Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.
Male ; Humans ; Carcinoma, Squamous Cell/drug therapy* ; Diosgenin/metabolism* ; Mouth Neoplasms/drug therapy* ; Apoptosis ; Prostatic Neoplasms/drug therapy*

Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).
Humans ; Mouth Neoplasms/pathology* ; Carcinoma, Squamous Cell/metabolism* ; Luteolin/therapeutic use* ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; Cell Line, Tumor

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.
Humans ; Carcinoma, Squamous Cell/therapy* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/therapy* ; Head and Neck Neoplasms ; Tumor Microenvironment

OBJECTIVE: To investigate the characteristics of pathogen infection and to establish a prediction model of infections in oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction. METHODS: The retrospective cohort study consisted of 1 596 patients undergoing tumor resection and free flap reconstruction for oral squamous cell carcinoma from January 2018 to December 2020. According to the postoperative infection, the patients were divided into the infected group (n=154) and non-infected group (n=1 442). The characteristics of pathogens were analyzed in the infected patients. The primary outcome variable was postoperative infection, and Logistic regression was used to determine risk factors of the infection. The prediction model was established and the discriminatory accuracy of the model was evaluated using receiver operating characteristic (ROC) curve. RESULTS: Totally 154 cases were infected in the 1 596 cases undergoing surgery with free flap reconstruction, and the infection rate was 9.65%. The most frequent sites of infection were the surgical wound and respiratory tract. A total of 268 pathogens were isolated and cultured, including 240 strains of Gram-negative bacteria, accounting for 89.55%, mainly Pseudomonas aeruginosa and Klebsiella pneumoniae; 23 strains of Gram-positive bacteria, accounting for 8.58%, mainly Enterococcus faecalis and Staphylococcus aureus; and 5 strains of fungi, accounting for 1.87%. The isolated Pseudomonas aeruginosa had high resistant rate to imipenem and meropenem, and was sensitive to antibiotics, such as ciprofloxacin. The isolated Staphylococcus aureus had high resistant rate to erythromycin and clindamycin, and was sensitive to vancomycin. According to the multivariate Logistic analysis, four independent variables were significantly associated with an increased risk of postoperative infection (P < 0.05): clinical N category≥1, the American Society of Anesthesiologists (ASA) grade ≥2, tracheotomy and length of hospital stay >13 d. The prediction model was established based on these factors and the expression of the risk prediction model was as follows: predicted probability value P=1/(1+e^-a), a=-0.803+0.674×(clinical N category ≥1)+0.518×(the ASA grade ≥2)+0.918×(tracheotomy)+1.581×(length of hospital stay >13 d), Hosmer-Lemeshow χ²=10.647, P=0.223, the degree of fitting of the model was good. The area under the ROC curve was 0.818 and 95%CI of the model for predicting infection was 0.789-0.846. CONCLUSION Oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction are prone to have a high incidence of postoperative infection and Gram-negative bacteria are the main pathogens causing an infection. The established prediction model is of good predictive effect. Rational antimicrobial use coupled with awareness of infection control measures is paramount to reduce the incidence of postoperative infection in the oral squamous cell carcinoma patients undergoing surgery with free flap reconstruction.
Anti-Bacterial Agents/therapeutic use* ; Carcinoma, Squamous Cell/surgery* ; Drug Resistance, Bacterial ; Free Tissue Flaps ; Head and Neck Neoplasms ; Humans ; Microbial Sensitivity Tests ; Mouth Neoplasms/surgery* ; Retrospective Studies ; Squamous Cell Carcinoma of Head and Neck/drug therapy*

Oral lichen planus (OLP) is a chronic and inflammatory oral mucosal disease that commonly affects middle-aged females. Most OLP cases might exhibit such symptom as pain, roughness and other discomfort, and more severe forms may show a high risk of developing oral cancer. Active preventive measure, precise diagnosis and standard therapeutic approach play a vital role in the management and prevention of OLP. This guideline is a revision on the base of trial in 2012, which mainly covers the following 8 aspects: etiology and medical records, clinical manifestations, pathological manifestations, diagnosis, differential diagnosis, laboratory examination, disease treatment and prevention, aiming at providing scientific evidence and guidance for the dental clinicians in diagnose and treatment of OLP.
Diagnosis, Differential ; Female ; Humans ; Lichen Planus, Oral/therapy* ; Middle Aged ; Mouth Neoplasms

Radiation-induced oral mucositis is an oral mucosal injury caused by radiation ionizing radiation, which often manifests as oral mucosal congestion, erosion, and ulcers. Radiation-induced oral mucositis manifesting as vascular proliferative changes in the oral mucosa has not been reported. We report a case of oral mucosal atypical vascular proliferation after radiotherapy for a malignant maxillofacial tumor. We discussed the mechanism and treatment of aty-pical vascular proliferation in the oral mucosa secondary to radiotherapy, including diagnosis, treatment, and previous literature.
Humans ; Stomatitis/therapy* ; Radiation Injuries ; Mouth Mucosa ; Neoplasms/complications* ; Cell Proliferation

Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8⁺ T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes/pathology* ; Carcinoma, Adenoid Cystic/pathology* ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Humans ; Immunosuppression Therapy ; Interferon-gamma/pharmacology* ; Mouth Neoplasms/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Salivary Gland Neoplasms/pathology*

The preliminary screening of oral cancer mostly depends on the experience of clinicians, The surgical margin of tumor is mostly based on physical examination and preoperative imaging examination. It lacks real-time and objective intraoperative evaluation methods. Indocyanine green (ICG), as a safe and pollution-free organic fluorescent pigments, combined with near-infrared fluorescence imaging can be applied in the screening of early oral cancer, the determination of tumor resection margins, sentinel lymph node biopsy, cervical lymph node dissection, targeted chemotherapy, and other aspects. Near-infrared fluorescence imaging may become a key link in the early diagnosis and accurate treatment for oral cancer in the future.
Humans ; Indocyanine Green ; Lymph Nodes ; Mouth Neoplasms/therapy* ; Optical Imaging ; Sentinel Lymph Node Biopsy

Large general hospitals currently play an increasingly important role in the diagnosis and treatment for acute critical patients and difficult diseases because of the development of dual referral system and hierarchical diagnosis, as well as the formation of medical treatment alliance. Patients with oral cancers are often associated with systemic diseases, which increases the complexity of the condition. Thus, meeting the demand through the traditional single medical model is difficult. As such, a multidisciplinary team (MDT) model has been proposed and has achieved a good clinical effect. To standardize the application of this model, we organized an event in which relevant experts discussed and formulated a consensus to provide standardized suggestions on the MDT process and the diagnosis and treatment of common systemic diseases as reference for clinical practice.
Consensus ; Humans ; Mouth Neoplasms/therapy* ; Patient Care Team ; Referral and Consultation