INTRODUCTION: Oral cancer is a major public health concern in India. Both conventional and altered fractionation radiotherapy schedules have been used in curative treatment of oral cancer. This study aimed to retrospectively evaluate the clinical profile and treatment outcomes of patients with carcinoma buccal mucosa who underwent treatment with definitive hypofractionated accelerated radiotherapy. METHODS: A total of 517 patients treated from January 2011 to December 2016 were eligible for the analysis. All patients were treated with definitive hypofractionated accelerated radiotherapy schedule of 5,250 cGy in 15 fractions over 3 weeks. Survival estimates were generated using the Kaplan-Meier method. RESULTS: At a median follow-up of 77.4 months, 473 (91.5%) patients attained complete remission with radiation therapy. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69% and 80.5%, respectively. The 5-year OS for stage I, II, III and IVa tumours was 80.3%, 84.4%, 81.4% and 73.7%, respectively, and the DFS was 75.7%, 73.2%, 69.6% and 60.2%, respectively. Age >50 years was found to be a significant factor affecting DFS ( P = 0.026) and OS ( P = 0.048) in multivariate analysis. Fifty-three (10.3%) patients developed osteoradionecrosis of the mandible. CONCLUSION Excellent outcome could be achieved in less-aggressive, low-volume carcinoma of the buccal mucosa with radical accelerated hypofractionated radiotherapy. A radiotherapy schedule over a 3-week period is useful in high-volume centres.
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; Mouth Neoplasms/mortality* ; Mouth Mucosa/radiation effects* ; Treatment Outcome ; Aged ; Adult ; Radiation Dose Hypofractionation ; Disease-Free Survival ; India ; Kaplan-Meier Estimate ; Dose Fractionation, Radiation ; Aged, 80 and over

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*

OBJECTIVE: To explore the technical key points and effectiveness of the facial artery perforator myomucosal flap (FAPMF) in repairing oral and perioral tissue defects. METHODS: Between June 2023 and December 2024, 8 patients with oral and perioral tissue defects were repaired with the FAPMF. There were 4 males and 4 females, with an average age of 57.6 years (range, 45-72 years). Among them, 4 cases had floor-of-mouth defects and 3 cases had buccal mucosa defects remaining after squamous cell carcinoma resection, and 1 case had lower lip defect caused by trauma. The size of tissue defects ranged from 4.5 cm×3.0 cm to 6.0 cm×5.0 cm. The preoperative mouth opening was (39.55±1.88) mm, and the preoperative swallowing score of the University of Washington Quality of Life Questionnaire (UW-QOL) was 64.64±8.47. Preoperatively, CT angiography and Doppler ultrasound were used to locate the perforator vessels. A myomucosal flap pedicled with the perioral perforators of the facial artery was designed, with the harvesting size ranging from 4.0 cm×2.5 cm to 6.5 cm×4.0 cm. The length of the vascular pedicle was 4.2-6.8 cm (mean, 5.2 cm). Postoperatively, FAPMF survival, complications, and functional recovery were observed. RESULTS: All 8 surgeries were successfully completed without conversion to other repair methods or complications such as facial nerve injury. The total operation time ranged from 110 to 180 minutes, with an average of 142.5 minutes; among this, the harvesting time of the FAPMF ranged from 35 to 65 minutes, with an average of 48.7 minutes. The intraoperative blood loss was 50-150 mL, with an average of 85.6 mL. All FAPMFs survived completely. One patient developed venous reflux disorder at 24 hours after operation, which relieved after conservative treatment. All patients were followed up 7-16 months (mean, 12.4 months). All FAPMFs achieved complete epithelialization at 3 months after operation, showing a similar soft texture to the surrounding mucosa. At 7 months after operation, the mouth opening was (39.11±1.79) mm, slightly lower than preoperative level, but the difference was not significant (P>0.05). The swallowing score of the UW-QOL was 63.78±8.31, which was significantly lower than preoperative score (P<0.05). The visual analogue scale (VAS) score for patient satisfaction was 7-10, with an average of 8.9. CONCLUSION The FAPMF has advantages such as reliable blood supply, high mucosal matching degree, and concealed donor site, making it an ideal option for repairing small and medium-sized oral and perioral tissue defects.
Humans ; Male ; Middle Aged ; Female ; Perforator Flap/blood supply* ; Aged ; Plastic Surgery Procedures/methods* ; Mouth Neoplasms/surgery* ; Mouth Mucosa/surgery* ; Mouth/surgery* ; Quality of Life ; Face/surgery* ; Treatment Outcome ; Carcinoma, Squamous Cell/surgery* ; Arteries/surgery*

Salivary gland tumor is one of the most common tumors in oral and maxillofacial regions. The diagnosis and treatment of salivary gland tumors had been a clinical characteristic project in Peking University School and Hospital of Stomatology since long time ago. Here we introduced the research progress in diagnosis and treatment of salivary gland tumors during the past 10 years. Among 7 190 cases of salivary gland tumors treated in this institution, 4 654 cases (64.7%) were benign, and 2 536 (35.3%) were malignant, with benign ∶ malignant ratio of 1.84 ∶ 1. Parotid was the most common location, followed by minor salivary gland and submandibular gland, while sublingular gland tumor was seldom seen. The proportion of minor salivary gland tumor was relatively high. Among 1 874 cases with primary malignant tumors, the cases with T3 and stage Ⅲ accounted for only 9.6% and 10.3%, respectively, which indicated that there was shortcoming in the T classification and clinical stage formulated by Union for International Cancer Control (UICC), and further revision was required. The 5, 10, and 15 year survival rates of 1 637 cases with postoperative follow-up were 93.1%, 87.2% and 79.3%, respectively, which were much higher than those we reported 30 years ago. The improvement of treatment results was related to more widely used combined treatment with surgery and postoperative radiotherapy, and the increase in patients with early stage. Adenoid cystic carcinoma was the malignant tumor with high rate of distant metastasis. The 5 and 10 year survival rates of the patients with pulmonary metastasis were 76.2% and 51.8%, respectively, which indicated that the pulmonary metastatic carcinomas developed slowly. Recurrent rate of carcinoma ex pleomorphic adenoma was 46.7% after single treatment of sur-gery, while it decreased to 27.5% after combined theraphy with surgery and radiotherapy, indicating that postoperative radiotheraphy could reduce the recurrent rate effectively. The normal myoepithelial cells had the inhibiting role in the invasion and metastasis of carcinoma ex pleomorphic adenoma. The evaluation of integrity of myoepithelial cells surrounding the tumor mass is helpful to understand the invasiveness of the tumors. The new surgical modalities such as extracapsular resection and partial sialoadenectomy were used in treatment of benign tumors of parotid gland and submandibular gland with advantages of decreased tissue damage and preservation of glandular function. Application of digital surgical techniques such as mixed reality combined with surgical navigation and real-time three-dimensional holograms in the surgical treatment of parotid gland tumors showed the benifits of more safety and precision, and less tissue da-mage.
Humans ; Salivary Gland Neoplasms/pathology* ; Carcinoma, Adenoid Cystic/therapy* ; Adenoma, Pleomorphic/therapy* ; Neoplasm Staging

OBJECTIVE: To explore the function of LIM and calponin homology domains 1 (LIMCH1) in the development and progression of oral squamous cell carcinoma (OSCC), along with their potential clinical applications. METHODS: By utilizing transcriptome sequencing data from two groups of oral squamous cell carcinoma patients, along with bioinformatics analytical techniques such as Gene Ontology (GO) and gene co-expression networks, we identified genes that might play a pivotal role in the pathogenesis of oral squamous cell carcinoma. We employed real-time quantitative PCR and Western blotting to validate the expression patterns of these genes across twelve patient tissue samples. Furthermore, we conducted CCK-8 assays, flow cytometry analyses, and scratch wound healing assays to assess the impact of key genes on the biological behaviors of both the Cal27 oral squamous cell carcinoma cell line and the potentially malignant DOK oral lesion cell line. Additionally, we examined correlations between these key genes and clinical disease parameters in 214 oral squamous cell carcinoma patients using The Cancer Genome Atlas (TCGA) data; gene set enrichment analysis (GSEA) analysis results were also incorporated to enhance our findings from real-time quantitative PCR and Western blotting regarding potential mechanisms underlying the action of these key genes. RESULTS: The integrated analysis of sequencing data and bioinformatics revealed that LIMCH1 exhibited significantly reduced mRNA (P < 0.001) and protein levels (P < 0.01) in the oral squamous cell carcinoma tissues compared with normal control tissues. In the Cal27 cells, the low LIMCH1 level group demonstrated a larger wound healing area within 24 hours than the control group (P < 0.01), enhanced proliferation capacity over 72 hours relative to the control group (P < 0.01), and an increased apoptosis rate within 24 hours compared with the high expression group (P < 0.05). However, no significant differences were observed between the low and high level groups in DOK cells. Furthermore, it was determined that low LIMCH1 level correlated with poor prognosis in the patients (P=0.013) and a higher lymph node metastasis rate (P < 0.05). Investigations into the potential mechanisms of action indicated that LIMCH1 did not influence the onset or progression of oral squamous cell carcinoma via the epithelial-mesenchymal transition pathway. CONCLUSION LIMCH1 level may function as a promising biomarker to aid in the prognostic assessment of oral squamous cell carcinoma; however, its precise mechanistic role requires further investigation.
Humans ; Mouth Neoplasms/metabolism* ; Prognosis ; Carcinoma, Squamous Cell/metabolism* ; Biomarkers, Tumor/metabolism* ; LIM Domain Proteins/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Male ; Female

OBJECTIVE: To investigate the effects of LncRNA SNHG20 on epithelial mesenchymal transition (EMT) and microtubule formation in human oral squamous cell carcinoma (OSCC) cells through targeted regulation of the miR-520c-3p/RAB22A pathway. METHODS: After real-time fluorescence quantitative detection of LncRNA SNHG20, miR-520c-3p, RAB22A mRNA expression levels in OSCC tissues and cells, dual luciferase reporter assay was used to detect the relationship between the three. OSCC cells were randomly separated into control group, sh-NC group, sh-SNHG20 group, sh-SNHG20+anti NC group, and sh-SNHG20+anti miR-520c-3p group. Western blotting was used to detect the expression of N-cadherin, vimentin, and E-cadherin proteins in the OSCC cells. The morphology of HSC-3 cells was observed under microscope. Changes in the number of microtubules formed were detected. The effect of LncRNA SNHG20 on the growth of OSCC tumors and the expression levels of LncRNA SNHG20, miR-520c-3p and RAB22 A in the transplanted tumors were detected by nude mice tumorigenesis experiment. RESULTS: LncRNA SNHG20 and RAB22A mRNA were upregulated in the OSCC tissues and cells, while miR-520c-3p was downregulated (P < 0.05). There were binding sites between LncRNA SNHG20 and miR-520c-3p, RAB22A and miR-520c-3p, which had targeted regulation relationship. Compared with the sh-NC group, the sh-SNHG20 group had fewer stromal like cells, more epithelial like cells, incomplete microtubule structure, and fewer nodules. LncRNA SNHG20, RAB22A, N-Cadherin, and vimentin were downregulated, while miR-520c-3p and E-cadherin were upregulated (P < 0.05). Compared with the sh-SNHG20+anti-NC group, the sh-SNHG20+anti-miR-520c-3p group had a higher number of stromal like cells, a lower number of epithelioid cells, tighter microtubule arrangement, and more microtubule nodules. miR-520c-3p and E-cadherin were downregulated, while RAB22A, N-cadherin, and vimentin were upregulated (P < 0.05). The transplanted tumor of OSCC in sh-SNHG20 group was smaller and lower than that in sh-NC group. The expression levels of LncRNA SNHG20 and RAB22A in the transplanted tumor tissues were lower than those in sh-NC group, and the expression level of miR-520c-3p was higher than that in sh-NC group (P < 0.05). CONCLUSION LncRNA SNHG20 promotes epithelial-mesenchymal transition and microtubule formation in human oral squamous cell carcinoma cells by targeting the miR-520c-3p/RAB22A pathway. Inhibiting the expression of LncRNA SNHG20 can target and regulate the miR-520c-3p/RAB22A pathway to inhibit EMT and microtubule formation in OSCC cells.
Humans ; RNA, Long Noncoding/genetics* ; MicroRNAs/metabolism* ; rab GTP-Binding Proteins/metabolism* ; Epithelial-Mesenchymal Transition/genetics* ; Cell Line, Tumor ; Carcinoma, Squamous Cell/metabolism* ; Animals ; Microtubules/metabolism* ; Mouth Neoplasms/genetics* ; Mice, Nude ; Mice ; Gene Expression Regulation, Neoplastic ; Mice, Inbred BALB C

OBJECTIVE: To explore whether microneedle pretreatment can significantly improve the efficacy and safety of 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) in the treatment of oral leukoplakia. METHODS: A non-randomized controlled clinical trial was conducted. Patients with clinical and pathological diagnosis of oral leukoplakia in the Department of Oral Mucosa, Peking University School and Hospital of Stomatology were divided into experimental group and control group. The control group was treated with conventional ALA-PDT, and the experimental group was pretreated with micro- needle buckling under superficial anesthesia with lidocaine before conventional ALA-PDT. The clinical manifestations of the two groups were recorded, the lesion area was measured, the clinical efficacy was evaluated, the number of treatment sessions and treatment unit duration were analyzed, and the pain after treatment was evaluated by visual analogue scale. The above data of the two groups were statistically analyzed. RESULTS: A total of 11 patients were included in the experimental group and 19 patients were included in the control group. The complete remission rate of the experimental group and the control group was 45.5% and 36.8%, the partial remission rate was 54.5% and 57.9%, and the no remission rate was 0% and 5%, respectively. There was no significant difference in the treatment effect between the two groups. Meanwhile, the treatment unit duration of the experimental group and the control group were (9.05±5.74) min/cm² and (21.38±15.44) min/cm², respectively, and the number of treatment sessions were (2.36±0.67) times and (3.58±1.57) times, respectively. These differences between the two groups were statistically significant (t=-3.125, P < 0.05; t=-2.932, P < 0.05). Similarly, multiple linear regression analysis with 7 factors including age, dysplastic pathology, lesion classification, etc., also confirmed that pretreatment could significantly shorten the treatment unit duration (P < 0.05). In addition, there was no significant difference in pain score (visual analogue scale) between the two groups after treatment, and the microneedle puncture pretreatment did not increase the adverse reactions of ALA-PDT treatment. CONCLUSION Microneedle pretreatment followed by conventional ALA-PDT shows a good clinical effect on oral leukoplakia, which can significantly shorten the clinical treatment time, reduce the number of visits, and save medical costs.
Humans ; Photochemotherapy/instrumentation* ; Leukoplakia, Oral/drug therapy* ; Aminolevulinic Acid/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Needles ; Photosensitizing Agents/therapeutic use* ; Aged ; Combined Modality Therapy

OBJECTIVE: To evaluate the clinical outcomes and explore the application of partial sialoadenectomy for the treatment of benign tumors in the submandibular gland (SMG). METHODS: Patients with pleomorphic adenoma of the SMG who underwent surgical treatment in the Department of Oral and Maxillofacial Surgery, Peking University Shenzhen Hospital, from October 2017 to February 2021, were enrolled and assessed in the follow-up. Fifteen patients underwent partial sialoadenectomy (PS group), and 18 patients underwent total sialoadenectomy (TS group). Postoperative salivary secretion, degree of dry mouth, appearance changes of the face and neck, nerve damage, and tumor recurrence were compared between the groups. The volume of the glands on the operated and contralateral sides of the patients in the PS group, the saliva flow rate, and their correlations, were also analyzed. RESULTS: There was no recurrence during the follow-up period. The whole saliva flow rate at rest in the PS group was higher than that in the TS group [(2.15±1.10) g/5 min vs. (1.35±0.97) g/5 min, t=2.208, P=0.035)], while the stimulated saliva flow rate was not significantly different. The objective feeling of dry mouth, evaluated by visual analogue scale (VAS) score, was more obvious in the TS group than in the PS group (Z=-2.244, P=0.025). In the PS group, the resting saliva flow rate of the SMG on the operated side was lower than that on the contralateral side of the same patient [(0.92±0.40) g/5 min vs. (1.18±0.40) g/5 min, t=-2.821, P=0.014], however, in the cases whose remaining SMG was more than 80% of the contralateral side, the saliva flow rate of both sides was not significantly different (t=-0.027, P=0.980). There was no significant difference in the saliva flow rate per unit volume of the gland on either side (t=-0.015, P=0.989), and the saliva flow rate of the operated SMG was positively correlated with the volume of the remaining gland (r=0.750, P=0.012). The VAS scores for neck deformity were not significantly different between the two groups (t=-0.997, P=0.319). No symptoms of nerve injury occurred in either group. CONCLUSION Partial sialoadenectomy in the SMG can safely remove benign tumors while preserving glandular secretory function, with fewer complications and improved quality of life.
Humans ; Submandibular Gland/pathology* ; Male ; Female ; Middle Aged ; Adenoma, Pleomorphic/surgery* ; Adult ; Treatment Outcome ; Submandibular Gland Neoplasms/surgery* ; Saliva/metabolism* ; Aged

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

Oral and maxillofacial tumors, due to their complex anatomical structures and vital physiological functions, pose significant risks, not only affecting patients' appearance and function but also potentially endangering their lives. Traditional tumor resection and reconstruction surgeries face challenges such as inadequate precision, long surgical durations, and unsatisfactory postoperative outcomes. In the treatment of oral and maxillofacial tumors, 3D printing technology can be used for preoperative planning, surgical guide plate production, and the design and manufacture of personalized prosthetics, providing new solutions for functional reconstruction after tumor resection. This article reviews the progress of 3D printing technology in the medical field and explores its potential value in the resection and reconstruction of oral and maxillofacial tumors, aiming to provide references for clinical practice and promote the further application and development of this technology in oral and maxillofacial surgery.
Printing, Three-Dimensional ; Humans ; Plastic Surgery Procedures/methods* ; Mouth Neoplasms/surgery*