Imaging of Laryngeal and Hypopharyngeal Squamous Cell Cancers.

Laryngeal cancer has one of the highest mortality rates of all head and neck cancers. DACT1 is a cuproptosis-related gene in laryngeal cancer and serves as a risk factor for patient prognosis. This study aimed to investigate the effects of DACT1 on the malignant behavior and cuproptosis of laryngeal squamous cell carcinoma (LSCC) cells. DACT1 expression in LSCC cells was measured using RT-qPCR and western blotting. To establish cuproptosis cell model, TU212 and TU686 cells were incubated with elesclomol (20nM) and CuCl2 (20nM) for 24h. Transfection of shRNA or pcDNA3.1 vectors was performed to interfere DACT1 expression. LY294002 (PI3K inhibitor) and 740Y-P (PI3K agonist) were used to silence and overexpress PI3K signaling in LSCC cells, respectively. A cuproptosis-specific inhibitor, tetrathiomolybdate, was used to suppress cuproptosis in LSCC cells. Cell viability, proliferation, migration, and invasion were assessed using CCK-8 assays, colony formation assays, Transwell migration, and Transwell invasion assays. Copper concentration and reactive oxygen species (ROS) level were also measured. Western blotting was performed to quantify protein levels of cuproptosis-related genes and factors involved in the PI3K/AKT pathway. DACT1 expression was upregulated in LSCC cells. DACT1 knockdown inhibited LSCC cell proliferation, migration, and invasion. DACT1 depletion enhanced cuproptosis, as evidenced by more pronounced decreases in cell viability, increased intracellular copper concentration and ROS levels, upregulation of HSP70, and downregulation of LIAS. Notably, treatment with the cuproptosis inhibitor tetrathiomolybdate reversed the pro-cuproptosis effects induced by DACT1 silencing. Furthermore, the silencing of DACT1 inactivated the PI3K/AKT signaling, as shown by reduced ratios of p-PI3K/PI3K and p-AKT/AKT. Conversely, DACT1 overexpression activated the PI3K/AKT pathway, an effect that was abolished by LY294002. Moreover, LY294002 reversed the promoting effects of DACT1 on LSCC cell malignancy and its inhibitory effects on cuproptosis. In contrast, activation of the PI3K signaling by 740Y-P reversed the enhancement of cuproptosis caused by DACT1 deficiency. DACT1 promotes the malignant behavior of LSCC cells and suppresses cuproptosis by activating the PI3K/AKT signaling.

Pretreatment determination of histological differentiation grade is critical for prognostic evaluation in laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). This study aimed to develop a contrast-enhanced CT (CECT)-based Vision Transformer (ViT) model for noninvasive evaluation of histological grades in LHSCC. In this retrospective multicenter study, a total of 1,648 LHSCC patients who underwent CECT scans were enrolled from three hospitals in this study. Participants were divided into a training cohort (n = 1,239), an internal validation cohort (n = 310) from one hospital, and an external validation cohort (n = 99) from the other two hospitals. The diagnostic model integrates a pre-trained ViT for CECT feature extraction and an XGBoost classifier for prediction. The model's predictive performance was evaluated using the area under the curve (AUC), decision curve analysis (DCA), and calibration curve. The ViT model achieved AUCs of 0.887 (95%CI: 0.848-0.927) in internal validation and 0.796 (95%CI: 0.693-0.899) in external validation cohorts, significantly outperforming the conventional radiomics model (AUCs: 0.775, 95%CI: 0.714-0.837 and 0.544, 95%CI: 0.388-0.699; p < 0.001 and 0.002, respectively). Clinically, DCA demonstrated superior clinical utility, while calibration curves showed excellent prediction reliability. Gradient-weighted Class Activation Mapping visualization identified CT image regions most influential for the model's predictions, providing interpretability for clinical decision-making. The ViT-based deep learning model developed in this study using CECT demonstrated excellent predictive performance for histological grading of LHSCC, with promising application for patient prognosis assessment.

ABSTRACTIntroductionPatients with T3 laryngeal squamous cell carcinoma (LSCC) face a high risk of local recurrence after chemoradiotherapy (CRT) or radiotherapy (RT). This study examines whether tumor volume and inner cortex cartilage invasion (ICCI) predict local recurrence and survival.Materials and MethodsEighty‐six patients with T3 LSCC, treated with RT or CRT at the Karolinska University Hospital between 2005 and 2021, were included. Cox regression assessed the effect of associations between tumor volume and ICCI on local failure and 5‐year mortality, adjusting for treatment modality, tumor subsite, and vocal cord mobility.ResultsHigh tumor volume (> 5 mL) was associated with a threefold increase in local failure risk (HR 3.11, 95% CI 1.47–6.55). No significant associations were found between tumor volume and mortality, ICCI and local failure, or ICCI and mortality.ConclusionThe results demonstrate that a larger tumor volume correlates with a reduced treatment response for patients with T3 LSCC treated with RT or CRT.

Laryngeal squamous cell carcinoma (LSCC) is recognized as the second most common malignant tumor of the respiratory tract. The study aimed to identify the roles of FOXO1, hsa-miR-96-5p, and lncRNA ADAMTS9-AS2 in the molecular pathogenesis of LSCC patients based on the systems biology data. The LSCC patient tissue samples (n = 50) and the same individual's adjacent normal tissues (n = 50) were collected from the candidates (aged 57.75 ± 9.3 years) of surgery. The miR-96-5p and lncRNA ADAMTS9-AS2 were predicted using the specific servers. The Kaplan Meier analysis was employed using TCGA data. The FOXO1and ncRNA gene expression levels were measured with the RT-qPCR technique. The Western blot technique was applied to estimate FOXO1/pFOXO1 protein values. A FOXO1/miR-96-5p/ADAMTS9-AS2 gene network was constructed and enriched using the bioinformatics data. The FOXO1 (p 0.037) correlated with ADAMTS9-AS2 (p 0.04) gene expression levels and was reduced in the LSCC patient tissue samples despite the elevated miR-96-5p expression levels (p 0.047). Moreover, the FOXO1 (p < 0.01) and pFOXO1 (p < 0.0001) protein values were reduced in the LSCC. The high FOXO1 and ADAMTS9-AS2 gene expression levels significantly increased the survival probability (HR 0.61 and 0.65, respectively). The FOXO1 and ADAMTS9-AS2 genes might act as molecular suppressors in the cell growth pathways. Furthermore, miR-96-5p is suggested as an oncogenic miRNA in the LSCC.

Laryngeal stenosis is a significant complication impairing quality of life after partial laryngectomy for laryngeal squamous cell carcinoma (LSCC). This study aimed to evaluate the efficacy of different management strategies (endoscopic vs. open). We conducted a retrospective cohort study who developed laryngeal stenosis following partial laryngectomy for LSCC between December 2011 and December 2023. Patient demographics, etiological factors, and therapeutic interventions were systematically analyzed to evaluate clinical outcomes and summarize management experience. The study cohort comprised 61 patients (4 females, 57 males) aged 25-77 years old. The overall decannulation rate was 52.5% (32/61). Endoscopic treatments included laser, balloon dilation and laser combined with balloon dilation, with a decannulation rate of 64.71%, 33.3%, and 45.45%, respectively. Of the 45 patients who received a single endoscopic treatment, successful decannulation was achieved in 25 cases (55.6%), while among the 11 patients that received multiple endoscopic treatment, only 3 (27.3%) patients attained successful decannulation. In contrast, open laryngotracheal reconstruction (LTR) with T-tube placement showed superior outcomes, with an 80% (4/5) decannulation rate. Among the 61 patients with laryngeal stenosis, those who underwent endoscopic treatment did not require postoperative nasogastric feeding, and their postoperative hospital stay was significantly shorter compared to those who underwent LTR with T-tube. Laser-assisted endoscopic techniques is recommended as the initial treatment for laryngeal stenosis following partial laryngectomy due to its minimally invasive nature and faster recovery. However, for patients who fail initial endoscopic treatment, LTR with T-tube is often recommended due to its higher decannulation rate, rather than repeated endoscopic attempts.

A novel tRNA-derived fragment tRF-Val-CAC-008 as a diagnostic biomarker and pyroptosis regulator in LSCC.

The oncogenic role of lncRNA DSG2-AS1 and its functional link to SGK1 in laryngeal squamous cell carcinoma.

SummaryObjectiveTo report the data obtained by translating the Swallowing Outcomes After Laryngectomy (SOAL) questionnaire in Italian to validate it and offer a valid tool for Italian-speaking patients and clinicians.MethodsA multicentre case-control study was performed between January 1st 2024 and October 1st 2024. In all, 494 patients consecutively treated for laryngeal squamous cell carcinoma were included in the study (group 1). Healthy controls and patients who underwent radiotherapy (group 2) or chemotherapy (group 3) of the head and neck district were the two control groups.ResultsStatistically significant differences were observed comparing SOAL scores among the three groups (ANOVA: p < 0.0001); significant differences were observed between group 1 (mean 0.89 +/- 1.31; 95% CI: 0-3) and group 2 (mean 6.78 +/- 4.59; 95% CI: 1-24) (Bonferroni-Holmes [BH] p < 0.01), and group 1 and group 3 (mean 11 +/- 7.47; 95% CI: 0-38) (BH: p 0 < 0.01). Statistically significant differences in the SOAL scores were also identified between group 2 and 3 (BH: p < 0.01).ConclusionsThe SOAL questionnaire may be a useful tool to correctly understand patients’ concerns for swallowing to promptly and rapidly manage them and improve patient’s quality of life.

Exosome-derived microRNAs (miRNAs) have been proposed as minimally invasive biomarkers for laryngeal squamous- cell carcinoma (LSCC). Because oral and maxillofacial surgeons are integral to head-and-neck oncologic and reconstructive pathways, such liquid-biopsy signals could support perioperative decision-making (selection for organ-preserving surgery), margin surveillance, and reconstructive planning. We conducted a preregistered, protocol-driven search of PubMed/MEDLINE, Web of Science, and Scopus from inception to 1 June 2025. Given the very small number of clinically comparable diagnostic studies, discordant index tests/thresholds, and high heterogeneity, we did not perform quantitative pooling or publication-bias testing. Instead, we undertook a narrative synthesis and constructed an evidence map; risk of bias tools (QUADAS-2; ROBINS-I) were applied descriptively to inform qualitative confidence. Nine studies were formally analysed based on eligibility to the study topic. Two serum-based case–control investigations (111 LSCC, 80 controls) reported areas under the ROC curve of 0.876 (miR-21 + HOTAIR) and 0.797 (miR-941), with corresponding sensitivities of 94% and 82%. Seven mechanistic papers showed that vesicular cargos—including miR-1246, circPVT1, and LINC02191—drive STAT3-dependent M2 polarisation, NOTCH1-mediated stemness, Rap1b-VEGFR2 angiogenesis, and glycolytic re-programming, producing 1.6–2.6-fold increases in invasion, tube formation, or xenograft growth. Only three studies fulfilled MISEV-2018 characterisation criteria, and none incorporated external validation. This narrative review and evidence map identifies promising but preliminary diagnostic signals and biologically plausible mechanisms for exosomal miRNAs in LSCC; however, the evidence is sparse, single-region, methodologically inconsistent, and at high risk of bias. Findings do not support clinical implementation at this stage. Priorities include harmonised EV workflows, prespecified thresholds, and prospective, multi-centre validation.

Introduction: Surgical manipulation of malignant tumors can lead to the detachment of cancer cells and their dissemination into the surrounding interstitial fluid, vasculature, or along the tract of biopsy needles, potentially resulting in implantation and secondary tumor growth, also known as tumor seeding. Although squamous cell carcinoma (SCC) is among the most prevalent malignancies of the head and neck region, reported cases of tumor seeding in SCC of the larynx remain exceedingly rare. Nevertheless, this possibility should be continually considered to mitigate adverse outcomes and further enhance the safety and effectiveness of surgical interventions.Case presentation: A 68-year-old male patient was diagnosed with squamous cell carcinoma (SCC) of the left vocal cord and subsequently underwent left-sided cordectomy. Due to positive surgical margins on histopathological examination, adjuvant radiotherapy was administered, achieving clinical remission as confirmed by direct laryngoscopy and multislice spiral computed tomography (MSCT) scans. However, three months post-radiotherapy, a small tumor mass was clinically identified at the laryngofissure incision site and was confirmed histologically as SCC. No intralaryngeal lesions or other locoregional pathology were detected on further evaluation. The lesion was interpreted as postoperative tumor seeding and was surgically excised, with no evidence of recurrence during one year of follow-up.Conclusion: Laryngeal squamous cell carcinoma possesses the potential for postoperative seeding, underscoring the importance of adhering to fundamental oncologic surgical principles. Additionally, the role of prophylactic measures against tumor seeding, and the exploration of the tumor microenvironment that facilitates such dissemination, merit further investigation.

To examine whether habitual tea consumption is associated with survival and early postoperative complications among patients with laryngeal squamous cell carcinoma (LSCC) [1-4]. Single-center retrospective cohort (2021-2024). Adults with primary LSCC treated with curative intent were included (N = 108). regular tea (≥ 3 times/week for ≥ 6 months; n = 73) vs. non-regular (n = 35). overall survival (OS) and recurrence-free survival (RFS) by Kaplan-Meier with log-rank tests; multivariable Cox adjusted for age, sex, T/N category, overall stage, treatment modality, smoking (pack-years), alcohol use, and Charlson Comorbidity Index (CCI). Median follow-up 23.0 months (interquartile range [IQR] 17.1-32.3). Two-year RFS was higher in regular tea drinkers than in non-regular drinkers (83.8% vs. 45.8%; log-rank p = 0.0043); two-year OS was similar (72.4% vs. 75.4%; p = 0.5651). Early complications were lower among tea drinkers: 30-day infection 6.8% vs. 20.0% (p = 0.0418) and borderline 90-day dysphagia 4.1% vs. 17.1% (p = 0.0556). Findings were directionally consistent in adjusted analyses. Habitual tea consumption was associated with higher RFS and fewer early infections after curative-intent therapy for LSCC, whereas OS did not differ. Results indicate association rather than causation and warrant prospective validation.

N6-methyladenosine (m6A) is the most prevalent mRNA internal modification in eukaryotic mRNAs and is frequently associated with progression and immune response in human cancers. This study delves into the function of m6A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the immune evasion and progression of laryngeal squamous cell carcinoma (LSCC), along with its underpinning mechanisms. We conducted integrated bioinformatics to examine m6A-modifying regulators and their prognostic values in LSCC. IGF2BP3 was identified as a promising candidate, which was verified to be highly expressed in LSCC tissues and cell lines. Furthermore, the aberrant IGF2BP3 upregulation in the context of LSCC was found to be partly ascribed to DNA hypomethylation. IGF2BP3 was found to elevate RMND5A expression in an m6A-dependent manner. Silencing either IGF2BP3 or RMND5A significantly decreased the viability, colony formation ability, and tumorigenicity of LSCC cells. Moreover, this intervention reduced the protein level of PD-L1 in cells while increasing CD8+ T cell infiltration in xenograft tumors. However, further upregulation of RMND5A negated the tumor-suppressive and immune-enhancing effects observed upon IGF2BP3 silencing. In conclusion, this study demonstrates that IGF2BP3 elevates RMND5A expression through m6A modification, thereby promoting malignant properties and immune evasion in LSCC cells.

BackgroundThe metastasis of laryngeal squamous cell carcinoma (LSCC) is not only caused by the tumor itself but is also closely related to cancer-associated fibroblasts (CAFs). The epithelial-mesenchymal transition (EMT) serves as a key event during its metastasis. However, the specific mechanisms underlying LSCC metastasis remain uncertain.MethodsA wound healing assay was utilized to evaluate the migratory capacity of LSCC cells (TU686 and TU212 cells). Immunofluorescence staining and Western blot analysis were conducted to demonstrate the expression levels of associated proteins. Migration and invasion assays were employed to assess the migration and invasion abilities of LSCC cells in vitro. A nude mouse metastasis model was used to detect LSCC metastasis in vivo.ResultsOur results revealed that interleukin-33 (IL-33) enhanced the migratory, invasive, and EMT capabilities of LSCC cells. In the co-culture model of LSCC cells and CAFs, silencing the expression of IL-33 inhibited the migratory, invasive, and metastasis potential of LSCC cells both in vitro and in vivo.ConclusionIL-33 derived from CAFs mediates EMT to promote the metastasis of LSCC cells. The findings of our study not only provide a new mechanism for the activation of CAFs and the metastasis of LSCC but also offer theoretical significance and application value for more effective prevention and treatment strategies in clinical practice.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40001-025-03431-4.

Laryngeal Squamous Cell Carcinoma (LSCC) has several treatment modalities available. Contrary to what has been observed in other cancers, the survival rates have worsened in recent years. Retrospective cohort study evaluating patients with T3 and T4a LSCC divided into two groups: those who were submitted to Total Laryngectomy (TL) or to Chemoradiation (CRT) or radiotherapy alone with curative intent between 2009 and 2019. Three hundred and twenty patients were considered eligible to participate in the study, of which 166 (51.87%) submitted to TL and 154 (48.12%) to CRT. Overall survival in the surgical group was higher compared to the CRT group only between 2009 and 2013. In 2014, a multidisciplinary meeting was organized at the institution where the study took place, and both treatment modalities reached similar oncological outcomes. Multidisciplinary discussion among experienced professionals has a positive impact on oncological outcomes.

BackgroundCurrent treatment options for nonmetastatic laryngeal squamous cell carcinoma include radiotherapy, chemoradiotherapy, and surgery, which can result in significant morbidity. This study reports the 20‐year outcomes of a single‐modality chemotherapy as a larynx preservation strategy in patients with stage II–IVa laryngeal squamous cell carcinoma (LSCC).MethodsIn this single‐institution, single‐arm, prospective clinical trial, 31 patients with stage II–IVa LSCC received three or four cycles of paclitaxel, ifosfamide, and a platinum agent (TIP). Patients with a pathologic complete response (pCR) by biopsy assessment received three additional cycles without local therapy. Patients with a partial response underwent conservation laryngeal surgery (CLS). The primary end point was 2‐year larynx preservation rate (LPR). Secondary end points included recurrence‐free survival (RFS), overall survival (OS), and long‐term complications.ResultsWith a median follow‐up time of 21 years, 11 patients (35%) achieved a pCR and were managed with chemotherapy alone. None required laryngectomy, and only one experienced recurrence, which was successfully salvaged with radiotherapy. Among 19 patients who underwent CLS or radiotherapy, seven experienced recurrence and six required laryngectomy. The 20‐year LPR was 72%; median OS was 13.5 years, and median RFS was 10.3 years. Patients with a pCR had significantly fewer long‐term complications, including lower rates of feeding tube and tracheostomy dependence (p < .01).ConclusionsThis long‐term follow‐up reinforces that TIP alone is an effective larynx preservation strategy in patients with LSCC who achieve a pCR. Further investigations of systemic therapy for laryngeal cancer treatment, including less toxic combinations and immunotherapy as well as incorporating tissue‐ and blood‐based biomarkers, are warranted.

Accurate assessment of thyroid cartilage invasion is crucial for treatment decision-making and prognosis evaluation in laryngeal squamous cell carcinoma (LSCC). This study aimed to compare the performance of the radiomics and deep learning (DL) models for predicting thyroid cartilage invasion in LSCC patients, and evaluate prognostic value of the optimal predictive model. A total of 418 pathologically confirmed LSCC patients from two centers were enrolled and divided into a training cohort (n = 247), an internal validation cohort (n = 110), and an external validation cohort (n = 61). Models were developed based on venous-phase CT images and compared with two radiologists. A nomogram incorporating the optimal model and clinical risk factors was also constructed. Additionally, the prognostic value of the optimal model was assessed regarding disease-free survival (DFS). The 2D DL model showed better performance in predicting thyroid cartilage invasion, and the corresponding nomogram integrating 2D DL signature and clinical risk factors achieved the highest AUCs. However, no differences in AUCs were found in the external validation cohort (p > 0.05 for all). Additionally, the 2D DL signature and clinical N stage were independent predictors of DFS. The 2D DL-based nomogram demonstrated satisfactory predictive performance for thyroid cartilage invasion and prognosis in patients with LSCC.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-23809-y.

Aims: Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent head and neck cancers, characterized by declining survival rates. Understanding prognostic factors is essential for improving patient outcomes, particularly in the context of angiogenesis. This study was designed to comprehensively evaluate the expression of endoglin (CD105) as a marker of angiogenesis in LSCC and to determine its potential association with MVD and other histopathological parameters. Methods: Forty-two previously untreated patients who underwent laryngectomy and neck dissection were retrospectively included in the current analysis. Regions of highest vascularization (“hot spots”) were delineated, and MVD was assessed using CD105 immunostaining. Results: Findings from this study reinforce the hypothesis that MVD might not constitute a reliable prognostic biomarker in LSCC, highlighting the complex and multifactorial nature of tumor angiogenesis. Conclusion: MVD has been reported as an independent prognostic indicator in various malignancies; however, evidence regarding CD105 expression in LSCC remains extremely limited. Previous studies have yielded conflicting results concerning the prognostic significance of MVD in head and neck SCCs, underscoring the complexity of tumor biology. This study adds to the existing discourse, attributing discrepancies to the absence of tumor-specific markers, intratumoral heterogeneity, and methodological variations.

To explore and compare the potential value of radiomics models based on contrast-enhanced computed tomography (CT) for noninvasive preoperative prediction of lymphovascular invasion (LVI) in laryngeal squamous cell carcinoma (LSCC). This multicenter diagnostic study retrospectively enrolled LSCC patients from three tertiary hospitals who underwent surgical treatment. Standardized preprocessing was performed on the CT images, followed by region-of-interest (ROI) segmentation and extraction of traditional radiomics features and deep learning features. Features were selected using least absolute shrinkage and selection operator (LASSO) regression. Traditional radiomics models and deep learning radiomics models (DLR) were established using logistic regression, random forest, and multilayer perceptron algorithms, respectively. A transformer-based hybrid model was developed by integrating radiomics and deep learning features. The predictive performance of the three types of models was evaluated and compared using the area under the curve (AUC), decision curve analysis (DCA), sample probability distribution histograms, confusion matrices, calibration curves, net reclassification index (NRI), and integrated discrimination improvement (IDI). A total of 1,024 patients were allocated to the training set (center1, n=291), internal validation set (n=126), and external test sets (center 2, n=437; center 3, n=170). Three radiomics models and three DLR models were constructed, and the optimal performance was observed in the DLR_ Random Forest model (AUC: 0.812-0.867). The transformer hybrid model demonstrated superior predictive performance, with AUC values of 0.881, 0.843, 0.833, and 0.836 in the training, internal validation, and external test sets, respectively. Decision curve analysis indicated a higher net benefit for the transformer model, along with an improved NRI and IDI. Radiomics models based on CT images exhibit potential for noninvasive prediction of LVI in LSCC, with the transformer hybrid model achieving the highest diagnostic performance. This approach may provide clinicians with a preoperative decision support tool to optimize treatment strategies for patients with LSCC.

Smoking-associated laryngeal squamous cell carcinoma (LSCC) is characterized by high metastatic potential and poor prognosis. However, the underlying molecular mechanisms remain insufficiently understood. This study utilized single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to explore the heterogeneity of the tumor microenvironment in smoking-associated LSCC. Thirteen distinct cellular subpopulations within the tumor microenvironment are identified, with STC2 and ITGA5 emerging as smoking-associated prognostic markers. STC2 exhibited bifurcated differentiation within tumor epithelial cells, categorized as Tumor_C1 and Tumor_C2. The two subtypes are linked to vascular permeability and DNA replication pathways, respectively. Mechanistically, nicotine activated the JAK2/STAT3 signaling pathway through CHRNA5, resulting in direct STAT3 binding to the STC2 promoter and modulation of its transcription. STC2 subsequently upregulated TGFBI, which interacted with ITGA5 on endothelial cells, regulating vascular permeability and facilitating hematogenous dissemination of LSCC cells. Furthermore, STC2 knockdown altered F-actin cytoskeletal dynamics by modulating small GTPase signaling, impairing filopodia formation and epithelial polarity restoration. This study elucidates the tumor-endothelial interactions mediated by STC2 and ITGA5 in smoking-associated LSCC, emphasizing their roles in tumor progression and vascular permeability. These findings suggest potential prognostic biomarkers and therapeutic targets to improve the clinical management of smoking-associated LSCC.