The Epstein-Barr Virus (EBV) DNA Test as a Predictor of The Course of Nasopharyngeal Cancer
Abstract
Background: Nasopharyngeal cancer (NPC) incidence has been largely found in Southern China and Southeast Asia and was associated with Epstein-Barr Virus (EBV). Some advanced-stage NPC may still rise to local recurrence or distant metastasis and higher plasma EBV DNA was still found in locally advanced nasopharyngeal cancer (LA-NPC) at 1 month or even 3 years after completing radiotherapy (RT). Even though EBV DNA has not been widely used in clinical practice, it could be an important value for determining treatment outcomes and risk of disease relapse.
Methods: This review article gathered studies from the PubMed database from 2021 to 2022. Using various searching terms 434 articles were found and were narrowed down to 7 according to the inclusion criteria. The individual review was made for each article and endpoints such as overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and local recurrence-free survival (LRFS) were drawn.
Results: Overall subjects for these studies ranged up to 2,354 LA-NPC patients (median of 1,073 subjects). All studies observed the pre-treatment and post-treatment EBV DNA and only two studies observed post-neoadjuvant chemotherapy (post-NAc). EBV DNA currently is the most reliable biomarker available for clinical purposes and its versatility can be useful, especially to value prognosis and to determine the course of treatment.
Conclusions: Apart from survival outcomes, pre-treatment EBV DNA is considered good for predicting the overall prognosis. Meanwhile, post-induction chemotherapy (post-IC) or post-NAc EBV DNA is suitable for adjuvant therapy indicators, especially in LA-NPC. Even though the cut-off value for the tests was still varied across laboratories (ranging from 1,500 to 4,000), post-NAc and post-treatment might have some benefit to help predict any locoregional recurrence and distant metastasis, considering pre-treatment will not change the therapeutic course completely.
Keywords
DOI: 10.33371/ijoc.v18i2.1120
Article Metrics
Abstract View: 253, 
PDF Download: 105
References
Au KH, Ngan RKC, Ng AWY, Poon DMC. Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity modulated radiotherapy (IMRT) in Hong Kong: A report of 3328 patients (HKNPCSG 1301 study). Oral Oncol. 2018 Feb;77:16–21.
Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 2023 Aug 20;41(24):3965-3972.
Chen H, Ji M, Zong JF, Ko JMY. Conventional and Novel Diagnostic Biomarkers and Approaches for Detection of Nasopharyngeal Carcinoma. In: Nasopharyngeal Carcinoma [Internet]. Elsevier; 2019 [cited 2023 Oct 14]. p. 129–53. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780128149362000079
Lee VH, Kwong DL, Leung TW, et al. Prognostication of serial post-intensity-modulated radiation therapy undetectable plasma EBV DNA for nasopharyngeal carcinoma. Oncotarget. 2017 Jan 17;8(3):5292-5308.
Leung SF, Chan KC, Ma BB, et al. Plasma Epstein-Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma. Ann Oncol. 2014 Jun;25(6):1204-8.
Gondhowiardjo SA, Handoko, Adham M, et al. Epstein–Barr Virus (EBV) Viral Load in Tumor Cells Did Not Predict Tumor Extensiveness in Nasopharyngeal Cancer. Microbiol Res. 2021 Mar 5;12(1):150–6.
Lo YM, Chan LY, Lo KW, et al. Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res. 1999 Mar 15;59(6):1188–91.
Hui EP, Ma BB, Chan KC, et al. Clinical utility of plasma Epstein-Barr virus DNA and ERCC1 single nucleotide polymorphism in nasopharyngeal carcinoma. Cancer. 2015 Aug 15;121(16):2720-9.
Wang WY, Twu CW, Chen HH, et al. Plasma EBV DNA clearance rate as a novel prognostic marker for metastatic/recurrent nasopharyngeal carcinoma. Clin Cancer Res. 2010 Feb 1;16(3):1016-24.
Tan R, Phua SKA, Soong YL, et al. Clinical utility of Epstein-Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma. Cancer Commun (Lond). 2020 Nov;40(11):564-585.
NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancer [Internet]. National Comprehensive Cancer Network; [cited 2023 Sep 13]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
Bossi P, Chan A, Licitra L, Trama A. Nasopharyngeal carcinoma: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up [Internet]. European Society of Medical Oncology; 2022 [cited 2023 Sep 13]. Available from: https://www.esmo.org/guidelines/guidelines-by-topic/head-and-neck-cancers/nasopharyngeal-carcinoma
Li YQ, Khin NS, Chua MLK. The evolution of Epstein-Barr virus detection in nasopharyngeal carcinoma. Cancer Biol Med. 2018 Feb;15(1):1-5.
Chan KC. Plasma Epstein-Barr virus DNA as a biomarker for nasopharyngeal carcinoma. Chin J Cancer. 2014 Dec;33(12):598-603.
Liu Y, Fang Z, Liu L, Yang S, Zhang L. Detection of Epstein-Barr virus DNA in serum or plasma for nasopharyngeal cancer: a meta-analysis. Genet Test Mol Biomarkers. 2011 Jul-Aug;15(7-8):495-502.
Liu W, Chen G, Gong X, et al. The diagnostic value of EBV-DNA and EBV-related antibodies detection for nasopharyngeal carcinoma: a meta-analysis. Cancer Cell Int. 2021 Dec;21(1):164.
Li WZ, Wu HJ, Lv SH, et al. Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus–Related Nasopharyngeal Carcinoma. JAMA Netw Open. 2021 Sep 23;4(9):e2124721.
El Alami I, Gihbid A, Charoute H, et al. Prognostic value of Epstein-Barr virus DNA load in nasopharyngeal carcinoma: a meta-analysis. Pan Afr Med J. 2022;41.
Prayongrat A, Chakkabat C, Kannarunimit D, et al. Prevalence and significance of plasma Epstein-Barr Virus DNA level in nasopharyngeal carcinoma. J Radiat Res. 2017 Jul 1;58(4):509-516.
Zong J, Ji P, Lin C, et al. Plasma Epstein-Barr viral DNA load after completion of two cycles of induction chemotherapy predicts outcomes for patients with advanced-stage nasopharyngeal carcinoma. Oral Oncol. 2022 Aug;131:105972.
Lv J, Wu C, Li J, et al. Improving on-treatment risk stratification of cancer patients with refined response classification and integration of circulating tumor DNA kinetics. BMC Med. 2022 Aug 23;20(1):268.
Lin C, Lin K, Zhang B, et al. Plasma Epstein-Barr Virus MicroRNA BART8-3p as a Diagnostic and Prognostic Biomarker in Nasopharyngeal Carcinoma. Oncologist. 2022 Apr 5;27(4):e340–9.
Hui EP, Li WF, Ma BB, et al. Integrating postradiotherapy plasma Epstein-Barr virus DNA and TNM stage for risk stratification of nasopharyngeal carcinoma to adjuvant therapy. Ann Oncol. 2020 Jun;31(6):769-779.
Liu LT, Guo SS, Li H, et al. Percent change in apparent diffusion coefficient and plasma EBV DNA after induction chemotherapy identifies distinct prognostic response phenotypes in advanced nasopharyngeal carcinoma. BMC Cancer. 2021 Dec;21(1):1320.
Adham M, Greijer AE, Verkuijlen SA, et al. Epstein-Barr virus DNA load in nasopharyngeal brushings and whole blood in nasopharyngeal carcinoma patients before and after treatment. Clin Cancer Res. 2013 Apr 15;19(8):2175-86.
Stevens SJC, Verkuijlen SAWM, Hariwiyanto B, et al. Diagnostic Value of Measuring Epstein-Barr Virus (EBV) DNA Load and Carcinoma-Specific Viral mRNA in Relation to Anti-EBV Immunoglobulin A (IgA) and IgG Antibody Levels in Blood of Nasopharyngeal Carcinoma Patients from Indonesia. J Clin Microbiol. 2005 Jul;43(7):3066–73.
Chan ATC, Hui EP, Ngan RKC, et al. Analysis of Plasma Epstein-Barr Virus DNA in Nasopharyngeal Cancer After Chemoradiation to Identify High-Risk Patients for Adjuvant Chemotherapy: A Randomized Controlled Trial. J Clin Oncol. 2018 Jul 10:JCO2018777847.
Zhang Y, Chen L, Hu GQ, et al. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124–35.
Ma J, Tang LL, Guo R, Zhang N. Radiotherapy alone versus concurrent chemoradiotherapy in intermediate risk nasopharyngeal carcinoma: A multicentre, open-label, noninferiority, randomised phase III trial. J Clin Oncol. 2022;40(16)suppl.
Kim KY, Le QT, Yom SS, et al. Current State of PCR-Based Epstein-Barr Virus DNA Testing for Nasopharyngeal Cancer. J Natl Cancer Inst. 2017 Apr 1;109(4):djx007
Miller JA, Pinsky BA, Le QT. Prognostic value of Epstein-Barr virus biomarkers for nasopharyngeal carcinoma staging and post-treatment surveillance. Ann Nasopharynx Cancer. 2022 Mar;6:2–2.
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Email this article 
