Search Results (254)

Background: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy arising from the nasopharyngeal mucosa. Despite treatment advances such as the use of intensity-modulated radiotherapy and immune checkpoint inhibitors, resistance remains a significant clinical challenge. Many tumours are also diagnosed at an advanced stage associated with poor prognosis. Objective: This review aims to explore the biological roles of autophagy in NPC, primarily highlighting its involvement in disease pathogenesis and treatment resistance. Methods: We performed a review of the recent literature examining the role of autophagy-related pathways in NPC pathogenesis, biomarker discovery, and therapeutic targeting. Results: Autophagy plays a dual role in NPC as it contributes to both tumour suppression and progression. It is involved in tumour initiation, metastasis, immune modulation, and treatment resistance. Autophagy-related genes such as SQSTM1, Beclin-1, and AURKA may serve as prognostic and therapeutic biomarkers. Various strategies are being investigated for their role to modulate autophagy using pharmacologic inhibitors, RNA interventions, and natural compounds. Conclusions: Further research into autophagy’s context-dependent roles in NPC may inform the development of personalised therapies and allow progress in translational and precision oncology. Full article

Nasopharyngeal carcinoma (NPC) represents a prevalent malignant tumor within the head and neck region, and enhancing the precision of prognostic assessments is a critical objective. Recent advancements in the integration of artificial intelligence (AI) and medical imaging have spurred a surge in research focusing on NPC image analysis through AI applications, particularly employing radiomics and artificial neural network approaches. This review provides a detailed examination of the prognostic advancement in NPC, utilizing imaging studies based on radiomics and deep learning techniques. The findings from these studies offer a promising outlook for achieving exceptionally precise prognoses regarding survival and treatment responses in NPC. The limitations of existing research and the potential for further application of radiomics and deep learning in NPC imaging are explored. It is recommended that future research efforts should aim to develop a comprehensive, labeled dataset of NPC images and prioritize studies that leverage AI for NPC screening. Full article

Background: Adaptive radiation therapy (ART) can improve prognosis for nasopharyngeal carcinoma (NPC) patients. However, the inter-individual variability in anatomical changes, along with the resulting extension of treatment duration and increased workload for the radiologists, makes the selection of eligible patients a persistent challenge in clinical practice. The purpose of this study was to predict eligible ART candidates prior to radiation therapy (RT) for NPC patients using a classification neural network. By leveraging the fusion of medical imaging and clinical data, this method aimed to save time and resources in clinical workflows and improve treatment efficiency. Methods: We collected retrospective data from 305 NPC patients who received RT at Hong Kong Queen Elizabeth Hospital. Each patient sample included pre-treatment computed tomographic (CT) images, T1-weighted magnetic resonance imaging (MRI) data, and T2-weighted MRI images, along with clinical data. We developed and trained a novel multi-modal classification neural network that combines ResNet-50, cross-attention, multi-scale features, and clinical data for multi-modal fusion. The patients were categorized into two labels based on their re-plan status: patients who received ART during RT treatment, as determined by the radiation oncologist, and those who did not. Results: The experimental results demonstrated that the proposed multi-modal deep prediction model outperformed other commonly used deep learning networks, achieving an area under the curve (AUC) of 0.9070. These results indicated the ability of the model to accurately classify and predict ART eligibility for NPC patients. Conclusions: The proposed method showed good performance in predicting ART eligibility among NPC patients, highlighting its potential to enhance clinical decision-making, optimize treatment efficiency, and support more personalized cancer care. Full article

Background: This study aimed at evaluating apparent diffusion coefficient (ADC) values of nasopharyngeal carcinoma (NPC) in the pre-treatment stages of NPC for establishing comparative quantitative parameters between children and adolescents compared to adults. Methods: A retrospective multicentric imaging study was conducted in three medical centers by collecting patient data over a 5-year timeframe. Patients were included in the study based on the following criteria: histopathologically proven carcinoma of the nasopharynx with all available medical records. The total sample included 20 patients (6 pediatric patients and 14 adults). A quantitative analysis of the ADC maps was performed. Two radiologists manually drew the region of interest (ROI) on ADC maps using the whole tumor on all magnetic resonance imaging (MRI) slices. The mean ADC was extracted for each patient and each radiologist’s evaluation. Differences in ADC values between pediatric and adult patients were evaluated using an independent samples t-test, with normality and variance assumptions tested via the Shapiro–Wilk and Levene’s tests, respectively. p-values less than 0.05 were considered statistically significant. Results: The mean ADC values extracted from the initial pre-treatment diffusion-weighted imaging (DWI) data from magnetic resonance imaging (MRI) in children were 712.22 × 10⁻⁶ mm²/s, compared to adults in whom the mean ADC values were 877.34 × 10⁻⁶ mm²/s. We found a statistically significant difference between the mean ADC values of pediatric patients and adult patients, t (17.44) = −3.15, p = 0.006, with the mean ADC values of pediatric patients (M = 712.22, standard deviation [SD] = 57.03) being lower, on average, than the mean ADC values of adult patients (M = 877.34, SD = 175.25). Conclusions: Our results showed significantly lower ADC values in pediatric patients than in adults, independent of tumor T-stage. Additionally, early-stage tumors, particularly in children, tended to exhibit even lower ADC values, suggesting potential biological distinctions across age groups. Full article

Background: The geriatric nutritional risk index (GNRI), a composite metric of serum albumin and body weight, has emerged as a prognostic tool in various cancers. However, its relevance in nasopharyngeal carcinoma (NPC) patients treated with volumetric modulated arc therapy (VMAT) remains unexplored. The aim of this study was to assess the effect of the GNRI in the prediction of the prognosis of nasopharyngeal carcinoma in the era of VMAT. Methods: This retrospective study analyzed 498 newly diagnosed, non-metastatic NPC patients treated with VMAT between 2010 and 2011. The GNRI was calculated using serum albumin and body weight ratios, with receiver operating characteristic (ROC) curve analysis determining its optimal prognostic cutoff. Patients were stratified into training (70%) and validation (30%) cohorts. Cox regression identified independent prognostic factors, which were integrated into a nomogram predicting 3- and 5-year overall survival (OS). Model performance was assessed via the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: In the study, 348 patients were included in the training cohort and 150 patients were included in the validation cohort according to a ratio of 7:3. The median follow-up was 68 months, with 5-year OS rates of 79.3%. A GNRI > 102 independently predicted improved survival (HR = 0.64; p = 0.044), alongside tumor volume, age, and N-stage. The nomogram demonstrated strong discrimination (C-index: 0.757–0.762 for training; 0.737–0.744 for validation) and calibration, aligning closely with observed survival. DCA confirmed superior clinical utility over default strategies. NPC patients treated with VMAT with a high GNRI, female sex, and a lower N-stage exhibited significantly better OS (p < 0.05). Conclusions: The GNRI is a robust prognostic marker for NPC patients receiving VMAT, reflecting the interplay of nutrition, inflammation, and treatment response. The validated nomogram provides a practical tool for individualized risk stratification, enhancing clinical decision-making in the era of precision radiotherapy. Full article

Epstein–Barr virus (EBV), a double-stranded DNA virus, is implicated in nasopharyngeal carcinoma (NPC), with particularly high incidence in regions such as southern China and Hong Kong. Although NPC is typically treated with radio- and chemotherapy, outcomes remain poor for advanced-stage diagnoses, highlighting the need for targeted therapies. This study explores the potential of CRISPR/CRISPR-associated protein 13 (Cas13) technology to target essential EBV RNA in NPC cells. Previous research demonstrated that CRISPR/Cas9 could partially reduce EBV load, but suppression was incomplete. Here, the combination of CRISPR/Cas13 with CRISPR/Cas9 shows enhanced viral clearance. Long-term EBNA1 suppression via CRISPR/Cas13 reduced the EBV genome, improved CRISPR/Cas9 effectiveness, and identified suitable AAV serotypes for delivery. Furthermore, cotreatment increased NPC cell sensitivity to 5-fluorouracil and cisplatin. These findings underscore the potential of CRISPR/Cas13 as an anti-EBV therapeutic approach, effectively targeting latent EBV transcripts and complementing existing treatments. The study suggests a promising new direction for developing anti-EBV strategies, potentially benefiting therapies for NPC and other EBV-associated malignancies. Full article

Introduction: The limited value of TNM staging in locally advanced (LA) nasopharyngeal carcinoma (NPC), defined as stage III or IV NPC, highlights the need for prognostic markers. Here, we aimed to evaluate the ability of the cancer stem cell markers, BMI1, ALDH1, CD44, and CD24, and the epithelial–mesenchymal transition marker, vimentin, as novel prognostic markers in LA-NPC. Methods: A cohort of 83 patients with LA-NPC, previously recruited for another trial with a different goal, was used. The marker expression in tissue sections was evaluated using immunohistochemistry, and the association of expression with survival outcomes was analyzed using the Kaplan–Meier method and Cox regression analysis. Results: The expression of BMI1 and ALDH1 was not associated with survival. The tumoral expression of CD24, CD44, and vimentin was significantly associated with disease-free survival (DFS), whereas only the expression of CD24 was also significantly associated with overall survival (OS). Indeed, CD24 expression emerged as an independent prognostic factor as it was associated with survival in univariate and multivariate Cox regression analysis. Interestingly, combining the status of CD24 expression in tumor cells with the density of CD3⁺ tumor-infiltrating lymphocytes (TIL), a microenvironment/immune-related marker, identified a high-risk subgroup with the worst DFS and OS. Conclusions: These results suggest the utility of combining tumoral CD24 expression and the CD3⁺ TIL density as a prognostic factor in LA-NPC, with potential application in disease management and future trial design. Our findings also highlight the potential of combining immune- and cancer stem cell-related factors in personalized treatment strategies for cancer. Full article

Nasopharyngeal carcinoma (NPC) is a multifactorial disease mainly affecting the Southeast Asian and North African populations. Critically, there is a dearth of available circulating biomarkers for NPC. Additionally, as of this writing, there have been no prior plasma proteomics studies on NPC in the Moroccan population. Accordingly, there has been no integrated analysis of tumor and plasma for NPC in the Moroccan sub-population. Label-free proteomics analysis was conducted on 25 samples of Moroccan origin (10 NPC samples and 15 healthy control samples). Each sample was depleted of albumin, fractionated into eight fractions, and then analyzed using Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS). A total of 291 proteins and 2702 unique peptides were identified across all samples. In total, 16 proteins were differentially expressed (DEPs) between NPC cases and healthy individuals. Of these, three showed prognostic significance, while four demonstrated diagnostic potential. A pathway analysis showed significantly enriched terms related to the immune response and chronic inflammation, revealing acute-phase proteins as differentially expressed. The investigation of patients with early and advanced stages of NPC revealed two DEPs, while four additional DEPs were identified across the three defined clusters of NPC. Across all comparisons, DEPs, such as H2A, IGHG2, SERPINA3, SAA1, CRP, PIGR, and APOA2, have shown potential as biomarkers for NPC, with several being identified for the first time. We additionally compared the plasma proteomic profile of NPC with the tumor proteomic profile, highlighting that deeper proteomics analysis of plasma may be required to quantify additional putative biomarkers that may be shed from the tumor into the blood. Our research presents the first plasma proteomic profile of NPC in Morocco and North Africa, identifying proteins that might ultimately have diagnostic and prognostic potential. Full article

Purpose: Cognitive decline is a major concern for nasopharyngeal carcinoma (NPC) survivors after radiotherapy (RT). We assessed whether the rates of cognitive decline in NPC survivors differed depending on the presence of epilepsy. Methods: Based on an ongoing prospective cohort study (NCT03908502), we included consecutive NPC patients with a history of radiotherapy who underwent a baseline and follow-up cognition assessment between January 2005 and December 2023. Patients who had a confirmed diagnosis of epilepsy before radiotherapy, had intracranial brain metastasis during follow-up, lacked baseline major clinical data, or lacked follow-up cognitive assessment of longer than six months were excluded. The outcome was cognitive function assessed by the Chinese version of the Montreal Cognitive Assessment (MoCA), with assessments being performed every 6 months through face-to-face interviews. Linear mixed-effect models were used to analyze the progression rate of MoCA scores by epilepsy status (incident, prevalent, or no epilepsy). Results: A total of 521 patients with a median follow-up period of 3.96 years were included in our study. The rate of decline in MoCA was significantly faster in patients with prevalent epilepsy compared with no epilepsy after adjusting for demographics, health behaviors, tumor-related history, complications, anti-seizure medication, and inflammatory blood index (estimate: −1.407; 95%CI: −2.419, −0.412; p = 0.007). However, the cognitive decline rate was similar in the incident epilepsy group compared with that in the non-epilepsy group (p = 0.126). Subgroup analysis showed that there was no significant difference in the effect of epilepsy status on cognitive deterioration among subgroups stratified by the pre-planned covariates. Conclusions: Global cognitive function declined more rapidly in NPC patients with prevalent epilepsy. The control of seizure attacks may be valuable to mitigate cognitive decline. Full article

Background/Objectives: To assess the pretreatment and posttreatment clinical factors associated with the rate of survival at 1, 3, and 5 years in stage IV nasopharyngeal carcinoma (NPC) patients. Methods: Clinicopathological characteristics of 61 Stage IV NPC patients diagnosed between 2008 and 2022 in a single tertiary medical center were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the prognostic factors associated with overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). A nomogram was developed to forecast DSS. Results: The OS at 1-year, 3-year, and 5-year were 93%, 70%, and 57%, while the DSS at 1-year, 3-year, and 5-year were 93%, 73%, and 58%, whereas the DFS at 1-year, 3-year, and 5-year were 51%, 44%, and 41%, respectively. In multivariate analyses, posttreatment body mass index (BMI) < 21.6 kg/m² (hazard ratio [HR] 2.717, 95% confidence interval [CI] 1.248–5.917, p = 0.012) was an independent indicator for worsened OS. Posttreatment BMI < 21.6 kg/m² (HR 3.003, 95% CI 1.340–6.757, p = 0.008) and pretreatment systemic inflammation response index (SIRI) ≥ 125 (HR 2.841, 95% CI 1.256–6.429, p = 0.012) were independent indicators for worsened DSS. Posttreatment BMI < 21.6 kg/m² (HR 3.650, 95% CI 1.757–7.576, p = 0.001), change in BMI < −1.93 kg/m² (HR 3.731, 95% CI 1.642–8.475, p = 0.002), and pretreatment SIRI ≥ 125 (HR 3.541, 95% CI 1.717–7.304, p = 0.001) were independent indicators for worsened DFS. A nomogram was created to predict DSS using posttreatment BMI and pretreatment SIRI. Conclusions: Associations with survival were observed between posttreatment BMI and OS, DSS, and DFS; pretreatment SIRI and DSS/DFS; and changes in BMI and DFS among patients with stage IV NPC. The developed nomogram aids in survival prediction. Full article

Background: Tegafur–uracil (UFT), an oral fluoropyrimidine developed in Asia, has been investigated as a maintenance or adjuvant therapy in various malignancies. Its use in head and neck cancers, however, remains limited to small retrospective studies, primarily from East Asia. Given the need for cost-effective maintenance strategies in resource-limited settings, we conducted an exploratory systematic review to evaluate the clinical utility of UFT in non-metastatic head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC). Methods: We systematically searched PubMed, EMBASE, and Cochrane Library from inception through 1 May 2025 for retrospective cohort studies evaluating UFT after definitive therapy in non-metastatic HNSCC or NPC. Study selection followed PRISMA guidelines. Given the heterogeneity of included studies, we performed a structured narrative synthesis using the SWiM (Synthesis Without Meta-analysis) framework to summarize survival outcomes, treatment settings, and clinical contexts. Results: Seven retrospective studies (four HNSCC, three NPC) involving 508 patients were included. UFT was generally administered at 300–400 mg/day for 6–12 months. Across studies, UFT use was associated with favorable disease-free and overall survival trends in high-risk subgroups, including patients with extranodal extension and persistent EBV DNA. Treatment adherence and toxicity profiles were acceptable. Conclusions: While the evidence remains limited and heterogeneous, this review highlights recurring signals of benefit associated with UFT maintenance therapy in selected high-risk patients. Prospective trials are warranted to confirm these findings and better define a possible role of UFT in maintenance therapy in some advanced non-metastatic HNSCC and NPC. Full article

The management of nasopharyngeal cancer (NPC) is rapidly evolving, with immune checkpoint inhibitors emerging as a prominent treatment approach. However, drug development targeting specific molecular and cellular abnormalities in NPC has slowed. Recent advancements in artificial intelligence (AI) and bioinformatics, particularly those integrating multi-omics data, offer a more effective alternative to traditional in vitro screening methods for identifying clinically actionable targets in NPC. Through a combination of multi-omics analyses and AI-driven screening, we identified CACNA2D1 as a novel cancer-cell-specific therapeutic target in NPC. Our research indicates that exploiting Epstein–Barr virus (EBV) tethering increases H3K27 acetylation near the CACNA2D1 promoter. Analysis of clinical specimens revealed significant upregulation of CACNA2D1 at both the transcriptional and translational levels (p-value < 0.01). Functional studies demonstrated that the mouse tumour size shrank by one-third upon the depletion of CACNA2D1, and there was an 85% reduction in cancer cell growth through the blockage of enhancers, while the presence of CACNA2D1 conferred a survival advantage during NPC tumour development. These findings highlight the potential of CACNA2D1 as a promising target for therapeutic intervention in NPC. Full article

Background: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer arising from the mucosal lining of the nasopharynx, for which systemic therapeutic options remain scarce, reflecting the limited characterization of its genomic profile. This study utilized a large patient-level genomic repository to characterize genetic alterations, identify potential therapeutic targets, and improve disease modeling in NPC. Methods: A retrospective analysis of NPC samples was conducted using the AACR Project GENIE database. Targeted sequencing data were analyzed for recurrent somatic mutations, tumor mutational burden, and chromosomal copy number variations, with significance set at p < 0.05. Results: Frequent mutations were identified in KMT2D (20%), TP53 (16%), CYLD (9.6%), NFKBIA (6.4%), and PIK3CA (5.6%), implicating the p53, NF-κB, and PI3K pathways in NPC development. Notably, significantly distinct mutational profiles were observed based on both sex and race, with female patients exhibiting higher frequencies of PIK3C2G, ETV6, and CDKN1B mutations and non-Asian patients showing enrichment in KDM5A, CCND2, and TP53 mutations. Conclusions: This study presents a detailed genomic profile of NPC, identifying key mutations within established cancer-associated pathways. The identification of frequently mutated pathways (p53, NF-κB, and PI3K) suggests potential targets for novel therapies. Furthermore, distinct mutational landscapes in female and Asian NPC patients offer possibilities for precision therapeutic interventions. Full article

Epstein–Barr virus (EBV), a ubiquitous human herpesvirus, has been robustly linked to the pathogenesis of nasopharyngeal carcinoma (NPC). The mechanism of EBV-induced NPC involves complex interactions between viral proteins and host cell pathways. This review aims to comprehensively outline the mechanism of EBV-induced NPC and the latest advances in targeted EBV vaccines for prophylaxis and treatment. This review explores the intricate molecular mechanisms by which EBV contributes to NPC pathogenesis, highlighting viral latency, genetic and epigenetic alterations, and immune evasion strategies. It emphasizes the pivotal role of key viral proteins, including EBNA1, LMP1, and LMP2A, in carcinogenesis. Subsequently, the discussion shifts towards the development of targeted EBV vaccines, including preventive vaccines aimed at preventing primary EBV infection and therapeutic vaccines aimed at treating diagnosed EBV-related NPC. The review underscores the challenges and future directions in the field, stressing the importance of developing innovative vaccine strategies and combination therapies to improve efficacy. This review synthesizes current insights into the molecular mechanisms of EBV-induced NPC and the development of EBV-targeted vaccines, highlighting the potential use of mRNA vaccines for NPC treatment. Full article

Background/Objective: Vascular abnormalities are the primary histological changes in individuals undergoing radiotherapy for nasopharyngeal carcinoma (NPC). We sought to validate the hypothesis that the duration post-radiotherapy is linked to the progression of carotid intima-media thickness (IMT) and further explored its connection with mortality. Methods: Twenty-nine NPC patients who underwent radiotherapy and seventeen healthy controls were examined by carotid ultrasound for measurement of IMT and carotid plaque score at the common carotid artery (CCA), carotid bifurcation, and internal carotid artery, with follow-ups more than 6 years. Results: Initially, there was no discernible difference in internal carotid IMT between NPC patients and normal controls. However, a noteworthy increase in carotid IMT was observed after 6 years of radiotherapy (p < 0.0001). The carotid plaque score in NPC patients significantly exceeded that of the control group after 6 years (p < 0.0001). Linear regression demonstrated a positive correlation between carotid IMT and the duration post-radiotherapy. Logistic regression suggested that age and carotid IMT were predictors of mortality in NPC patients. Conclusions: Our study substantiates the positive correlation between carotid IMT and the duration of follow-up after radiotherapy. It found an increase in carotid IMT and plaque formation six years after radiotherapy compared to the control group. An increased carotid IMT may be correlated to an increased mortality rate and needs to be explored in future studies. Consequently, we recommend regular follow-up carotid ultrasonography for NPC patients undergoing radiation therapy. Full article