Search Results (65)

Background: This study aimed to evaluate the clinical effectiveness of dupilumab and its impact on CRSwNP and type 2 inflammatory biomarkers in patients with severe uncontrolled asthma, with or without comorbidities, within a real-life cohort. Methods: This was a single-center, prospective, and observational real-life study conducted at the Severe Asthma Unit of Germans Trias i Pujol University Hospital. The objective of this study was to assess the real-world response to dupilumab treatment in patients with severe asthma, with or without nasal polyposis, bronchiectasis, obesity, or switching from another biologic drug for their asthma. Results: The ACT score significantly increased (13.7 vs. 20.6; p = 0.001), while the number of exacerbations decreased (3.1 vs. 0.7; p = 0.005). Patients with CRSwNP showed an increase in the ACT score (13.1 vs. 19.8; p = 0.011) and a decrease in the number of exacerbations (3.0 vs. 1.3; p = 0.217). Patients with nasal polyps showed an increase in both SNOT22 (78.3 vs. 38.3; p = 0.013) and global VAS (8 vs. 4.2; p = 0.028). Patients with bronchiectasis receiving dupilumab showed an increase in the ACT score (12.7 vs. 21.3; p = 0.039) and a marked decrease in the number of exacerbations (2.8 vs. 0; p = 0.025). Obese patients treated with dupilumab showed an improvement in the ACT score (14.1 vs. 21.3; p = 0.044) and a decrease in the rate of exacerbations (3.2 vs. 1.3; p = 0.030). Patients with rhinoconjunctivitis receiving dupilumab showed an increase in the ACT score (13.4 vs. 19.1; p = 0.017) and a decrease in the number of exacerbations (3.3 vs. 0.8; p = 0.024). Conclusions: Dupilumab is a highly effective treatment for severe asthma, showing significant improvements in lung function, reductions in exacerbations, and enhanced quality of life for patients with and without nasal polyps. The results of this real-life study support dupilumab as a valuable addition to the therapeutic armamentarium for asthma, particularly for those with type 2 inflammation despite the presence of comorbidities such as bronchiectasis or obesity, or for patients in whom a previous biologic treatment failed. Full article

Background/Objectives: Biological therapies have emerged as targeted treatments for chronic rhinosinusitis with nasal polyps (CRSwNP), yet direct comparisons between agents remain limited. This network meta-analysis (NMA) aimed to evaluate and rank the efficacy and safety of biological therapies for CRSwNP in adult patients. Methods: We conducted a systematic review and NMA of randomized controlled trials (RCTs) assessing biological therapies for CRSwNP. A literature search was conducted through July 2025. Eligible RCTs compared approved or investigational biologics with a placebo and reported clinical, functional, or safety outcomes in adults with CRSwNP. The mean differences (MDs) in the least-squares mean change from baseline were used for continuous outcomes, and odds ratios (ORs) were used for binary outcomes. A frequentist random-effects model was used to estimate pooled effects and treatment rankings. SUCRA values and rank probabilities were derived to determine the relative efficacy and safety. Results: A total of 22 RCTs (46 reports; 4068 patients) evaluating eight biologics were included. Dupilumab consistently ranked among the top three agents across most efficacy outcomes, including nasal polyp score (NPS), nasal congestion score (NCS), SNOT-22, UPSIT, and endoscopic scores. CM310 and Tezepelumab also demonstrated strong performance in objective and symptom-based outcomes. For responder outcomes, CM310 was ranked best in minimal clinically important differences across multiple domains. PF-06817024 ranked best in minimizing any adverse events and serious adverse events. The placebo ranked worst across nearly all endpoints. Conclusions: Dupilumab, CM31 0, and Tezepelumab exhibit the most favorable efficacy profiles across multiple CRSwNP domains, while all drugs show a nearly similar safety profile. Full article

Background: Cystic Fibrosis (CF) is an autosomal recessive inherited disease caused by mutations of the CF–transmembrane conductance regulator (CFTR), leading to impaired chloride ion trafficking, thickened secretions, and chronic rhinosinusitis (CF-CRS). CF-CRS was historically managed with intranasal corticosteroids (INCS) and endoscopic sinus surgery (ESS). Nowadays, the triple highly effective modulator therapy elexacaftor–tezacaftor–ivacaftor (ETI) is showing promising results in improving CF-CRS. Methods: This is a monocentric, retrospective study comparing Sinonasal Outcome Test-22 (SNOT-22), Nasal Polyps Score (NPS), modified Lund–Kennedy score (mLKS), sniffin’ sticks identification test (SSIT), and Lund–Mackay score (LMS) in patients affected by CF-CRS and treated with ESS or ETI. ETI patients were further subdivided based on previous surgery. Results: A total of 25 patients were surgically treated, and 54 were treated with ETI (specifically, 17 surgically naïve and 37 post-FESS patients). Patients undergoing ESS and those receiving ETI experienced statistically significant improvements in SNOT-22, SSIT, and LMS with no differences between groups and regardless of genetic or demographic characteristics. Conversely, ESS patients experienced significantly higher mean changes in NPS and mLKS. Conclusions: ETI and FESS were safe and effective in reducing the symptomatologic burden of CF-CRS. Even in the ETI epoch, surgery may play a crucial role in managing CF-CRS, particularly in patients not eligible for ETI or experiencing severe disease not adequately controlled with medical therapy alone. Full article

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic otitis media (EOM) are frequently co-existing eosinophilic disorders related to type 2 inflammation, which significantly impair the quality of life of patients. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha and anti-IL-13, has demonstrated a promising profile of efficacy and safety in the treatment of CRSwNP; however, evidence on its role in concomitant EOM and CRSwNP remains limited in the literature. This study aims to evaluate the clinical efficacy of dupilumab in patients with concomitant CRSwNP and EOM over a six-month observational period. Materials and Methods: A retrospective observational cohort study was conducted on twenty-two patients (aged 18–75 years) over six months with severe uncontrolled CRSwNP and confirmed refractory EOM who were treated with dupilumab (300 mg every two weeks). Demographic data are collected, and outcome measures included Nasal Polyp Score (NPS), Sino-Nasal Outcome Test (SNOT-22), Visual Analog Scale for nasal congestion (VAS), tympanogram classification, and Chronic Otitis Media Outcome Test (COMOT-15), evaluated at baseline and 6 months. Results: Over the six-month treatment period, patients with coexisting CRSwNP and eosinophilic otitis media experienced significant improvements across the multiple validated clinical and patient-reported outcome measures. The Nasal Polyp Score (NPS) significantly decreased from a median of 5.7 (IQR: 1.2) at baseline to 1.5 (IQR: 1.3) at six months (p < 0.0001). The SNOT-22 showed a substantial decline from a median of 77.6 (IQR: 19.0) to 21.5 (IQR: 13.4), p < 0.0001. Visual Analog Scale (VAS) scores for nasal congestion improved significantly from 8.4 (IQR: 1.1) to 1.7 (IQR: 1.2), p < 0.0001. Tympanogram scores improved from Tympanogram type “B” to Tympanogram type “A” (p = 0.018). COMOT-15 scale decreased from a median of 51.3 (IQR: 8.4) to 19.2 (IQR: 5.0) (p < 0.0001). Peripheral eosinophil counts remained unchanged or increased (baseline 0.80 vs. 0.84 cells/μL at six months, (p = 0.834)). Conclusions: Dupilumab treatment in patients with CRSwNP and EOM led to significant clinical improvements in sinonasal symptoms, middle ear function, and quality of life over six months, with no significant change in peripheral eosinophilia. Full article

Purpose: Mucormycosis is a life-threatening fungal infection, where rapid diagnosis is critical. We developed a deep learning approach using paranasal computed tomography (CT) images to test whether mucormycosis can be detected automatically, potentially aiding or expediting the diagnostic process that traditionally relies on biopsy. Methods: In this retrospective study, 794 CT images (from patients with mucormycosis, nasal polyps, or normal findings) were analyzed. Images were resized and augmented for training. Two transfer learning models (ResNet50 and ConvNeXt Small) were fine-tuned to classify images into the three categories. We employed a 70/30 train-test split (with five-fold cross-validation) and evaluated performance using accuracy, precision, recall, F1-score, and confusion matrices. Results: The ConvNeXt Small model achieved 100% accuracy on the test set (precision/recall/F1-score = 1.00 for all classes), while ResNet50 achieved 99.16% accuracy (precision ≈0.99, recall ≈0.99). Cross-validation yielded consistent results (ConvNeXt accuracy ~99% across folds), indicating no overfitting. An ablation study confirmed the benefit of transfer learning, as training ConvNeXt from scratch led to lower accuracy (~85%) Conclusions: Our findings demonstrate that deep learning models can accurately and non-invasively detect mucormycosis from CT scans, potentially flagging suspected cases for prompt treatment. These models could serve as rapid screening tools to complement standard diagnostic methods (histopathology), although we emphasize that they are adjuncts and not replacements for biopsy. Future work should validate these models on external datasets and investigate their integration into clinical workflows for earlier intervention in mucormycosis. Full article

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient’s quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0–8) was reduced significantly in the cohort (mean change: −2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (−3.57, p < 0.0001) and smell impairment (−4.0, p < 0.0001) visual analog scale scores (0–10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population. Full article

Background/Objective: Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disease with a significant impact on quality of life and is frequently associated, from a pathogenetic perspective, with type 2 inflammation. The introduction of biologic therapies has marked a turning point in the management of severe forms of the disease, offering a valuable treatment option. However, selecting the most suitable biologic agent for a specific patient remains a clinical challenge. Artificial intelligence, and, in particular, ChatGPT, has recently been proposed as a potential tool to support medical decision-making and guide therapeutic choices. To evaluate the concordance between the therapeutic recommendations provided by ChatGPT and those of a multidisciplinary expert board in selecting the most appropriate biologic therapy for CRSwNP patients, based on the analysis of their phenotype and endotype. Methods: A multicenter observational cohort study was conducted. Clinical data from 286 patients with CRSwNP were analyzed. For each case, the therapeutic choice among Dupilumab, Mepolizumab, and Omalizumab was compared between the board and ChatGPT. Concordance rates and Cohen’s Kappa coefficient were calculated. Results: Overall concordance was 59.2%, with a Cohen’s Kappa coefficient of 0.116. Concordance by drug was 62.8% for Dupilumab, 26.5% for Mepolizumab, and 9.1% for Omalizumab. Patients presented with severe clinical profiles, with an average Nasal Polyp Score of 6.22 and an average SNOT-22 score of 64.5. Conclusions: This study demonstrates that, despite its substantial theoretical potential, ChatGPT is currently not a reliable tool for the autonomous selection of biological therapies in patients with CRSwNP. Further studies are necessary to enhance its reliability and integration into clinical practice. Full article

Background: Chronic rhinosinusitis with or without nasal polyps (CRSwNPs/CRSsNPs) is an inflammatory disease that is becoming increasingly associated with laryngopharyngeal reflux disease (LPRD). Although symptom-based questionnaires, such as the Reflux Symptom Index (RSI) and Reflux Symptom Score (RSS), are widely used, there is a lack of objective endoscopic tools for assessing the nasopharyngeal and nasal manifestations of reflux. The Nasopharyngeal Reflux Endoscopic Score (NRES) is a novel endoscopic scoring system that was developed to address this issue. Objective: The objective of this study was to evaluate the diagnostic accuracy of the NRES in identifying LPRD in patients with CRS, compared with a clinical reference standard. Methods: A prospective diagnostic accuracy cohort study was conducted at two tertiary care centers in Astana, Kazakhstan, from September 2023 to February 2025. A total of 216 adults were enrolled and divided into three groups: CRS with suspected LPRD (n = 116), CRS without LPRD (n = 69), and healthy controls (n = 31). CRS was diagnosed according to the EPOS 2020 criteria. LPRD was defined using a composite reference standard comprising clinical assessment, RSS > 13, RSI, and selective 24 h pH monitoring and gastrointestinal endoscopy. All participants underwent nasopharyngeal and laryngeal endoscopy, with NRES, L-K, RFS, RSI, and RSS assessments at baseline and at 6 and 12 months. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance, and Wilcoxon tests were used to analyze the changes in scores. Correlation and regression analyses were used to explore associations between scales and predictive factors. Results: At baseline, NRES scores were significantly higher in the CRS with LPRD group (mean: 11.59) than in the CRS without LPRD group (mean: 3.10) and the healthy control group (mean: 2.16) (p < 0.001). ROC analysis demonstrated excellent diagnostic accuracy, with an area under the curve (AUC) of 0.998 (95% confidence interval (CI): 0.994–1.000), a sensitivity of 98% (95% CI: 94–100%) and a specificity of 96% (95% CI: 91–99%) at an optimal cut-off point of 8.5. NRES scores showed strong correlations with RSI, RSS, and RFS scores (r > 0.76, p < 0.001). A longitudinal assessment revealed significant reductions in all scores after treatment with proton pump inhibitors and lifestyle modifications, with sustained improvement at 12 months. Regression analysis found no significant effect of age, gender, or GERD severity (LA classification) on NRES scores. Conclusions: The NRES is a highly sensitive and specific endoscopic tool for identifying nasopharyngeal changes associated with LPRD in CRS patients. It demonstrates strong correlations with established symptom-based and laryngoscopic reflux assessments and responds to anti-reflux therapy over time. The NRES may, therefore, be a valuable objective adjunct in the comprehensive evaluation and longitudinal monitoring of LPRD-associated CRS. Full article

Chronic rhinosinusitis with nasal polyps is a Type 2 inflammatory disease associated with a significant burden on quality of life. While biological therapies have shown efficacy in randomized controlled trials, data on long-term real-world outcomes remain limited. This retrospective cohort study evaluated the clinical efficacy, safety, and treatment dynamics of biologics, particularly anti-IL-4 (dupilumab), over a five-year period at a tertiary medical center. Fifty-two patients with CRSwNP meeting the EPOS/EUFOREA eligibility criteria were included. Clinical parameters, including nasal polyp score, SNOT-22, and olfactory function, were assessed across follow-up intervals. Anti-IL-4 therapy demonstrated the most consistent and sustained improvements in all clinical parameters, with a significant proportion of patients maintaining response beyond 36 months. A subset of patients underwent interval extension of dupilumab injections without loss of efficacy. Subdomain analysis of the SNOT-22 questionnaire revealed improvements predominantly in nasal and emotional domains. Treatment response, assessed according to the EUFOREA criteria, favored anti-IL-4 over anti-IL-5 and anti-IgE. Side effects were infrequent and mostly mild. These findings support the durable effectiveness of biologics in real-world CRSwNP management and suggest that tapering down the injection intervals may be a feasible strategy for selected patients. Further studies are needed to refine treatment response definitions and optimize patient-specific therapeutic approaches. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory disorder of the upper airways, severely impacting quality of life. Dupilumab, targeting type 2 inflammatory pathways, is effective in managing severe, uncontrolled CRSwNP. However, the comparative accuracy of endoscopic scoring systems in monitoring therapeutic response to dupilumab remains unclear. This study compared the accuracy of the nasal polyp score (NPS) and the modified Lund–Kennedy endoscopic score (M-LKS) in assessing dupilumab response. Methods: A retrospective cohort analysis included 66 severe CRSwNP patients treated with dupilumab at Padua University. Endoscopic scores (NPS and M-LKS), patient-reported outcome mesures (PROMs), and clinician-reported outcome measures (CROMs), including peak nasal inspiratory flow (PNIF) and the Sniffin’ Sticks test, were evaluated at baseline and over 24 months. Results: Both NPS and M-LKS showed significant reductions over time (p < 0.001), significantly correlating with PNIF (p < 0.001). Given time and patient, PNIF emerged to be the only covariate related to endoscopic scores. No significant differences were observed between NPS and M-LKS regarding clinical outcome associations, suggesting equivalent accuracy. PNIF was identified as a critical predictor of endoscopic improvement, highlighting its clinical utility. These findings reinforce the role of standardized endoscopic metrics in assessing the efficacy of biologic therapies for CRSwNP. Full article

Background: Olfactory recovery plays an important role in improving the quality of life in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP), and Dupilumab therapy shows promising results. The Nasal Polyp Score (NPS), Visual Analog Scale (VAS) for olfactory disorders (ODs), and the Sniffin’ Sticks 16-item identification test (SS-I) are three of the main indices of efficacy in CRSwNP treatment. Although mechanical obstruction appears to be a major cause of olfactory disorders in this condition, the three indices can often vary with different trends. Aim: The aim is to assess whether there is a correlation between the sense of smell recovery and the volumetric reduction in polyps and to assess how the reduction in NPS affects the improvement in olfactory symptoms. Methods: An observational monocentric retrospective cohort study was conducted on a sample of 50 patients, enrolled in treatment with Dupilumab for 12 months at the ENT Unit of Rodolico Hospital. We investigated the relationship between NPS changes and olfactory recovery using the Sniffin’ Stick 16-item identification test and the VAS for ODs at baseline and follow-up endpoints (1-, 3-, 6-, 9-, and 12-month assessments). Results: During the follow-up, according to the data in the literature, the patients showed a faster improvement in terms of SS-I and VAS for ODs than expressed in terms of NPS variation. Conclusions: This study shows that, in patients treated with Dupilumab, there is no strong correlation between the reduction in NPS and the recovery of the sense of smell evaluated by an improvement in the SS-I and VAS for ODs in the 12 months of follow-up, suggesting that, in patients with CRSwNP, the improvement in olfactory symptoms following treatment with Dupilumab is mainly related to its anti-inflammatory effects and not to the reduction in mechanical obstruction caused by nasal polyps. Full article

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are mutually correlated with Type-2 inflammation. Dupilumab is effective in uncontrolled and relapsing CRSwNP. However, the precise characterization of Type-2 inflammation and the impact of previous surgery on clinical outcomes need clarification. Methods: We present a prospective observational study on a 38 CRSwNP-patient cohort, whose Type-2 endotype was confirmed after a multidisciplinary approach shared among ENTs, pneumologists and allergologists. Patients were treated with dupilumab and evaluated at 15 days and 1-3-6-12-18-24-30 months, focusing on clinical (VAS, nasal polyp score—NPS), radiological (Lund-Mackay) and quality of life (SNOT-22) parameters, as well olfactory function, asthma control, variation of Type-2 markers and number and extent (ACCESS score) of previous surgeries. Results: We confirmed the efficacy of dupilumab in total and sub-items VAS, NPS, SNOT-22 and sniffing score, as well as Lund–Mackay score improvements, observable and significant after 2 weeks of treatment (p < 0.0001) and long-lasting over 30 months. Good to excellent response criteria to biologic treatment at 6 months was observed in 30/32 patients. Comorbid asthma reached rapid control (p < 0.0001) and exhaled nitric oxide normalization was achieved. One single “not adequate” surgery showed a trend to milder improvement, as well as a higher ACCESS score to better olfactory outcome. Conclusions: The accurate selection of uncontrolled relapsing CRSwNP in terms of Type-2 endotyping by multidisciplinary approach can maximize dupilumab efficacy. The number and extent of previous surgeries may differentiate the response, although this effect is difficult to catch in real life. “Adequate” ESS surgery before dupilumab may drive mostly effective disease control. Full article

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) poses significant therapeutic challenges. The introduction of Mepolizumab, an anti-interleukin-5 monoclonal antibody, offers a new therapeutic option for patients with severe, uncontrolled CRSwNP. This prospective observational study aims to assess the efficacy and safety of Mepolizumab for treating severe CRSwNP in Italy. Methods: A single-center prospective observational study conducted in real-life settings with the patients of our center. Prior to enrollment, each patient underwent an interdisciplinary evaluation involving a pulmonologist and an allergologist if deemed necessary. All patients who were referred for treatment with Mepolizumab in compliance with the AIFA guidelines and the EPOS/EUFOREA update were included in the study population: (1) subjects who were over the age of 18, (2) who had severe CRSwNP, (3) whose condition was not successfully managed with standard therapies alone, and (4) whose blood eosinophil counts were greater than 150 cells/mL. Mepolizumab was administered subcutaneously through a 100 mg injection once every four weeks in addition to the standard-of-care therapy. Results: At the end of the enrollment process, 20 patients with severe CRSwNP were enrolled. Significant improvements were observed in Nasal Polyp Score, quality of life (SNOT-22; p < 0.05), and nasal obstruction and rhinorrhea (p < 0.05), while no significant improvements were seen in olfactory function (p < 0.05). Eosinophil levels also significantly decreased (p < 0.05). Conclusions: Mepolizumab effectively manages severe CRSwNP, showing improvements in symptom control and quality of life with an acceptable safety profile. Full article

Background: Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are chronic respiratory conditions that frequently coexist. However, an integrated assessment tool for both conditions is currently lacking. This study aimed to develop and preliminarily evaluate a composite score capable of simultaneously assessing asthma and CRSwNP in comorbid patients. Methods: An expert panel comprising three pulmonologists, one allergist/clinical immunologist, and four ear, nose and throat (ENT) specialists developed a tool to capture asthma and CRSwNP severity. The tool (D’Amato-De Corso score, or DAMADECO score) incorporates eight parameters, four specific to asthma and four specific to CRSwNP, to assign individual scores for each condition. A composite score is then calculated to reflect the overall disease burden (ranging from −8: poor control and +8: optimal control). A retrospective pilot study was conducted to evaluate the tool. Results: The DAMADECO composite score was applied to 21 comorbid patients. The mean partial scores for asthma and CRSwNP were −1.57 and −1.67, respectively, with a mean total composite score of −3.24. A total of 13 out of 21 patients had uncontrolled domains in both diseases, while fewer patients had only uncontrolled domains in asthma (1/21) or CRSwNP (6/21). The DAMADECO score also allows researchers to track disease progression and monitor treatment effectiveness. Conclusions: The preliminary results suggest that the DAMADECO score is a promising tool for simultaneously assessing asthma and CRSwNP, addressing the unmet need for an integrated approach to comorbid respiratory diseases. Further validation studies are needed to validate the tool in larger patient populations. Full article

Sinonasal squamous cell carcinoma (SNSCC) is a rare tumor with high mortality and recurrence rates. However, SNSCC carcinogenesis mechanisms and potential therapeutic drugs have not been fully elucidated. This study investigated the key molecular mechanisms and hub proteins involved in SNSCC carcinogenesis using proteomics and bioinformatic analysis. Dysregulated proteins were validated by RT-qPCR in SNSCC and nasal polyp (NP) tissues. Proteomic analysis revealed that differentially expressed proteins were clustered using MCODE scores ≥ 4 into three modules. The specific hub proteins in each module were analyzed in carcinogenesis pathways using STRING, highlighting potential mechanisms of histone modification and spliceosome dysregulation. Spliceosome components SNRNP200 and SF3A3 were significantly downregulated in SNSCC by RT-qPCR. Web-based applications L1000CDS² and iLINCS were applied to identify 10 potential repurposable drugs that could reverse the gene expression pattern associated with SNSCC. Docking studies of TAF1, a protein in histone modification, with these 10 small molecule inhibitors indicated OSI-027 to be the most promising due to its strong binding interactions with key residues. These findings suggest that hub proteins involved in the underlying mechanism of SNSCC carcinogenesis may serve as valuable targets for drug development, with OSI-027 emerging as a novel candidate against TAF1 in SNSCC. Full article