B-rich OCSCC. Conclusions: The presence of TIL-Bs is associated with a more favorable prognosis in OCSCC, in particular for early-stage disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Discharge against medical advice (DAMA) is a complex phenomenon with the potential to disrupt care in hospitalized patients, particularly in oncology, where continuous treatment is crucial for managing disease progression and improving outcomes. This study aimed to explore the prevalence of DAMA among cancer patients in Germany and identify factors associated with its occurrence. Analysis of data from over 51,000 patients hospitalized across 36 facilities revealed a DAMA rate of 0.9%. Younger age (especially under 60 years) and male sex were associated with higher DAMA rates. Patients with cancers of the lip, oral cavity, pharynx, larynx, and liver had the highest DAMA prevalence, while distant metastases showed no significant association. These findings highlight the multifaceted nature of DAMA and suggest that non-clinical factors, such as psychological, social, and economic pressures, may play a critical role in patients' decisions. This study provides a foundation for further research into strategies to better understand and address DAMA in vulnerable groups, improving care and outcomes for hospitalized cancer patients. Background: Discharge against medical advice (DAMA) disrupts continuity of care and is associated with increased readmission rates, morbidity, and mortality. While extensively studied in general hospital populations, its prevalence and associated factors in cancer patients, where treatment adherence is critical for outcomes, remain underexplored. Methods: This multicenter, cross-sectional study analyzed anonymized data from the IQVIA hospital database, including cancer patients hospitalized in 36 German hospitals between January 2019 and December 2023. Multivariate logistic regression assessed associations between DAMA and factors such as age, sex, cancer type, metastases, and comorbidities. Results: Among 51,505 cancer patients, DAMA occurred in 0.9% of hospitalizations. The highest rates were observed in cancers of the lip, oral cavity, and pharynx (2.1%), larynx (2.0%), and liver (1.8%). DAMA was more frequent in younger patients (≤50 years) (OR: 1.73; 95% CI: 1.30–2.14) and males (OR: 1.46; 95% CI: 1.23–1.72). Distant metastases showed no significant association (OR: 0.96; 95% CI: 0.81–1.13). Conclusions: The findings suggest that DAMA in cancer patients is more strongly associated with demographic and social factors than with disease severity. These results provide a basis for exploring strategies that address underlying psychosocial and economic challenges during hospitalization, particularly in younger and male patients. Further research is needed to better understand these associations and their implications for clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: This review explores the interpretation of intraepithelial papillary capillary loop (IPCL) classification in the narrow band imaging (NBI) magnification endoscopy of oral lesions. IPCLs are classified from Type 0 to IV. NBI magnification endoscopy is a useful noninvasive method for identifying the malignant transformation of oral potentially malignant disorders (OPMDs). Oral lesions classified as IPCL Type II or higher are atypical epithelial or oral squamous cell carcinoma (OSCC); oral biopsy is recommended for early and accurate diagnosis, and is an indicator of the appropriate biopsy site in the follow-up for OPMDs. The accuracy of NBI magnification endoscopy regarding the malignant transformation of OPMDs and OSCC will be further confirmed in the future. It is expected that NBI magnification endoscopy will be widely used by dentists in hospitals and general dental clinics. Narrow band imaging (NBI) magnification endoscopy for the diagnosis of early-stage oral cavity-related cancer and precancerous lesions can recognize oral lesions as brownish areas, and can observe intraepithelial papillary capillary loops (IPCLs) in the mucosa and submucosa to make a qualitative diagnosis of the lesion and highlight the mucosal surface microstructure to facilitate appropriate diagnosis and early treatment. IPCLs are classified from Type 0 to IV: Type 0 is normal mucosa or no blood vessels observed, e.g., in keratinization; Type I is mainly normal mucosa; Type II is mainly inflammatory sites or non-malignant lesions; Type III is mainly precancerous or suspected malignant lesions; and Type IV is cancerous or malignant lesions. NBI magnification endoscopy is a useful noninvasive method for identifying the malignant transformation of oral potentially malignant disorders (OPMDs). Oral lesions classified as IPCL Type II or higher are atypical epithelial or oral squamous cell carcinoma (OSCC); oral biopsy is recommended for early and accurate diagnosis, and is an indicator of the appropriate biopsy site in the follow-up for OPMDs. In the future, the accuracy of NBI magnification endoscopy for malignant transformation of OPMDs and OSCC will be further confirmed. [ABSTRACT FROM AUTHOR]

Simple Summary: Saliva is a vital fluid with diverse roles in oral and systemic health, including digestion, oral protection, and microbiome balance and support wound healing. It also serves as a non-invasive diagnostic tool, reflecting overall health and cancer. While saliva can protect against oral cancer, it may promote tumor progression and metastasis through exosomes and microRNA components. This review explores saliva's biological functions, its role in head and neck cancer progression/metastasis, and the potential therapeutic tool. Saliva plays a multifaceted role in oral health and systemic well-being. It supports digestion, protects oral tissues, maintains a healthy oral microbiome, and facilitates wound healing. Additionally, saliva serves as a diagnostic tool that reflects systemic health and disease/therapeutic states. Furthermore, although saliva shows a protective effect against oral cancer development, once tumor formation occurs, it may be involved in tumor progression and metastasis via exosomes and microRNAs. This review discusses the essential role of saliva; its relationship with the development, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC); liquid biopsy tools for early diagnosis and monitoring of HNSCC; and the potential of exosomes as therapeutic agents. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer remains one of the most common cancers globally, with invasive treatment often resulting in significant disfigurement and psychosocial distress. During the COVID-19 pandemic, the mandatory mask-wearing policies offered a unique opportunity to assess the impact of facial coverings on the quality of life (QoL) of these patients. This study provides valuable insights into how a simple intervention—mask-wearing—can positively influence the well-being of patients. It enhanced the QoL of oral cancer patients, reduced social anxiety and improved self-perception, indicating the dual role of masks as both a health protective measure and a psychosocial tool. Background: Treatments for oral squamous cell carcinomas (OSCCs) often result in significant aesthetic and functional issues, impacting patients' quality of life (QoL). The COVID-19 pandemic's mask mandates may have provided psychosocial benefits by concealing facial disfigurements, potentially reducing stigma. This study aimed to assess the impact of mask-wearing on the QoL of patients surgically treated for OSCC. Methods: This single-center, cross-sectional study, conducted from June 2022 to December 2023, included patients who had completed their treatment and returned home before or during the mask-wearing mandate. They answered a questionnaire using a four-point Likert scale to evaluate the mask-wearing's impact on QoL and the influence on it of physical appearance, tumor localization, radiotherapy, and treatment end date. Results: The questionnaire analysis found a high internal consistency among the questions (Cronbach's alpha = 0.931). Considering 41 patients (median age 69, 63% male), wearing a mask significantly improved QoL, with a mean score of 1.66 compared to a score of 2.00 for patients not wearing it (p < 0.001). This improvement was particularly notable for appearance concerns, fear of perception by family or others, and sociability apprehension. The QoL, with or without mask use, was not significantly modified when considering physical appearance, tumor localization, radiotherapy, or end date of the treatment, as demonstrated by two-way ANOVA tests and multiple linear regression. Conclusions: Mask-wearing positively impacted QoL in OSCC patients, providing psychological relief from disfigurement and social stigma. Masks offer a simple, accessible solution to enhance QoL while awaiting a definitive prosthetic treatment, suggesting that their continued use could be beneficial in supportive care strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Lip and oral cavity cancer caused over 177,000 deaths globally in 2020, but patient survival increases with earlier diagnosis. One barrier to early diagnosis is the invasive nature of biopsies needed for diagnosis. Automated diagnosis systems have the potential to perform non-invasive diagnosis by pairing novel imaging data with deep learning models. Given the variability between patients, access to a sufficiently large training database from human subjects limits deep learning applications. We propose a model that maps non-invasive images of oral tissue to a diagnosis by encouraging the model to group normal samples close together (reducing variability between patients). Our model improves non-invasive oral cancer diagnosis through a robust training process that only requires a small amount of data. This work shows how we can address small data challenges through model architecture and training, rather than through the collection of larger databases or manual corrections and normalizations. Background: Multispectral autofluorescence lifetime imaging systems have recently been developed to quickly and non-invasively assess tissue properties for applications in oral cancer diagnosis. As a non-traditional imaging modality, the autofluorescence signal collected from the system cannot be directly visually assessed by a clinician and a model is needed to generate a diagnosis for each image. However, training a deep learning model from scratch on small multispectral autofluorescence datasets can fail due to inter-patient variability, poor initialization, and overfitting. Methods: We propose a contrastive-based pre-training approach that teaches the network to perform patient normalization without requiring a direct comparison to a reference sample. We then use the contrastive pre-trained encoder as a favorable initialization for classification. To train the classifiers, we efficiently use available data and reduce overfitting through a multitask framework with margin delineation and cancer diagnosis tasks. We evaluate the model over 67 patients using 10-fold cross-validation and evaluate significance using paired, one-tailed t-tests. Results: The proposed approach achieves a sensitivity of 82.08% and specificity of 75.92% on the cancer diagnosis task with a sensitivity of 91.83% and specificity of 79.31% for margin delineation as an auxiliary task. In comparison to existing approaches, our method significantly outperforms a support vector machine (SVM) implemented with either sequential feature selection (SFS) (p = 0.0261) or L1 loss (p = 0.0452) when considering the average of sensitivity and specificity. Specifically, the proposed approach increases performance by 2.75% compared to the L1 model and 4.87% compared to the SFS model. In addition, there is a significant increase in specificity of 8.34% compared to the baseline autoencoder model (p = 0.0070). Conclusions: Our method effectively trains deep learning models for small data applications when existing, large pre-trained models are not suitable for fine-tuning. While we designed the network for a specific imaging modality, we report the development process so that the insights gained can be applied to address similar challenges in other non-traditional imaging modalities. A key contribution of this paper is a neural network framework for multi-spectral fluorescence lifetime-based tissue discrimination that performs patient normalization without requiring a reference (healthy) sample from each patient at test time. [ABSTRACT FROM AUTHOR]

Simple Summary: This article discusses the potential benefits and limitations of oral cancer screening. While early detection can be beneficial, there is limited evidence that screening programs significantly reduce deaths from oral cancer. The issue lies partly in how the effectiveness of screening programs is measured, with studies showing that higher detection rates do not necessarily translate to fewer deaths. The review highlights the importance of critical evaluation of screening programs and the need for improved dentist education and technology to reduce the burden of oral cancer. The authors advocate for a balanced, evidence-based approach to integrate screening into broader oral health strategies. Screening is widely believed to facilitate early detection and improve health outcomes; however, recent evidence questions its overall benefits, highlighting the need for a critical assessment of cancer screening programs. The simplicity of clinical oral examination and the easy accessibility of the oral cavity make oral cancer a suitable candidate for opportunistic screening. Despite this uniqueness, studies that solidly assess the efficacy and cost-effectiveness of oral cancer screening are scanty, and the only large randomized trial undertaken so far shows limited evidence of mortality reduction through population screening. Research indicates that while early detection rates following screening may increase, they do not necessarily translate into decreased oral cancer deaths. This article emphasizes the need for a nuanced understanding of the benefits of screening, awareness of deceptive metrics and inherent biases in the context of early detection, and the importance of improving dentist education and introducing new technologies to enhance clinical decision-making. The review calls for a balanced and evidence-based approach to oral cancer screening, integrating it with broader oral health initiatives to maximize public health outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This article aims to provide a first-of-its-kind summary of the literature on oral capillaroscopy—a non-invasive technique used to study the structure of tiny blood vessels beneath the mouth's surface in different conditions and lesions. This research has shown that oral capillaroscopy can provide both qualitative and quantitative insights into the health of these microvessels and highlight differences and peculiarities in specific diseases and conditions. This technology has promising applications in oral pathology and oncology, where it can be used to study cancer-related blood vessel growth in real time and monitor chronic inflammatory diseases. Future research may focus on using capillaroscopy to image oral potentially malignant disorders and better understand their microvascular components for diagnostic and prognostic purposes. The oral cavity may suffer from diseases and lesions of different natures that can result in changes to the underlying microvasculature. These changes are typically observed during the examination of biopsy samples, but there is still a need to investigate methods for characterizing them in live tissues. Capillaroscopy, a medical imaging technique using polarized light and magnification, has shown promise in providing enhanced imaging of the oral mucosa microvasculature in preliminary studies. The present work proposed to review the literature on what capillaroscopy is, its applications in the imaging of oral mucosa microvasculature, and its diagnostic and prognostic significance in various diseases and conditions. While there is the limited literature available, further research in oral capillaroscopy, particularly in the field of oral oncology, is needed to determine its potential benefits in diagnosing and predicting outcomes for potentially malignant oral disorders and cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Therapeutic decisions made during the treatment of patients with oral squamous cell carcinomas (OSCCs) significantly impact the overall course of the disease. A critical stage in the treatment process is the accurate histopathological assessment of excised tumors. The precision of the specimen description and the comprehensiveness of the information provided to the pathologist are of paramount importance. To address this, a multidisciplinary team comprising a maxillofacial surgeon, a pathologist, and an engineer was assembled. The team's objective was to devise a user-friendly protocol for virtual communication between the surgeon and the pathologist. Leveraging available software and a 3D scanner, a virtual communication protocol was formulated, enabling the generation of virtual images of excised tumors. Moreover, a methodology for applying annotations and marking specific areas (e.g., margins) directly on the tumor surfaces was developed. Consequently, this approach has afforded the team extensive capabilities for effectively conveying and archiving precise information. Background: The histopathological assessment is critical in the comprehensive treatment process for patients diagnosed with oral squamous cell carcinoma (OSCC). A detailed and precise specimen characterization is essential to facilitate effective surgeon–pathologist communication. Methods: In response to this need, a user-friendly virtual communication protocol utilizing a 3D scanner has been developed. This study involved 50 patients with OSCC, whose resected tumors were directly scanned in the operating room and subsequently annotated and characterized using available software. Results: The direct application of annotations and descriptions onto the virtual tumor specimens significantly enhanced the quantity and accuracy of information conveyed to the pathologist. Conclusions: The proposed solution's repeatability and standardized approach make integration into routine clinical practice feasible, thereby establishing a potential new standard in the field. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck cancer (HNC), especially oral squamous cell carcinoma (OSCC), is a common and increasingly prevalent cancer worldwide. OSCC is challenging to treat due to its aggressive nature and resistance to standard therapies like surgery, radiation, and chemotherapy, particularly in advanced stages. Cetuximab, a drug targeting EGFR (a protein that supports cancer cell growth), is often used but has limitations in effectiveness. This study explores a new approach by combining Cetuximab with drugs that target proteins involved in cell division, specifically MPS-1, Aurora-B, and KSP. These proteins help cancer cells progress through the cell cycle and are crucial for tumor survival. By blocking both EGFR and these cell division proteins, the study aimed to increase the effectiveness of Cetuximab in killing OSCC cells. Results showed that targeting MPS-1, Aurora-B, or KSP alongside EGFR led to more cancer cell death, suggesting that this combined approach could reduce treatment resistance. Analysis of patient samples confirmed that these proteins are significant in OSCC. This combined therapy strategy shows promise for improving outcomes in OSCC and potentially other head and neck cancers. Background/Objectives: Head and neck cancer (HNC) is among the most common cancer types globally, with its incidence expected to increase significantly in the coming years. Oral squamous cell carcinoma (OSCC), the predominant subtype, exhibits significant heterogeneity and resistance to treatment. Current therapies, including surgery, radiation, and chemotherapy, often result in poor outcomes for advanced stages. Cetuximab, an EGFR inhibitor, is widely used but faces limitations. This study explores the combined inhibition of EGFR and mitotic proteins to enhance treatment efficacy. Methods: We analyzed the effects of co-treating OSCC cells with small molecules targeting MPS-1 (BAY1217389), Aurora-B (Barasertib), or KSP (Ispinesib), alongside Cetuximab. The rationale is based on targeting EGFR-mediated survival pathways and the mitotic checkpoint, addressing multiple cell cycle phases and reducing resistance. Results: Our findings indicate that inhibiting MPS-1, Aurora-B, or KSP enhances Cetuximab's therapeutic potential, promoting increased cancer cell death. Additionally, we examined EGFR, MPS-1, Aurora-B, and KSP expression in OSCC patient samples, revealing their clinicopathologic significance. Conclusions: This combinatorial approach suggests a promising strategy to improve treatment outcomes in OSCC. [ABSTRACT FROM AUTHOR]

Background and Aims: To study the unknown influencing factors of delayed medical treatment behavior in oral cancer patients in western China and to develop a prediction model on the risk of delayed medical treatment in oral cancer patients. Method: We investigated oral cancer patients attending a tertiary Grade A dental hospital in western China from June 2022 to July 2023. The logistic regression and four machine learning models (nearest neighbors, the RBF SVM, random forest, and QDA) were used to identify risk factors and establish a risk prediction model. We used the established model to predict the data before and after the COVID-19 pandemic and test whether the prediction effect can still remain stable and accurate under the interference of COVID-19. Result: Out of the 495 patients included in the study, 122 patients (58.65%) delayed seeking medical treatment before the lifting of the restrictions of the pandemic, while 153 patients (53.13%) did so after the lifting of restrictions. The logistic regression model revealed that living with adult children was a protective factor for patients in delaying seeking medical attention, regardless of the implementation of pandemic control measures. After comparing each model, it was found that the statistical indicators of the random forest algorithm such as the AUC score (0.8380) and specificity (0.8077) ranked first, with the best prediction performance and stable performance. Conclusions: This study systematically elucidates the critical factors influencing patient delay behavior in oral cancer diagnosis and treatment, employing a comprehensive risk prediction model that accurately identifies individuals at an elevated risk of delay. It represents a pioneering large-scale investigation conducted in western China, focusing explicitly on the multifaceted factors affecting the delayed medical treatment behavior of oral cancer patients. The findings underscore the imperative of implementing early intervention strategies tailored to mitigate these delays. Furthermore, this study emphasizes the pivotal role of robust social support systems and positive family dynamics in facilitating timely access to healthcare services for oral cancer patients, thereby potentially improving outcomes and survival rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer represents a main public health issue around the world due to the mortality rates associated with it, the lack of effective and potent drugs, the multitude of side effects and the expensive treatments. Until now, no natural alternative therapeutic methods have been found beneficial enough to replace conventional drugs. Thus, bioactive compounds with anticancer properties can represent a necessary alternative through a targeted molecular approach to the multiple pathways involved in carcinogenesis. This review explores how the therapeutic potential of natural compounds can be harnessed and how they can be used as adjuvant therapies for oral cancer treatment. The collected results focused only on plant extracts and biologically active metabolites known for their antioxidant, anti-inflammatory and antitumor potential, which can be described as future chemopreventive agents against oral cancer, alone or in therapeutic combinations. Background: With a significant increase in both incidence and mortality, oral cancer—particularly oral squamous cell carcinoma (OSCC)—is one of the main causes of death in developing countries. Even though there is evidence of advances in surgery, chemotherapy, and radiotherapy, the overall survival rate for patients with OSCC has improved, but by a small percentage. This may be due, on the one hand, to the fact that the disease is diagnosed when it is at a too-advanced stage, when metastases are already present. Methods: This review explores the therapeutic potential of natural herbal products and their use as adjuvant therapies in the treatment of oral cancer from online sources in databases (PubMed, Web of Science, Google Scholar, Research Gate, Scopus, Elsevier). Results: Even if classic therapies are known to be effective, they often produce many serious side effects and can create resistance. Certain natural plant compounds may offer a complementary approach by inducing apoptosis, suppressing tumor growth, and improving chemotherapy effectiveness. The integration of these compounds with conventional treatments to obtain remarkable synergistic effects represents a major point of interest to many authors. This review highlights the study of molecular mechanisms and their efficiency in in vitro and in vivo models, as well as the strategic ways in which drugs can be administered to optimize their use in real contexts. Conclusions: This review may have a significant impact on the oncology community, creating new inspirations for the development of more effective, safer cancer therapies with less toxic potential. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates how personal and health-related factors impact the quality of life of head and neck cancer survivors treated with radiotherapy and surgery. By studying 150 patients—60 with nasopharyngeal cancer and 90 with oral cavity cancer—researchers utilized a specific survey to assess the effects of various elements, including cancer type, age, gender, relationship status, education, and employment. Findings revealed that cancer type, treatment history, and employment status significantly influenced quality of life. Patients with nasopharyngeal cancer reported better social and functional outcomes than those with oral cavity cancer. Additionally, unemployment was correlated with lower quality of life, while having a partner and undergoing certain surgeries positively impacted outcomes. These insights can aid research efforts to better support cancer survivors and customize treatment approaches for improved well-being. Objectives: This study aimed to examine the relationship between health-related quality of life (HRQoL) and sociodemographic and clinical variables in survivors of head and neck cancer (HNC) treated with radiotherapy, with or without surgery. Materials and Methods: HRQoL was measured using the functional assessment of cancer therapy—head and neck (FACT-H&N) in a cross-sectional survey involving 150 patients. Of these, 60 had nasopharyngeal cancer (NPC), treated exclusively with radiotherapy, while 90 had oral cavity squamous cell cancer (OSCC), undergoing radical surgery followed by adjuvant radiotherapy. Key variables included cancer type, age, gender, partnership status, education, and employment, with additional clinical variables assessed in patients with OSCC. Statistical analyses included multiple regression, ANOVA, and t-tests to explore relationships between variables and HRQoL. Results: Cancer type, surgical treatment, and employment status emerged as significant independent predictors of HRQoL in HNC patients. Patients with NPC reported better HRQoL on three FACT-H&N subscales—social/family well-being, functional well-being, and additional concerns—compared to patients with OSCC. Unemployed individuals exhibited lower HRQoL on four subscales. In patients with OSCC, partnership status and segmental mandibulectomy were found to predict HRQoL independently. Conclusions: This study concludes that cancer type, surgical intervention, and employment status notably influence HRQoL among HNC patients undergoing radiotherapy. In addition, partnership status is a key factor affecting HRQoL in patients with OSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: This research explores non-invasive methods for detecting Human Papillomavirus (HPV) in patients with oral squamous cell carcinoma (OSCC). The study compares two self-collection techniques, oral rinse vs. salivary sponge, to determine their effectiveness in identifying HPV DNA. Results from 26 patients indicated that the salivary sponge method was more accurate and sensitive compared to the oral rinse. This finding suggests that a salivary sponge may be a superior option, especially for patients with functional limitations caused by OSCC. Our research could lead to improved non-invasive diagnostic tools for HPV in clinical settings. Background/Objectives: Human Papillomavirus (HPV) is a significant etiological factor in the development of oropharyngeal carcinogenesis. The detection of HPV in oral squamous cell carcinoma (OSCC) could be also crucial for diagnosis, prognosis, and treatment planning. This study compares the efficacy and accuracy of two non-invasive sampling methods, oral rinse, and oral sponge, in detecting HPV DNA in patients with OSCC. Methods: Twenty-six patients with histologically confirmed OSCCs were recruited (M/F = 15/11; mean age 68.6). From each patient, two self-collected oral specimens, in the form of an oral rinse and a salivary sponge (i.e., LolliSponge), were collected, and subsequently processed, utilizing INNO-LiPA HPV Genotyping Extra II for HPV DNA detection; Results: Oral sponge detection showed high specificity (100%), sensitivity (85.7%), and accuracy (96.2%) compared to the oral rinse sampling, also demonstrating an area AUC for its diagnostic performance significantly greater than 0.5 (0.93 vs. 0.5, p < 0.0001). Conclusions: This study supports that oral sponge sampling offers valuable non-invasive alternatives for HPV detection in patients with OSCC, with the potentiality to facilitate saliva sampling in patients that may exhibit functional deficit due to OSCC. Further research is recommended to validate these findings in larger cohorts and to explore the integration of these methods into routine clinical practice for the management of HPV-related OSCC. [ABSTRACT FROM AUTHOR]

Background: Periodontal disease is an inflammatory, chronic, and multifactorial disease. The objective of this study is to analyze the association between periodontal disease and some disorders such as papillomas (benign lesions), lichen planus (a chronic immune-mediated disorder), leukoplakia (potentially malignant lesions), and oral cancer (malignant lesions). Methods: For this study, 42 patients were recruited whose supragingival and subgingival plaque was qualitatively analyzed using a phase-contrast microscope, which allowed for the detection of compatible bacterial flora (immobile and composed mainly of cocci) indicative of periodontal health and incompatible bacterial flora (mobile and composed mainly of spirochetes) indicative of periodontal pathology. Patients with incompatible bacterial flora were then subjected to a laser-assisted periodontal treatment with irrigation with hydrogen peroxide within the periodontal pockets (a non-surgical laser-assisted periodontal protocol which is referred to as dye-free photodynamic therapy). Results: Based on the 42 patients recruited, there was no association between oral cavity lesions and periodontal pathogenic bacteria. Four of them were found to have incompatible bacterial flora. Indeed, it was found that almost all the patients had been previously instructed in the proper techniques of home oral hygiene, and more than half of them reported that they carried out periodic check-ups by a dental hygienist. Of the four patients with signs and symptoms of periodontitis, two stated a willingness to undergo the non-surgical laser-assisted periodontal protocol and showed improvements in periodontal indices such as CAL, PPD, and BoP. Conclusions: hygienists and dentists are determining factors in the prevention of periodontal disease and for the maintenance of good oral health. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer is a challenging disease to treat, and new therapies are needed to improve patient outcomes. Okanin, a natural compound derived from Bidens pilosa L., has been known for its anti-inflammatory properties, but its effects on cancer, particularly oral cancer, are less understood. In this study, we investigated the anticancer potential of okanin in human oral cancer cells. Our results showed that okanin effectively reduced the growth of oral cancer cells by inducing cell death through mechanisms involving both apoptosis and pyroptosis. Additionally, okanin inhibited tumor growth in a mouse model of oral cancer. These findings suggest that okanin may be a promising natural compound for developing new treatments for oral cancer. Background: Okanin, a flavonoid compound derived from Bidens pilosa L., has garnered attention for its anti-inflammatory properties. Although Bidens pilosa is commonly used in healthcare products and functional foods, the anticancer potential of okanin, particularly in oral cancer, remains underexplored. This study aims to investigate the effects of okanin on oral cancer cell lines and its potential as a therapeutic agent. Methods: The study involved assessing the cytotoxic effects of okanin on oral cancer cell lines SAS, SCC25, HSC3, and OEC-M1. The IC50 values were determined using methylene blue assays, and the clonogenic capacity was evaluated through colony formation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis. Caspase-3/7 activity assays and annexin V/7-AAD staining confirmed the induction of apoptosis and pyroptosis. In vivo efficacy was assessed using a SAS xenograft model, and immunohistochemical analysis of xenograft tissue was performed to examine pyroptosis-related markers. Results: Okanin exhibited potent cytotoxic effects with IC50 values of 12.0 ± 0.8, 58.9 ± 18.7, 18.1 ± 5.3, and 43.2 ± 6.2 μM in SAS, SCC25, HSC3, and OEC-M1 cells, respectively. It caused dose- and time-dependent reductions in cell viability and significantly impaired clonogenic capacity. Flow cytometry revealed G2/M cell cycle arrest and increased sub-G1 population, indicating cell cycle disruption and death. Okanin induced both apoptosis and pyroptosis, as confirmed by caspase-3/7 activity and annexin V/7-AAD staining. In vivo, okanin reduced tumor growth and involved pyroptosis-related markers such as CASP1, GSDMC, GSDMD, and GSDME. Conclusions: Okanin demonstrates significant anticancer potential, particularly in oral cancer, by inducing both apoptosis and pyroptosis. Its efficacy in reducing tumor growth in vivo further supports its potential as a novel therapeutic option. Further mechanistic studies are needed to elucidate the pathways involved in okanin-mediated cell death and to explore its clinical applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancers of the lip and oral cavity are common cancers worldwide. Up to 46% of oral cancers are preventable if risk factors are avoided and if precancerous lesions are detected at an early stage. To reduce the incidence of oral cancer and its mortality rate, there is ongoing research studying new diagnostic and treatment methods. This review aims to present a novel glance at oral cancer—its current classification and epidemiology—and will provide new insights into the development of new diagnostic methods and therapies of oral cancer. Oral cavity and lip cancers are the 16th most common cancer in the world. It is widely known that a lack of public knowledge about precancerous lesions, oral cancer symptoms, and risk factors leads to diagnostic delay and therefore a lower survival rate. Risk factors, which include drinking alcohol, smoking, HPV infection, a pro-inflammatory factor-rich diet, and poor oral hygiene, must be known and avoided by the general population. Regular clinical oral examinations should be enriched in an oral cancer search protocol for the most common symptoms, which are summarized in this review. Moreover, new diagnostic methods, some of which are already available (vital tissue staining, optical imaging, oral cytology, salivary biomarkers, artificial intelligence, colposcopy, and spectroscopy), and newly researched techniques increase the likelihood of stopping the pathological process at a precancerous stage. Well-established oral cancer treatments (surgery, radiotherapy, chemotherapy, and immunotherapy) are continuously being developed using novel technologies, increasing their success rate. Additionally, new techniques are being researched. This review presents a novel glance at oral cancer—its current classification and epidemiology—and will provide new insights into the development of new diagnostic methods and therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a widespread health problem with limited treatment options and poor survival rates. Metformin, a common medication for managing diabetes, has recently shown promise as a potential treatment for various cancers, including OSCC. This review examines the potential benefits of repurposing metformin to treat oral cancer. Studies have shown that metformin can reduce the growth of cancer cells, induce cancer cell death, and improve the effectiveness of existing treatments. It works by affecting several pathways involved in cancer development, such as those related to cell energy and inflammation. However, using metformin for cancer treatment comes with challenges, including possible side effects and interactions with other medications. More research and clinical trials are needed to understand how metformin can be effectively used in cancer treatment and to ensure its safety. If proven effective, metformin could provide a new, cost-effective option for treating oral cancer, potentially improving outcomes and quality of life for patients. Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease's prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin's ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin's application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin's potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: The problems associated with oral squamous cell carcinoma (OSCC) are becoming increasingly apparent. Namely, cancer of the oral cavity is the most common malignant tumor in the head and neck area worldwide. In addition to the usual risk factors for the development of OSCC, such as smoking and alcohol consumption, recent research has shifted its focus to the oral cavity microbiome, specifically dysbiosis. Numerous studies have concluded that disrupting the eubiosis of the oral cavity promotes the growth of oral pathogens, which, through their virulence factors and manifold pathogenicity factors, lead to inflammatory conditions that can damage tissue cells, potentially leading to cancer development. From an aetiological point of view, these pathogens can be bacteria, viruses, fungi, and parasites. Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Although the oral cavity is an easily accessible area for visual examination, the OSCC is more often detected at an advanced stage. The global prevalence of OSCC is around 6%, with increasing trends posing a significant health problem due to the increase in morbidity and mortality. The oral cavity microbiome has been the target of numerous studies, with findings highlighting the significant role of dysbiosis in developing OSCC. Dysbiosis can significantly increase pathobionts (bacteria, viruses, fungi, and parasites) that trigger inflammation through their virulence and pathogenicity factors. In contrast, chronic bacterial inflammation contributes to the development of OSCC. Pathobionts also have other effects, such as the impact on the immune system, which can alter immune responses and contribute to a pro-inflammatory environment. Poor oral hygiene and carbohydrate-rich foods can also increase the risk of developing oral cancer. The risk factors and mechanisms of OSCC development are not yet fully understood and remain a frequent research topic. For this reason, this narrative review concentrates on the issue of dysbiosis as the potential cause of OSCC, as well as the underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, liquid biopsy has been introduced as a new method for the detection and management of cancer, but the studies on oral squamous cell carcinoma (OSCC) are lacking conclusive evidence. The aim of this study was to evaluate the expression of six circulating salivary and plasmatic miRNAs (-21, -31, -138, -145, -184, and -424) as diagnostic biomarkers in patients affected by OSCC and by oral potentially malignant disorders (OPMDs). Our results showed that liquid biopsy from saliva may be a useful tool for the identification of these biomarkers; in particular, miR-138 and miR-424 showed decreased expression levels in saliva samples in OSCC and OPMD patients compared to healthy controls. The introduction of liquid biopsy in daily clinical practice could revolutionize the approach to oral lesions by allowing the mass screening, stratification and monitoring of patients at risk, the monitoring of the response to treatment and the early identification of any recurrences. This study aims to evaluate the expression of salivary and plasmatic miRNAs as diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A total of 25 patients were divided into three groups, according to their diagnosis: OSCC patients (n = 14); OPMDs patients (n = 6); and healthy controls (n = 5). At the time at diagnosis/enrolment, patients underwent salivary and plasmatic collection. The expression of miRNA -21, -31, -138, -145, -184, and -424 were evaluated by real-time PCR. An F-test and ANOVA test were performed to evaluate the miRNA levels (significance at p < 0.05). By comparing miRNA expression levels from saliva, a statistically significant difference emerged in the expression of miR-138 and miR-424 between the three groups (p < 0.05). In particular, these two miRNAs showed decreased expression levels in saliva samples from OSCC and OPMD patients compared to those from healthy controls. On the other hand, miRNA expression levels in plasma were low in all the groups, and no statistically significant differences were found. Overall, our results showed that liquid biopsy from saliva may be a useful tool for the identification of diagnostic molecular biomarkers in OSCC and OPMDs. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer affects the mouth and throat areas. It is a major cause of death for older people in developed countries. This review looked at how living in rural areas influences oral cancer trends in these countries. The studies from these countries showed increasing rates of oral cancer in rural areas of the US, Australia, Canada, and Europe. Older people are more affected by these cancers than younger groups. The main risk factors are tobacco use, alcohol consumption, and HPV infections. People in rural areas often do not know much about HPV-related cancers. They also tend to use more tobacco and alcohol than city dwellers. Even in developed countries, living in rural areas can lead to shorter lifespans for oral cancer patients. This is mainly because it is harder for them to access specialized cancer treatment centres and advanced medical care. In summary, where people live can significantly impact their chances of surviving oral cancer, even in wealthy nations. Oral cancer is the general term used to describe cancers of the oral cavity and oropharyngeal region. These cancers are one of the leading causes of death in elderly residents within the Organisation for Economic Co-operation and Development (OECD) member countries in the 21st century. This scoping review was carried out to assess the influence of rurality on oral cancer trends and patterns among OECD member countries. Four online databases (Medline, PubMed, Scopus, and CINAHL) were searched for studies that reported on oral cancer trends in rural and remote areas in OECD member countries. A total of 1143 articles were obtained initially; among them, 995 papers were screened to include 18 articles for this scoping review. Studies have reported increasing incidence and prevalence in the United States, Australia, Canada, and European countries wherein risk factors such as tobacco, alcohol, and human papilloma virus (HPV) infections were associated with oral and oropharyngeal cancers. Awareness among people living in rural areas about HPV-related cancers was very low, while rates of tobacco and alcohol abuse were noted to be rising more rapidly than among their urban counterparts. Furthermore, the ageing population was most affected compared to the younger age groups of people with oral and oropharyngeal cancer that are prevalent in these regions. Overall, despite living in developed countries, rurality was noted to be a significant factor in the lower life expectancy of oral cancer patients, mainly due to the limited accessibility to tertiary cancer care centres and advanced medical care. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanocytic tumors (MTs) are more prevalent in dogs than in cats. In dogs, they are the most frequent malignancy of the oral cavity, whereas in cats, ocular melanomas predominate. This study provides epidemiologic data (2005–2024) on MTs for both dogs and cats. Totals of 21128 canine and 4808 feline tumors were analyzed by the Veterinary Pathology Service of the Department of Veterinary Medicine (University of Perugia). Among these, 845 canine MTs (329 melanocytomas; 512 melanomas) were diagnosed, 485 from the skin, 193 from the oral mucosa, and 104 from the mucocutaneous junction. Older dogs were more likely to develop melanomas than melanocytomas (p < 0.001). In contrast, among feline tumors, only 60 were melanocytic (6 melanocytomas, 53 melanomas). Of these, 29 were cutaneous, 18 were ocular, and 9 were oral. In dogs, melanomas were more common in mucocutaneous locations than in cutaneous locations (p < 0.05); moreover, they were more common in the oral cavity compared to all other sites (p < 0.001). In cats, ocular melanomas were more common than cutaneous ones (p < 0.05). This study provides the prevalence of MTs in dogs and cats, supporting distinct epidemiological patterns of MTs, and confirming the significance of species-specific differences in the tumor prevalence, localization, and age distribution. MTs are prevalent in dogs, representing the most frequent oral malignancy, compared to cats, in which ocular melanomas predominate. This study investigates the canine and feline MT epidemiology (2005–2024) of cases submitted to the Veterinary Pathology Service (University of Perugia). Among the canine neoplasms, 845 (4%) were melanocytic: 329 (39%) melanocytomas; 512 (61%) melanomas. Of these, 485 (57%) were cutaneous (4% of canine cutaneous neoplasms), 193 (23%) were oral (50% of oral canine neoplasms), and 104 (12%) were mucocutaneous. The average age of affected dogs was 10 years. Older dogs were more likely to have melanomas compared to melanocytomas (p < 0.001). There were 60 (1%) feline MTs: 6 (10%) melanocytomas; 53 (88%) melanomas. Of these, 29 (48%) were cutaneous (1% of feline cutaneous tumors), 18 (30%) were ocular, and 9 (15%) were oral (22% of feline oral tumors). The average age of affected cats was 11 years. In dogs, mucocutaneous melanomas were more common compared to cutaneous ones (p < 0.05); oral melanomas were more common compared to all other sites (p < 0.001). In cats, ocular melanomas were more common compared to cutaneous ones (p < 0.05). Our study provides the MT prevalence in a selected canine and feline population, revealing MT epidemiological patterns, highlighting species-specific differences in the tumor prevalence, localization, and age distribution. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck cancer disparities in outcomes for Black Americans have been well recognized. However, the specific drivers of the inferior outcomes remain poorly understood. We investigated the biologic features of patient oral cancers and performed a follow-up study of the patient post-surgery recurrences and metastases aiming to explore potential mechanisms that might underpin the poorer outcomes among Black American patients. It was found that high levels of tumor stemness and tumor-promoting stromal characteristics were linked to patient recurrence and metastasis. There were more cases of Black American than White American exhibiting high stemness traits and strong tumor-promoting stromal features associated with tumor recurrences and metastases, although the investigated cases displayed comparable clinical diagnoses. Our findings revealed that the differences in tumor stemness and stromal property among cancers with similar diagnoses contribute to patient outcome disparities. Black Americans (BAs) with head and neck cancer (HNC) have worse survival outcomes compared to the White patients. While HNC disparities in patient outcomes for BAs have been well recognized, the specific drivers of the inferior outcomes remain poorly understood. Here, we investigated the biologic features of patient tumor specimens obtained during the surgical treatment of oral cancers and performed a follow-up study of the patients' post-surgery recurrences and metastases with the aim to explore whether tumor biologic features could be associated with the poorer outcomes among BA patients compared with White American (WA) patients. We examined the tumor stemness traits and stromal properties as well as the post-surgery recurrence and metastasis of oral cancers among BA and WA patients. It was found that high levels of tumor self-renewal, invasion, tumorigenesis, metastasis, and tumor-promoting stromal characteristics were linked to post-surgery recurrence and metastasis. There were more BA than WA patients demonstrating high stemness traits and strong tumor-promoting stromal features in association with post-surgery tumor recurrences and metastases, although the investigated cases displayed clinically comparable TNM stages and histological grades. These findings demonstrated that the differences in tumor stemness and stromal property among cancers with comparable clinical diagnoses contribute to the outcome disparity in HNCs. More research is needed to understand the genetic and molecular basis of the biologic characteristics underlying the inferior outcomes among BA patients, so that targeting strategies can be developed to reduce HNC disparity. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancers are associated with high mortality in advanced stages. Early diagnosis is associated with better patient outcomes, but this is challenging to achieve as benign lesions look similar to lesions of concern, and multiple biopsies may be required to ensure the most pathologic tissue is sampled. This work leverages a previously developed endoscopic imaging system and deep learning segmentation tool to provide measurements of subsurface changes in the first few millimeters of oral tissue. We present seven quantitative features that allow for rapid examination of tissue, which we propose may be useful for biopsy site or treatment margin selection. Optical coherence tomography is a noninvasive imaging technique that provides three-dimensional visualization of subsurface tissue structures. OCT has been proposed and explored in the literature as a tool to assess oral cancer status, select biopsy sites, or identify surgical margins. Our endoscopic OCT device can generate widefield (centimeters long) imaging of lesions at any location in the oral cavity—but it is challenging for raters to quantitatively assess and score large volumes of data. Leveraging a previously developed epithelial segmentation network, this work develops quantifiable biomarkers that provide direct measurements of tissue properties in three dimensions. We hypothesize that features related to morphology, tissue attenuation, and contrast between tissue layers will be able to provide a quantitative assessment of disease status (dysplasia through carcinoma). This work retrospectively assesses seven biomarkers on a lesion-contralateral matched OCT dataset of the lateral and ventral tongue (40 patients, 70 sites). Epithelial depth and loss of epithelial–stromal boundary visualization provide the strongest discrimination between disease states. The stroma optical attenuation coefficient provides a distinction between benign lesions from dysplasia and carcinoma. The stratification biomarkers visualize subsurface changes, which provides potential for future utility in biopsy site selection or treatment margin delineation. [ABSTRACT FROM AUTHOR]

Simple Summary: The National Comprehensive Cancer Network guidelines provide evidence-based consensus for optimal individual site- and stage-specific treatments. We evaluated the National Cancer Database (NCDB) with a cohort of 11,121 late-stage oral cancer patients. We assessed differences in treatment choices, type of facility, and survival outcome in relation to distance traveled to receive treatment. White patients were most likely to travel farthest for treatment compared to Black patients. Urban area patients traveled shorter distances than those from rural areas. Farther travel distance was associated with surgery as the primary modality and treatment at academic/research centers was associated with improved overall survival. Recognition that these factors contribute to positive outcomes may help improve survival for this patient population. The National Comprehensive Cancer Network guidelines provide evidence-based consensus for optimal individual site- and stage-specific treatments. This is a cohort study of 11,121 late-stage oral cancer patients in the National Cancer Database from 2010 to 2016. We hypothesized that patient travel distance may affect treatment choices and impact outcome. We split travel distance (miles) into quartiles (D1–4) and assessed treatment choices, type of facility, and survival outcome in relation to distance traveled. Univariate and multivariate analyses addressed contributions of specific variables. White patients were most likely to travel farthest (D4) for treatment compared to Black patients (D1). Urban area patients traveled shorter distances than those from rural areas. Greater travel distance was associated with patients undergoing surgical-based therapies and treatment at academic centers. Patients in D1 had the lowest median survival of all distance quartiles. Surgery-based multimodality treatment (surgery and radiation) had a median survival significantly greater than for non-surgical therapy. Several factors including travel distance and treatment facility were associated with survival outcomes for late-stage oral cavity cancers. Consideration of these factors may help improve the outcome for this patient population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate knowledge about HPV and its vaccine, additionally, to examine the effect of knowledge about HPV and its vaccine on perceived benefits and barriers to HPV vaccination among individuals in the western region of Saudi Arabia. Methods: A cross-sectional design was employed in the western region of Saudi Arabia through a self-administered web-based survey. The survey assessed knowledge, perceived benefits, and perceived barriers to HPV vaccination. Results: A total of 1149 eligible participants completed the survey. Participants exhibited limited knowledge of HPV and its vaccine, with an average total score of 4.76 out of 15. Over 80% of participants were unaware that HPV may not show symptoms, cannot lead to HIV, and is not treatable with antibiotics. Over half were unaware that HPV can cause cervical cancer, oral cancer, or genital warts. Unmarried and graduate-educated participants demonstrated greater knowledge. Perceived benefits were positively associated with knowledge levels, while perceived barriers were negatively associated with knowledge levels after controlling for other variables. Conclusions: This study highlights the need for education and healthcare efforts to raise knowledge about HPV and its vaccine in the western region of Saudi Arabia. Also, this study indicated that enhanced knowledge boosts positive attitudes towards HPV vaccination, while reducing perceived barriers, thereby increasing vaccination rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Some cases of oral cancer are inoperable, and some of these cases also show a limited response to cisplatin. The chemokine receptor CXCR4 has been shown to be involved in tumor growth and metastasis via tumor angiogenesis, and its expression on oral squamous cell carcinoma (OSCC) cells was associated with recurrence and lymph node metastasis. Therefore, we investigated the effects of adding the CXRC4 inhibitor AMD3100 to cisplatin on OSCC cells in vitro and in mouse xenograft models in vivo. The addition of AMD to cisplatin had no additional anti-tumor effect in vitro, but improved the anti-tumor effect of cisplatin and reduced the number of CXCR4-positive blood vessels in cisplatin-resistant OSCC xenografts in vivo. These findings suggest that the addition of a CXCR4 inhibitor may increase the anti-tumor effects of cisplatin in patients with refractory OSCC. Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin–AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral squamous cell carcinoma is a global health concern, particularly affecting the South Asian population. The South Asian community is among Canada's largest and most rapidly expanding minority groups. This study compared the outcomes of South Asian patients with oral squamous cell carcinoma to the general population at a Canadian cancer center. In total, 697 patients who underwent surgery for oral squamous cell carcinoma between 2009 and 2022 were evaluated, with South Asian patients constituting 9% of the cohort. Despite similar tumor characteristics and treatments, South Asian patients had double the risk of cancer recurrence and significantly worse survival compared to non-South Asian patients. Understanding the association between South Asian ethnicity and outcomes in OSCC is crucial for informing public health initiatives to meet the distinctive needs of this population, thus fostering a more inclusive and supportive environment. (1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/− adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan–Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients (p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28–3.14), DSS: HR 1.79 (1.12–2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusions: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds. [ABSTRACT FROM AUTHOR]

Simple Summary: Scientists are studying proteins like kinesin spindle protein and Aurora B, crucial for cell division and potential targets in cancer treatment. Drugs aimed at these proteins show promise in lab tests for killing cancer cells, but in clinical trials alone, they are not always effective, possibly due to varied cancer cell responses. To enhance their efficacy, researchers are exploring combinations with other cell-killing drugs. Our study focused on Navitoclax, an inducer of cancer cell death, tested alongside Ispinesib and Barasertib, targeting kinesin spindle protein and Aurora B, respectively. Together, these drugs induced significant cancer cell death, mainly through apoptosis. Moreover, imaging techniques revealing their combined effects suggest that combining these drugs could be a potent cancer treatment strategy, warranting further investigation in clinical trials. Many proteins regulating mitosis have emerged as targets for cancer therapy, including the kinesin spindle protein (KSP) and Aurora kinase B (AurB). KSP is crucial for proper spindle pole separation during mitosis, while AurB plays roles in chromosome segregation and cytokinesis. Agents targeting KSP and AurB selectively affect dividing cells and have shown significant activity in vitro. However, these drugs, despite advancing to clinical trials, often yield unsatisfactory outcomes as monotherapy, likely due to variable responses driven by cyclin B degradation and apoptosis signal accumulation networks. Accumulated data suggest that combining emerging antimitotics with various cytostatic drugs can enhance tumor-killing effects compared to monotherapy. Here, we investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic Navitoclax in oral cancer cells treated with the selective KSP inhibitor, Ispinesib, or AurB inhibitor, Barasertib, aiming to potentiate cell death. The combination of BH3-mimetics with both KSP and AurB inhibitors synergistically induced substantial cell death, primarily through apoptosis. A mechanistic analysis underlying this synergistic activity, undertaken by live-cell imaging, is presented. Our data underscore the importance of combining BH3-mimetics with antimitotics in clinical trials to maximize their effectiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: This article discusses a common approach to the early detection of oral cancer, which focuses on identifying and monitoring certain mouth conditions, known as oral potentially malignant disorders (OPMDs). However, despite this strategy, the death rates from cancers of the lip and mouth have not improved in 30 years. Surprisingly, only around 10% of oral cancers actually start as premalignant, and most OPMDs rarely turn into cancer. The article suggests that only a few specific types of these disorders, which have a higher risk of becoming cancerous and/or are prevalent in populations, really need intervention. It also questions the effectiveness of regarding OPMDs as heralding malignancy and calls for a different approach to reduce deaths for oral cancer. Despite the profession placing great emphasis on oral potentially malignant disorders (OPMDs) as a gateway for early recognition and consequently better outcomes for oral cancer, the death rates for lip and oral cavity cancer have remained stagnant for three decades. Evidence shows that only a small fraction of oral cancers are in fact preceded by OPMDs, and that most OPMDs have an annual transformation rate of less than 1%. As OPMDs encompass a very heterogeneous group of oral conditions, it could be argued that only patients with oral mucosal diseases bearing a substantial risk of malignant transformation warrant close surveillance and treatment, these include proliferative leukoplakia, erythroplakia, non-homogeneous leukoplakia, as well as diseases presenting with severe dysplasia at biopsy. In this narrative review, I discuss the intricate epidemiology of the malignancies that we colloquially refer to as oral cancer, explore the limitations of focusing on OPMDs to reduce the incidence and mortality of oral cavity cancer, and argue that a may-be cancer label represents overdiagnosis for most OPMDs. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with oral cancer, the risk factors for local, regional, and distant recurrence according to margin status have not been well established. The aims of the present study were to identify a margin cut-off point for improved survival in patients with close margins. A retrospective review of adult patients treated surgically at our centre for primary oral cavity squamous cell cancer from 2009 to 2021 was carried out. Margins (mucosal and deep) were classified as positive (<1 mm), close (1 to 4.9 mm), or clear (>5 mm). A total of 326 patients (210 men; 64.4%) were included. Margin status was as follows: close (n = 168, 51.5%), clear (n = 83, 25.4%), and positive (n = 75, 23.0%). The optimal cut-off for disease-free survival was a deep margin > 3 mm. In the close margin group, survival was significantly better in patients with a deep margin > 3 mm. Moreover, in this subset of patients, survival was comparable to the outcomes observed in patients with clear margins, suggesting that surgical margins smaller than the standard cut-off (5 mm) may be sufficient in certain well-defined cases. In patients with oral cancer, the risk factors for local, regional, and distant recurrence according to margin status have not been well established. We aimed to determine the risk factors for recurrence by margin status and to identify a margin cut-off point for improved survival in patients with close margins. We retrospectively reviewed adult patients treated at our centre from 2009 to 2021 for primary oral cancer. Margins were classified as positive (<1 mm), close (1 to 4.9 mm), or clear (>5 mm). Univariate and multivariate analyses were performed. A total of 326 patients (210 men) were included. The mean age was 59.1 years. Margin status was close (n = 168, 51.5%), clear (n = 83, 25.4%), or positive (n = 75, 23.0%). In the univariate analysis, positive surgical margins (HR = 7.53) had the greatest impact on distant failure. Positive surgical margins—without nodal involvement—had the greatest impact on the risk of distant failure. In the close margin group, the optimal cut-off for disease-free survival (AUC = 0.58) and overall survival (AUC = 0.63) was a deep margin > 3 mm, with survival outcomes that were comparable to the clear margin group. These finding suggest that margins < 5 mm may be sufficient in certain well-defined cases. Prospective studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Transoral Robotic Surgery (TORS) is increasingly used for various conditions, yet its success and failure remain underexplored. In this multicenter study, we assessed 220 TORS interventions across 211 patients. Success criteria differed by condition, including tumor identification for CUP, resection margins for malignancies, and symptom improvement for benign cases like OSA and chronic lingual tonsillitis. Predictors of success varied, with factors such as patient comorbidity, tumor characteristics, and demographics playing roles. Conversely, failure predictors encompassed postoperative complications and pain, linked to patient health and demographics. These insights into TORS outcomes may aid in patient selection and counseling across different conditions, informing clinical practice and enhancing patient care. Transoral Robotic Surgery (TORS) is utilized for treating various malignancies, such as early-stage oropharyngeal cancer and lymph node metastasis of an unknown primary tumor (CUP), and also benign conditions, like obstructive sleep apnea (OSA) and chronic lingual tonsillitis. However, the success and failure of TORS have not been analyzed to date. In this retrospective observational multicenter cohort study, we evaluated patients treated with TORS using the da Vinci surgical system. Success criteria were defined as identification of the primary tumor for CUP, >2 mm resection margin for malignant conditions, and improvement on respiratory polygraphy and tonsillitis complaints for benign conditions. A total of 220 interventions in 211 patients were included. We identified predictors of success, such as low comorbidity status ACE-27, positive P16 status, and lower age for CUP, and female gender and OSA severity for benign conditions. For other malignancies, no predictors for success were found. Predictors of failure based on postoperative complications included high comorbidity scores (ASA) and anticoagulant use, and for postoperative pain, younger age and female gender were identified. This study provides valuable insights into the outcomes and predictors of success and failure in TORS procedures across various conditions and may also help in patient selection and counseling. [ABSTRACT FROM AUTHOR]

Simple Summary: Circular RNAs (circRNAs) are a new class of unique RNAs that have single-stranded, covalently closed, and continuous loop structures, which confer stability and resistance to endonuclease-mediated degradation that in turn affords substantially longer circulatory half-lives relative to linear RNAs. In this study, we established a novel synthetic circRNA that carries miR-1269a binding sequences and investigated its potential application as a therapeutic tool to slow cancer progression. Briefly, phospholipase C gamma 2 (PLCG2), which is related to oral squamous cell carcinoma (OSCC) clinical stage and overall survival, was affected by the circRNA-1269a/miR-1269a axis. Our confirmation that circRNA-1269a/miR-1269a/PLCG2 can inhibit OSCC proliferation and migration by promoting apoptosis in OSCC cells in vitro indicates that PLCG2 overexpression via the circRNA1269a/miR-1269a axis may be a valuable tool for controlling OSCC growth. Therefore, these data suggest that circRNA-1269a/miR-1269a could act as a potential therapeutic axis for OSCCs. microRNAs (miRs) function in cancer progression as post-transcriptional regulators. We previously reported that endogenous circular RNAs (circRNAs) function as efficient miR sponges and could act as novel gene regulators in oral squamous cell carcinoma (OSCC). In this study, we carried out cellular and luciferase reporter assays to examine competitive inhibition of miR-1269a, which is upregulated expression in several cancers, by circRNA-1269a, a synthetic circRNA that contains miR-1269a binding sequences. We also used data-independent acquisition (DIA) proteomics and in silico analyses to determine how circRNA-1269a treatment affects molecules downstream of miR-1269a. First, we confirmed the circularization of the linear miR-1269a binding site sequence using RT-PCR with divergent/convergent primers and direct sequencing of the head-to-tail circRNA junction point. In luciferase reporter and cellular functional assays, circRNA-1269a significantly reduced miR-1269a function, leading to a significant decrease in cell proliferation and migration. DIA proteomics and gene set enrichment analysis of OSCC cells treated with circRNA-1269a indicated high differential expression for 284 proteins that were mainly enriched in apoptosis pathways. In particular, phospholipase C gamma 2 (PLCG2), which is related to OSCC clinical stage and overall survival, was affected by the circRNA-1269a/miR-1269a axis. Taken together, synthetic circRNA-1269a inhibits tumor progression via miR-1269a and its downstream targets, indicating that artificial circRNAs could represent an effective OSCC therapeutic. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, much research has focused on how exercise improves cancer prognosis and how the protein myokine, which is associated with exercise, inhibits cancer progression. However, there have been few detailed studies on oral cancer. This study is the first to show that exercise inhibits the progression of oral cancer. While other studies have shown that exercise suppresses growth, decreases the tumor formation rate, or improves survival in patients with other organ cancers, this study showed that exercise inhibits tumor formation and growth in oral cancer and prolongs survival. Furthermore, while many studies have demonstrated an indirect immune-mediated mechanism by which exercise suppresses cancer, this study suggests the additional possibility that myokines released by exercise directly affect oral cancer cells. This study has the above novelties. Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM. [ABSTRACT FROM AUTHOR]

Simple Summary: This systematic review evaluates techniques defining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). Residual SCC and dysplasia demand distinct adjuvant treatment, such as re-resection and radiation for SCC or CO2-laser evaporation for severe dysplasia, necessitating accurate differentiation between SCC and dysplasia during surgery. The study includes eight investigations into margin visualization techniques—autofluorescence, iodine staining, and narrow-band imaging—concluding that, except for autofluorescence, there is considerable variability in negative predictive values. Autofluorescence does not significantly enhance margin outcomes compared to conventional white light-guided surgery, while iodine does. Studies on narrow-band imaging did not report a comparison with a white light-guided surgery cohort. The review advocates for more comprehensive studies comparing the diagnostic accuracy of iodine staining or narrow-band imaging, with a specific focus on diagnostic accuracy and the discrimination between SCC and dysplasia. Background: This systematic review investigates techniques for determining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). The primary treatment involves surgical removal with ≥5 mm margins, highlighting the importance of accurate differentiation between SCC and dysplasia during surgery. Methods: A comprehensive Embase and PubMed literature search was performed. Studies underwent quality assessment using QUADAS-2. Results: After the full-text screening and exclusion of studies exhibiting high bias, eight studies were included, focusing on three margin visualization techniques: autofluorescence, iodine staining, and narrow-band imaging (NBI). Negative predictive value (NPV) was calculable across the studies, though reference standards varied. Results indicated NPVs for autofluorescence, iodine, and NBI ranging from 61% to 100%, 92% to 99%, and 86% to 100%, respectively. Autofluorescence did not significantly enhance margins compared to white light-guided surgery, while iodine staining demonstrated improvement for mild or moderate dysplasia. NBI lacked comparison with a white light-guided surgery cohort. Conclusions: We recommend studying and comparing the diagnostic accuracy of iodine staining and NBI in larger cohorts of patients with oral SCC, focusing on discriminating between SCC and (severe) dysplasia. Furthermore, we advise reporting the diagnostic accuracy alongside the treatment effects to improve the assessment of these techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: Trismus is a common complication in oral cancer patients that may influence surgical outcomes. This retrospective matched cohort analysis examined the influence of preoperative trismus on survival outcomes in 40 male Taiwanese oral cancer patients undergoing transoral robotic surgery (TORS). Through 1:1 propensity score matching, 20 trismus patients were compared to 20 non-trismus controls. TORS demonstrated comparable short-term surgical outcomes in trismus patients compared to non-trismus patients. There were no significant differences between groups in operation time, blood loss, margin status, flap reconstruction rates, duration of nasogastric tube feeding, or length of hospital stay. Analysis of long-term oncological outcomes demonstrated similar 5-year disease-free survival between groups, indicating comparable tumor control. However, trismus patients experienced significantly poorer 5-year overall survival. After adjusting for confounders, trismus independently conferred a 13-fold higher long-term mortality risk. Ultimately, this study highlights preoperative trismus as a harbinger of non-inferior short-term surgical outcomes, but diminished long-term survival in oral cancer patients treated robotically, even among those with equivalent tumor persistence following surgery. Further research should explore mechanisms linking trismus to mortality and approaches to improve outcomes in this population. Trismus, defined as restricted mouth opening, is a common complication among Taiwanese oral cancer patients, especially those who chew betel quid. However, the impact of trismus on survival outcomes in oral cancer patients undergoing transoral robotic surgery (TORS) is unclear. This study aimed to investigate the associations between trismus and surgical outcomes in Taiwanese male oral cancer patients treated with TORS. We conducted a retrospective propensity score-matched cohort study of 40 Taiwanese male oral cancer patients who underwent TORS between 2016 and 2022. Overall, 20 patients with trismus were matched to 20 patients without trismus. TORS achieved similar operative and short-term clinical outcomes in trismus patients to non-trismus patients. There were no significant differences between groups in operation time, blood loss, margin status, flap reconstruction rates, duration of nasogastric tube feeding, or length of hospital stay. Kaplan–Meier and Cox proportional hazard regression analyses were performed to compare overall survival (OS) and disease-free survival (DFS) between the two groups. The overall survival (OS) rate at three years was significantly lower in patients with trismus than those without trismus (27.1% vs. 95.0%, log-rank p = 0.02). However, there was no significant difference in disease-free survival (DFS) rates between the trismus and non-trismus groups (36.6% vs. 62.7%, log-rank p = 0.87). After adjusting for confounders, trismus was independently associated with a 13-fold increased risk of mortality (adjusted HR 12.87, 95% CI 1.55–106.50, p < 0.05). In conclusion, trismus appears to be an independent prognostic factor for reduced long-term OS in Taiwanese male oral cancer patients undergoing TORS, though short-term surgical outcomes were non-inferior in the trismus patients. Further research is warranted to clarify the mechanisms linking trismus and survival in this population. [ABSTRACT FROM AUTHOR]

Simple Summary: Transformer models, originally successful in natural language processing, have found application in computer vision, demonstrating promising results in tasks related to cancer image analysis. Despite being one of the prevalent and swiftly spreading cancers globally, there is a pressing need for accurate automated analysis methods for oral cancer. This need is particularly critical for high-risk populations residing in low- and middle-income countries. In this study, we evaluated the performance of the Vision Transformer (ViT) and the Swin Transformer in the classification of mobile-based oral cancer images we collected from high-risk populations. The results showed that the Swin Transformer model achieved higher accuracy than the ViT model, and both transformer models work better than the conventional convolution model VGG19. Oral cancer, a pervasive and rapidly growing malignant disease, poses a significant global health concern. Early and accurate diagnosis is pivotal for improving patient outcomes. Automatic diagnosis methods based on artificial intelligence have shown promising results in the oral cancer field, but the accuracy still needs to be improved for realistic diagnostic scenarios. Vision Transformers (ViT) have outperformed learning CNN models recently in many computer vision benchmark tasks. This study explores the effectiveness of the Vision Transformer and the Swin Transformer, two cutting-edge variants of the transformer architecture, for the mobile-based oral cancer image classification application. The pre-trained Swin transformer model achieved 88.7% accuracy in the binary classification task, outperforming the ViT model by 2.3%, while the conventional convolutional network model VGG19 and ResNet50 achieved 85.2% and 84.5% accuracy. Our experiments demonstrate that these transformer-based architectures outperform traditional convolutional neural networks in terms of oral cancer image classification, and underscore the potential of the ViT and the Swin Transformer in advancing the state of the art in oral cancer image analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: Stimulated Raman Histology (SRH) is a technique that uses laser light to create detailed images of tissues without the need for traditional staining. This study aimed to use deep learning to classify oral squamous cell carcinoma (OSCC) and different non-malignant tissue types using SRH images. The performances of the classifications between SRH images and the original images obtained from stimulated Raman scattering (SRS) were compared. A deep learning model was trained on 64 images and tested on 16, showing that it could effectively identify tissue types during surgery, potentially speeding up decision making in oral cancer surgery. Stimulated Raman Histology (SRH) employs the stimulated Raman scattering (SRS) of photons at biomolecules in tissue samples to generate histological images. Subsequent pathological analysis allows for an intraoperative evaluation without the need for sectioning and staining. The objective of this study was to investigate a deep learning-based classification of oral squamous cell carcinoma (OSCC) and the sub-classification of non-malignant tissue types, as well as to compare the performances of the classifier between SRS and SRH images. Raman shifts were measured at wavenumbers k1 = 2845 cm−1 and k2 = 2930 cm−1. SRS images were transformed into SRH images resembling traditional H&E-stained frozen sections. The annotation of 6 tissue types was performed on images obtained from 80 tissue samples from eight OSCC patients. A VGG19-based convolutional neural network was then trained on 64 SRS images (and corresponding SRH images) and tested on 16. A balanced accuracy of 0.90 (0.87 for SRH images) and F1-scores of 0.91 (0.91 for SRH) for stroma, 0.98 (0.96 for SRH) for adipose tissue, 0.90 (0.87 for SRH) for squamous epithelium, 0.92 (0.76 for SRH) for muscle, 0.87 (0.90 for SRH) for glandular tissue, and 0.88 (0.87 for SRH) for tumor were achieved. The results of this study demonstrate the suitability of deep learning for the intraoperative identification of tissue types directly on SRS and SRH images. [ABSTRACT FROM AUTHOR]

Simple Summary: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive tumor phenotype in head and neck cancer (HNC) and an important adverse prognostic factor for recurrence, metastasis, and patient survival. According to the previous studies, the LNM characteristics of HNC (i.e., the growth and spread of LNM) well correlate with the ECS occurrence, but there has been a disagreement about the primary tumor characteristics and ECS. Thus, we investigated the risk factors of ECS across different HNC subsites comparatively. In this study, we confirmed that LNM variables were significant risk factors for ECS in all subsites of HNC. Interestingly, in oral tongue cancer, tumor dimensional variables were significantly related to ECS; however, in oro- and hypopharyngeal cancer, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. Site-dependent primary tumor characteristics or nodal status might contribute differentially to the ECS development of LNM in HNC. Background: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive primary tumor phenotype in head and neck cancer (HNC); however, the factors influencing ECS are poorly understood. Patients and Methods: This was a retrospective study, including 190 cases of oral tongue cancer (OTC), 148 cases of oropharyngeal cancer (OPC) (118 HPV-positive and 30 HPV-negative), and 100 cases of hypopharyngeal cancer (HPC). Tumor dimension, tumor biological variables (lymphovascular/perineural invasion and histologic grade), and LNM variables (LNM number and size) were analyzed according to the presence of ECS using multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. Results: LNM variables were significant factors for ECS in all subsites of HNC (p < 0.05), except HPV-positive OPC. In OTC, tumor dimensional variables were significantly related to ECS (p < 0.01). Meanwhile, in OPC and HPC, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. The predictability of ECS by ROC curve using multiple variables was 0.819 [95% confidence interval: 0.759–0.878] in OTC, 0.687 [0.559–0.815] in HPV-positive OPC, 0.823 [0.642–1.000] in HPV-negative OPC, and 0.907 [0.841–0.973] in HPC. Conclusion: LNM variables were correlated with ECS occurrence for most HNC subsites, and site-dependent primary tumor characteristics might contribute differentially to the ECS development of LNM in HNC. [ABSTRACT FROM AUTHOR]

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]

Simple Summary: Oral cancer is among the twenty most common cancers worldwide. Finding and treating this cancer early improves survival rates. Screening the whole population to check for oral cancer is unlikely to be an efficient use of resources; however, screening only individuals at higher risk has been shown to reduce oral cancer deaths and be cost-effective for healthcare services. Mathematical models have previously been developed to identify these high-risk groups; however, it is not known whether any of these would be suitable for use in clinical practice. In this study, we identified and compared previously published models. We found several that had potential, but only two had been tested outside the original study population. We suggest that future research should focus on (a) testing how well the models identify those at high risk within potential screening populations and (b) assessing how the models might be included within the healthcare systems. In the last 30 years, there has been an increasing incidence of oral cancer worldwide. Earlier detection of oral cancer has been shown to improve survival rates. However, given the relatively low prevalence of this disease, population-wide screening is likely to be inefficient. Risk prediction models could be used to target screening to those at highest risk or to select individuals for preventative interventions. This review (a) systematically identified published models that predict the development of oral cancer and are suitable for use in the general population and (b) described and compared the identified models, focusing on their development, including risk factors, performance and applicability to risk-stratified screening. A search was carried out in November 2022 in the Medline, Embase and Cochrane Library databases to identify primary research papers that report the development or validation of models predicting the risk of developing oral cancer (cancers of the oral cavity or oropharynx). The PROBAST tool was used to evaluate the risk of bias in the identified studies and the applicability of the models they describe. The search identified 11,222 articles, of which 14 studies (describing 23 models), satisfied the eligibility criteria of this review. The most commonly included risk factors were age (n = 20), alcohol consumption (n = 18) and smoking (n = 17). Six of the included models incorporated genetic information and three used biomarkers as predictors. Including information on human papillomavirus status was shown to improve model performance; however, this was only included in a small number of models. Most of the identified models (n = 13) showed good or excellent discrimination (AUROC > 0.7). Only fourteen models had been validated and only two of these validations were carried out in populations distinct from the model development population (external validation). Conclusions: Several risk prediction models have been identified that could be used to identify individuals at the highest risk of oral cancer within the context of screening programmes. However, external validation of these models in the target population is required, and, subsequently, an assessment of the feasibility of implementation with a risk-stratified screening programme for oral cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: There have been no analyses of tumor budding (TB) in different margin sections and using the fixation method in HNSCC in the literature. The mean TB (TB rel) of all tumor-positive margin sections (n = 443) of the primary tumor was analyzed in an FFPE-fixed tumor from 66 patients with HNSCC, and they were compared with cryo-fixed sections. TB rel correlates significantly with tumor aggressiveness. TB often varies between the different tumor margins of FFPE sections of the same patient, and they differ depending on the fixation method. Our data show that a randomly selected margin section does not reliably reflect the TB, and thus, it cannot predict the prognostic outcome. TB rel could compensate for the differences in TB score analysis. The determination of the TB score in cryo sections seems to be inaccurate compared with analyses in FFPE. The method shown here is cost effective, easy to integrate into a clinical workflow, and seems useful for future studies. Background: Tumor budding (TB) is a histomorphological characteristic of the tumor invasion front and it has an impact on the tumor outcome prediction for head and neck squamous cell carcinoma (HNSCC) aetiopathology. Patients and methods: The average TB score (TB rel) of all tumor-positive marginal sections (n = 443) in the primary tumor was analyzed in the FFPE-fixed tumor slices of 66 patients with HNSCC, and they were compared with cryo-fixed sections. Results: TB rel correlates with tumor aggressiveness (i.e., lymph node metastasis quantity, lymph node ratio, extra capsular growth, Pn1, pV1, grading). The TB scores often vary between the different tumor margins of FFPE sections in the same patient, and in many cases, they differ depending on the fixation method. Conclusion: Our data show that a randomly selected marginal cut cannot reliably mirror the TB score, and thus, they cannot predict the prognostic outcome. However, TB rel could be a tool that compensates for differences in TB score analysis. TB score determination in cryo sections seems to be inaccurate compared with TB determination in FFPE. [ABSTRACT FROM AUTHOR]

Simple Summary: There are many aspects of oral cancer invasion and metastasis that remain to be elucidated. It has been suggested that chronic inflammation caused by bacteria may be a cause of carcinogenesis, invasion, and metastasis. PD-L1 expression is associated with lymph node metastasis and poor prognosis in several cancers. Lipopolysaccharide (LPS) from Porphyromonas gingivalis, which is known to be the main cause of bacterial periodontitis, induced PD-L1 expression and partial epithelial–mesenchymal transition (pEMT) expression in oral cancer cells. Moreover, we identified PD-L1 expression within the exosomes of oral cancer cells. Exosomes may function as carriers of PD-L1. Background: Expression of programmed death ligand-1 (PD-L1) is related to the prognosis of many solid malignancies, including oral squamous cell carcinoma (OSCC), but the mechanism of PD-L1 induction remains obscure. In this study, we examined the expression of PD-L1 and partial epithelial–mesenchymal transition (pEMT) induced by bacterial lipopolysaccharide (LPS) in OSCC. Methods: The expression of Toll-like receptor 4 (TLR4) recognizing LPS in OSCC cell lines was analyzed. Moreover, the induction of PD-L1 expression by Porphyromonas gingivalis (P.g) or Escherichia coli (E. coli) LPS and EMT was analyzed by western blotting and RT-PCR. Morphology, proliferation, migration, and invasion capacities were examined upon addition of LPS. PD-L1 within EXOs was examined. Results: PD-L1 expression and pEMT induced by LPS of P.g or E. coli in TLR4-expressing OSCC cell lines were observed. Addition of LPS did not change migration, proliferation, or cell morphology, but increased invasive ability. Moreover, higher expression of PD-L1 was observed in OSCC EXOs with LPS. Conclusion: Oral bacterial LPS is involved in enhanced invasive potential in OSCC cells, causing PD-L1 expression and induction of pEMT. The enhancement of PD-L1 expression after addition of LPS may be mediated by EXOs. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer stem cell have certain metabolic properties that are distinct from their differentiated counterparts. Our aim is to characterize CSC metabolism in oral cancer. Our study have several impacts: 1. Previous metabolic studies of CSC mainly focused on few energy metabolism pathway. Here we used novel transcription/metabolic joint analysis to reveal comprehensive metabolic alteration of CSC in oral cancer. 2. Assessing CSC metabolic phenotype in vivo is challenging. Here We used single-cell sequencing to explore the metabolic characteristics of CSC in vivo. 3. Our data suggested oral CSCs are metabolically inactive compared with differentiated cancer cells. This state may allow CSCs to resist the metabolic therapeutic strategies currently used for highly proliferative tumors. This knowledge may allow us to better develop metabolic therapy against CSC in oral cancer. Understanding the distinct metabolic characteristics of cancer stem cells (CSC) may allow us to better cope with the clinical challenges associated with them. In this study, OSCC cell lines (CAL27 and HSC3) and multicellular tumor spheroid (MCTS) models were used to generate CSC-like cells. Quasi-targeted metabolomics and RNA sequencing were used to explore altered metabolites and metabolism-related genes. Pathview was used to display the metabolites and transcriptome data in a KEGG pathway. The single-cell RNA sequencing data of six patients with oral cancer were analyzed to characterize in vivo CSC metabolism. The results showed that 19 metabolites (phosphoethanolamine, carbamoylphosphate, etc.) were upregulated and 109 metabolites (2-aminooctanoic acid, 7-ketocholesterol, etc.) were downregulated in both MCTS cells. Integration pathway analysis revealed altered activity in energy production (glycolysis, citric cycle, fatty acid oxidation), macromolecular synthesis (purine/pyrimidine metabolism, glycerophospholipids metabolism) and redox control (glutathione metabolism). Single-cell RNA sequencing analysis confirmed altered glycolysis, glutathione and glycerophospholipid metabolism in in vivo CSC. We concluded that CSCs are metabolically inactive compared with differentiated cancer cells. Thus, oral CSCs may resist current metabolic-related drugs. Our result may be helpful in developing better therapeutic strategies against CSC. [ABSTRACT FROM AUTHOR]

Oral cancer (OC), characterized by malignant tumors in the mouth, is one of the most prevalent malignancies worldwide. Chemotherapy is a commonly used treatment for OC; however, it often leads to severe side effects on human bodies. In recent years, nanotechnology has emerged as a promising solution for managing OC using nanomaterials and nanoparticles (NPs). Nano-drug delivery systems (nano-DDSs) that employ various NPs as nanocarriers have been extensively developed to enhance current OC therapies by achieving controlled drug release and targeted drug delivery. Through searching and analyzing relevant research literature, it was found that certain nano-DDSs can improve the therapeutic effect of drugs by enhancing drug accumulation in tumor tissues. Furthermore, they can achieve targeted delivery and controlled release of drugs through adjustments in particle size, surface functionalization, and drug encapsulation technology of nano-DDSs. The application of nano-DDSs provides a new tool and strategy for OC therapy, offering personalized treatment options for OC patients by enhancing drug delivery, reducing toxic side effects, and improving therapeutic outcomes. However, the use of nano-DDSs in OC therapy still faces challenges such as toxicity, precise targeting, biodegradability, and satisfying drug-release kinetics. Overall, this review evaluates the potential and limitations of different nano-DDSs in OC therapy, focusing on their components, mechanisms of action, and laboratory therapeutic effects, aiming to provide insights into understanding, designing, and developing more effective and safer nano-DDSs. Future studies should focus on addressing these issues to further advance the application and development of nano-DDSs in OC therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral squamous cell carcinoma is the most common oral carcinoma worldwide. Despite medical improvements and applied research, the 5-year- overall survival rate amounts to ca 51 percent. Early recurrence diagnosis is a key driver for increasing the cure rate which underlines the importance of this study. The study aims to show how surveillance imaging of OSCC patients might be influenced by factors such as radiotherapy treatment, contrast enhancement, and the type of imaging (CT, NMRI). Further analysis is needed to determine if there is any difference between patients showing clinical and radiological patterns or only radiological patterns and if there is any connection between the histopathological result and those influence factors to improve the value of surveillance imaging in follow-up treatment and thus the cure rate. The evaluation of surveillance imaging of OSCC patients is a difficult task physicians have to face daily. Multiple patients experience a recurrence of this disease, which underlines the importance of regular patient monitoring programs. Our study analysed the value of surveillance imaging, such as computed tomography (CT) and nuclear magnetic resonance imaging (NMRI), as a patient monitoring programme and its effectiveness in achieving improvement in early recurrence detection. The study comprised 125 patients, out of which 56 (n = 56) showed radiological and 69 (n = 69) showed clinical and radiological conspicuous patterns in domestic follow-ups, respectively. The use of CT and NMRI showed a significant dependence on the histological result (p = 0.03). However, the different groups showed no significant dependence on the histological result (p = 0.96). The distribution of the histological biopsies, which were taken due to radiological changes, were prone to wrong positive diagnoses (false positives) in 71 percent. To conclude, imaging modalities should be chosen for each patient individually to reduce false positives, improve the early detection of recurrence, and increase the cure rate. [ABSTRACT FROM AUTHOR]

Simple Summary: Several factors may influence the outcome of a patient with cancer, including oral cancer. Modern diagnostic tools have had a great impact on the success of patient care. However, diagnostic methods, even at the moment of surgery, contributing to the development of personalized oncological treatment are indispensable. In parallel with the increasing number of oncological cases, the need for faster and more efficient diagnostic tools has also appeared. Different diagnostic approaches are available, such as radiological imaging or histological staining methods, but these do not provide adequate information regarding the resection margin, intraoperatively, or are time consuming. The purpose of this review is to summarize the current knowledge on spectrometric diagnostic modalities suitable for intraoperative use, with an emphasis on their relevance in the management of oral cancer. The literature agrees on the sensitivity, specificity, and accuracy of spectrometric diagnostic modalities, but further long-term prospective, multicentric clinical studies are needed, which may standardize the intraoperative assessment of the resection margin and the use of real-time spectroscopic approaches. [ABSTRACT FROM AUTHOR]