Dataset Information

Current State of PCR-Based Epstein-Barr Virus DNA Testing for Nasopharyngeal Cancer.

ABSTRACT: Clinical studies have shown plasma Epstein-Barr virus (EBV) DNA level to be an independent prognostic biomarker for nasopharyngeal carcinoma (NPC). However, the proportion of NPC patients whose tumors are associated with EBV vary with geographic location, and there are a variety of assays for plasma EBV. To develop the level of evidence needed to demonstrate the clinical utility of plasma EBV DNA detection for NPC patients and encourage widespread adoption of this biomarker test in clinical laboratories, validated harmonized assays are needed. In 2015, the National Cancer Institute (NCI) convened a Workshop on Harmonization of EBV Testing for Nasopharyngeal Cancer, where experts in head and neck oncology and laboratory medicine addressed the limitations of currently available polymerase chain reaction-based EBV DNA quantitation assays and discussed strategies for advancing the development of harmonized EBV DNA assays and their appropriate clinical use. This article presents the key recommendations to direct future efforts in assay harmonization and validation.

SUBMITTER: Kim KY

PROVIDER: S-EPMC6279258 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Current State of PCR-Based Epstein-Barr Virus DNA Testing for Nasopharyngeal Cancer.

Kim Kelly Y KY Le Quynh-Thu QT Yom Sue S SS Pinsky Benjamin A BA Bratman Scott V SV Ng Raymond H W RH El Mubarak Haja S HS Chan K C Allen KC Sander Miriam M Conley Barbara A BA

Journal of the National Cancer Institute 20170401 4

Clinical studies have shown plasma Epstein-Barr virus (EBV) DNA level to be an independent prognostic biomarker for nasopharyngeal carcinoma (NPC). However, the proportion of NPC patients whose tumors are associated with EBV vary with geographic location, and there are a variety of assays for plasma EBV. To develop the level of evidence needed to demonstrate the clinical utility of plasma EBV DNA detection for NPC patients and encourage widespread adoption of this biomarker test in clinical labo ...[more]

PMID: 28376165

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Project description:Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) infection in regions in which it is endemic, including Southern China and Southeast Asia. The high mortality rates of NPC patients with advanced and recurrent disease highlight the urgent need for effective treatments. While recent genomic studies have revealed few druggable targets, the unique interaction between the EBV infection and host cells in NPC strongly implies that targeting EBV may be an efficient approach to cure this virus-associated cancer. Key features of EBV-associated NPC are the persistence of an episomal EBV genome and the requirement for multiple viral latent gene products to enable malignant transformation. Many translational studies have been conducted to exploit these unique features to develop pharmaceutical agents and therapeutic strategies that target EBV latent proteins and induce lytic reactivation in NPC. In particular, inhibitors of the EBV latent protein EBNA1 have been intensively explored, because of this protein's essential roles in maintaining EBV latency and viral genome replication in NPC cells. In addition, recent advances in chemical bioengineering are driving the development of therapeutic agents targeting the critical functional regions of EBNA1. Promising therapeutic effects of the resulting EBNA1-specific inhibitors have been shown in EBV-positive NPC tumors. The efficacy of multiple classes of EBV lytic inducers for NPC cytolytic therapy has also been long investigated. However, the lytic-induction efficiency of these compounds varies among different EBV-positive NPC models in a cell-context-dependent manner. In each tumor, NPC cells can evolve and acquire somatic changes to maintain EBV latency during cancer progression. Unfortunately, the poor understanding of the cellular mechanisms regulating EBV latency-to-lytic switching in NPC cells limits the clinical application of EBV cytolytic treatment. In this review, we discuss the potential approaches for improvement of the above-mentioned EBV-targeting strategies.

Project description:ImportanceNonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups.ObjectiveTo refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status.Design, setting, and participantsThis multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021.ExposuresCurative intensity-modulated radiotherapy with or without platinum-based chemotherapy.Main outcomes and measuresThe primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology.ResultsA total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA-positive patients but not in those with EBV DNA-negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA-negative T1-3N1 cancers), RPA-II (EBV DNA-positive T1-3N1-2 or EBV DNA-negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA-positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated.Conclusions and relevanceAn RPA-based staging system for EBV-related NPC cases was associated with improved outcomes. This staging system may facilitate prognostic stratification and clinical trial designs.

Dataset Information

Current State of PCR-Based Epstein-Barr Virus DNA Testing for Nasopharyngeal Cancer.

Publications

Current State of PCR-Based Epstein-Barr Virus DNA Testing for Nasopharyngeal Cancer.

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