Oral oncology最新文献

Purpose: Cancer stem cells (CSCs) are considered key drivers of progression in head and neck squamous cell carcinoma (HNSCC). Our single-cell RNA sequencing (scRNA-seq) analysis revealed predominant expression of CD271 in CSCs, however, its role as a CSC marker in HNSCC requires further elucidation. We investigated the stemness characteristics of CD271^high HNSCC cells and their interactions with the tumor immune microenvironment.

Methods: scRNA-seq data from hypopharyngeal squamous cell carcinoma (HPSCC) tissues were analyzed to identify expression profile of CSCs. Overall survival was compared between CD271^high and CD271^low patients based on immunostaining of HPSCC samples. The stemness of CD271^high HNSCC cells was evaluated via an in vivo limiting dilution assay. In a C57BL/6 mice model, the percentage of immune cells and macrophage subtypes were analyzed by flow cytometry. The role of CD271 in macrophage polarization was further examined by in vitro coculture of CD271^high cells with CD14⁺ monocytes. Gene expressions were analyzed by qPCR.

Results: CD271 is predominantly expressed in CSCs identified by scRNA-seq analysis. CD271 enhances HNSCC cell proliferation and is negatively correlated with patient prognosis in HPSCC. CD271 knockdown suppressed HNSCC tumor growth and regulated macrophage polarization within the TME. CD271^high cells exhibited stemness features and enhanced tumor growth in vivo.

Conclusions: CD271^high HNSCC cells exhibit CSC characteristics and regulate macrophage polarization. Targeting CD271 may improve the immunosuppressive TME to inhibit tumor growth. Combining CD271-targeting agents with other therapies presents a promising strategy that may enhance therapeutic efficacy and prognosis in HNSCC.

The purpose of this systematic review and meta-analysis was to identify the prevalence of synchronous contralateral tonsil carcinoma (SCTC) amongst patients with tonsil carcinoma or head and neck squamous cell carcinoma of unknown primary (HNSCCUP). Thirteen retrospective studies, comprising 2623 patients, were analysed, revealing an overall pooled SCTC prevalence of 4%, rising to 10% in HNSCCUP cases. HPV/p16 positivity was associated with SCTC prevalence of 3%, while HPV/p16 negativity was greater at 8%. Clinical or imaging evaluations often missed SCTC preoperatively, emphasising the importance of contralateral tonsillectomy. Morbidity varied among patients undergoing contralateral tonsillectomy. The prevalence of SCTC is significant in cases of HNSCCUP and tonsil malignancy, emphasising the importance of informed discussions regarding contralateral tonsillectomy. Tailored approaches considering individual patient and tumour characteristics are crucial, with contralateral tonsillectomy generally warranted in HNSCCUP. Further research, including prospective studies with standardised protocols, is needed to improve the understanding and management of SCTC, specifically the clinical significance of occult SCTC.

Objectives: Salivary gland cancer is a rare disease composed of more than 20 histological types with different grades of malignancy. The aim of this multicenter, retrospective study was to identify the most important predictors affecting recurrence and survival after surgery.

Material and methods: A total of 543 patients with salivary gland cancers that underwent curative surgery between 2012 and 2022 in 13 institutions in northern Japan were evaluated in this study. Predictors affecting recurrence and survival were identified by univariate and multivariate Cox regression analyses. Age, sex, primary site, histological type, pathological T status, surgical margin, lymph node metastasis, extranodal extension, and postoperative radiotherapy were the variables evaluated.

Results: Multivariate Cox regression analysis showed that increasing age, submandibular cancer, pathological T status 3 or 4, positive surgical margin, and lymph node metastasis, especially with extranodal extension, were independent risk factors for both recurrence and survival. Sublingual cancer was an independent risk factor for recurrence. Postoperative radiotherapy was associated with a lower risk of recurrence and a good prognosis, and adenoid cystic carcinoma was associated with a good prognosis.

Conclusion: Lymph node metastasis with extranodal extension was the most important prognostic factor affecting both recurrence and survival after surgery, adenoid cystic carcinoma was associated with a good prognosis, and postoperative radiotherapy was associated with a lower risk of recurrence and a good prognosis.

Pedicled, fasciocutaneous and visceral flaps are all widely adopted for reconstruction after ablative surgery for advanced laryngeal, hypopharyngeal and cervical oesophageal cancers. With multiple options available, the choice depends on type and extent of the defect, patient's general conditions and institution expertise or preference. Since its first description in 1959, the use of jejunal free flap (JFF) has been refined thanks to the introduction of microvascular anastomoses, progressively allowing to achieve low mortality and morbidity rates. Both swallowing and speech outcomes are also positively reported across studies. A systematic review of English literature on JFF in H&N cancer reconstruction published after 2000 was carried out on Medline and Embase. Thirty-six studies were included in the analysis with a total of 3191 JFF reconstructions. Primary outcomes were surgical complications and functional outcomes (quality of speech and oral alimentation). A cumulative review was created pooling complication rates reported in single studies, and overall rates were obtained for fistulas (11.39%), strictures (14.17%), total and partial flap failure (4.79 and 6.15% respectively) and perioperative mortality (3.1%). Functional outcomes were variably reported, with different qualitative and quantitative assessment methods showing overall positive results. When reported, we've included impact of adjuvant radiotherapy and the ability of JFF to tolerate it has been widely confirmed. Above results have also been compared with same outcomes registered for different flaps. Overall, studies over the past 20 years demonstrate good clinical and functional outcomes, proving JFF to be a reliable and safe method for reconstructing circumferential pharyngoesophageal defects.

Head and neck squamous cell carcinoma (HNSCC) is the 7th most common cancer globally with a 40-50 % survival rate. Although macrophage migration inhibitory factor (MIF) is overexpressed in most solid tumors and promotes tumor growth and invasion, the therapeutic potential of MIF inhibition in HNSCC is yet to be explored. In this study, we investigated the efficacy of CPSI-1306, a small-molecule MIF inhibitor, on HNSCC cell growth and cancer associated signaling pathways in vitro, as well as its impact on T cells in the HNSCC tumor microenvironment in vivo. CPSI-1306 did not reduce HNSCC cell proliferation in vitro, and mildly decreased VEGF and EGFR expression. However, CPSI-1306 significantly reduced tumor development in two orthotopic mouse oral cancer (MOC-2 and MOC-1) HNSCC models. Interestingly, CPSI-1306 treatment increased T cell infiltration to the tumor microenvironment and completely abrogated immunosuppressive checkpoint markers TIGIT, TIM3, and CTLA-4, but not PD-1 on tumor infiltrating CD8⁺ T cells. This was accompanied by increased CD8⁺ T cell expression of antitumoral cytokines IFN-γ and TNF-α in the draining lymph nodes and Granzyme B in the tumor microenvironment of CPSI-1306 treated tumor bearing mice. Our studies demonstrate that the small molecule MIF inhibitor CPSI-1306 potently inhibits T cell immunosuppression in the tumor microenvironment and reduces tumor growth in HNSCC. These studies open a novel therapeutic option for modulating anti-tumoral T cell immunity to improve HNSCC outcomes by targeting MIF.

Importance: The role of prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement in head and neck cancer (HNC) patients treated with chemoradiation remains controversial and varies by center.

Objective: To evaluate the impact of prophylactic PEG tube placement in patients undergoing chemoradiation for HNC PEG tube use for more than 6 months and weight loss.

Design, setting, and participants: This single-institution retrospective study included 502 patients with head and neck cancer.

Exposures: Concurrent Chemoradiation (CCRT) and prophylactic PEG tube placement.

Main outcomes and measures: Univariate analyses were performed to determine risk factors for long term PEG tube and weight loss. Outcomes that were significantly associated with prophylactic PEG were selected for a multivariate analysis. The Kaplan-Meier method was used to estimate survival and the time to PEG removal, with comparisons between groups analyzed by log-rank tests. The global health status score from the EORTC QLQ30 was utilized to assess impact on quality of life.

Results: Significantly higher weight loss was seen with the following variables: 1) omitting prophylactic PEG tube (p < 0.00001), 2) younger age (p = 0.0032), and 3) adjuvant CCRT (p = 0.0005). There was significantly higher risk of feeding tube duration longer than 6 months in those who: received prophylactic PEG tube (p < 0.0001) and were older than the median age of 60.8 years (p = 0.0165) on multivariate analysis. Prophylactic PEG tube was not associated with improved global health status, overall survival, or progression-free survival on univariate analysis.

Conclusions and relevance: Prophylactic feeding tubes significantly decreased weight loss during treatment. Prophylactic PEG tube and older than median age was significantly associated with higher risk of feeding tube duration longer than 6 months.