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*

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*

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*

As the field of oral pathology has evolved, the nomenclature and classification of oral mucosal diseases with a remarkable risk of malignant transformation have undergone several modifications. In 2005, the World Health Organization (WHO) introduced the concept of oral potentially malignant disorders (OPMDs) as an alternative to the terms for oral precancerous lesions and precancerous conditions. In the consensus report by the WHO Collaborating Center for Oral Cancer of 2021, OPMD is defined as "any oral mucosal abnormality that is associated with a statistically increased risk of developing oral cancer."This definition encompasses a range of conditions, in-cluding oral leukoplakia, oral submucous fibrosis, proliferative verrucous leukoplakia, oral lichen planus, and other lesions. In light of the complex etiology, unclear pathogenesis, and carcinogenesis of OPMDs, early and precise diagnosis and treatment can contribute to the secondary prevention of oral cancer. For this reason, this review, which aims to provide a basis for the precise clinical diagnosis of OPMDs, was performed. Its aim was achieved by reviewing the historical evolution and research progress of the nomenclature, classification, and histopathological diagnostic criteria of OPMDs.
Humans ; Mouth Neoplasms/diagnosis* ; Precancerous Conditions/diagnosis* ; Leukoplakia, Oral/diagnosis* ; Lichen Planus, Oral/pathology* ; Oral Submucous Fibrosis/pathology* ; Mouth Mucosa/pathology* ; World Health Organization

OBJECTIVES: This study aimed to construct a risk prediction model for the occurrence of the demora-lization syndrome in patients with oral cancer and provide a scientific basis for the prevention of this syndrome in patients with oral cancer and the development of personalized care programs. METHODS: A total of 486 patients with oral cancer in West China Hospital of Stomatology of Sichuan University and Sun Yat-sen Memorial Hospital of Sun Yat-sen University from 2024 March to July were selected by convenience sampling. We integrated clinical data and evidence from previous studies to identify the key variables affecting the demoralization syndrome in patients with oral cancer. The 486 patients were divided into a training set and a validation set in an 8∶2 ratio. A clinical risk prediction model was established based on the individual data of 365 patients in the development cohort. Through least absolute shrinkage and selection operator (LASSO) regression, a moderate to severe risk prediction model of demoralization syndrome in oral cancer was constructed, and a clinical machine-learning nomogram was constructed. Bootstrap resampling was used for internal validation. The data of 121 patients in the validation cohort were externally validated. RESULTS: The incidence of the demoralization syndrome in patients with oral cancer was 405 cases (83.3%), of which 279 cases (57.4%) were mild, 176 cases (36.2%) were moderate, and 31 cases (6.4%) were severe. The core model, including patient education level, disease understanding, and MDASI-HN score, was used to predict the risk of outcome. Internal validation of the model yielded C statistic of 0.783 6 (95% CI: 0.78-0.87), beta of 0.843 4, and calibration intercept of -0.040 6. Through external validation, the validation set C statistic was 0.80 (95%CI: 0.71-0.87), beta was 0.80, and calibration intercept was -0.08. CONCLUSIONS Our risk prediction mo-del of the demoralization syndrome in patients with oral cancer performed robustly in validation cohorts of different nur-sing environments. The model has good correction and good discrimination and can be used as an evaluation and prediction item at admission.
Humans ; Mouth Neoplasms/complications* ; Male ; Female ; Nomograms ; Middle Aged ; Syndrome ; Aged ; Adult ; Risk Factors ; Risk Assessment ; Machine Learning

OBJECTIVES: This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC. METHODS: The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model. RESULTS: LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor. CONCLUSIONS LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Animals ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness ; Cell Proliferation ; Mice, Nude ; Cell Movement ; Lysosomal Membrane Proteins/genetics* ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis

OBJECTIVES: To analyze the trends of disease burden of lip and oral cancers in East Asia from 1990 to 2021 and its future projections. METHODS: We used the Global Burden of Disease 2021 database to conduct a comprehensive analysis of disease burden data from China (including Taiwan Province of China), Japan, Republic of Korea, Democratic People's Republic of Korea and Mongolia. The data were stratified by age, gender and major risk factors, and a Bayesian age-period-cohort model was employed to predict the future trends. RESULTS: From 1990 to 2021, the burden of lip and oral cancers in East Asian countries exhibited a steady increase. Taiwan Province of China experienced the most significant increases in incidence, prevalence, mortality, and disability-adjusted life years (DALYs), while Mongolia saw a decline in both mortality and DALYs. In 2021, Taiwan Province of China reported the highest rates of lip and oral cancer incidence (27.50 per 100 000), prevalence (137.92 per 100 000), mortality (9.59 per 100 000), and DALYs (292.07 person-years per 100 000), particularly among male and elderly populations. Tobacco use and alcohol consumption significantly exacerbated the disease burden in Taiwan Province of China and Japan. Future projections indicate that the incidence and prevalence of lip and oral cancer in China (excluding Taiwan Province of China) will continue to rise, while their mortality rates are expected to decline in most regions, except for Taiwan Province of China and Democratic People's Republic of Korea. CONCLUSIONS By the year 2035, the disease burden of lip and oral cancers in East Asia is expected to continue to increase, especially in Taiwan Province of China. To address this challenge, it is essential to implement effective measures to control major risk factors, promote early screening, and ensure equitable distribution of healthcare resources.
Humans ; Mouth Neoplasms/epidemiology* ; Incidence ; Lip Neoplasms/epidemiology* ; Asia, Eastern/epidemiology* ; Male ; Disability-Adjusted Life Years ; Prevalence ; Female ; Forecasting ; Risk Factors ; Cost of Illness ; Middle Aged ; Global Burden of Disease ; Aged ; Bayes Theorem

Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Oral squamous cell carcinoma (OSCC) is the most common manifestation of oral cancer. It has been proposed that periodontal pathogens contribute to OSCC progression, mainly by their virulence factors. However, the main periodontal pathogen and its mechanism to modulate OSCC cells remains not fully understood. In this study we investigate the main host-pathogen pathways in OSCC by computational proteomics and the mechanism behind cancer progression by the oral microbiome. The main host-pathogen pathways were analyzed in the secretome of biopsies from patients with OSCC and healthy controls by mass spectrometry. Then, functional assays were performed to evaluate the host-pathogen pathways highlighted in oral cancer. Host proteins associated with LPS response, cell migration/adhesion, and metabolism of amino acids were significantly upregulated in the human cancer proteome, whereas the complement cascade was downregulated in malignant samples. Then, the microbiome analysis revealed large number and variety of peptides from Fusobacterium nucleatum (F. nucleatum) in OSCC samples, from which several enzymes from the L-glutamate degradation pathway were found, indicating that L-glutamate from cancer cells is used as an energy source, and catabolized into butyrate by the bacteria. In fact, we observed that F. nucleatum modulates the cystine/glutamate antiporter in an OSCC cell line by increasing SLC7A11 expression, promoting L-glutamate efflux and favoring bacterial infection. Finally, our results showed that F. nucleatum and its metabolic derivates promote tumor spheroids growth, spheroids-derived cell detachment, epithelial-mesenchymal transition and Galectin-9 upregulation. Altogether, F. nucleatum promotes pro-tumoral mechanism in oral cancer.
Humans ; Fusobacterium nucleatum/metabolism* ; Mouth Neoplasms/metabolism* ; Disease Progression ; Proteomics ; Carcinoma, Squamous Cell/metabolism* ; Host-Pathogen Interactions ; Metabolic Networks and Pathways ; Case-Control Studies ; Mass Spectrometry