Background: Locally advanced oral squamous cell carcinoma (LAOSCC) is associated with a high rate of recurrence and poor survival. Given the recent successes of neoadjuvant immunochemotherapy (NAICT) in solid tumors, it is promising to use this treatment modality to achieve a better pathological response and improve the survival of LAOSCC, and clinical evidence is needed to assess its safety and efficacy. Patients and Methods: A prospective trial of NAICT with toripalimab (PD-1 inhibitor) and albumin paclitaxel/cisplatin (TTP) was conducted in patients with clinical stage III and IVA OSCC. Intravenous albumin paclitaxel (260 mg/m²), cisplatin (75 mg/m²), and toripalimab (240 mg) were given in sequence on day 1 of each 21 day cycle for two cycles, followed by radical surgery and risk-adapted adjuvant (chemo)radiotherapy. The primary endpoints were safety and major pathological response (MPR). Targeted next generation sequencing and multiplex immunofluorescence were performed to assess clinical molecular characteristics and the tumor immune microenvironment in the pre-NAICT and post-NAICT tumor samples. Results: Twenty patients were enrolled. NAICT was well-tolerated with a low incidence of grades 3–4 adverse events in three patients. The completion rates of NAICT and subsequent R0 resection were 100%. The MPR rate was 60%, including a 30% pathological complete response. MPR was achieved in all four patients with a combined positive score of PD-L1>10. The density of tertiary lymphatic structure in post-NAICT tumor samples predicted the pathological response to NAICT. During the median 23-month follow-up, the disease-free survival was 90%, and the overall survival was 95%. Conclusions: NAICT with the TTP protocol in LAOSCC is feasible and well tolerated, with a promising MPR and no obstruction on subsequent surgery. This trial is supportive of further randomized trials using NAICT in LAOSCC.

Purpose: To examine the association of preoperative dental anxiety with the severity of postoperative symptoms among patients undergoing lower third molar (LM3) extraction surgery.Materials and methods: We conducted a hospital-based prospective study with a sample size of 213 patients. All the patients underwent LM3 extraction surgery at the Stomatology Hospital of Tianjin Medical University. Preoperative dental anxiety was measured using the Dental Anxiety Scale for Third Molar Surgery (DAS-TMS) and classified into four categories: No anxiety, Some unease, Anxious, and Very anxious. The primary outcome was defined using the postoperative symptom severity scale on the seventh day after surgery. The patients' clinical characteristics, radiologic features, and surgery-related variables were used as control variables. Bivariate analysis involved Fisher's exact test and Kruskal–Wallis test. Multivariable logistic analysis was used to assess preoperative dental anxiety in relation to the severity of postoperative symptoms. We applied a two-piecewise regression model to examine the potential non–linear associations.Results: The mean (SD) dental anxiety score was 10.56 (3.84). The proportion of dental anxiety was as follows: No anxiety, 7.5%; Some unease, 46.9%; Anxious, 31.0%; Very anxious, 14.6%. The multivariable-adjusted ORs with 95% CIs of postoperative symptoms were 1.00 for No anxiety, 3.63 (0.90–14.68) for Some unease, 5.29 (1.25–22.33) for Anxious, and 4.75 (1.02–22.18) for Very anxious (P for trend = 0.047). The risk of serious postoperative symptoms increased with the dental anxiety level up to 7 points (adjusted OR 1.94, 95% CI 1.12–3.74; P = 0.012). When the dental anxiety level exceeded 7 points, the level of DAS-TMS was not associated with the risk of serious postoperative symptoms (OR 0.98, 95% CI 0.88–1.08; P = 0.756).Conclusions: Findings suggest that dental anxiety is associated with a risk of serious postoperative symptoms following LM3 removal. The degree of dental anxiety in patients before LM3 extraction surgery should be of concern to clinicians.

Carrimycin is a newly synthesized macrolide antibiotic with good antibacterial effect. Exploratory experiments found its function in regulating cell physiology, proliferation and immunity, suggesting its potential anti-tumor capacity. The aim of this study is to investigate the anti-tumor effect of carrimycin against human oral squamous cell carcinoma cells in vitro and in vivo. Human oral squamous cell carcinoma cells (HN30/HN6/Cal27/HB96 cell lines) were treated with gradient concentration of carrimycin. Cell proliferation, colony formation and migration ability were analyzed. Cell cycle and apoptosis were assessed by flow cytometry. The effect of carrimycin on OSCC in vivo was investigated in tumor xenograft models. Immunohistochemistry, western blot assay and TUNEL assays of tissue samples from xenografts were performed. The key proteins in PI3K/AKT/mTOR pathway and MAPK pathway were examined by western blot. As the concentration of carrimycin increased, the proliferation, colony formation and migration ability of OSCC cells were inhibited. After treating with carrimycin, cell cycle was arrested in G0/G1 phase and cell apoptosis was promoted. The tumor growth of xenografts was significantly suppressed. Furthermore, the expression of p-PI3K, p-AKT, p-mTOR, p-S6K, p-4EBP1, p-ERK and p-p38 were down-regulated in vitro and in vivo. Carrimycin can inhibit the biological activities of OSCC cells in vitro and in vivo, and regulate the PI3K/AKT/mTOR and MAPK pathways.

Background: Surgery and postoperative adjuvant therapy comprise the standard treatment for locally advanced resectable oral squamous cell carcinoma (LAROSCC), while preoperative neoadjuvant therapy is being explored without sufficient confirmation of improved survival. De-escalation regimens after neoadjuvant therapy, such as those omitting adjuvant radiotherapy, may provide comparable or better outcomes, suggesting rigorous assessment of adjuvant therapy outcomes is needed in LAROSCC patients. The authors thus performed this retrospective study in LAROSCC patients who received neoadjuvant therapy and surgery, to compare the outcomes for overall survival (OS) and locoregional recurrence-free survival (LRFS) between the adjuvant radiotherapy (radio) and nonradiotherapy (nonradio) cohorts. Materials and methods: Patients diagnosed with LAROSCC who received neoadjuvant therapy and surgery were enrolled and divided into radio and nonradio cohorts to determine whether adjuvant radiotherapy could be omitted after neoadjuvant therapy and surgery. Results: From 2008 to 2021, 192 patients were enrolled. No significant differences were found in OS or LRFS between the radio and nonradio patient cohorts. The 10-year estimated OS rates were 58.9 versus 44.1% in radio versus nonradio cohorts, while 10-year estimated LRFS rates were 55.4 versus 48.2%, respectively. For clinical stage III patients, 10-year OS rates were 62.3 versus 62.6% (radio vs. nonradio), and estimated 10-year LRFS rates were 56.5 versus 60.7% (radio vs. nonradio). Multivariate Cox regression modeling of postoperative variables showed pathologic response of primary tumor and pathologic regional lymph nodes staging were associated with survival, while the adjuvant radiotherapy exposure was not included in the model due to nonsignificance. Conclusion: These findings support further prospective evaluation of adjuvant radiotherapy omission, and suggest that de-escalation trials are warranted for LAROSCC surgery patients who received neoadjuvant therapy.

Background: Annexin A1, a member of the Annexin superfamily, has been shown to play a vital role in a broad range of molecular and cellular processes. This study aims to explore the relationship between the Annexin A1 expression and the clinical response to cisplatin, docetaxel and 5‐fluorouracil (TPF) as induction chemotherapy in patients with oral squamous cell carcinoma (OSCC).Methods: This study recruited two hundred thirty‐two patients from a III/IVA OSCC trial. Immunohistochemistry was used to assess the level of Annexin A1 expression. Overexpression and knockdown methods in HB96, HN4 and CAL27 cell lines were used to assess the role of Annexin A1 in the neoplastic cellular response to chemotherapy.Results: We found that reduced expression of Annexin A1 conferred a prognostic benefit from induction chemotherapy based on the TPF drug combination in patients with moderately/poorly differentiated disease. Using an in vitro model, we found that low Annexin A1 enhanced cellular proliferation by activating the EGFR/AKT signalling pathway and inhibiting p27 expression. Furthermore, low Annexin A1 initiated a significant decrease in cell viability after treatment with TPF agents. In addition, downregulation of Annexin A1 promoted apoptosis induced by docetaxel, cisplatin and 5‐fluorouracil, and upregulation of Annexin A1 inhibited apoptosis.Conclusion: Annexin A1 may be of prognostic value in patients with locally advanced OSCC who are managed with TPF chemotherapy, as low Annexin A1 promotes chemosensitivity to TPF chemotherapy in oral cancer cells via enhanced caspase‐dependent apoptosis.