Search Results (2,951)

Background/Objectives: Early detection and intervention are critical for improving outcomes in head and neck cancer. Although endoscopy is commonly used for screening, it requires specialist expertise and may cause patient discomfort. Therefore, there is a need for a simpler and less invasive screening method. This study aimed to evaluate the clinical feasibility of Fourier-transform infrared (FTIR) spectroscopy-based exhaled breath analysis as a non-invasive screening tool for head and neck cancer. Methods: This single-center study was conducted at the Department of Otolaryngology–Head and Neck Surgery, Showa Medical University. Outpatients with head and neck cancer (n = 10) and healthy controls (n = 14) were enrolled. Exhaled breath samples and ambient air surrounding the patient and lesion were analyzed using FTIR spectroscopy. Infrared absorption spectra were obtained, divided into 7667 discrete wavenumber points across the measured range, and compared between the patient and control groups. Results: FTIR spectroscopy revealed significant differences between patients and controls, with 2691 wavenumber points showing statistically significant differences (p < 0.05). Among these, the wavenumber at 3917.3 cm⁻¹ showed a particularly strong difference (p = 0.00015). Receiver operating characteristic analysis demonstrated good discriminative performance, with an area under the curve of 0.929. The maximum Youden index was 0.829, with an optimal threshold of 0.234. Conclusions: FTIR-based exhaled breath analysis is a non-invasive and feasible approach for screening head and neck cancer. These findings suggest that this technique has potential clinical applicability as a screening tool and may also be extendable to the detection of other diseases. Full article

Background: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. Objective: We aimed to structure XN’s mechanistic hierarchy with emerging translational relevance across disease areas. Methods: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. Results: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-oncogenic and pro-inflammatory pathways, such as NF-κB, PI3K/Akt/mTOR, STAT3, HIF-1α, and selective MAPK cascades, while activating cytoprotective signaling, such as the Nrf2/ARE and AMPK pathways. Through these coordinated actions, XN modulates redox homeostasis, mitochondrial integrity, apoptosis, autophagy, ferroptosis, and inflammatory responses. In oncology, XN demonstrates broad-spectrum anticancer activity in preclinical models by inhibiting proliferation; inducing cell cycle arrest and apoptosis; suppressing epithelial–mesenchymal transition, angiogenesis, and metastasis; and restoring chemosensitivity in resistant cancers, including breast, lung, gastric, liver, and head-and-neck carcinomas. Beyond cancer, XN exhibits multi-organ protective bioactivities through antioxidative, antimicrobial, antiviral, and anti-inflammatory activities; inhibition of ferroptosis and excitotoxicity; and preservation of mitochondrial integrity. It shows beneficial effects in preclinical models of Parkinson’s disease, Alzheimer’s disease, hepatic steatosis and fibrosis, renal ischemia–reperfusion injury, cardiovascular dysfunction, skin photoaging, and atopic dermatitis. Human subject studies demonstrate that XN is safe and well tolerated, with observed reductions in oxidative DNA damage and inflammatory cytokine release. Recent advances in micellar formulations have improved XN’s systemic bioavailability and thus its translational feasibility. Conclusions: In summary, XN is a safe, multifunctional natural compound with strong potential for modulating disease-relevant biological pathways associated with cancer, neurodegenerative diseases, metabolic disorders, and inflammatory skin conditions. Continued efforts to enhance its bioavailability and conduct rigorous clinical trials are essential to fully establish its clinical relevance in patient populations. Full article

Objective: The primary objective of this study is to investigate the prevalence of unexpected findings requiring treatment after routine histological examinations following tonsillectomy, tonsillotomy, adenotomy, or conchotomy (TTAC) in a retrospective study and to discuss whether routine histological examination is useful in patients without clearly defined risk factors or whether it would be better to reduce unnecessary costs and resource utilisation. Materials and methods: The present retrospective study encompasses 5709 patients who underwent routine histological examinations following TTAC and were treated as inpatients at the University Medical Center Freiburg, Department of Otolaryngology, Head and Neck Surgery, between 2011 and 2021. The data was collected based on patient characteristics, including date of birth, gender, age of patients at the time of surgery, date of surgery, indication for surgery, tissue examined, and histological result. Results: Of a total of 6687 patients who underwent TTAC, 5709 with routine histological examinations were included in the analysis, of whom only four showed abnormal findings, corresponding to an overall prevalence of 0.07%. Three of these four patients were adults. These included two cases of granulomatous inflammation, one instance of Burkitt lymphoma, and one instance of chronic lymphocytic leukaemia/small cell B-lymphoma. Following the exclusion of tuberculosis and sarcoidosis, and the lymphoma board’s decision to adopt a watch-and-wait approach in the case of chronic lymphocytic leukaemia/small cell B-cell lymphoma, only n = 1/0.0175% of patients were found to require treatment. Conclusions: The study demonstrated that only four abnormal histological findings occurred in 5709 inpatient TTACs, of which only one, namely Burkitt lymphoma, ultimately required treatment. Consequently, it can be concluded that routine histological examinations following TTAC are not beneficial in patients without clearly defined risk factors, such as blood in the saliva, history of smoking or alcohol consumption, unexplained pain, previous cancer, mucosal changes, or tissue asymmetries. However, in instances where clinical or anamnestic suspicion of malignancy is present, a histological examination should be conducted. Full article

Laser-induced autofluorescence (LIAF) spectroscopy is a label-free optical technique sensitive to biochemical and structural tissue properties. Its application in upper aerodigestive tract malignancies is in its early stages. This study evaluates the feasibility of a matrix scan-based LIAF approach for examining differences between normal and malignant tissues. An exploratory case series involving three patients with oropharyngeal malignancies was conducted. Tissue sections from normal and tumor regions were analyzed using LIAF spectroscopy, including intensity and lifetime measurements, implemented through a matrix scanning protocol with fixed excitation, detection sensitivity, and sample thickness. Complementary Fourier-transform infrared (FTIR) spectroscopy was used to qualitatively assess biochemical variations, and spectroscopic findings were correlated with histopathological evaluation. Within individual cases, consistent differences in autofluorescence spectral and lifetime characteristics were observed between benign and malignant tissue regions. FTIR analysis revealed concurrent biochemical variations that qualitatively supported the autofluorescence observations. This exploratory study demonstrates the potential of combining LIAF matrix scan with FTIR spectroscopy to investigate tissue-specific spectral variations in upper aerodigestive tract lesions. The findings are preliminary and motivate further investigation using larger patient groups and clinically relevant acquisition conditions. Full article

Background/Objectives: Precise staging and tumor delineation are essential for optimizing treatment and enhancing outcomes of radiotherapy (RT). While computed tomography (CT)-based RT remains standard, fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) offers improved detection of primary and nodal disease. This study investigates the role of PET/CT in RT planning of HNSCC. Methods: Fifty-one HNSCC patients underwent radical volumetric modulated arc RT with concurrent cisplatin chemotherapy in a prospective study. Two RT plans per patient were sequentially created by a single oncologist using CT-only and PET/CT data, respectively. Planning target volumes (PTVs) for primary and nodal regions were independently defined, and dose–volume histograms were analyzed and compared. Results: PET/CT significantly affected TNM staging, increasing the T-stage in 11.8% of patients and the N-stage in 33.3%. Distant metastases were found in 9.8% of patients, leading to a redefinition of the overall treatment policy. PET/CT-based planning improved primary tumor PTV coverage (PTV4) in 37.2% (19/51) of cases. The tumor areas excluded from the CT-based planning received an average of 85.6% of the prescribed PTV4 dose (range 18–93%), while in PET/CT planning, they received 95.4% (range 93–99%) (p < 0.0001). Nodal PTV areas requiring a booster dose (PTV2) were adjusted in 33.3% (17/51) of patients during PET-CT planning. These nodal areas received an average of 85.6% of the prescribed dose for PTV2 (range 18–93%) during CT planning, compared to 95.4% (range 93–99%) during PET/CT planning. There was no statistically significant difference in the dose received by organs at risk between CT- and PET/CT-RT planning. Conclusions: PET/CT improves target delineation for primary tumors and lymph nodes, also allowing for dose escalation in metabolically highly active lesions in patients with HNSCC. The method also reveals occult distant metastases in a subset of patients, enabling personalized treatment strategies. Full article

Boron neutron capture therapy (BNCT) is experiencing a global resurgence driven by advances in boron pharmacology, accelerator-based neutron sources, and molecular imaging-guided theranostics. BNCT produces high linear energy transfer particles with micrometer-range energy deposition, enabling cell-selective irradiation confined to boron-enriched tumor cells in a geometrically targeted region by the neutron beam. This mechanism offers the potential for exceptionally high therapeutic ratios, provided two core requirements are met: sufficient differential tumor uptake of ¹⁰B and a neutron beam with appropriate energy and penetration. After early clinical attempts in the mid-20th century were hindered by inadequate boron agents and reactor-based neutron beams, recent technological breakthroughs have made BNCT clinically viable. The development of hospital-compatible accelerator neutron sources, next-generation boron delivery systems (such as receptor-targeted compounds and nanoparticles), advanced theranostic approaches (such as ¹⁸F-BPA positron emission tomography and boron-sensitive magnetic resonance imaging), and AI-driven biodistribution modeling now support personalized treatment planning and patient selection. These innovations have catalyzed modern clinical implementation, exemplified by Japan’s regulatory approval of BNCT for recurrent head and neck cancer and the rapid expansion of clinical programs across Asia, Europe, and South America. Building on these foundations, BNCT has transitioned from a predominantly academic experimental modality into an increasingly commercialized and industrially supported therapeutic platform. The emergence of dedicated BNCT companies, international collaborations between accelerator manufacturers and hospitals, and pharmaceutical development pipelines for next-generation boron carriers has accelerated clinical translation. Moreover, BNCT now occupies a unique position among radiation modalities due to its hybrid nature, namely combining the biological targeting of radiopharmaceutical therapy with the external-beam controllability of radiotherapy, thereby offering new therapeutic opportunities where competitive approaches fall short. Emerging evidence suggests therapeutic promise in glioblastoma, recurrent head and neck cancers, melanoma, meningioma, lung cancer, sarcomas, and other difficult-to-treat malignancies. Looking ahead, continued innovation in compact neutron source engineering, boron nanocarriers, multimodal theranostics, microdosimetry-guided treatment planning, and combination strategies with systemic therapies such as immunotherapy will be essential for optimizing outcomes. Together, these converging developments position BNCT as a biologically targeted and potentially transformative modality in the era of precision oncology. Full article

Secretory Leukocyte Protease Inhibitor (SLPI) is a conserved serine protease inhibitor expressed on mucosal surfaces, which has multiple functions including anti-protease, anti-microbial and anti-inflammatory properties. SLPI plays critical roles in tissue homeostasis and pathology. Through its anti-protease ability, SLPI safeguards tissues from excessive damage caused by proteolytic enzymes released during inflammation and contributes to extracellular matrix remodeling, thereby influencing the cellular and tumor microenvironment. Furthermore, SLPI expression is implicated in shaping the immune landscape that facilitates tumor progression, and in driving epithelial–mesenchymal transition (EMT). Consequently, it is not surprising that SLPI plays a complex and context-dependent role across various malignancies. It is overexpressed in most cancers such as colorectal, gastric, pancreatic, and breast carcinomas, and this overexpression often correlates with a more advanced and aggressive disease. Conversely, its levels are reduced in head and neck squamous cell carcinoma and hepatocellular carcinoma, where elevated expression may be associated with a more favorable prognosis. This diverse behavior underscores that SLPI function in cancer is tissue-specific and dependent on the functional or pathological state. In prostate cancer, SLPI expression exhibits a bimodal behavior: levels are reduced in the early stages of the disease compared to normal tissues but become significantly upregulated in more advanced and aggressive stages of disease, with significantly higher levels observed in patients with castration-resistant prostate cancer. Elevated SLPI levels in prostate cancer correlate with a reduced prostate-specific antigen (PSA) progression-free survival. In this review, we outline the current evidence regarding the multifaceted functions of SLPI and its expanding role in cancer, focusing primarily on the recently described molecular mechanisms and clinical significance of SLPI in prostate carcinoma. Full article

Background/Objectives: Persistent human papillomavirus (HPV) infection can lead to malignancies of the cervix, vulva, vagina, penis, anus, and oropharynx. The increasing incidence of HPV-related head and neck cancers has raised concerns regarding potential occupational exposure and transmission risks among healthcare workers. This study aimed to systematically evaluate the evidence on occupational HPV transmission in healthcare settings. Methods: A systematic review of the literature was conducted using three electronic databases (PubMed, Scopus, and Web of Science) from inception to August 2025, following PRISMA 2020 guidelines. A total of 34 studies met the inclusion criteria and were included in the review. Expert opinions and practical recommendations from members of the European Society of Gynaecological Oncology (ESGO) Prevention Committee were included to support interpretation of the results. Results: The available literature on occupational HPV transmission was limited, with a paucity of high-quality studies. Nevertheless, existing data suggest a potential occupational risk, particularly during aerosol or smoke-generating procedures performed for cervical intraepithelial neoplasia or cervical cancer. Several studies reported the detection of HPV DNA in surgical smoke or on instruments used during such procedures, indicating possible exposure among healthcare workers. Conclusions: Although current evidence is insufficient to definitively classify HPV infection as an occupational disease, available data indicate a potential exposure risk for healthcare workers involved in HPV-related procedures. Preventive measures, like personal protective equipment, should be emphasized. HPV vaccination has been recommended by some professional societies for healthcare workers performing gynecological procedures, though further research is needed to evaluate vaccine efficacy beyond the standard age range and its cost-effectiveness in this context. Full article

Laryngeal squamous carcinoma is a major type of head and neck cancer. Despite a wide range of treatment options, it remains a challenge to identify which ones are the most effective for which groups of patients. One solution is to analyse selected biomarkers. In this paper, biomarkers are divided into distinctive groups according to the molecular pathways analysed or specific molecules within the cell or in tissue fluids. The paper provides a description of these groups, including genetic and apoptosis-associated factors, factors regulating angiogenesis, cell structure regulators, immune factors in the form of programmed cell death ligand (PD-L1), hormone receptors, molecules involved in growth factor pathways, and cell cycle regulators. Representative examples are discussed for each of these groups, indicating their potential usefulness in staging, assessing tumour aggressiveness, and making a prognosis. Full article

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) causes half a million deaths each year; therefore, it is essential to understand the factors that affect patient prognosis. Many studies fail to investigate the biological drivers behind survival disparities, especially sex-specific differences within racial groups. This study serves as a foundational project to begin elucidating biological differences in the tumor microenvironment between male and female African American HNSCC patients. Methods: A total of 111 patients who were diagnosed with HNSCC and identify as African American were grouped by sex. Analyses of socioeconomic status, co-morbidities, tumor characteristics, and treatment were conducted. Spatial transcriptomic analysis was performed on four randomly selected primary HNSCC tumor tissues. Results: No sex-based differences were observed in socioeconomic measures, treatments, tumor stage, follow-up, recurrence, or cause of death (all p > 0.15), though females had higher median income than males (p = 0.035). Comorbidity profiles were also largely comparable between males and females. Evaluating tumor microenvironments, we found that male tumors were dominated by malignant cells and fibroblasts, with limited adaptive immune infiltration. By contrast, female tumors displayed markedly higher proportions of immune cells, including T cells and B cells. Male tumors harbored sparse T cells, largely skewed toward exhausted phenotypes while female tumors displayed abundant T cell infiltration consistent with immunologically active tumor microenvironment. Conclusions: Clinical and demographic factors showed minimal sex-based differences among African American HNSCC patients, spatial transcriptomic profiling revealed strikingly distinct immune microenvironments by sex. These findings suggest that biological, rather than simply clinical, differences may drive survival disparities. This project serves as a novel and foundational study promoting the use of spatial transcriptomics to evaluate possible survival disparities within HNSCC populations to alleviate survival disparities. Full article

Neoadjuvant chemoimmunotherapy has emerged as a promising treatment strategy for head and neck squamous cell carcinoma (HNSCC). There is an urgent need to improve patient responses to this approach. In this study, we aim to elucidate the mechanisms underlying poor response to neoadjuvant chemoimmunotherapy and to identify strategies to enhance therapeutic efficacy in HNSCC. We identified a cancer stem-like cell (CSC) population enriched in patients with partial response (PR) to neoadjuvant chemoimmunotherapy, characterized by high CD80 expression. CD80 was likewise highly expressed in ALDH^highCD44⁺ and BMI1⁺ populations. Functionally, CD80 knockdown attenuated tumor-sphere-forming capacity and reduced the migration and invasion of tumor cells, whereas CD80 overexpression potentiated these pro-tumorigenic activities. Moreover, CD80 inhibition activated signaling pathways of Th1 immune responses and IL-2 production. CD80 blockade enhanced T cell cytotoxicity. In preclinical HNSCC models, inhibition of CD80 significantly decreased tumor burden, accumulated CD8⁺ T cells, and increased the production of cytotoxic effector molecules. Our data demonstrated that CD80 modulated tumor-cell stemness and malignant phenotype while restraining antitumor T cell immunity. Targeting CD80 augments antitumor immunity and provides a compelling strategy to enhance treatment responses to neoadjuvant chemoimmunotherapy in HNSCC. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) remains a major global health concern, with cervical lymph node metastasis being one of the most important determinants of prognosis. Level II (2A/2B) lymph nodes, in particular, play a key role in disease spread and survival outcomes. This study aimed to assess the prognostic impact of level II lymph node metastasis and evaluate the concordance between clinical and pathological staging in patients undergoing neck dissection. Methods: We retrospectively analyzed 138 non-metastatic HNSCC patients treated between 2007 and 2015. Clinical staging was standardized according to the AJCC 8th edition. Level II lymph nodes were dissected and evaluated separately by two independent pathologists. Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards models. Correlation between clinical and pathological staging was examined using Pearson correlation analysis. Results: The median follow-up was 55.6 months. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 62.4% and 60.1%, respectively. There was a strong correlation between clinical and pathological staging (r = 0.871, p < 0.001). Patients with level II metastasis had significantly worse outcomes, with median OS of 27 months versus an estimated 128 months among those without involvement (p = 0.008), and median DFS of 17.3 versus 114 months (p = 0.004). Age was identified as an independent predictor of mortality in multivariate analysis. Conclusions: Metastasis to level II lymph nodes is a strong adverse prognostic factor in HNSCC. These findings highlight the importance of detailed nodal evaluation in guiding neck dissection strategy, risk stratification, and subsequent adjuvant treatment decisions. Full article

Retinoic acid receptor (RARγ) mRNA is expressed spatially and temporally during mouse embryogenesis and largely within stem and progenitor cells, indicating a role in organ formation. RARγ agonism promoted the maintenance of hematopoietic stem cells, and blocked stem cell development as shown for hematopoiesis, zebrafish development, and chondrogenesis. Transgene expression enhanced the generation of induced pluripotent stem cells, indicating a role in ground-state pluripotency. RARγ is oncogenic in acute myeloid leukemia, cholangiocarcinoma, and colorectal, head and neck, hepatocellular, ovarian, pancreatic, prostate, and renal cancers. RARγ agonism or overexpression enhanced the proliferation of cancer cells. Conversely, antagonism or inhibition of all-trans retinoic acid synthesis led to the death of cancer cells including cancer stem cells. The pathways regulated by RARγ, via canonical activation and repression of gene expression, include Wnt/β-catenin and Notch signaling. RARγ also acts as a co-factor to Smad3 and reduced or enhanced TGFβ-driven and Smad3-mediated events when liganded and non-liganded, respectively. Collectively the findings support the view that RARγ plays a crucial role in controlling stem and progenitor cell behavior. Full article

Background: Osteoradionecrosis (ORN) following head and neck radiotherapy has been demonstrated to induce structural and functional alterations of the upper airway, with the potential to complicate the process of tracheal intubation. Despite its clinical relevance, there is a paucity of systematic evidence on airway characteristics in ORN and reliable predictors of difficult tracheal intubation. This study compares preoperative airway parameters and tracheal intubation outcomes in irradiated patients with and without ORN and introduces a novel preoperative ORN-Difficult-Airway Score for risk stratification. Methods: In this retrospective cohort study, airway assessments, tracheal intubation methods, and perioperative visualization parameters were evaluated in 105 patients following head and neck radiotherapy. Group differences between non-ORN and ORN were analyzed using chi-square tests. A preoperative ORN-Difficult-Airway Score was constructed using exclusively bedside parameters, based on statistically and clinically relevant predictors. Results: Patients with ORN showed significantly restricted mouth opening (p < 0.001), higher Mallampati classes, particularly Mallampati IV, and a greater need for fiberoptic tracheal intubation (p < 0.01). Direct laryngoscopy (DL) was significantly less feasible in ORN, while hyperangulated videolaryngoscopy (VL) yielded consistently positive visualization (first-pass success (FPS) 100% in both groups). Under DL, FPS was lower in ORN (54.2% vs. 79.5%), resulting in an odds ratio of 0.305. Based on observed predictors, ORN status, mouth opening <3 cm, Mallampati class, restricted neck reclination, and history of difficult intubation, a preoperative ORN-Difficult-Airway Score was developed. Conclusions: ORN has been associated with distinct alterations in airway anatomy and visualization, resulting in increased tracheal intubation complexity after head and neck radiotherapy. The proposed ORN-Difficult-Airway Score presents a clinically practical, bedside-applicable approach to stratifying the risk of tracheal intubation in this population. Prior to clinical implementation, prospective validation in larger cohorts is warranted. Full article

The radiosensitivity of cancer patients determines the efficacy of radiotherapy, and patients with low radiosensitivity cannot benefit from radiotherapy. Therefore, accurately predicting radiosensitivity before treatment is essential for personalized and precise radiotherapy. However, most existing studies rely solely on genomic and clinical features, neglecting the tumor microenvironmental information embedded in histopathological images, which limits prediction accuracy. To address this issue, we propose Resfusion, a deep multimodal fusion framework that integrates patient-level gene expression profiles, clinical records, and histopathological images for tumor radiosensitivity prediction. Specifically, the pre-trained large-scale pathology model is used as an image encoder to extract global representations from whole-slide pathological image. Radiosensitivity-related genes are selected using an autoencoder combined with univariate Cox regression, while clinically relevant variables are manually curated. The three modalities are first concatenated and then refined through a self-attention-based module, which captures inter-feature dependencies within the fused representation and highlights complementary information across modalities. The model was evaluated using five-fold cross-validation on two common tumor datasets suitable for radiotherapy: the Breast Invasive Carcinoma (BRCA) dataset (282 patients in total, with each fold partitioned into 226 training samples and 56 validation samples) and the Head and Neck Squamous Cell Carcinoma (HNSC) dataset (200 patients in total, with each fold partitioned into 161 training samples and 39 validation samples). The average AUC values obtained from the five-fold cross-validation reached 76.83% and 79.49%, respectively. Experimental results demonstrate that the Resfusion model significantly outperforms unimodal methods and existing multimodal fusion methods, verifying its effectiveness in predicting the radiosensitivity of tumor patients. Full article