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Cancer Epidemiology, Biomarkers &... Jun 2021The epidemiology of nasopharyngeal carcinoma (NPC) has long been a source of fascination due to the malignancy's striking geographic distribution, the involvement of the... (Review)
Review
BACKGROUND
The epidemiology of nasopharyngeal carcinoma (NPC) has long been a source of fascination due to the malignancy's striking geographic distribution, the involvement of the oncogenic Epstein-Barr virus (EBV), the unique association with intake of Chinese-style salt-preserved fish, and etiologic heterogeneity by histologic subtype.
METHODS
This review summarizes the current epidemiologic literature on NPC, highlighting recent results from our population-based case-control study in southern China.
RESULTS
Findings from our case-control study provide new insight into the epidemiology of NPC, including a diminished role of Chinese-style salt-preserved fish, a profound impact of EBV genetic sequence variation, modest positive associations with passive smoking and household air pollution, and possible effects of oral health and the oral microbiome. Recent findings from other studies include a protective association with infectious mononucleosis, suggesting a causal role of early EBV infection; familial risk conferred by shared genetic variation in the host antibody-mediated immune response to EBV infection; and an unclear association with occupational exposure to formaldehyde.
CONCLUSIONS
To shed further light on the interplay of environmental, genetic, and viral causes of NPC, large pooled studies must accumulate sufficient cases with detailed exposure data.
IMPACT
New epidemiologic findings have reshaped the causal model for NPC.
Topics: Animals; Case-Control Studies; China; Epstein-Barr Virus Infections; Feeding Behavior; Fishes; Food, Preserved; Geography; Herpesvirus 4, Human; Humans; Incidence; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Risk Factors; Sodium Chloride, Dietary
PubMed: 33849968
DOI: 10.1158/1055-9965.EPI-20-1702 -
The British Journal of Radiology Oct 2019The prevalence of nasopharyngeal carcinoma is characterized by an unbalanced distribution: the disease is particularly prevalent in East and Southeast Asia. In this... (Review)
Review
The prevalence of nasopharyngeal carcinoma is characterized by an unbalanced distribution: the disease is particularly prevalent in East and Southeast Asia. In this article, we review the evolution of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. With the increasing using of newer imaging methods, more advanced radiotherapy techniques and systemic chemotherapy, we also discuss newer clinical features that might affect staging. Finally, we propose the future direction of staging and potential prognostic factors that have a major influence on the treatment outcomes of this disease.
Topics: Cervical Vertebrae; Forecasting; Herpesvirus 4, Human; Humans; Lymph Nodes; Lymphatic Metastasis; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Parotid Neoplasms; Spinal Neoplasms
PubMed: 31298937
DOI: 10.1259/bjr.20190244 -
International Journal of Oncology Aug 2023Nasopharyngeal carcinoma (NPC) is an epithelial tumor located in the nasopharynx and is highly associated with Epstein‑Barr virus (EBV) infection. Although... (Review)
Review
Nasopharyngeal carcinoma (NPC) is an epithelial tumor located in the nasopharynx and is highly associated with Epstein‑Barr virus (EBV) infection. Although radiotherapy alone can cure ~90% of patients with early‑stage disease, >70% of patients with NPC have locoregionally advanced or metastatic disease at the first diagnosis due to the insidious and aggressive nature of NPC. After comprehensive radiochemotherapy, 20‑30% of patients with advanced NPC still fail treatment, mainly due to recurrence and/or metastasis (R/M). Conventional salvage treatments, such as radiotherapy, chemotherapy and surgery, are suboptimal and frequently accompanied by severe adverse effects and limited efficacy. In recent years, immunotherapy has emerged as a promising treatment modality for R/M NPC. An increasing number of clinical studies have investigated the safety and efficacy of immunotherapy for advanced NPC and have shown considerable progress. In the present review, the rationale for the use of immunotherapy to treat NPC was summarized and the current status, progress and challenges of NPC clinical research on different immunotherapeutic approaches were highlighted, including immune checkpoint inhibitors, vaccines, immunomodulators, adoptive cell transfer and EBV‑specific monoclonal antibodies. The comprehensive overview of immunotherapy in NPC may provide insight for clinical practice and future investigation.
Topics: Humans; Nasopharyngeal Carcinoma; Epstein-Barr Virus Infections; Nasopharyngeal Neoplasms; Herpesvirus 4, Human; Immunotherapy
PubMed: 37417358
DOI: 10.3892/ijo.2023.5545 -
Cancer Communications (London, England) Nov 2021Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop...
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.
Topics: China; Humans; Medical Oncology; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
PubMed: 34699681
DOI: 10.1002/cac2.12218 -
Nature Communications Feb 2023Although radiotherapy can promote antitumour immunity, the mechanisms underlying this phenomenon remain unclear. Here, we demonstrate that the expression of the E3...
Although radiotherapy can promote antitumour immunity, the mechanisms underlying this phenomenon remain unclear. Here, we demonstrate that the expression of the E3 ubiquitin ligase, tumour cell-intrinsic tripartite motif-containing 21 (TRIM21) in tumours, is inversely associated with the response to radiation and CD8 T cell-mediated antitumour immunity in nasopharyngeal carcinoma (NPC). Knockout of TRIM21 modulates the cGAS/STING cytosolic DNA sensing pathway, potentiates the antigen-presenting capacity of NPC cells, and activates cytotoxic T cell-mediated antitumour immunity in response to radiation. Mechanistically, TRIM21 promotes the degradation of the mitochondrial voltage-dependent anion-selective channel protein 2 (VDAC2) via K48-linked ubiquitination, which inhibits pore formation by VDAC2 oligomers for mitochondrial DNA (mtDNA) release, thereby inhibiting type-I interferon responses following radiation exposure. In patients with NPC, high TRIM21 expression was associated with poor prognosis and early tumour relapse after radiotherapy. Our findings reveal a critical role of TRIM21 in radiation-induced antitumour immunity, providing potential targets for improving the efficacy of radiotherapy in patients with NPC.
Topics: Humans; DNA, Mitochondrial; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Ubiquitination
PubMed: 36797289
DOI: 10.1038/s41467-023-36523-y -
JAMA Aug 2022Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy.... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial.
IMPORTANCE
Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT).
OBJECTIVE
To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022.
INTERVENTIONS
Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]).
MAIN OUTCOMES AND MEASURES
The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms).
RESULTS
Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation.
CONCLUSIONS AND RELEVANCE
Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02633202.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Quality of Life; Radiotherapy, Intensity-Modulated
PubMed: 35997729
DOI: 10.1001/jama.2022.13997 -
Current Treatment Options in Oncology Sep 2023Nasopharyngeal carcinoma (NPC) is distinct in its anatomic location and biology from other epithelial head and neck cancer (HNC). There are 3 WHO subtypes, which... (Review)
Review
Nasopharyngeal carcinoma (NPC) is distinct in its anatomic location and biology from other epithelial head and neck cancer (HNC). There are 3 WHO subtypes, which considers the presence of Epstein-Barr virus (EBV) and other histopathology features. Despite the survival benefit obtained from modern treatment modalities and techniques specifically in the local and locally advanced setting, a number of patients with this disease will recur and subsequently die of distant metastasis, locoregional relapse, or both. In the recurrent setting, the ideal therapy approach continues to be a topic of discussion and current recommendations are platinum-based combination chemotherapy. Phase III clinical trials which led to the approval of pembrolizumab or nivolumab for head and neck squamous cell carcinoma (HNSCC) specifically excluded NPC. No immune checkpoint inhibitor therapy, to date, has been approved by the FDA to treat NPC although the National Comprehensive Cancer Network (NCCN) recommendations do include use of these agents. Hence, this remains the major challenge for treatment options. Nasopharyngeal carcinoma is challenging as it is really 3 different diseases, and much research is required to determine best options and sequencing of those options. This article is going to address the data to date and discuss ongoing research in EBV + and EBV - inoperable recurrent/metastatic NPC patients.
Topics: Humans; Nasopharyngeal Carcinoma; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Neoplasm Recurrence, Local; Head and Neck Neoplasms; Nasopharyngeal Neoplasms
PubMed: 37318724
DOI: 10.1007/s11864-023-01101-3 -
Nature Communications Mar 2021The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this...
The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.
Topics: B-Lymphocytes; Fibroblasts; Gene Expression Regulation, Neoplastic; Humans; Myeloid Cells; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Phenotype; Prognosis; Progression-Free Survival; Sequence Analysis, RNA; Stromal Cells; T-Lymphocytes; Tumor Microenvironment
PubMed: 33750785
DOI: 10.1038/s41467-021-21795-z -
Annals of Oncology : Official Journal... Apr 2021
Topics: Follow-Up Studies; Humans; Medical Oncology; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Staging; Societies, Medical
PubMed: 33358989
DOI: 10.1016/j.annonc.2020.12.007 -
The British Journal of Radiology Oct 2019
Topics: Age Factors; Artificial Intelligence; Big Data; Chemoradiotherapy; Fluorodeoxyglucose F18; Geography, Medical; Humans; Nasopharyngeal Carcinoma; Organs at Risk; Positron-Emission Tomography; Radiation Exposure; Radiopharmaceuticals; Radiotherapy Dosage; Software
PubMed: 31526301
DOI: 10.1259/bjr.20199004