Search Results (3,239)

Early cancer detection can expand treatment options and improve patient survival, but it requires tests that can be repeated with minimal patient burden. Urine and saliva can be collected non-invasively and may contain cancer-associated nucleic acids, proteins, and extracellular vesicles. Clinical analysis of these body fluids is complicated by low biomarker abundance, inter-individual variation, and matrix components that interfere with surface-based sensing. Plasmonic nanoarray biosensors address some of these analytical constraints by concentrating local electromagnetic fields, supporting multiplexed optical readout, and accommodating surface chemistry and microfluidic handling. This review examines nanoarray architectures, fabrication methods, surface functionalization, and signal generation for cancer-associated biomarkers in urine and saliva. Localized surface plasmon resonance, surface-enhanced Raman scattering, and metal-enhanced fluorescence are discussed together with applications to bladder, prostate, pancreatic, oral, and head-and-neck cancers. Remaining barriers include biofouling, pre-analytical variation, fabrication reproducibility, limited validation using authentic biofluids, and incomplete sample-to-answer integration. Addressing these challenges through standardized biofluid processing, scalable nanoarray fabrication, and integrated microfluidic platforms will be essential for translating plasmonic nanoarray biosensors into clinically applicable cancer screening tools. Full article

Cold atmospheric plasma (CAP), a non-thermal ionized gas, is gaining attention in biomedicine due to its unique properties such as the generation of reactive oxygen and nitrogen species (RONS), immunomodulatory effects, and selective cytotoxicity. This review explores the potential of CAP as a therapeutic tool in otorhinolaryngology (ORL). CAP has shown promising applications in wound healing, pathogen eradication, and antitumor strategies, particularly in head and neck cancers. Mechanistically, CAP promotes tissue regeneration through redox signaling, stimulates immune cell activity, induces immunogenic cell death, and enhances epithelial proliferation while offering broad-spectrum antimicrobial efficacy. The review also discusses the development of miniaturized CAP delivery systems, including endoscope-integrated plasma jets (e.g., PLASMASKOP), to facilitate clinical use in anatomically complex ORL regions. Given the nascent stage of clinical translation in ORL, the authors highlight the need for interdisciplinary research and device innovation to realize the full therapeutic potential of CAP in this field. Full article

Currently, the global incidence of head and neck squamous cell carcinoma (HNSCC) continues to increase, with a large proportion of cases being diagnosed at advanced stages. Conventional oncological treatments are often associated with poor quality of life, while the aggressive biological behavior of these tumors results in recurrence in approximately half of treated patients according to current evidence. The need for rapid, targeted diagnosis and personalized treatment has driven research toward the identification of tumor biomarkers with diagnostic, prognostic, and predictive value for treatment response. In this scoping review, we performed a comprehensive literature search to map the available evidence on tumor biomarkers in HNSCC. We identified a wide range of biomarkers, several of which exhibit overlapping roles, and classified them according to their genomic, proteomic, cytokine-related, tumor microenvironment, metabolic, and microbiota-associated characteristics. This scoping review also summarizes the current evidence regarding biomarkers involved in carcinogenesis, treatment response and therapy resistance, while highlighting their current level of clinical applicability. Although only a limited number of biomarkers have currently been implemented in routine clinical practice in head and neck cancers, the studies included in this review identified several promising candidates with the potential to be incorporated into clinical practice following further prospective validation and methodological standardization. Many additional biomarkers are still under investigation, opening new perspectives for future diagnostic and therapeutic targets and supporting the development of personalized multimodal treatment strategies for patients with HNSCC. Full article

Background: Osteoradionecrosis (ORN) is a severe late complication of radiotherapy for head and neck cancer, associated with impaired bone healing, infection, pain, and exposed bone. Periodontal disease may contribute to ORN by maintaining inflammatory and infectious foci within irradiated tissues with reduced vascularity and repair capacity. Objective: To evaluate whether periodontal disease or poor periodontal status is associated with increased ORN risk in patients with head and neck cancer undergoing radiotherapy. Methods: This systematic review and meta-analysis followed PRISMA 2020 recommendations and was structured according to the PECO framework. Searches were conducted in PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, WHO databases, and gray literature. Observational studies involving head and neck cancer patients treated with radiotherapy and reporting periodontal status in relation to ORN were included. Risk of bias was assessed using a domain-based approach. Random-effects models estimated pooled relative effect estimates and ORN prevalence. Results: Six studies were included in the primary association meta-analysis. Periodontal disease was significantly associated with increased ORN risk, with a pooled relative effect estimate of 4.83 (95% CI: 1.96–11.93; p = 0.0006; I² = 50.4%). Seven studies including 1785 patients and 118 ORN events were included in the prevalence meta-analysis, showing a pooled ORN prevalence of 9% (95% CI: 6–13%; I² = 78.0%). Conclusions: The findings suggest that periodontal disease or poor periodontal status may be associated with an increased likelihood of ORN in patients with head and neck cancer undergoing radiotherapy. Given the observational nature of the evidence and the moderate between-study heterogeneity, this association should be interpreted cautiously. Comprehensive periodontal assessment and long-term oral surveillance may be considered as components of multidisciplinary care before and after radiotherapy. Full article

Background/Objectives: Supraglottic and hypopharyngeal carcinomas are aggressive malignancies that are often diagnosed at advanced stages. Timely recognition of these malignancies is influenced by many factors, such as endoscope quality and experience. This study evaluated the potential of artificial intelligence (AI) to support real-time detection and classification of such lesions during flexible endoscopy in the outpatient clinic. Methods: A previously developed deep learning (DL) algorithm was extended from a glottic lesion model to the unified localization and classification of glottic, supraglottic, and hypopharyngeal lesions during flexible endoscopy. Lesion frames were extracted from endoscopy videos obtained at two head and neck oncology centers and one secondary referral center between 2012 and 2024. These frames were annotated and labeled based on histopathological or clinically confirmed reference diagnoses. The primary outcome was the unified model’s performance in detection of lesions per frame. After training (70% of data), the positive predictive value (precision) and sensitivity (recall) of this model were calculated on an independent test set (30% of data), stratified by subsite and tumor (T-) classification. Secondly, the model’s binary classification performance (benign or malignant) was evaluated. Results: From 490 supraglottic and hypopharyngeal endoscopy videos, 40,059 frames with a benign or malignant lesion were extracted and added to the 56,036 glottic lesion frames in the database, comprising 1336 lesion videos and 123 healthy control videos (total n = 1459). On the test set, the model achieved a detection precision of 92.1% (95% CI: 90.9–93.2) and a recall of 73.3% (95% CI: 69.8–76.6). Detection performance increased with higher T-stage. Among correctly detected lesion instances in a malignancy-dominated test set (65.3% of lesion instances), sensitivity for malignancy detection was 94.3% (95% CI: 91.8–96.5). Combined end-to-end performance for correct malignant lesion detection and classification was estimated at 69.1% (object-level recall 73.3% × classification sensitivity 94.3%). Evaluation of 33 lesion-free videos demonstrated a mean frame-level specificity of 46.6% and a median of 19 false positive detections per video. Conclusions: This is the first study to report a DL model for real-time endoscopic detection and classification of benign and malignant laryngeal and pharyngeal lesions. The developed model showed promising lesion detection and cancer classification performance in the evaluated test set. T1 tumor detection remains an important limitation, particularly because early-stage detection is a primary aim of AI-assisted endoscopy. Further model testing is required in real-world lesion prevalence settings, where external validation and clinical usability should be investigated. Full article

Objective: While advancements in radiotherapy and systemic agents have significantly improved survival rates in head and neck squamous cell carcinoma (HNSCC), managing long-term, treatment-induced toxicities remains a critical clinical challenge. This study aimed to develop a personalized, supervised machine learning-driven predictive model for multiple chronic toxicities by integrating clinical, dosimetric, and genetic data specifically evaluating the impact of the NBN gene rs1805794 (c.553G>C) polymorphism. Methods: This study enrolled 125 patients with HNSCC who received curative-intent radiotherapy and remained disease-free during follow-up with a median of 98 months. Comprehensive clinical and dosimetric data were collected, and chronic toxicities were recorded. Peripheral blood samples were analyzed for the NBN rs1805794 polymorphism using allele-specific PCR (AS-PCR). Following feature selection, four supervised machine learning classifiers were trained and evaluated to identify the optimal model for predicting multiple chronic toxicities. Results: The XGBoost algorithm emerged as the highest performing model. Baseline clinico-dosimetric predictors of multiple chronic toxicities included PTV70 volume, the addition of concurrent chemotherapy, advanced T and N stages, and continued smoking. Integrating the NBN rs1805794 genotype into the XGBoost architecture enhances its predictive capability. The final model accurately identified patients at high risk for multiple chronic toxicities, achieving an area under the curve (AUC) of 0.78, an accuracy of 0.77, a sensitivity of 0.74, and a specificity of 0.79. Conclusions: Integrating clinical, dosimetric, and genetic data within a machine learning framework effectively predicts multiple chronic toxicities in HNSCC. This approach enabled early risk stratification, providing the potential for personalized therapy. Full article

Background/Objectives: Frailty is increasingly recognized as a clinically relevant marker of reduced physiological reserve in surgical oncology. The modified 5-item frailty index (mFI-5) is simple and practical, but its clinical significance in oral squamous cell carcinoma (OSCC) remains incompletely defined. This study evaluated the association between mFI-5-defined frailty and postoperative complications, especially postoperative delirium, as well as survival outcomes in patients undergoing surgery for OSCC. Methods: We retrospectively analyzed 127 patients who underwent surgical resection for OSCC with postoperative high care unit (HCU) management between 2013 and 2021. Frailty was defined as an mFI-5 score of ≥2. Clinical characteristics, postoperative outcomes, HCU stay, length of hospital stay, overall survival (OS), and disease-free survival (DFS) were compared between frail and non-frail groups. Univariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for postoperative complications. An exploratory multivariable logistic regression analysis for postoperative delirium was performed using age ≥65 years and sex as covariates. Delirium was retrospectively assessed from clinical documentation considered consistent with DSM-5 criteria. Results: Twenty-one patients (16.5%) were classified as frail. Postoperative delirium occurred more frequently in frail patients than in non-frail patients (42.9% vs. 19.8%; p = 0.023). In a multivariable logistic regression model adjusted for age ≥65 years and sex, mFI-5-defined frailty was significantly associated with postoperative delirium (adjusted OR, 3.07; 95% CI, 1.08–8.60; p = 0.035). No significant association was observed for pneumonia, surgical site infection, or free-flap reoperation. Frailty was not significantly associated with HCU stay, length of hospital stay, OS, or DFS. Conclusions: mFI-5-defined frailty was associated with postoperative delirium but not with survival outcomes in this OSCC cohort. Because this retrospective study was limited by sample size, comorbidity-driven mFI-5 scoring, non-standardized delirium screening, and potential residual confounding, mFI-5 should be interpreted as a convenient screening marker rather than a stand-alone predictor. Comprehensive perioperative assessment incorporating frailty, nutrition, sarcopenia, cognition, tumor burden, and treatment-related factors may better identify patients at risk. Full article

Head and neck cancer (HNC) remains a major therapeutic challenge due to high recurrence rates, limited efficacy of current treatments, and the frequent emergence of therapeutic resistance. Curcumin and its analogs have gained increasing interest as adjuvant compounds capable of potentiating the efficacy of conventional anticancer strategies, including chemotherapy with cisplatin, paclitaxel, and 5-fluorouracil, as well as radiotherapy. This review summarizes preclinical and translational evidence investigating combination approaches involving curcumin-based compounds and standard therapies in HNC models, highlighting their synergistic effects on tumor growth inhibition, apoptosis induction, modulation of therapy resistance mechanisms, and mitigation of treatment-related toxicity. Strategies aimed at overcoming the pharmacokinetic limitations of curcumin, including nanoformulations, co-delivery systems, and targeted delivery platforms, are also discussed. By integrating current evidence, this review highlights the translational potential of curcumin and its analogs as adjuvant agents in multimodal HNC therapy, while identifying current gaps in clinical validation, and outlining future directions for improving therapeutic efficacy and safety. Full article

Background: Human papillomavirus (HPV) is associated with multiple head and neck cancers, many of which are preventable with the 9-valent HPV vaccine. We developed an interactive HPV vaccination education program (IHVEP) to equip patients with HPV-associated cancers to serve as health educators. Objective: To pilot test the adapted IHVEP, evaluate its content using the Information-Motivation-Behavioral Skills (IMB) model and the Suitability Assessment of Materials (SAM) instrument, and identify factors relevant to optimizing digital health interventions. Methods: A previously developed cervical cancer–focused IHVEP was adapted for patients with oropharyngeal cancer. Participants completed the program and participated in semi-structured interviews. Feedback was analyzed and organized into themes aligned with the IMB and SAM frameworks. Results: Participants generally perceived the adapted IHVEP as informative, motivating, and empowering. Key motivators included physician recommendation and a desire to protect others. The program appeared to enhance participants’ perceived ability and self-efficacy to promote HPV vaccination. Modules were described as clear, well-organized, linguistically accessible, and culturally appropriate. Feedback identified areas for improvement related to technology, content, and functionality. Conclusions: Findings suggest that effective digital health interventions may benefit from incorporating training in evaluating health information, ensuring intuitive design and navigation, and including content featuring real individuals. These results will inform further refinement of IHVEP and the development of future digital health interventions. Full article

Background: Human papillomavirus (HPV)-attributable cancers remain largely preventable but continue to generate increasing treatment costs where vaccination and screening coverage are limited. We estimated direct inpatient pharmaceutical reimbursement attributable to HPV-related cancers in Bulgaria and examined the drivers of expenditure growth. Methods: National Health Insurance Fund reimbursement data (2021–2025) were analysed for antineoplastic medicines used to treat eight HPV-associated cancer sites. Site-specific population-attributable fractions (PAFs) were applied to estimate HPV-attributable expenditure. Uncertainty in PAFs was quantified using 10,000 Monte Carlo simulations and discrete attribution scenarios. Expenditure growth was decomposed into price, volume, and net product-entry/exit effects using Fisher indices. Expenditure was additionally expressed in constant 2021 euros using the Harmonised Index of Consumer Prices. Results: Estimated HPV-attributable inpatient pharmaceutical reimbursement totalled EUR 54.2 million (probabilistic median; 95% uncertainty interval: EUR 53.3–55.0 million). Cervical cancer accounted for 81.8% of the total. Results varied by less than ±6% across attribution scenarios and remained EUR 44.6 million when head-and-neck cancers were excluded. Annual expenditure increased from EUR 3.67 million in 2021 to EUR 19.89 million in 2025, representing a 5.4-fold nominal and 4.2-fold inflation-adjusted increase. Growth was concentrated in cervical cancer and was driven primarily by the introduction of new therapies rather than higher prices or greater use of existing medicines. Net product entry explained 88.8% of total log growth, while reimbursement prices for continuing products declined by approximately 31%. Pembrolizumab, first reimbursed for cervical cancer in 2023, accounted for EUR 16.03 million of cervical cancer expenditure in 2025. Conclusions: These ecological estimates indicate a rapid increase in HPV-attributable inpatient pharmaceutical reimbursement in Bulgaria, largely driven by cervical cancer and the introduction of immunotherapy. The findings have implications for budget forecasting, procurement planning, and economic evaluation of HPV prevention strategies. Full article

Background/Objectives: Metatypical basal cell carcinoma (MTBCC) is a rare and aggressive variant of non-melanoma skin cancer (NMSC) characterised by overlapping histological features of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Owing to its increased propensity for local invasion, recurrence, and metastasis, MTBCC poses diagnostic and therapeutic challenges. This study aimed to characterise the epidemiological, histopathological, and clinical features of MTBCC and to evaluate temporal changes in tumour characteristics and aggressiveness before, during, and after the COVID-19 pandemic. Methods: A retrospective cohort study was conducted on 129 histologically confirmed MTBCC lesions diagnosed in the Pathology Department of the Mures Clinical County Hospital, Targu Mures, Romania, between January 2017 and December 2025. Demographic data, tumour location, histological subtypes, differentiation of the squamous component, aggressiveness parameters, and volumetric measurements of tumours and excision specimens were analysed. Volumetric analyses were restricted to cases with complete three-dimensional measurements. Statistical comparisons were performed across demographic variables and the following three time periods: pre-pandemic, pandemic, and post-pandemic. Results: The median age at diagnosis was 71 years, with a slight male predominance (p = 0.25) and a significant predominance of patients from urban areas (p < 0.001). Most tumours were located in the head and neck region. Mixed-type MTBCC was significantly associated with higher tumour aggressiveness (p = 0.0019) and with high-risk histological subtypes, particularly micronodular and adenoid–cystic variants. Tumour volume showed a significant inverse correlation with year of diagnosis (p = 0.0139; r = (−) 0.50), whereas excision specimen volume differed significantly according to year of diagnosis (p = 0.0425). Neither tumour volume nor excision specimen volume was associated with histopathological aggressiveness. Conclusions: Metatypical basal cell carcinoma is a rare skin malignancy in which biological behaviour appears to be determined primarily by histopathological architecture rather than tumour size. Mixed-type lesions were associated with significantly higher aggressiveness, underscoring the need for accurate histopathological assessment. These findings support a pathology-driven approach to management and emphasise the importance of adequate surgical treatment and long-term follow-up in patients with MTBCC. Full article

Objectives: Ultrasound is the primary modality for salivary gland tumor (SGT) evaluation, yet its reliance on subjective interpretation can lead to diagnostic variance. This study aims to develop and validate a two-stage deep learning system to automate SGT detection and classification. Methods: The study compiled a dataset of ultrasound images from patients with pathologically confirmed SGTs across three sequential cohorts: a training set (687 images, 2007–2020), a validation set (78 images, 2021), and a testing set (101 images, 2022). A YOLOv8 model was trained for tumor detection, and a modified ResNet50V2 model was utilized for benign versus malignant classification. The resulting two-stage pipeline was deployed on a local desktop system and further evaluated using two independent datasets: an internal validation set (56 images, 2023) and an external online dataset (57 images). Results: On the testing set, the YOLOv8 model achieved a bounding-box precision of 0.94 and a recall of 0.95 for tumor detection. When integrated with the classification model, the two-stage desktop system yielded an accuracy of 84%, sensitivity of 74%, and specificity of 87%. This system maintained comparable performance, demonstrating accuracies of 82% and 81%, sensitivities of 100% and 71%, and specificities of 81% and 86% on the internal and external validation sets, respectively. Conclusions: This study introduced a two-stage deep learning desktop system for automated SGT diagnosis. The edge-deployed system may serve as an objective adjunct to conventional ultrasound interpretation, potentially assisting clinicians during preoperative evaluation. Full article

This work reports the synthesis, characterization and in vitro evaluation of three organometallic triorganotin(IV) complexes bearing a dicarbamido-bis-organosilane benzoate ligand as potential anticancer agents against colorectal cancer cells. The complexes, Sn(IV)-biSi-1, Sn(IV)-biSi-2 and Sn(IV)-biSi-3, differ in the alkyl groups directly bound to the Sn(IV) center (methyl, n-propyl and isopropyl, respectively). Their structures were confirmed by ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy, FTIR and ESI-MS, supporting monodentate carboxylate coordination and a solvent-dependent Sn(IV) coordination environment. Biological assays in HCT116 cells showed that the final bis-organosilane complexes were markedly more active than their aminobenzoate intermediates and, under several conditions, more effective than cisplatin. Sn(IV)-biSi-2 and Sn(IV)-biSi-3 reduced cell viability to approximately 30% at 0.5 μM after 5 days and to about 11% and 7%, respectively, at 12.5 μM. In repeated-treatment assays, these complexes maintained antiproliferative activity more efficiently than cisplatin, limiting resistance-like cell recovery. Western blot analysis revealed increased γ-H2AX, p53, cleaved caspase-3 and cleaved PARP, indicating DNA damage-associated apoptotic signaling. Overall, these results identify bis-organosilane triorganotin(IV) benzoates, especially Sn(IV)-biSi-2 and Sn(IV)-biSi-3, as promising metal-based anticancer candidates that sustain antiproliferative activity after repeated exposure in colorectal cancer cells and may contribute to strategies aimed at therapy-resistant colorectal tumors. Full article

Background: Squamous cell carcinomas (SCCs) share squamous differentiation and may engage the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway, although their causes, biology, and treatment differ by anatomical site. We evaluated tumor response, short-term survival, and grade 3–4 adverse events after neoadjuvant immune-checkpoint blockade, with or without chemotherapy, followed by surgery. Methods: A comprehensive search of PubMed, Embase, the Cochrane Library, and clinical trial registries was conducted from inception to October 2024. Prospective and retrospective studies evaluating neoadjuvant immunotherapy, with or without chemotherapy, before surgery in patients with SCC were included. In mixed-histology studies, data were eligible only when SCC outcomes could be extracted separately. Pooled proportions and 95% confidence intervals (CIs) were estimated with random-effects models. Results: A total of 44 studies involving 2586 patients with six anatomical SCC groups were included. The pooled objective response rate (ORR) was 0.70 (95% CI, 0.59–0.80), clinical complete response (cCR) rate was 0.17 (95% CI, 0.10–0.28), and pathological complete response (pCR) rate was 0.30 (95% CI, 0.27–0.34). The pooled 1-year progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS) rates were 0.82 (95% CI, 0.79–0.86), 0.86 (95% CI, 0.75–0.92), and 0.92 (95% CI, 0.90–0.93), respectively. The pooled incidence of grade 3–4 adverse events was 0.18 (95% CI, 0.14–0.23). Because the PD-L1 subgroup contained only one study for most outcomes, checkpoint-target subgroup findings were considered exploratory. Conclusions: Existing predominantly single-arm evidence suggests antitumor activity of neoadjuvant immune-checkpoint blockade, with or without chemotherapy, in selected patients with resectable SCC. Because esophageal SCC accounted for most studies and clinical heterogeneity was substantial, these pooled proportions should not be interpreted as comparative effects or as evidence of uniform benefit across SCC sites. Full article