Search Results (320)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have emerged as targeted therapies for OSCC in clinical trials. However, their clinical efficacy remains a challenge. Cannabidiol (CBD), a non-psychoactive phytochemical from cannabis, has demonstrated anticancer and immunomodulatory properties. CBD induces apoptosis and autophagy and modulates signaling pathways often dysregulated in HNSCC. This review summarizes the molecular mechanisms of EGFR-TKIs and CBD and their clinical insights and further discusses potential implications of combination targeted therapies. Full article

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in OSCC could enable new therapeutic approaches and effective ICI combinations. Methods: The aim of this cross-sectional study was to investigate the significance of the differential expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD28 and their ligands CD80 and CD86 for the diagnosis and treatment of OSCC. To this end, mRNA expression was analysed by RT-PCR and compared in 65 healthy oral mucosa samples (NOM) and 104 OSCC samples. Results: The expression of CTLA-4 (a soluble and membrane-bound isoform) was increased in OSCC by 1.72-fold (p = 0.004) and 6.88-fold (p < 0.001), respectively. There was no significant difference for CD28 (p = 0.283), nor for the soluble isoform of CD86 (p = 0.845). The membrane isoform of CD86 was increased in OSCC by a factor of 1.39 (p = 0.009) and CD80 by 6.11-fold (p < 0.001). Conclusions: The results show a significant association between CTLA-4, CD80 and membrane-bound CD86 expression and diagnosis. They could improve diagnostics in multi-marker approaches and serve as therapeutic targets for ICI strategies. In particular, the data indicate a stronger immunosuppressive role of CD80 compared to CD86 in a tumor tissue context, suggesting the exploration of anti-CTLA-4 and anti-CD80 antibody combinations in animal models. Full article

Oral squamous cell carcinoma (OSCC), an aggressive and poorly prognosed subtype of head and neck squamous cell carcinoma (HNSCC), has prompted urgent calls for innovative therapeutic approaches. Evodiamine (EVO), a natural alkaloid extracted from the Chinese herb Evodia rutaecarpa, has demonstrated significant potential in curbing tumor cell proliferation and slowing tumor expansion. However, its specific effects on cell senescence within the context of OSCC have remained shrouded in uncertainty. This study delves into the mechanisms of EVO’s impact on OSCC by harnessing databases such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and CellAge to pinpoint potential targets and carry out in-depth bioinformatics analysis. The findings reveal that EVO can markedly enhance the expression of the androgen receptor (AR) in OSCC cells, inducing cellular senescence and thereby inhibiting tumor progression. Furthermore, the research indicates that AR expression is considerably lower in OSCC tissues than in normal tissues. This low expression of AR in tumor tissues is closely associated with advanced clinical stages and unfavorable prognoses in HNSCC patients. These discoveries open up new avenues for therapeutic strategies, and suggest that AR holds promise as a potential therapeutic target for OSCC, and EVO may amplify its antitumor effects by enhancing AR-mediated cellular senescence in the treatment of OSCC. Full article

Oral squamous cell carcinoma (OSCC) remains one of the most common malignancies in the head and neck region, often preceded by a spectrum of oral potentially malignant disorders (OPMDs). Despite advances in diagnostic methods, reliable and non-invasive biomarkers for early detection and prognostic stratification are still lacking. In recent years, circulating cell-free DNA (cfDNA) has emerged as a promising liquid biopsy tool in several solid tumors, offering insights into tumor burden, heterogeneity, and molecular dynamics. However, its application in oral oncology remains underexplored. This study aims to review and discuss the current evidence on cfDNA quantification and mutation analysis (including TP53, NOTCH1, and EGFR) in patients with OPMDs and OSCC. Particular attention is given to cfDNA fragmentation patterns, methylation signatures, and tumor-specific mutations as prognostic and predictive biomarkers. Moreover, we highlight the challenges in standardizing pre-analytical and analytical workflows in oral cancer patients and explore the potential role of cfDNA in monitoring oral carcinogenesis. Understanding cfDNA dynamics in the oral cavity might offer a novel, minimally invasive strategy to improve early diagnosis, risk assessment, and treatment decision-making in oral oncology. Full article

Head and neck squamous cell carcinomas (HNSCCs) that develop from the mucosal epithelium in the oral cavity, pharynx, and larynx are a heterogeneous group of malignant tumors. A lack of appropriate screening and diagnostic methods leads to late diagnoses, with the majority of patients having locally advanced disease, which is associated with a high risk of local recurrence and a poor prognosis and is usually treated with combination therapies. Biomarkers for predicting the therapy response and risk of recurrence in HNSCC patients are urgently needed. Liquid biopsy, e.g., the profiling of circulating biomarkers in bodily fluids, is a promising approach with increasing utility in the early detection and diagnosis of cancer, monitoring cancer progression, patient stratification and treatment selection, detecting minimal residual disease (MRD), and predicting recurrence across different cancer types, including HNSCC. Among liquid biomarkers, circulating tumor DNA (ctDNA), which is based on detecting tumor-specific mutations, insertions/deletions, copy number alterations, and methylation, is the most promising transformative tool in cancer management and personalized cancer treatment. In this review, we provide an update of recent data on the role of non-viral ctDNA in the management of HNSCC patients. Accumulating data suggests the enormous potential of ctDNA profiling by serial sampling during and after definitive therapy in detecting MRD and predicting recurrence in HNSSC patients treated with a single treatment modality (surgery or radiotherapy) or with combination therapies, including immune-checkpoint-inhibitor-based immunotherapy. By incorporating the latest immunotherapy trials and organizing the data by the treatment modality, this review offers a novel perspective not found in previous surveys. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity and is frequently diagnosed at an advanced stage, resulting in poor prognosis and limited treatment options. Identifying reliable biomarkers that can predict tumor progression and serve as therapeutic targets remains an urgent clinical need. Methods: To identify key molecular drivers in OSCC, we performed an integrative bioinformatics analysis of five OSCC-related microarray datasets from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified and subjected to functional enrichment, protein–protein interaction (PPI) network construction, and hub gene ranking using Cytoscape. Candidate genes were further validated using TCGA, UALCAN, and the Human Protein Atlas. In vitro functional assays were performed to evaluate the effect of TK1 knockdown on cell migration. Results: A total of 138 common DEGs were identified across datasets. GO enrichment revealed that these genes were associated with cell proliferation, extracellular matrix organization, and metastasis-related processes. Thymidine kinase 1 (TK1) was identified as a key hub gene and found to be consistently overexpressed in OSCC tissues. Kaplan–Meier analysis showed that high TK1 expression correlated with poor overall survival in head and neck cancer. TK1 knockdown in OSCC cell lines significantly impaired cell migration and wound-healing ability. Conclusions: Our findings suggest that TK1 plays an active role in promoting OSCC progression and may serve as a prognostic biomarker and potential therapeutic target for metastatic OSCC. Full article

Head and neck squamous cell carcinoma (SCC), particularly in the oral cavity, is among the most prevalent and lethal forms of cancer globally. Current therapeutic strategies, predominantly involving cisplatin, face challenges like chemoresistance and toxicity to normal cells, justifying the exploration of new approaches. This study evaluates the antitumor, antiproliferative, and immunomodulatory potential of a synthetic peptide derived from IsCT1 (Isalo scorpion cytotoxic peptide), named AC-AFPK-IsCT1, in combination with cisplatin in oral squamous cell carcinoma cellular models. Tumor and normal cells were treated with varying concentrations of cisplatin and peptide, and the cytotoxicity was measured through an MTT assay, while apoptosis and cell cycle alterations were assessed via flow cytometry. Interestingly, the combination of AC-AFPK-IsCT1 with cisplatin exhibited higher specificity for tumor cells, significantly reducing IC50 values compared to cisplatin used as a single agent. Moreover, the combination treatment induced pronounced S-phase cell cycle arrest and enhanced apoptotic activity, evidenced by the upregulation of caspase-3, caspase-8, and p53, while maintaining low toxicity in normal fibroblast cells. The peptide also modulated the mitochondrial membrane potential, further contributing to the activation of intrinsic apoptotic pathways. The data suggest that AC-AFPK-IsCT1 potentiates the antitumor effects of cisplatin by engaging both intrinsic and extrinsic apoptotic pathways while preserving normal cell viability. These findings underscore the potential of combining cisplatin with AC-AFPK-IsCT1 as a promising therapeutic strategy for improving the efficacy of chemotherapy in SCC, reducing systemic toxicity, and overcoming chemoresistance. Full article

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck squamous cell carcinoma (HNSCC), is a significant global health burden owing to its late-stage diagnosis and poor prognosis. Recent advancements in molecular biology, genomics, and imaging have transformed the landscape of OSCC diagnosis and treatment. This review provides a comprehensive synthesis of early molecular diagnostic strategies, including biomarker discovery using next-generation sequencing, liquid biopsy, and salivary exosomal microRNAs. In addition, we highlight the emerging role of non-invasive optical imaging technologies and their clinical integration for improved surgical precision and early lesion detection. This review also discusses evolving therapeutic approaches, including immunotherapy, neoadjuvant chemotherapy, and patient-centered multimodal regimens tailored through molecular profiling. We emphasized balancing therapeutic efficacy with the quality of life in patients undergoing chemoradiotherapy. The convergence of multi-omics, artificial intelligence, and precision medicine holds promise for revolutionizing early detection and personalized treatment of OSCC, ultimately improving patient survival and clinical outcomes. Full article

Background and Objectives: Oral cancer remains a critical global health burden. Oral potentially malignant disorders (OMPDs) such as leukoplakia and oral lichen planus can precede oral squamous cell carcinoma (OSCC). Inflammation, tissue remodeling, and dysregulated signaling pathways are central to malignant transformation. This observational study aimed to evaluate the expression patterns of Maspin, β-catenin, and MMP-14 by immunohistochemistry (IHC) in oral leukoplakia, oral lichen planus, OSCC, and normal mucosa, exploring associations with lesion type, with no prognostic inferences drawn from a single timepoint. Materials and Methods: Biopsy specimens from 67 patients presenting with oral lesions (27 leukoplakia, 22 lichen planus, 18 OSCC), and 10 healthy controls were collected between January 2015 and January 2023. Inclusion criteria were age over 18 years and no other chronic illness, and a histopathologic diagnosis of oral leukoplakia, oral lichen planus or OSCC. Exclusion criteria were smokers, alcohol abuse, and prior head and neck radiotherapy, prior immunosuppressive therapy, systemic inflammatory diseases, absence of histopathological confirmation of the clinical diagnosis, and squamous cell carcinoma of the vermilion. Two pathologists independently scored staining in 10 high-power fields. Normal mucosa served as baseline. Immunohistochemical analysis was conducted using specific antibodies targeting Maspin, β-catenin, and MMP-14. Marker expression was assessed using a semi-quantitative scoring system based on staining intensity and classified into four categories: negative (−), weakly positive (+) for 1–10%, moderately positive (++) for 11–50%, and highly positive (+++) for more than 50%. Results: Maspin showed moderate (++) cytoplasmic/nuclear staining in leukoplakia and lichen planus in 78% of cases and high (+++) in OSCC and stroma in all cases. β-catenin shifted from membranous moderate positivity in 100% of OPMD cases to cytoplasmic/nuclear high positivity in all cases of OSCC. MMP-14 showed positivity (+) in 89% of OPMDs and high positivity (+++) in 100% of OSCC. Conclusions: Maspin, β-catenin, and MMP-14 exhibit distinct expression patterns across lesion types. While Maspin may reflect early tissue remodeling, β-catenin and MMP-14 changes suggest Wnt signaling activation and matrix remodeling in OSCC. Longitudinal studies are needed to establish their predictive value. This observational study refrains from prognostic claims and instead highlights biomarkers for future validation. Full article

Background/Objectives: In recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), the overall prognosis is poor, and systemic treatment options remain limited. While precision therapy approaches have revolutionized treatment strategies in several tumor types, molecularly informed therapies in R/M HNSCC are rare, primarily due to the low number of actionable genetic alterations identified through next-generation sequencing (NGS) panels. There is an urgent need to establish precision therapy approaches in R/M HNSCC using innovative predictive testing. Methods: We report the case of a 43-year-old patient with recurrent oral cancer who was extensively pretreated and comprehensively characterized using both descriptive and functional testing. Results: NGS revealed no targetable alterations. A tumor tissue slice radiosensitivity assay suggested radioresistance, arguing against re-irradiation. Kinome profiling identified upregulated Src-family kinases (SFK), and SFK inhibition reduced kinase activity in vitro. Most notably, mRNA analysis demonstrated high Trop-2 overexpression, confirmed by immunohistochemistry (3+ in 100% of tumor cells). Following six cycles of the Trop-2-directed antibody–drug conjugate Sacituzumab govitecan (SG), the patient had an impressive clinical response. Conclusions: Tumor characterization beyond genetic profiling can identify novel treatment options in therapy-refractory HNSCC. This is the first report of “real-world” data on promising antitumor efficacy of SG in a heavily pretreated oral cancer patient with Trop-2 overexpression. Consistent with the findings of the Basket TROPiCS-03 study, SG appears to be a promising novel therapy option for R/M HNSCC after failure of immunotherapy and chemotherapy, particularly in patients with Trop-2 overexpression. Full article

Background: Tegafur–uracil (UFT), an oral fluoropyrimidine developed in Asia, has been investigated as a maintenance or adjuvant therapy in various malignancies. Its use in head and neck cancers, however, remains limited to small retrospective studies, primarily from East Asia. Given the need for cost-effective maintenance strategies in resource-limited settings, we conducted an exploratory systematic review to evaluate the clinical utility of UFT in non-metastatic head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC). Methods: We systematically searched PubMed, EMBASE, and Cochrane Library from inception through 1 May 2025 for retrospective cohort studies evaluating UFT after definitive therapy in non-metastatic HNSCC or NPC. Study selection followed PRISMA guidelines. Given the heterogeneity of included studies, we performed a structured narrative synthesis using the SWiM (Synthesis Without Meta-analysis) framework to summarize survival outcomes, treatment settings, and clinical contexts. Results: Seven retrospective studies (four HNSCC, three NPC) involving 508 patients were included. UFT was generally administered at 300–400 mg/day for 6–12 months. Across studies, UFT use was associated with favorable disease-free and overall survival trends in high-risk subgroups, including patients with extranodal extension and persistent EBV DNA. Treatment adherence and toxicity profiles were acceptable. Conclusions: While the evidence remains limited and heterogeneous, this review highlights recurring signals of benefit associated with UFT maintenance therapy in selected high-risk patients. Prospective trials are warranted to confirm these findings and better define a possible role of UFT in maintenance therapy in some advanced non-metastatic HNSCC and NPC. Full article

Despite significant progress in its prevention, diagnosis, and treatment, head and neck cancer (HNC) remains a major global health issue due to its multifactorial pathogenesis. Indeed, HNCs have been found to be associated with different environmental and lifestyle factors, as well as with infection with oncogenic viruses. To date, seven viruses are recognized for their tumorigenic properties and have been proposed as implicated in HNC development, including Merkel Cell Polyomavirus (MCPyV). MCPyV is well recognized as the major etiological agent of Merkel cell carcinoma (MCC), a rare but rapidly metastasizing skin neoplasm. Specifically, in almost 80% of MCC cases, viral genome integration occurs, and a truncated form of Large T Antigen (tLT) is expressed. Although MCC is a rare cancer, MCPyV is a ubiquitous virus, widely distributed among the human population. Therefore, a plausible role of the virus has been proposed, even for other tumors. The current review provides an overview of the available data describing the presence of MCPyV in non-MCC tumors, such as HNCs, with the aim of elucidating the potential contribution of MCPyV to oral cancer. Understanding the role of viral infections in the etiology of cancer opens up the opportunity for developing preventive measures and targeted therapies that effectively address HNC progression while reducing treatment-related side effects. Full article

Objective: In Mexico, head and neck cancers pose a significant health burden. GLOBOCAN reported approximately 3183 new cases and 1636 deaths in 2020. Despite being the sixth leading cause of cancer incidence and mortality worldwide, data on epidemiology and treatment patterns in Mexico remain limited. This study aimed to characterize the profile, clinical features, and management of patients with Stage III–IVB head and neck squamous cell carcinoma (HNSCC) in a real-world setting. Methods: We retrospectively analyzed a database of 187 patients with Stage III, IVA, or IVB HNSCC treated at the University Hospital Dr. José Eleuterio González. Demographics, disease characteristics, and treatment patterns were summarized as frequencies and percentages. Exploratory endpoints included clinical outcomes and recurrence types. Results: The cohort was 82.9% male (n = 155). The most frequent tumor sites were the oral cavity (36.9%) and larynx (36.9%), with 55% (n = 103) diagnosed at stage IVA. Of 75 cases tested for p16, 35.3% (n = 36) were positive. The median time from symptom onset to diagnosis was 166.5 days (95% CI: 123.4–197.8) and from diagnosis to treatment 42 days (95% CI: 31.6–50.4). Initial treatments included surgery (36.4%), chemoradiotherapy (24.6%), induction chemotherapy (19.8%), supportive care (11.2%), and radiotherapy (8%). Locoregional control was achieved in 42.8% of patients, with an overall recurrence rate of 2.8%. Conclusions: This study provides real-world insights into the epidemiology and management of locally advanced HNSCC in Mexico, outlining the patient journey from initial symptoms to treatment and underscoring the need for more individualized therapeutic strategies based on molecular profiling and clinical characteristics. Full article

Background: The treatment of head and neck cancer primarily involves surgical tumor removal combined with radiotherapy and/or chemotherapy. It often leads to significant side effects, impacting the anatomical structures of the oral cavity and resulting in major functional, esthetic, and socio-relational alterations. Case presentation: This clinical report aims to demonstrate the effectiveness of a hospital-based approach incorporating general anesthesia (GA) and computer-aided design and manufacturing (CAD/CAM) technology in the oral rehabilitation of a 58-year-old woman in remission from intraoral squamous cell carcinoma of the mandibular symphysis. The patient presented with oral pain, radiation-induced caries, reduced occlusal vertical dimension, and severely compromised teeth. Treatment Approach: The treatment plan included the removal of two non-restorable teeth, root canal treatment for the remaining teeth, and the placement of ceramic crowns and a partial removable prosthesis. Due to the complexity of the case and the patient’s limitations, the treatment was performed under GA, allowing for a staged approach. Digital technologies, including intraoral scanning and CAD-CAM, enhanced precision and patient comfort. This approach facilitated tooth preservation and minimized the number of extractions while achieving satisfactory functional and esthetic outcomes. Conclusion: The case highlights the value of GA and digital techniques in managing special-needs patients with a history of irradiated head and neck cancer. Full article

Oral squamous cell carcinoma (OSCC) is a common type of head and neck malignancy that represents a significant global health issue. Sialylations are common events in tumor transformation, proliferation, metastasis, and immune evasion. Modifications in sialylation can be detected by lectins, whose changes in OSCC have been related to grade, invasion, and metastasis. The presence of 9-O-acetylated sialic acid (Neu5,9Ac₂) in OSCC cells and its potential expression, modification, and role are unknown. This study aimed to analyze the expression of Neu5,9Ac₂ using the Macrobrachium rosenbergii lectin (MrL) that recognizes this sialic acid (Neu5Ac) residue and also compare its effect on the SCC-152 cell line (CRL-3240, ATCC) and immortalized keratinocytes (HaCaT) as a control. We observed by immunocytochemistry that SCC-152 cells expressed more Neu5,9Ac₂ compared to HaCaT cells; the specificity of MrL was confirmed after the sialidase treatment of cells in which the loss of lectin’s recognition of Neu5,9Ac₂ was observed. The electrophoretic profile was similar between both cell line types; however, the Western blot showed differences in the glycoprotein patterns recognized by lectin for each cell type. MrL increased the proliferation of SCC-152 cells, as well as the integrity and morphology of the colonies. Therefore, our results suggest that Neu5,9Ac₂ glycosylated receptors could be involved in the survival and proliferation of OSCC cells, which offers a promising avenue for developing diagnostic and prognostic tools (tumor markers) against oral squamous cell carcinoma in the future. Full article