In this study we assessed the clinical significance of an epithelial-mesenchymal transition (EMT) gene signature and explored its association with the tumor microenvironment related to immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC). Genes were selected when mRNA levels were positively or negatively correlated with at least one well-known EMT marker. We developed an EMT gene signature consisting of 82 genes. The patients were classified into epithelial or mesenchymal subgroups according to EMT signature. The clinical significance of the EMT signature was validated in three independent cohorts and its association with several immunotherapy-related signatures was investigated. The mesenchymal subgroup showed worse prognosis than the epithelial subgroup, and significantly elevated PD-1, PD-L1, and CTLA-4 levels, and increased interferon-gamma, cytolytic, T cell infiltration, overall immune infiltration, and immune signature scores. The relationship between PD-L1 expression and EMT status in HNSCC after treatment with TGF-β was validated in vitro. In conclusion, the EMT gene signature was associated with prognosis in HNSCC. Additionally, our results suggest that EMT is related to immune activity of the tumor microenvironment with elevated immune checkpoint molecules.

SOX2 copy number and mRNA expression were analysed to examine the clinical significance of SOX2 activation in HNSCC. Gene expression signatures reflecting SOX2 activation were identified in an HNSCC cohort. Patients with HNSCC were classified into two subgroups according to the gene expression signature: SOX2-high and SOX2-low. The clinical significance of SOX2 activation was further validated in two independent cohorts. Moreover, clinical significance of SOX2 activation in response to radiotherapy was assessed in patients with HNSCC. The relationship between SOX2 activation and radiotherapy was validated in an in vitro experiment. Patients in the SOX2-high subgroup had a better prognosis than patients in the SOX2-low subgroup in all three patient cohorts. Results of multivariate regression analysis showed that SOX2 signature was an independent predictor of the overall survival of patients with HNSCC (hazard ratio, 1.45; 95% confidence interval, 1.09–1.92; P = 0.01). Interestingly, SOX2 activation was a predictor of therapy outcomes in patients receiving radiotherapy. Moreover, SOX2 overexpression enhanced the effect of radiotherapy in HNSCC cell lines. SOX2 activation is associated with improved prognosis of patients with HNSCC and might be used to predict which patients might benefit from radiotherapy.

Background: Currently, high-speed digital imaging (HSDI), especially endoscopic HSDI, is routinely used for the diagnosis of vocal cord disorders. However, endoscopic HSDI devices are usually large and costly, which limits access to patients in underdeveloped countries and in regions with inadequate medical infrastructure. Modern smartphones have sufficient functionality to process the complex calculations that are required for processing high-resolution images and videos with a high frame rate. Recently, several attempts have been made to integrate medical endoscopes with smartphones to make them more accessible to people in underdeveloped countries. Objective: This study aims to develop a smartphone adaptor for endoscopes, which enables smartphone-based vocal cord imaging, to demonstrate the feasibility of performing high-speed vocal cord imaging via the high-speed imaging functions of a high-performance smartphone camera, and to determine the acceptability of the smartphone-based high-speed vocal cord imaging system for clinical applications in developing countries. Methods: A customized smartphone adaptor optical relay was designed for clinical endoscopy using selective laser melting–based 3D printing. A standard laryngoscope was attached to the smartphone adaptor to acquire high-speed vocal cord endoscopic images. Only existing basic functions of the smartphone camera were used for HSDI of the vocal cords. Extracted still frames were observed for qualitative glottal volume and shape. For image processing, segmented glottal and vocal cord areas were calculated from whole HSDI frames to characterize the amplitude of the vibrations on each side of the glottis, including the frequency, edge length, glottal areas, base cord, and lateral phase differences over the acquisition time. The device was incorporated into a preclinical videokymography diagnosis routine to compare functionality. Results: Smartphone-based HSDI with the smartphone-endoscope adaptor could achieve 940 frames per second and a resolution of 1280 by 720 frames, which corresponds to the detection of 3 to 8 frames per vocal cycle at double the spatial resolution of existing devices. The device was used to image the vocal cords of 4 volunteers: 1 healthy individual and 3 patients with vocal cord paralysis, chronic laryngitis, or vocal cord polyps. The resultant image stacks were sufficient for most diagnostic purposes. The cost of the device including the smartphone was lower than that of existing HSDI devices. The image processing and analytics demonstrated the successful calculation of relevant diagnostic variables from the acquired images. Patients with vocal pathologies were easily differentiable in the quantitative data. Conclusions: A smartphone-based HSDI endoscope system can function as a point-of-care clinical diagnostic device. The resulting analysis is of higher quality than that accessible by videostroboscopy and promises comparable quality and greater accessibility than HSDI. In particular, this system is suitable for use as an accessible diagnostic tool in underdeveloped areas with inadequate medical service infrastructure.

Although the genetic alteration of CUB and Sushi multiple domains 1 (CSMD1) is known to be associated with poor prognosis in several cancers, there is a lack of clinical relevance in head and neck cancer. The aim of this study was to offer insight into the clinical significance of CSMD1, utilizing a multimodal approach that leverages publicly available independent genome-wide expression datasets. CSMD1-related genes were found and analyzed to examine the clinical significance of CSMD1 inactivation in the HNSCC cohort of publicly available databases. We analyzed the frequency of somatic mutations, clinicopathologic characteristics, association with immunotherapy-related gene signatures, and the pathways of gene signatures. We found 363 CSMD1-related genes. The prognosis of the CSMD1-inactivated subgroup was poor. FBXW7, HLA-A, MED1, NOTCH2, NOTCH3, and TP53 had higher mutation rates in the CSMD1-inactivated subgroups. The Interferon-gamma score and immune signature score were elevated in CSMD1-inactivated subgroups. We identified several CSMD1-related pathways, such as the phosphatidylinositol signaling system and inositol phosphate metabolism. Our study using three large and independent datasets suggests that CSMD1-related gene signatures are associated with the prognosis of HNSCC patients.

Objectives. Effective treatment of laryngeal cancer requires clinical decision-making that balances survival outcomes with the preservation of essential functions, such as voice and swallowing. This study, led by the Clinical Practice Guideline Committee of the Korean Society of Head and Neck Surgery, aims to establish evidence-based recommendations to guide surgeons in optimizing treatment decisions for patients with laryngeal cancer.Methods. A literature search was performed in the PubMed, Embase, Cochrane Library, and KoreaMed databases by a literature search expert and subsequently reviewed by a panel of 39 committee experts. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method was employed to assess the quality of evidence and develop and report the recommendations. The strength of each recommendation reflects the guideline panel’s confidence that the benefits of an intervention outweigh its risks for the target population. After drafting the guidelines, Delphi questionnaires were distributed to members of the Korean Society of Head and Neck Surgery and an external reviewer panel.Results. In total, 15 evidence-based recommendations are provided, addressing six critical aspects of laryngeal cancer treatment: early-stage treatment, treatment of locally advanced cancer, neck management, adjuvant therapy, swallowing rehabilitation, and salvage treatment for recurrent tumors.Conclusion. The guidelines provide evidence-based, validated recommendations to support clinicians in making optimal treatment decisions for laryngeal cancer.