Nasopharyngeal Carcinoma Cases Research Articles

Meta-analysis of Epstein-Barr virus genomes in Southern Chinese identifies genetic variants and high risk viral lineage associated with nasopharyngeal carcinoma.

Genetic variants in Epstein-Barr virus (EBV) have been strongly associated with nasopharyngeal carcinoma (NPC) in South China. However, different results regarding the most significant viral variants, with polymorphisms in EBER2 and BALF2 loci, have been reported in separate studies. In this study, we newly sequenced 100 EBV genomes derived from 61 NPC cases and 39 population controls. Comprehensive genomic analyses of EBV sequences from both NPC patients and healthy carriers in South China were conducted, totaling 279 cases and 227 controls. Meta-analysis of genome-wide association study revealed a 4-bp deletion downstream of EBER2 (coordinates, 7188-7191; EBER-del) as the most significant variant associated with NPC. Furthermore, multiple viral variants were found to be genetically linked to EBER-del forming a risk haplotype, suggesting that multiple viral variants might be associated with NPC pathogenesis. Population structure and phylogenetic analyses further characterized a high risk EBV lineage for NPC revealing a panel of 38 single nucleotide polymorphisms (SNPs), including those in the EBER2 and BALF2 loci. With linkage disequilibrium clumping and feature selection algorithm, the 38 SNPs could be narrowed down to 9 SNPs which can be used to accurately detect the high risk EBV lineage. In summary, our study provides novel insight into the role of EBV genetic variation in NPC pathogenesis by defining a risk haplotype of EBV for downstream functional studies and identifying a single high risk EBV lineage characterized by 9 SNPs for potential application in population screening of NPC.

Nasopharyngeal Mucoepidermoid Carcinoma: A Rare Case Report

Introduction : Mucoepidermoid carcinoma is one of the common malignancies of the salivary glands. Nasopharyngeal mucoepidermoid carcinoma cases are rare. The treatment of these rare cases depends on the stage of the tumor and its invasion into the surrounding tissues. Case: A 63-year-old male patient, who was followed up for thyroid papillary carcinoma in 2006, was referred to our clinic after incidentally detected asymmetrical thickening of the nasopharynx on the left as a result of brain MRI during medical oncology follow-ups. The patient had a complaint of pain in the left neck region for about a month. Excisional biopsy from the lymph node that increased FDG uptake in the left jugulodigastric region in PET/CT and multiple punch biopsy from the nasopharynx were performed. The patient, whose pathology resulted in mucoepidermoid carcinoma, was referred to oncology to receive radiochemotherapy. Discussion: Although rare, it should be kept in mind that in patients presenting with a mass in the nasopharynx, mucoepidermoid carcinoma may be present. Although there is information about treatment options in the studies carried out to date, prospective studies are needed for prognosis and treatment selection.

The circadian clock gene BMAL1 increases radiosensitivity in nasopharyngeal carcinoma cell CNE2

ObjectiveTo investigate the involvement of the circadian clock gene BMAL1 in regulating radiosensitivity in nasopharyngeal carcinoma (NPC). MethodsThe regulatory role of BMAL1 in NPC radiotherapy was investigated using 44 NPC cases and the NPC cell line CNE2, which had been genetically modified to either overexpress or silence BMAL1. Infected CNE2 cells were divided into four groups, including those with BMAL1 overexpression and BMAL1 RNA interference (RNAi), as well as their respective control groups. The group responses to different doses of radiotherapy were examined. ResultsThe 5-year survival rates of the BMAL1 overexpression group demonstrated a significant increase compared to those of the low expression group (p < 0.05). Furthermore, the BMAL1 overexpression group exhibited a higher tumor-growth inhibition rate (p < 0.001) and apoptotic rate (p = 0.004) following radiotherapy; a decreased proportion of S-phase cells (p < 0.001) but an increased proportion of G2/M-phase cells (p = 0.001) after 24 h of 8Gy irradiation; reduced number of cell colonies (p = 0.042), and a lower survival score (p = 0.037). ConclusionsOur findings demonstrate a positive correlation between BMAL1 expression and NPC survival, suggesting that BMAL1 promotes NPC radiosensitivity.

Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population.

Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy associated with both genetic and environmental factors. Polymorphic deletions of the phase I and phase II genes involved in the detoxification of potential carcinogens may be a risk factor for nasopharyngeal carcinoma. In this study, we investigated the relationship between CYP2E1 (rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) gene variations and NPC risk in North African countries with the highest incidence of NPC (Morocco, Algeria and Tunisia). and the evaluation of the potential use of these variants as potential biomarkers for NPC management. A total of 600 NPC cases and 545 controls frequency-matched on ethnicity, sex, age and childhood household type, were recruited from three North African countries (Morocco, Algeria and Tunisia) and analysed. Genotyping of CYP2A6 and CYP2E1(rs3813867) was performed by polymerase chain reaction restriction (PCR)-fragment length polymorphism (RFLP) analysis and the GSTM1 (rs1183423000) and GSTT1(rs1601993659) genetic variations were evaluated using the PCR technique. The genotype distributions of CYP2E1(rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) genotypes did not differ significantly among NPC cases and controls (p>0.05). Furthermore, our data did not reveal any association with smoking and the studied variants, even when the samples were stratified by the duration period of smoking. In this large studied North African population, our findings suggest that the functional CYP2E1, CYP2A6, GSTM1 and GSTT1 variations did not influence NPC susceptibility.

Efficacy of immune checkpoint inhibitors differs in various status of carcinoma: a study based on 29 cohorts with 3255 participants

BackgroundPre-clinical data have revealed that viral infection, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human Papilloma virus (HPV), may lead to the development of “hot” or “immune-sensitive” tumors, which may impact the efficacy of immune checkpoint inhibitor (ICIs). Therefore, This study aimed to investigate the impact of viral status on the efficacy of ICIs.MethodsElectronic databases were searched to identify relevant trials. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by hazard ratio (HR). Stratified analyses were accomplished based on viral types, treatment regimens, and patient locations.ResultsA total of 3255 participants were recruited, including 252 cases of gastric cancer, 156 cases of nasopharyngeal carcinoma, 1603 cases of hepatocellular carcinoma, and 1244 cases of head and neck squamous cell carcinoma. Pooled results demonstrated a significant association between viral infection and favorable outcomes in patients receiving ICIs, including improved OS [HR = 0.67, 95%CI (0.57–0.79), P < 0.0001], increased ORR [OR = 1.43, 95%CI (1.14–1.80), P = 0.0018], and a trend toward enhanced PFS [HR = 0.75, 95%CI (0.56–1.00), P = 0.05]. In subgroup analyses, patients treated with ICIs who were exposed to HBV/HCV or HPV infection exhibited an evidently superior OS without heterogeneity, compared to those without infection.ConclusionsThis study indicated that the presence of viral infection was evidently associated with improved outcomes in cancer patients undergoing ICIs, particularly in cases of HBV/HCV and HPV infections.

Clinical, Epidemiological, Morphological, and Immunohistochemical Aspects of Nasopharyngeal Carcinoma-4-Year Retrospective Study in the Western Part of Romania.

Nasopharyngeal carcinoma is one of the most common malignant tumors in the head and neck region. The carcinogenesis is a complex process stimulated by many factors. Although the etiological factors and pathogenic mechanisms are not elucidated, the genetic susceptibility, environmental factors, and association with latent infection with Epstein-Barr Virus play an important role. The aim of this study was to present the main clinical and epidemiological data, as well as the morphological aspects and the immunohistochemical profile, of patients with nasopharyngeal carcinoma diagnosed in western Romania. The study was retrospective and included 36 nasopharyngeal carcinomas. The histopathological diagnosis was completed using immunohistochemical reactions for the following antibodies: p63, p53 and p16 protein, cytokeratins (CK) AE1/AE3, CK5, CK7, CK20 and 34βE12, epithelial membrane antigen (EMA), Epstein-Barr virus (EBV), leukocyte common antigen (LCA), CD20, CD4, CD8, CD68, CD117, and CD1a. The squamous malignant component of nasopharyngeal carcinoma presented with positivity for cytokeratins AE1/AE3, CK5, 34βE12, and p63. Undifferentiated nasopharyngeal carcinoma was positive for EMA in 67% of cases, and 28% of cases showed an immunoreaction for CD117 in the malignant epithelial component. Also, the p53 protein was positive in all the cases. One case of undifferentiated nasopharyngeal carcinoma was p16-positive, and two cases were positive for EBV. A peri- and intratumor cellular infiltrate rich in lymphocytes, with a predominance of CD20-positive B lymphocytes, interspersed with T lymphocytes, was observed. The T cells were CD4- and CD8-positive, predominantly intratumoral, and the CD4:CD8 ratio was 1:1 for 75% of the undifferentiated subtype and 89% for differentiated non-keratinized squamous cell carcinoma. All subtypes of nasopharyngeal carcinoma presented with an inflammatory infiltrate with numerous plasma cells, eosinophils, and dendritic cells, presenting as antigen CD1a- and CD68-positive, as well as in CD117-positive mast cells.

Abstract 5481: Spatial multiplex proteins profiling of tumor microenvironment to decipher de novo metastasis in nasopharyngeal carcinoma

Abstract Background: Nasopharyngeal carcinoma (NPC) has a high incidence rate in Southeast Asia, where more than 90% of NPC cases are associated with Epstein-Barr virus (EBV). Although NPC patients are generally sensitive to radiotherapy and chemotherapy, about 20-30% of patients have treatment failure due to the development of distant metastasis, i.e. de novo metastasis. In this study, we utilized GeoMx Digital Spatial Profiler (DSP), a multiplex and high-throughput sequencing platform designed for spatially- and morphologically resolved protein expression profiling to investigate the intra-tumoral and inter-tumoral heterogeneity of tumor microenvironment (TME) and identify the mechanisms underlying distant failure in NPC. Methods: We utilized GeoMx Protein Assays consisting of 147 proteins from 15 functional modules to compare the difference between NPC cases developing distant failure (DF) (n=21) and stage-, age-, gender- and treatment-matched NPC cases without developing distant failure (noDF) (n=15) within five years of treatment. Two fluorescent morphological markers including PanCK and CD45, were used for delineating the structural architecture of the tissues, identifying cell types, and selecting regions of interest (ROIs), followed by sequencing for protein expression quantification. NanoString GeoMx DSP Analysis Suite was used for quality control and data normalization. The NPC TME heterogeneity was further investigated by the 10X Visum platform for spatial transcriptome. The public single-cell RNA sequencing (scRNA-Seq) and bulk RNA sequencing datasets were obtained for the downstream analyses. Results: By analyzing protein expression profiles, the study revealed the intratumoral and intertumoral heterogeneity associated with EBV latent infection in the TME of NPC. Regions with high EBV latent gene expression exhibited a noticeable reduction in T cell infiltration, indicating an "immune cold" phenotype, whereas regions with low EBV latent gene expression displayed heavy T cell infiltration, indicating an "immune hot" phenotype. Moreover, the study identified a panel of autophagic and anti-apoptotic proteins that were significantly upregulated in the cancer cells of NPC cases developing distant failure after treatment. This observation, supported by the single-cell RNA sequencing datasets, further implicated EBV latent infection for the upregulation of autophagic and anti-apoptotic genes. Notably, the study also demonstrated that the genes upregulated in the immune cells in NPC cases with distant failure were associated with poor progression-free survival in an independent NPC cohort. Conclusions: These findings shed light on the crucial role of EBV latent infection in TME heterogeneity and highlight the potential involvement of autophagy and anti-apoptosis in de novo metastasis in NPC. Citation Format: Larry Ka-Yue Chow, Ying Wang, Lanqi Gong, Siqi Xu, Zhaozheng Hou, Xinyuan Guan, Dora Lai-Wan Kwong, Victor Ho-Fun Lee, Wai To ng, Anne Wing-Mui Lee, Zhonghua Liu, Yunfei Xia, Wei Dai. Spatial multiplex proteins profiling of tumor microenvironment to decipher de novo metastasis in nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5481.

CLINICOPATHOLOGICALCHARACTERISTICS OF NASOPHARYNGEALCARCINOMA AT CENTRAL GENERAL HOSPITAL PROF. DR. I.G.N.G. NGOERAH DENPASAR IN 2021-2022

ABSTRACT&#x0D; &#x0D; Nasopharyngeal carcinoma (NPC) epidemiologically occupies the fourth position as the highest number of malignancy cases in Bali, Indonesia. The most common histological type of NPC cases are non-keratinizing squamous cell carcinoma (NKSCC) undifferentiated subtype. This research aims to know the clinicopathological aspect of nasopharyngeal carcinoma at Central General Hospital Prof. Dr. I.G.N.G Ngoerah Denpasar in 2021-2022 regarding the distribution of age range, gender, education, occupation, clinical stage, histological type, as well as the results of anamnesis. The research design is a descriptive study of 70 cases of NPC at Central General Hospital Prof. Dr. I.G.N.G Ngoerah Denpasar from 2021 to 2022. Samples were collected retrospectively from secondary data using a total sampling technique through a cross-sectional study, samples were obtained from medical record data and hospital management system of Central General Hospital Prof. Dr. I.G.N.G Ngoerah Denpasar. In this study, the most cases of NPC were found in the range of 51-60 years old (32.9%), male sex (65.7%), high school education status (48.6%), private employee employment (32.9%), anamnesis results of a lump in the neck (77.1%), stage IVA (40%), and with the histological type of NKSCC undifferentiated subtype (90%). Men have twice the risk of suffering from NPC compared to women, most cases have complained of a lump in the neck and other symptoms such as nasal congestion, tinnitus, headaches. The most common histological type found is the NKSCC undifferentiated subtype, which mostly occurs in advanced stages of an IVA.&#x0D; Keywords : Clinicopathology, NPC, Nasopharynx

Diagnostic value of apparent diffusion coefficient histograms using multiplexed sensitivity encoding diffusion-weighted imaging for distinguishing nasopharyngeal carcinoma from benign hyperplasia

The data of 115 patients with nasopharyngeal masses (78 males and 37 females) aged between 12 and 78 years at the Sun Yat-sen University Cancer Center from May 2022 to July 2023 were retrospectively reviewed, including 70 cases of nasopharyngeal carcinoma and 45 cases of benign hyperplasia. The mean, median, and percentiles (10th, 25th, 75th, and 90th) of the apparent diffusion coefficient (ADC) histogram derived from multiplexed sensitivity encoding diffusion-weighted imaging (MUSE-DWI) of the benign hyperplasia group were significantly higher than those of the nasopharyngeal carcinoma group (all P<0.05). Conversely, the kurtosis and skewness of benign hyperplasia group were significantly lower than those of the nasopharyngeal carcinoma group (both P<0.05). The area under receiver operating characteristic (ROC) curve of the combined ADC histogram parameters was 0.812 (95%CI: 0.732-0.892), and the sensitivity, specificity and accuracy were 92.86%, 57.78% and 79.13%, respectively. The current study indicates ADC histogram parameters derived MUSE-DWI exhibit significant discriminatory value between nasopharyngeal carcinoma and benign hyperplasia.

Quantitative Histomorphometrical Analysis in Distinguishing Non-Hodgkin Malignant Lymphoma, Large Cell Type with Nasopharyngeal Carcinoma

Background Non-Hodgkin’s Malignant Lymphomas (NHMLs) with large cell morphology have similar histopathological appearance with Nasopharyngeal Carcinoma, undifferentiated type therefore ancillary examination such as Immunohistochemistry (IHC) are required. Quantitative histomorphometrical analysis able to identify subtle detail. The aim of this study is to measure the accuracy of quantitative histomorphometrical analysis to distinguishing NHML, large cell type with Nasopharyngeal Carcinoma. Methods Up to 33 Hematoxylin and Eosin (HE) slides from NHML, large cell type, and 27 cases of Nasopharyngeal Carcinoma were photographed under 400 times magnification with a total of 7131 images. Background, nuclei, and extra-nuclear components between cells are segmented as mathematical objects. Objects’ properties were measured and represented as distribution factors (minimum, quartile 1, median, quartile 3, maximum, range, and interquartile range). Significant factors that can differentiate the study groups are measured with a fisher-exact statistical test. Models to predict NHML, large cell type from nasopharyngeal carcinoma were formulated with different numbers of factors. The HE diagnosis accuracy compared to IHC was measured Results A sum of 7131 with 3893 from NHMLs, large cell type, and 3238 images of nasopharyngeal carcinoma were collected. After features selection, up to 76 properties factors are selected. Models' accuracy are ranging from 72.67% with a single factor and up to 89.9% with the whole selected factors. Summary Models’ accuracy are higher (72.6-89.9%) compared to HE primary diagnosis (60%) in distinguishing NHML, large cell againts nasopharyngeal carcinoma. Quantitative histomorphometry can assist pathologist for early screening to distinguishing NHML, large cell type with Nasopharyngeal Carcinoma.

Serum 25-Hydroxyvitamin D Is Inversely Associated with Nasopharyngeal Carcinoma: A Hospital-Based Matched Case-Control Study in Malaysia.

Serum 25(OH)D deficiency consistently demonstrated molecular mechanisms through which chronic inflammation is associated with the risk of nasopharyngeal carcinoma (NPC). This study aimed to determine the association between serum 25(OH)D and NPC. A matched case-control study was conducted at two local hospitals. A total of 300 histologically confirmed NPC cases were matched with controls for age, gender, and ethnicity, and assessed for vitamin D status and other nutritional factors. Mean Vitamin D concentration was significantly lower among cases compared to controls (63.17 ± 19.15 nmol/L and 67.34 ± 23.06 nmol/L) (t = -2.41, p = 0.016). Multiple conditional logistic regression analysis indicated that higher levels of serum 25(OH)D were associated with reduced odds of NPC (AOR = 0.73, 95% CI = 0.57-0.94, p = 0.016) controlling for confounders including BMI, physical activity, smoking status, alcohol consumption, consumption of food high in vitamin D, salted fish consumption, and family history of NPC. There was a significant association between inadequate serum 25(OH)D status with accumulation of four risk factors and increased odds of getting NPC using polynomial regression analysis. Increased NPC odds ratios were observed after sequential accumulation of additional risk factors with the presence of inadequate serum 25(OH)D status (OR = 0.54, 95% CI = 0.27, 4.77, p = 0.322, OR = 1.04, 95% CI = 0.64, 1.72, p = 0.267, OR = 1.15, 95% CI = 0.73, 1.80, p = 0.067, OR = 1.93, 95% CI = 1.13, 3.31, p = 0.022, and OR = 5.55, 95% CI = 1.67, 10.3, p < 0.001 respectively). Future research in Malaysia should involve both prospective cohort studies and randomized controlled trials to confirm and further clarify the role of vitamin D in NPC outcomes.

Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes.

The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia and North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated with almost all of the undifferentiated NPC cases. Over the past three decades, radiation therapy and chemotherapy have formed the cornerstone of NPC treatment. However, recent advancements in immunotherapy have introduced a range of promising approaches for managing NPC. In light of these developments, it has become evident that a deeper understanding of the tumor microenvironment (TME) is crucial. The TME serves a dual function, acting as a promoter of tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression and enabling immune evasion. Consequently, a comprehensive comprehension of the TME and its intricate involvement in the initiation, progression, and metastasis of NPC is imperative for the development of effective anticancer drugs. Moreover, given the complexity of TME and the inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy and circumvent drug resistance. This review aims to provide an in-depth exploration of the TME within the context of EBV-induced NPC, with a particular emphasis on its pivotal role in regulating intercellular communication and shaping treatment responses. Additionally, the review offers a concise summary of drug resistance mechanisms and potential strategies for their reversal, specifically in relation to chemoradiation therapy, targeted therapy, and immunotherapy. Furthermore, recent advances in clinical trials pertaining to NPC are also discussed.

Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.

A case of nasopharyngeal carcinoma with involvement of nine cranial nerves including inner ear dysfunction as primary symptoms:

A case of nasopharyngeal carcinoma with involvement of nine cranial nerves including inner ear dysfunction as primary symptoms:

Enhanced MRI Radiomics Based Model for Predicting Recurrence or Metastasis of Nasopharyngeal Cancer (NC) Undergoing Concurrent Chemoradiotherapy: A Retrospective Study.

Nasopharyngeal Carcinoma (NC) refers to the malignant tumor that occurs at the top and side walls of the nasopharyngeal cavity. The NC incidence rate always dominates the first among the malignant tumors of the ear, nose and throat, and mainly occurs in Asia. NC cases are mainly concentrated in southern provinces in China, with about 4 million existing NC. With the pollution of environment and pickled diet, and the increase of life pressure, the domestic NC incidence rate has reached 4.5-6.5/100000 and is increasing year by year. It was reported that the known main causes of NC include hereditary factor, genetic mutations, and EB virus infection, common clinical symptoms of NC include nasal congestion, bloody mucus, etc. About 90% of NC is highly sensitive to radiotherapy which is regard as the preferred treatment method; However, for NC with lower differentiation, larger volume, and recurrence after treatment, surgical resection and local protons and heavy ions therapy are also indispensable means. According to reports, the subtle heterogeneity and diversity exists in some NC, with about 80% of NC undergone radiotherapy and about 25% experienced recurrence and death within five years after radiotherapy in China. Therefore, screening the NC population with suspected recurrence after concurrent chemoradiotherapy may improve survival rates in current clinical decision-making.

Ethno-geographic distribution and histopathological classification of nasopharyngeal carcinoma in a single center in Nepal.

Nasopharyngeal carcinoma (NPC) shows geographic and ethnic variation with specific etiopathogenesis. This study characterized the distribution of NPC patients stratified by ethnicity, geography, and histology in a tertiary-level cancer center in Nepal. A descriptive retrospective study was designed to analyze NPC cases from different regions among patients visiting the hospital from 2016 to 2021. Demographic and clinical information was obtained from medical records. Ethical approval was granted by the Nepal Health Research Council (NHRC). Data analyses and visualization were carried out with R software. During the six-year period, a total of 65 individuals were diagnosed with NPC, comprising 42 males and 23 females. Patient median age was 43 years (range 11-85 years). A bimodal age distribution of cases was observed with peaks in patients aged 30-39 years and 50-59 years. Of the NPC patients studied, 29 were from Koshi Province, with 7 cases from Ilam district and 6 cases from Morang district. There were 18 patients in Bagmati Province, and Kathmandu district had the highest number of cases within this region, with 8 patients. The highest proportion of cases were observed among patients of Janajati ethnicity (60%), including Rai, Limbu, and Sherpa people. Histologically, undifferentiated non-keratinizing NPC was the most commonly observed subtype, accounting for 43.1% of cases, followed by 20% differentiated non-keratinizing NPC and 4.6% keratinizing NPC across the entire sample population. The majority of patients (75.3%) were diagnosed at an advanced stage (stage III or IV) with none diagnosed at stage I. In our study, most cases of NPC occurred in patients from provinces in eastern Nepal (Koshi province), and of the Janajati ethnic community. The most common histological subtype was undifferentiated non-keratinizing carcinoma. Further epidemiological studies could address differences in prevalence and the challenge of late presentation of NPC patients in Nepal.

Diagnostic Performance of Node Reporting and Data System Magnetic Resonance Imaging Score in Detecting Metastatic Cervical Lymph Nodes of Nasopharyngeal Carcinoma.

The Node Reporting and Data System (Node-RADS) is a recently proposed classification system for the categorization of lymph nodes in radiological images. This study was conducted to retrospectively evaluate the diagnostic accuracy of the Node-RADS score for metastatic cervical lymph nodes on magnetic resonance imaging (MRI) of patients with nasopharyngeal carcinoma (NPC). We retrospectively analyzed cervical lymph nodes of NPC cases. Two radiologists independently evaluated each lymph node on the MRI scans using Node-RADS. Interobserver agreement between 2 radiologists for Node-RADS score assessment was evaluated by linear weighted kappa statistics. The correlation between metastasis and the Node-RADS score of each lymph node was analyzed using multivariate regression analysis. To investigate the diagnostic performance of the Node-RADS score, we further conducted receiver operating characteristic curve analysis. Correspondently, the sensitivity, specificity, positive predictive value, and negative predictive value of each different cutoff (>1, >2, >3, and >4) were computed. In all, 119 patients with NPC were assessed, including 203 cervical lymph nodes consisting of 140 (69%) of 203 metastatic and 63 (31%) of 203 benign. The kappa agreement between the 2 readers for the Node-RADS score was 0.863 (95% CI = 0.830-0.897, P < .001). Node-RADS score on MRI scan was shown to be an independent predictive factor of lymph node metastasis after multivariate regression analysis (odds ratio [OR] = 6.745, 95% CI = 3.964-11.474, P < .001). Node-RADS achieved an area under the curve (AUC) of 0.950 (95% CI = 0.921-0.979) in diagnosing metastatic lymph nodes. When Node-RADS >2 was identified as the best cutoff based on balanced values, the sensitivity and positive predictive value were 0.92 and 0.94, respectively. Our study suggests that the Node-RADS score has high accuracy in predicting NPC cervical lymph node metastasis. Nevertheless, this conclusion requires confirmation in a larger cohort of patients with NPC.

Distribution of regional lymph nodes metastasis in 870 cases of nasopharyngeal carcinoma and the suggestions for individualized elective prophylactic neck irradiation with intensity-modulated radiotherapy.

To explore the feasibility of individualized elective prophylactic neck irradiation (iEPNI) for optimizing current approach by investigating metastatic lymph nodes (LNs) distribution in nasopharyngeal carcinoma (NPC). Records of 870 NPC patients without distant metastasis in Hunan Cancer Hospital from January 2019 to December 2019 were reviewed. LNs' locations were identified based on the 2013 guidelines. The intra-regional lymphatic drainage (IRLD) areas included Station 1st (level VIIa and II), Station 2nd (level III and Va), and Station 3rd (level IV, Vb, and Vc). Other levels were categorized as extra-regional areas. Among the 870 patients, 94.5% cases exhibited LNs metastasis, including unilateral metastasis in 198 patients and bilateral metastasis in 624 patients. In the whole cohort, the most common involved IRLD areas were level IIb (87.1%), VIIa (80.0%), IIa (61.8%), Va (30.6%), IV (21.4%), Vb (8.9%), and Vc (1.1%). Besides, rates of LNs metastasis in Station 1st, 2nd, and 3rd were 94.3%, 61.1%, and 22.9%, respectively. Only four patients (4, 0.5%) revealed skipping metastasis among the three stations. Lymph node metastasis follows an organized pattern from Station 1st to 3rd with scarce skipping metastasis. A potential iEPNI strategy of prophylactic neck irradiation to the ipsilateral latter node-negative station appears promising in NPC patients. Further prospective investigations are warranted to validate the approach.

AI-Based Risk Score from Tumour-Infiltrating Lymphocyte Predicts Locoregional-Free Survival in Nasopharyngeal Carcinoma.

Locoregional recurrence of nasopharyngeal carcinoma (NPC) occurs in 10% to 50% of cases following primary treatment. However, the current main prognostic markers for NPC, both stage and plasma Epstein-Barr virus DNA, are not sensitive to locoregional recurrence. We gathered 385 whole-slide images (WSIs) from haematoxylin and eosin (H&E)-stained NPC sections (n = 367 cases), which were collected from Sun Yat-sen University Cancer Centre. We developed a deep learning algorithm to detect tumour nuclei and lymphocyte nuclei in WSIs, followed by density-based clustering to quantify the tumour-infiltrating lymphocytes (TILs) into 12 scores. The Random Survival Forest model was then trained on the TILs to generate risk score. Based on Kaplan-Meier analysis, the proposed methods were able to stratify low- and high-risk NPC cases in a validation set of locoregional recurrence with a statically significant result (p < 0.001). This finding was also found in distant metastasis-free survival (p < 0.001), progression-free survival (p < 0.001), and regional recurrence-free survival (p < 0.05). Furthermore, in both univariate analysis (HR: 1.58, CI: 1.13-2.19, p < 0.05) and multivariate analysis (HR:1.59, CI: 1.11-2.28, p < 0.05), we also found that our methods demonstrated a strong prognostic value for locoregional recurrence. The proposed novel digital markers could potentially be utilised to assist treatment decisions in cases of NPC.

Leukocyte immunoglobulin-like receptor A3 gene deletion in five Chinese populations and protective association with nasopharyngeal carcinoma.

Among the thirteen leukocyte Ig-like receptor (LILR) loci located at 19q13.4, LILRA3 is unique in that it encodes a soluble protein lacking the transmembrane and cytoplasmic domains, and a 6.7 kb deletion spanning the first seven exons has been detected in some human individuals. Presently, there is a lack of data about the distribution of LILRA3 gene deletion in more diverse ethnic groups. Also, no previous studies have investigated the correlation between copy number variation (CNV) of LILRA3 and nasopharyngeal carcinoma (NPC). In this study, five populations from China mainland: two Southern Han populations, Hunan (N = 1478) and Guandong (N = 107); one Southeastern Han population, Fujian (N = 439); and two Northern populations, Inner Mongolia Han (N = 104) and Mongol population from Inner Mongolia (N = 158) were investigated for CNV of LILRA3 using polymerase chain reaction-sequence-specific priming (PCR-SSP) method. LILRA3 variants were also examined in a cohort of NPC cases (N = 1142) in Hunan Han population. The five Chinese populations demonstrated northward increase in frequency of the deleted form of LILRA3 gene (LILRA3*Del) (all corrected p values < 0.05). Inter-population comparison also uncovered significant differentiation in the distribution of CNV of LILRA3 among modern human populations. LILRA3*Del was found to confer significantly reduced risk to NPC in Hunan Han population (at allelic level: OR = 0.79, 95% CI = 0.71-0.89, p < 0.0001; at genotype level: OR= 0.63, 95% CI = 0.51-0.79, p < 0.0001). No interaction was found between LILRA3 variants and HLA-A*02:07, HLA-A*11:01, HLA-B*13 and HLA-B*46:01 alleles in susceptibility to NPC. Our study constitutes the first demonstration of LILRA3 gene as a locus linked to NPC susceptibility in a southern Chinese population. Future independent studies in other populations are warranted to confirm the findings reported in this study.