Search Results (198)

Oral cancer, the most common head and neck malignancy, has a high recurrence rate and poor prognosis largely owing to chemotherapy resistance. The adverse effects of conventional therapies have prompted investigations into safer and more effective alternative therapies. Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown potential owing to their roles in autophagy modulation and immune regulation. This study clarifies the selective efficacy of hydroxychloroquine (HCQ) and chloroquine (CQ) in oral squamous cell carcinoma models, emphasizing distinct responses in gingival (Ca9-22) and tongue (SCC-9) carcinoma cells. Non-oncogenic oral epithelial cells (GMSM-K) and oral carcinoma cell lines from the tongue (SCC-9, Cal-27) and gingiva (Ca9-22) were used. Cell viability, cytotoxicity, and colony formation were assessed via MTT, LDH, and crystal violet assays. Flow cytometry was used to measure apoptosis, autophagy, oxidative stress, mitochondrial membrane potential, and DNA damage. The transcriptomic profiles of apoptosis and autophagy-related genes were assessed by qPCR arrays. Bioinformatics analysis allowed estimation of the main gene interaction networks. Pre-screening showed that GMSM-K and Cal-27 cells were non-responsive or exhibited non-specific toxicity at high doses; therefore, subsequent analyses focused on Ca9-22 (GC) and SCC-9 (TC). HCQ significantly reduced viability and colony formation in Ca9-22 cells while moderately affecting SCC-9 cells. Autophagy inhibition was accompanied by compensatory up-regulation of autophagy-related genes, consistent with feedback activation of TFEB and FOXO3a pathways. Gene expression profiling and flow-cytometry analyses revealed cell-type-specific differences in apoptosis, mitochondrial potential, and DNA damage, suggesting HCQ’s selective anti-tumor potential in gingival carcinoma. These findings highlight HCQ as a repurposed adjuvant therapy that modulates autophagy and apoptosis to enhance chemosensitivity in oral cancer. Full article

Background/Objectives: Total glossectomy (TG) is among the most radical operations in head and neck oncology. While it can achieve local control in advanced oral tongue squamous cell carcinoma, survival and functional outcomes are inconsistently reported, and pooled estimates remain limited. This study aimed to systematically evaluate survival, functional recovery, and prognostic factors following primary TG. Methods: We conducted a proportional meta-analysis of studies reporting outcomes after primary TG for oral tongue squamous cell carcinoma. Studies combining TG with laryngectomy, salvage settings, or second primary tumors were excluded. Two reviewers independently screened, extracted data, and assessed quality with the Newcastle–Ottawa Scale. Pooled 1-, 3-, and 5-year overall survival (OS) with 95% confidence intervals (CIs) was calculated using a random-effects model. Heterogeneity was quantified (Q, τ², I²), and robustness was assessed with sensitivity analyses. Disease-free survival (DFS) and functional outcomes (swallowing, airway, speech) were narratively summarized due to inconsistent reporting. Results: Ten studies (1992–2022) comprising 261 patients met the criteria. Pooled OS was 81% (95% CI, 71–90) at 1 year, 55% (95% CI, 41–68) at 3 years, and 47% (95% CI, 27–67) at 5 years, with rising heterogeneity (I² up to 89%). The post-2000 series showed improved 5-year OS (63%). Adverse prognostic factors included advanced T stage, nodal disease (N+), and positive margins. Functional recovery varied: 15–30% remained gastrostomy-dependent and 20–25% aspirated, while reconstruction and structured rehabilitation improved outcomes. Conclusions: Survival after TG declines beyond the first year, with under half surviving at 5 years, though modern outcomes appear better. Significant functional morbidity underscores the need for multidisciplinary care. Future biomarker-driven studies should refine patient selection and prognostic assessment. Full article

Purpose: Cervical lymph node status is the strongest prognostic factor in oral squamous cell carcinoma (OSCC). While 18F-FDG-PET and cervical ultrasonography are widely used for preoperative staging, their diagnostic accuracy remains limited for small or equivocal nodes. This study compared both modalities against histopathology on a per-level basis and examined correlations of SUVmax and RECIST values with metastatic involvement. Methods: This retrospective single-centre study included patients with histologically confirmed OSCC who underwent preoperative 18F-FDG-PET and cervical ultrasonography, followed by resection and neck dissection (October 2018–December 2024). Imaging was interpreted independently and blinded to clinical and histopathological data. Histopathology served as the reference standard. Diagnostic accuracy was assessed on a level-by-level basis. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated and compared using McNemar’s test and logistic regression. Results: Among 100 patients (mean age 63.5 ± 10.6 years; 54% male, 46% female), the lateral tongue was the most frequent site (44%), and 31% showed nodal involvement on PET imaging. PET imaging yielded 59% sensitivity, 87% specificity, and 77% accuracy; ultrasonography achieved higher sensitivity (76%) but lower specificity (67%). Combined assessment improved sensitivity (78%) and NPV (82%) but reduced specificity. PET imaging was more specific, while ultrasonography was more sensitive. SUVmax and RECIST values were higher in metastatic nodes and independently predicted metastasis, though with substantial overlap and no reliable cut-off. Conclusions: PET imaging offers higher specificity, whereas ultrasonography provides greater sensitivity. Their complementary performance supports a multimodal approach to cervical staging in OSCC. Neither SUVmax nor RECIST values reliably distinguished benign from malignant lymph nodes. Full article

Background: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity, often necessitating extensive surgical resection. Such interventions may result in complex intraoral defects requiring immediate reconstruction to restore function and aesthetics. Objective: This case report highlights the surgical management of a patient with OSCC involving the tongue, floor of the mouth and mandibular ridge, reconstructed using a radial forearm free flap (RFFF). Case report: A 51-year-old male with a history of heavy smoking presented with a necrotic lesion affecting the left mandibular alveolar ridge, floor of the mouth, and tongue. Methods: Histopathological examination confirmed a diagnosis of moderately differentiated keratinizing OSCC (G2). After oncologic resection and selective neck dissection, the defect was reconstructed using an RFFF harvested from the left forearm. The facial artery and anterior jugular vein served as recipient vessels for microvascular anastomosis. A split-thickness skin graft (STSG) was used to close the donor site. Results: The postoperative course was generally favorable. Minor complications, including a localized hematoma and neck wound dehiscence, were conservatively managed. Functional outcomes such as oral intake and wrist mobility were successfully restored with rehabilitation. The RFFF provided durable, well-vascularized coverage over exposed mandibular bone, critical for minimizing the risk of osteoradionecrosis in the context of planned adjuvant radiotherapy. Conclusions: The radial forearm free flap remains a reliable reconstructive option for complex oral defects post-OSCC resection. Multidisciplinary collaboration and meticulous surgical technique are essential to achieve optimal oncologic, functional, and aesthetic outcomes. Full article

Background/Objectives: Lymph node metastases represent the most important prognostic factor for survival in patients with localized squamous cell carcinoma (SCC) of the oral cavity. In patients with carcinoma of the tongue or floor of the mouth, elective neck dissection (END) has been the standard of care, but it has been replaced at many centers by sentinel lymph node biopsy (SLNB). This study’s purpose was to measure and compare recurrence rates between END and SLNB in patients with early SCC of the oral cavity. Methods: Patients were included in this retrospective monocenter cohort study, performed at the University Hospital of Zürich, if they underwent either END or SLNB for oral squamous cell carcinoma (OSCC) of the tongue or floor of the mouth between January 2008 and December 2018. Only patients with early-stage tumors and a clinically negative neck (T1 or T2; cN0) who had a follow-up period of at least 5 years were included. Patients with a T3 or T4 tumor or a clinically positive neck were excluded, as were those who previously underwent therapy for another head and neck carcinoma. The predictor variable was the surgical treatment used, with subjects divided into two groups: END and SLNB. The main outcome variable was the time to recurrent disease, defined as the time between the primary surgical treatment and the diagnosis of recurrence. The covariates were primary tumor location, pT status, pN status, histopathological grade and postoperative radiotherapy. We used descriptive analysis, univariate analysis and the logrank test, with a p-value < 0.05 considered statistically significant. We deliberately refrained from multivariate analysis due to insignificant statistical results in the univariate analysis. Results: In total, 82 patients (46 male, 36 female; median age at the time of surgery: 58.9 years) were included, with a median observation period of 4.3 years. The main primary tumor location was the floor of the mouth (62.2%). The SLNB cohort had smaller primary tumors in comparison to the END cohort (20% vs. 37% pT2, respectively). Furthermore, pN+ disease was more prevalent in the END group in comparison to the SLNB group (81.8% vs. 74.1% pN0, respectively). Recurrence-free survival was not significantly different between the two groups. Subgroup analysis demonstrated a higher risk of recurrent disease in pN+ groups undergoing SLNB compared to those undergoing END. Conclusions: We demonstrate that SLNB is a useful tool for assessing lymph nodes of the neck. In cases of pN+ necks after SLNB and subsequent neck dissection, patients need to be closely followed up with due to the risk of recurrent disease. Full article

Cervical lymph node metastasis is the strongest prognostic factor in oral tongue carcinoma, yet current clinical guidelines rely primarily on depth of invasion to guide elective neck dissection. This approach results in unnecessary surgery in up to 70% of patients. Cancer-testis antigens (CTAs) are a family of genes associated with tumor aggressiveness and may serve as predictive biomarkers for nodal spread. A multi-step analysis integrating large-scale public datasets, including microarray (GSE78060), bulk RNA-seq emerging from the cancer genome atlas (TCGA), and single-cell RNA-seq (GSE103322), was employed to identify CTA genes active in oral tongue cancer. Selected genes were validated using NanoString nCounter RNA profiling of 16 patients undergoing curative glossectomy with elective neck dissection. Machine learning algorithms, including decision trees, t-distributed stochastic neighbor embedding (t-SNE), and convolutional neural networks (CNN), were applied to assess predictive power for nodal metastasis. Computational analysis initially identified 40 cancer-active CTA genes, of which four genes (LY6K, MAGEA3, CEP55, and ATAD2) were most indicative of nodal spread. In our patient cohort, NanoString nCounter profiling combined with machine learning confirmed these four genes as highly predictive. We present a proof-of-concept CTA-based genetic diagnostic tool capable of discriminating nodal involvement in oral tongue cancer. This approach may reduce unnecessary neck dissections, minimizing surgical morbidity. Full article

Background/Objectives: The deep circumflex iliac artery (DCIA) free flap with internal abdominal oblique muscle (IAOM) is a well-known method of reconstruction used in cases of oral cavity neoplasms. Because the IAOM can be insufficient for extensive defects after removal of advanced carcinomas of the tongue, floor of the mouth, or gingiva, the additional preparation of a perforator-supported external abdominal oblique (EAOM) muscle flap can be useful. The aim of this study was to introduce the use of a DCIA flap with an IAOM and EAOM island in the reconstruction of oral cavity compound defects. Methods: A retrospective analysis was performed involving eight patients who underwent reconstruction using a DCIA free flap with IAOM and perforator-supported EAOM island. Patients underwent the operation between June 2021 and February 2025 in the Department of Maxillofacial Surgery of the Rydygier Hospital in Kraków, Poland. Results: A group of eight patients underwent an operation due to squamous cell carcinoma of the oral cavity. The most common primary subsite of disease was the floor of the mouth (n = 4, 50%), followed by the lower gingiva (n = 2, 25%) and retromolar area (n = 2, 25%). All patients required resection involving part of the mandible, the floor of the mouth, and part of the tongue simultaneously with reconstruction using a DCIA free flap with IAOM and perforator-supported EAOM island. Osteotomies were performed in two flaps (one single osteotomy, one double osteotomy). Reconstruction was successfully performed in seven out of eight patients (overall success rate 88%). Conclusions: The DCIA free flap with IAOM and perforator-supported EAOM flap is a reliable method for compound soft tissue and bone defects in maxillofacial reconstruction. The use of IAOM and EAOM can be helpful in cases of three-dimensional soft tissue defects of the lower gingiva, the floor of the mouth, and the tongue. The lower gingiva and floor of the mouth can be reconstructed with IAOM, while the more mobile part of the tongue can be reconstructed with a perforator-supported EAOM island. Full article

Objectives: Tobacco has been associated with the development of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). This study aimed to evaluate the in vitro and in vivo changes caused by carcinogen 4-nitroquinoline 1-oxide (4NQO), simulating smoking conditions. Materials and Methods: In the in vitro study, normal keratinocytes were exposed to 1.3 µM and 2.6 µM concentrations of 4NQO to induce dysplastic transformation (H-DISP) and malignant transformation (H-SCC), respectively. The cells were collected and subjected to hematoxylin and eosin (H&E) staining and immunocytochemistry with Ki-67. For the in vivo study, female C57BL/6J mice were divided into a pure control (PC) group and experimental groups exposed to 50 µg/mL (NQ) and 100 µg/mL (CM) of 4NQO in autoclaved drinking water. Each group was euthanized after 8, 12, 16, and 20 weeks of exposure. The tongues were collected, processed, stained with H&E, and analyzed using conventional light microscopy. Results: In vitro, significant morphological changes were observed in the H-DISP and H-SCC groups, with a cell proliferation index exceeding 30% in the H-DISP group. In vivo, the CM group showed greater progression to severe dysplasia/carcinoma within a shorter treatment period compared to the NQ group. Conclusions: We established critical doses and exposure durations for 4NQO, both in vitro and in vivo, to induce cellular changes and the formation of OL and OSCC, providing a standardized model for studies related to oral carcinogenesis. Full article

Background/Objectives: Recurrences of squamous cell carcinoma (SCC) at the base of the tongue (BoT) after primary radiochemotherapy (RT-CHT) are associated with low survival rates, poor functional outcomes, and high morbidity following salvage surgery. Transoral robotic surgery (TORS) has emerged as a less invasive alternative to open surgical approaches. This study aims to describe our clinical experience with TORS in patients with BoT SCC recurrence after RT-CHT, focusing on oncological outcomes—relapse-free survival (RFS) and disease-specific survival (DSS)—as well as functional outcomes, particularly swallowing function. Methods: We conducted a retrospective review of four patients who underwent salvage TORS for BoT recurrence between September 2013 and September 2014 at a single tertiary referral center. All patients had been previously treated with primary RT-CHT for oropharyngeal squamous cell carcinomas. Oncological events (recurrence, death) and functional endpoints (dietary limitations, MD Anderson Dysphagia Inventory [MDADI] scores) were retrieved from medical records. Results: Four patients were included. All achieved unrestricted oral intake by one month post-TORS, showing functional improvement compared to their preoperative status. Three of the four patients remained free of locoregional recurrence during follow-up. No major perioperative complications were reported. Conclusions: In selected patients with BoT SCC recurrence after primary RT-CHT, TORS may offer a viable and less morbid salvage treatment option with favorable early functional outcomes and acceptable oncologic control. Based on both our institutional experience and the supporting literature, we propose selection criteria to guide TORS indication in this clinical setting. Full article

Oral tongue squamous cell carcinoma (OTSCC) is a common type of oral cancer influenced by genetic, epigenetic, and environmental factors like exposure to environmental toxins. These environmental toxins can decrease the effectiveness of established chemotherapy drugs, such as Irinotecan, used in OTSCC treatment. Bioinformatics, drug discovery, and machine learning techniques were employed to investigate the impact of Irinotecan on OTSCC patients by identifying targets and signaling pathways, including those that positively influence protein phosphorylation, protein tyrosine kinase activity, the PI3K-Akt (Phosphatidylinositol 3-kinase- Protein Kinase B) signaling system, cancer pathways, focal adhesion, and the HIF-1 (Hypoxia-Inducible Factor 1) signaling pathway. Later, the protein–protein interactions (PPIs) network, along with twelve cytoHubba approaches to finding the most interacting molecule, was employed to find the important proteins BCL2 and EGFR. Drugs related to BCL2 and EGFR were extracted from the DGIdb database for further molecular docking. Molecular docking revealed that Docetaxel, Paclitaxel, Imatinib, Ponatinib, Ibrutinib, Sorafenib, and Etoposide showed more binding affinity than Irinotecan (i.e., −9.8, −9.6). Of these, Paclitaxel (−10.3, −11.4) and Imatinib (−9.9, −10.4) are common in targeting BCL2 and EGFR. Using these identified candidate genes and pathways, we may be able to uncover new therapeutic targets for the treatment of OTSCC. Furthermore, molecular dynamics (MD) simulations were performed for selected ligand–receptor complexes, revealing stable binding interactions and favorable energetic profiles that supported the docking results and strengthened the reliability of the proposed drug repurposing strategy. Full article

Background: This systematic review evaluates the effectiveness and safety of brachytherapy (BT), including low-dose-rate (LDR) and high-dose-rate (HDR) techniques, in the treatment of oral squamous cell carcinoma (OSCC). Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science up to April 2025, according to PRISMA guidelines. The review was registered in PROSPERO (CRD42024581512). Eligible studies included cohort, case-control, and longitudinal studies in English investigating BT in OSCC patients. Risk of bias was assessed using ROBINS-I. Results: A total of 26 studies with 2286 patients were included where BT was employed as primary or adjuvant therapy, primarily for tumors of the tongue and floor of the mouth. Local control rates ranged from 72% to 95% for both LDR and HDR. HDR BT showed similar efficacy to LDR and offered logistical advantages. Acute and late toxicities included mucositis, soft tissue necrosis, and osteoradionecrosis, particularly with higher doses and large volumes. Combined BT and external beam radiotherapy (EBRT) improved outcomes in selected patients. Conclusions: BT remains an effective, organ-preserving option for early-stage OSCC. HDR BT is increasingly adopted due to its comparable efficacy and improved practicality. Optimal patient selection and precise dosimetric planning are crucial to minimize complications. Further prospective studies are warranted to define its role in modern multimodal treatment strategies. Full article

Background: Tongue squamous cell carcinoma (TSCC) is an aggressive oral malignancy characterized by early submucosal invasion and a high risk of cervical lymph node metastasis. Accurate and timely diagnosis is essential, but it remains challenging when relying solely on conventional imaging and histopathology. This systematic review aimed to evaluate studies applying artificial intelligence (AI) in the diagnostic imaging of TSCC. Methods: This review was conducted under PRISMA 2020 guidelines and included studies from January 2020 to December 2024 that utilized AI in TSCC imaging. A total of 13 studies were included, employing AI models such as Convolutional Neural Networks (CNNs), Support Vector Machines (SVMs), and Random Forest (RF). Imaging modalities analyzed included MRI, CT, PET, ultrasound, histopathological whole-slide images (WSI), and endoscopic photographs. Results: Diagnostic performance was generally high, with area under the curve (AUC) values ranging from 0.717 to 0.991, sensitivity from 63.3% to 100%, and specificity from 70.0% to 96.7%. Several models demonstrated superior performance compared to expert clinicians, particularly in delineating tumor margins and estimating the depth of invasion (DOI). However, only one study conducted external validation, and most exhibited moderate risk of bias in patient selection or index test interpretation. Conclusions: AI-based diagnostic tools hold strong potential for enhancing TSCC detection, but future research must address external validation, standardization, and clinical integration to ensure their reliable and widespread adoption. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral cancer, progressing from hyperplasia to dysplasia, carcinoma in situ (CIS), and finally invasive squamous cell carcinoma (ISCC). Developing an animal model that mimics both early and advanced OSCC stages has been challenging. The 4-Nitroquinoline 1-oxide (4NQO) model is considered one of the most suitable, as it represents all stages of OSCC. Nevertheless, thoroughly understanding the properties of the 4NQO model is essential for preclinical testing of novel therapeutics. Methods: We aimed to characterize the 4NQO rat model using two application methods—drinking water and topical application—over eight months. Monthly sacrifices allowed histopathological analysis and ex vivo magnetic resonance imaging (MRI) to track tumor progression. Results: CIS was observed at three months in the drinking water group, evolving into ISCC by six months, while topical application induced CIS at eight months without ISCC formation. The tongue was divided into three regions and histological properties, lesion size, and invasion depth were analyzed. In the drinking water group, particularly in the body of the tongue, we saw earlier CIS development, larger lesions, and deeper invasion. Additionally, assessment of proliferative properties showed an increased cell division in dysplastic lesions that reduced upon invasion. MRI was able to show macroscopic tumoral lesions, in concordance with histology. Conclusions: Overall, the drinking water method closely mimics human OSCC, validating the 4NQO model for translational OSCC research. 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

RNA-binding proteins (RBPs) critically regulate post-transcriptional gene networks, yet their roles and mechanisms in oral squamous cell carcinoma (OSCC) remain underexplored. Dysregulated RBPs were identified through integrated analysis of RNA-seq and single-cell RNA-seq. The oncogenic functions of IGF2BP2 were evaluated through tissue microarrays, CCK-8, transwell assays, mouse xenografts, and Igf2bp2-deficient mouse models of tongue SCC (TSCC). Subsequently, we utilized RNA-seq, RIP-seq, RIP/MeRIP-qPCR, and dual-luciferase reporter assays to investigate IGF2BP2-target genes. Furthermore, cell co-culture system and mouse TSCC models were used to validate the therapeutic effect of the IGF2BP2 inhibitor. IGF2BP2 was the most markedly upregulated RBP in OSCC cells and cancer-associated fibroblasts (CAFs), correlating with unfavorable prognosis. IGF2BP2 deprivation significantly impaired human OSCC proliferation and metastasis, and delayed mouse TSCC onset. Mechanistically, IGF2BP2 stabilized EGFR and PIK3R1 mRNA via m6A-dependent interactions, thereby sustaining activation of the EGFR/PI3K/AKT oncogenic axis. Pharmacological inhibition of IGF2BP2 exhibited anti-OSCC efficacy in vivo and in vitro by concurrently suppressing EGFR and PI3K/AKT pathway activity, overcoming anti-EGFR resistance resulting from cell-intrinsic PI3K/AKT hyperactivation and CAF-secreted factors. Our findings identified IGF2BP2 as a master regulator of OSCC progression and a promising therapeutic target, offering an alternative strategy for OSCC patients suffering anti-EGFR resistance. Full article