Epstein—Barr virus-associated solid malignancies

Sergeeva N.S.; Marshutina N.V.; Solokhina M.P.; Alentov I.I.; Poljakov A.P.; Gevorkov A.R.; Pirogov S.S.; Khomyakov V.M.; Kaprin A.D.

doi:https://doi.org/10.17116/onkolog2018705180

Close metadata

Recommended articles:

Features of the clinical course of reccurent diseases lymphoepithelial ring of the pharynx in children. Russian Bulletin of Otorhinolaryngology. 2025;(4):27-32

Abstract:

The review provides information on Epstein—Barr virus (EBV) and describes the functions of its main marker molecules: six types of EBV nuclear antigen (EBNA), nuclear BARF1 protein, members of the family of latent membrane proteins (LMP) (LMP-1, LMP-2A, and LMP-2B), EBV-encoded small RNAs (EBERs), microRNA from the BART and BHRF1 regions of the virus genome. The review also gives the data available in the literature on the frequency of clinico-morphological and molecular biological characteristics of EBV-associated gastric cancer (EBV+GC) and nasopharyngeal cancer (EBV+NPC), as well as on the role of EBV in the etiopathogenesis of these tumors. It considers methods for specifying the diagnosis of EBV-associated diseases on the basis of molecular genetic markers of the virus and for determining a number of antibodies to viral proteins. Whether it is expedient to determine circulating EBV DNA in the monitoring of patients with EBV+NPC for the evaluation of the efficiency of treatment and preclinical detection of relapses is discussed.

Keywords:

Epstein—Barr virus

forms of latent virus carriage

EBV-associated gastric cancer

EBV-associated nasopharyngeal cancer

Authors:

Sergeeva N.S.

Russian University of Peoples' Friendship

Marshutina N.V.

FGBU "Moskovskiĭ nauchno-issledovatel'skiĭ onkologicheskiĭ institut im. P.A. Gertsena" Minzdravsotsrazvitiia Rossii

Solokhina M.P.

FGBU "Moskovskiĭ nauchno-issledovatel'skiĭ onkologicheskiĭ institut im. P.A. Gertsena" Minzdravsotsrazvitiia Rossii

Alentov I.I.

FGBU "Moskovskiĭ nauchno-issledovatel'skiĭ onkologicheskiĭ institut im. P.A. Gertsena" Minzdrava Rossii

Poljakov A.P.

FGBU «Moskovskiĭ nauchno-issledovatelskiĭ onkologicheskiĭ institut im. P.A. Gertsena» Minzdrava Rossii

Gevorkov A.R.

P.A. Herzen Moscow Oncology Research Institute, Ministry of Health of Russia, Moscow, Russian Federation

Pirogov S.S.

P.A. Gertsen Moscow Research Oncological Institute affiliated with the National Medical Research Centre of Radiology, Ministry of Health of the Russia, Russia

Khomyakov V.M.

Military medical unit, Golytsino, Moscow region, Russia, P.A. Gertsen Moscow scientific and research oncologic institute, National medical research center of radiology trust, Moscow, Russia

SPIN RSCI: 4081-7701
Scopus AuthorID: 56740937000
ORCID: 0000-0001-8301-4528

Kaprin A.D.

FGBU "Moskovskiĭ nauchno-issledovatel'skiĭ onkologicheskiĭ institut im. P.A. Gertsena" Minzdrava Rossii

SPIN RSCI: 1759-8101
Scopus AuthorID: 6602709853
ResearcherID: K-1445-2014
ORCID: 0000-0001-8784-8415

Close metadata

References:

Zaridze D, ed. Kantserogenez. Moscow: Meditsina; 2004. (In Russ.)
Epstein MA, Achong BG, Barr VM. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet. 1964;283(7335):702-703. https://doi.org/10.1016/s0140-6736(64)91524-7
Crawford DH. Biology and disease associations of Epstein—Barr virus. Philos Trans R Soc Lond B Biol Sci. 2001;356(1408):461-473. https://doi.org/10.1098/rstb.2000.0783
Williams H, Crawford DH. Epstein—Barr virus: the impact of scientific advances on clinical practice. Blood. 2006;107(3):862-869. https://doi.org/10.1182/blood-2005-07-2702
Hudnall SD, Chen T, Allison P, Tyring SK, Heath A. Herpesvirus prevalence and viral load in healthy blood donors by quantitative real-time polymerase chain reaction. Transfusion. 2008;48(6):1180-1187. https://doi.org/10.1111/j.1537-2995.2008.01685.x
Young LS, Rickinson AB. Epstein—Barr virus: 40 years on. Nat Rev Cancer. 2004;4(10):757-768. https://doi.org/10.1038/nrc1452
Steven N. Infectious mononucleosis. EBV Reports. 2006;3:91-95.
Sculley TB, Apolloni A, Hurren L, Moss DJ, Cooper DA. Coinfection with A- and B-type Epstein—Barr virus in human immunodeficiency virus-positive subjects. J Infect Dis. 1990;162(3):643-648. https://doi.org/10.1093/infdis/162.3.642
Gratama JW, Ernberg I. Molecular epidemiology of Epstein—Barr virus infection. Adv Cancer Res. 1995;67:197-255.
Krasil’nikov MA, Zborovskaya IB, eds. Molekulyarnyi kantserogenez. Moscow: ABV-press; 2016. (In Russ.)
Fingeroth JD, Weis JJ, Tedder TF, Strominger JL, Biro PA, Fearon DT. Epstein—Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci. USA. 1984;81(14):4510-4514. https://doi.org/10.1073/pnas.81.14.4510
Young LS, Arrand JR, Murray PG. EBV gene expression and regulation. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K, eds. Human herpesviruses: biology, therapy, and immunoprophylaxis. Cambridge, UK: Cambridge University Press; 2007;461-489.
Williams H, Macsween K, McAulay K, Higgins C, Harrison N, Swerdlow A, et al. Analysis of immune activation and clinical events in acute infectious mononucleosis. J Infect Dis. 2004;190(1):63-71. https://doi.org/10.1086/421276
Näher H, Gissmann L, Freese UK, Petzoldt D, Helfrich S. Subclinical Epstein—Barr virus infection of both the male and female genital tract: indication for sexual transmission. J Invest Dermatol. 1992;98(5):791-793. https://doi.org/10.1111/1523-71747.ep12499958
Tsang CM, Tsao SW. The role of Epstein—Barr virus infection in the pathogenesis of nasopharyngeal carcinoma. Virol Sin. 2015;30(2):107-121. https://doi.org/10.1007/s12250-015-3592-5
De Paschale M, Clerici P. Serological diagnosis of Epstein—Barr virus infection: Problems and solutions. World J Virol. 2012;1(1):31-43. https://doi.org/10.5501/wjv.v1.i1.31
Schillinger M, Kampmann M, Henninger K, Murray G, Hanselmann I, Bauer G. Variability of humoral immune response to acute Epstein—Barr virus (EBV) infection: evaluation of the significance of serological markers. Med Microbiol Lett. 1993;2:296-303.
Bauer G. Simplicity through complexity: immunoblot with recombinant antigens as the new gold standard in Epstein—Barr virus serology. Clin Lab. 2001;47(5-6):223-30.
Glaser SL, Lin RJ, Stewart SL, Ambinder RF, Jarrett RF, Brousset P, et al. Epstein—Barr virus-associated Hodgkin’s disease: epidemiologic characteristics in international data. Int J Cancer. 1997;70(4):375-382.
Molyneux EM, Rochford R, Griffin B, Newton R, Jackson G, Menon G, et al. Burkitt’s lymphoma. Lancet. 2012;379(9822):1234-1244. https://doi.org/10.1016/S0140-6736(11)61177-X
Cesarman E. Pathology of lymphoma in HIV. Curr Opin Oncol. 2013;25(5):487-494. https://doi.org/10.1097/01.cco.0000432525.70099.a4
Oyama T, Ichimura K, Suzuki R, Suzumiya J, Ohshima K, Yatabe Y, et al. Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol. 2003;27(1):16-26. https://doi.org/10.1097/00000478-200301000-00003
Goodlad JR. Epstein—Barr virus-associated lymphoproliferative disorders in the skin. Surg Pathol Clin. 2017;10(2):429-453. https://doi.org/10.1016/j.path.2017.01.001
Rowe M, Fitzsimmons L, Bell AI. Epstein—Barr virus and Burkitt lymphoma. Chin J Cancer. 2014;33(12):609-619. https://doi.org/10.5732/cjc.014.10190
Chen JN, Dan He, Tang F, Shao C. Epstein—Barr virus-associated gastric carcinoma. A newly defined entity. J Clin Gastroenterol. 2012;46(4):262-271. https://doi.org/10.1097/MCG.0b013e318249c4b8
Mansouri S, Pan Q, Blencowe BJ, Claycomb JM, Frappier L. Epstein—Barr virus EBNA1 protein regulates viral latency through effects on let-7 microRNA and dicer. J Virol. 2014;88(19):11166-11177. https://doi.org/10.1128/JVI.01785-14
Alfieri C, Birkenbach M, Kieff E. Early events in Epstein—Barr virus infection of human B lymphocytes. Virology. 1991;181(2):595-608. https://doi.org/10.1016/0042-6822(91)90893-G
Hoebe EK, Le Large TYS, Greijer AE, Middeldorp JM. BamHI-A rightward frame 1, an Epstein—Barr virus-encoded oncogene and immune modulator. Rev Med Virol. 2013;23(6):367-383. https://doi.org/10.1002/rmv.1758
Takada K. Role of EBER and BARF1 in nasopharyngeal carcinoma (NPC) tumorigenesis. Semin Cancer Biol. 2012;22(2):162-165. https://doi.org/10.1016/j.semcancer.2011.12.007
Kim DH, Chang MS, Yoon CJ, Middeldorp JM, Martinez OM, Byeon SJ, et al. Epstein—Barr virus BARF1-induced NFκB/miR-146a/SMAD4 alterations in stomach cancer cells. Oncotarget. 2016;7(50):82213-82227. https://doi.org/10.18632/oncotarget.10511
Mancao C, Altmann M, Jungnickel B, Hammerschmidt W. Rescue of ‘crippled’ germinal center B cells from apoptosis by Epstein—Barr virus. Blood. 2005;106(13):4339-4344. https://doi.org/10.1182/blood-2005-06-2341
Liu HP, Chen CC, Wu CC, Huang YC, Liu SC, Liang Y, et al. Epstein—Barr virus-encoded LMP1 interacts with FGD4 to activate Cdc42 and thereby promote migration of nasopharyngeal carcinoma cells. PLoS Pathog. 2012;8(5):e1002690. https://doi.org/10.1371/journal.ppat.1002690
Lo AK, Lo KW, Ko CW, Young LS, Dawson CW. Inhibition of the LKB1-AMPK pathway by the Epstein—Barr virus-encoded LMP1 promotes proliferation and transformation of human nasopharyngeal epithelial cells. J Pathol. 2013;230(3):336-346. https://doi.org/10.1002/path.4201
Fukuda M, Kawaguchi Y. Role of the immunoreceptor tyrosine-based activation motif of latent membrane protein 2A (LMP2A) in Epstein—Barr virus LMP2A-induced cell transformation. J Virol. 2014;88(9):5189-5194. https://doi.org/10.1128/JVI.03714-13
Allen MD, Young LS, Dawson CW. The Epstein—Barr virus-encoded LMP2A and LMP2B proteins promote epithelial cell spreading and motility. J Virol. 2005;79(3):1789-1802. https://doi.org/10.1128/JVI.79.3.1789-1802.2005
Rechsteiner MP, Berger C, Zauner L, Sigrist JA, Weber M, Longnecker R, et al. Latent membrane protein 2B regulates susceptibility to induction of lytic Epstein—Barr virus infection. J Virol. 2008;82(4):1739-1747. https://doi.org/10.1128/JVI.01723-07
Iwakiri D. Epstein—Barr virus-encoded RNAs: key molecules in viral pathogenesis. Cancers (Basel). 2014;6(4):1615-1630. https://doi.org/10.3390/cancers6031615
Ruf IK, Rhyne PW, Yang C, Cleveland JL, Sample JT. Epstein—Barr virus small RNAs potentiate tumorigenicity of Burkitt lymphoma cells independently of an effect on apoptosis. J Virol. 2000;74(21):10223-10228. https://doi.org/10.1128/jvi.74.21.10223-10228.2000
Murphy G, Pfeiffer R, Camargo MC, Rabkin CS. Metaanalysis shows that prevalence of Epstein—Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology. 2009;137:824-833. https://doi.org/10.1053/j.gastro.2009.05.001
Akiba S, Koriyama C, Herrera-Goepfert R, Eizuru Y. Epstein—Barr virus associated gastric carcinoma: epidemiological and clinicopathological features. Cancer Sci. 2008;99(2):195-201. https://doi.org/10.1111/j.1349-7006.2007.00674.x
Geddert H, Zur Hausen A, Gabbert HE, Sarbia M. EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1. Anal Cell Pathol. 2010;33:143-149. https://doi.org/10.3233/ACP-CLO-2010-0540
zur Hausen A, Brink AA, Craanen ME, Middeldorp JM, Meijer CJ, van den Brule AJ. Unique transcription pattern of Epstein—Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene. Cancer Res. 2000;60(10):2745-2748.
Chen JN, Jiang Y, Li HG, Ding Y, Fan X, Xiao L, et al. Epstein—Barr virus genomepolymorphisms of Epstein—Barr virus-associated gastric carcinoma in gastric remnant carcinoma in Guangzhou, southern China, an endemic area of nasopharyngeal carcinoma. Virus Res. 2011;160(1-2):191-199. https://doi.org/10.1016/j.virusres.2011.06.011
Strong MJ, Xu G, Coco J, Baribault C, Vinay DS, Lacey MR, et al. Differences in gastric carcinoma microenvironment stratify according to EBV infection intensity: implications for possible immune adjuvant therapy. PLoS Pathog. 2013;9(5):e1003341. https://doi.org/10.1371/journal.ppat.1003341
Matsusaka K, Kaneda A, Nagae G, Ushiku T, Kikuchi Y, Hino R, et al. Classification of Epstein—Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes. Cancer Res. 2011;71:7187-7197. https://doi.org/10.1158/0008-5472.CAN-11-1349
Iwakiri D, Eizuru Y, Tokunaga M, Takada K. Autocrine growth of Epstein—Barr virus-positive gastric carcinoma cells mediated by an Epstein—Barr virus-encoded small RNA. Cancer Res. 2003;63(21):7062-7067.
Wang Q, Tsao SW, Ooka T, Nicholls JM, Cheung HW, Fu S, et al. Anti-apoptotic role of BARF1 in gastric cancer cells. Cancer Lett. 2006;238(1):90-103. https://doi.org/10.1016/j.canlet.2005.06.023
Fukuda M, Longnecker R. Latent membrane protein 2A inhibits transforming growth factor-beta 1-induced apoptosis through the phosphatidylinositol 3-kinase/Akt pathway. J Virol. 2004;78(4):1697-1705. https://doi.org/10.1128/jvi.78.4.1697-1705.2004
Hino R, Uozaki H, Murakami N, Ushiku T, Shinozaki A, Ishikawa S, et al. Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res. 2009;69(7):2766-2774. https://doi.org/10.1158/0008-5472.CAN-08-3070
Zhu JY, Pfuhl T, Motsch N, Barth S, Nicholls J, Grässer F, et al. Identification of novel Epstein-Barr virus microRNA genes from nasopharyngeal carcinomas. J Virol. 2009;83(7):3333-3341. https://doi.org/10.1128/JVI.01689-08
Wee JT, Ha TC, Loong SL, Qian CN. Is nasopharyngeal cancer really a «Cantonese cancer»? Chin J Cancer. 2010;29(5):517-526.
Kaprin AD, Starinskii VV, Petrova GV, eds. Malignant neoplasms in Russia in 2015 (morbidity and mortality) (Zlokachestvennye novoobrazovaniya v Rossii v 2015 (zabolevaemost’ i smertnost’). Moscow: MNIOI im. P.A. Gertsena — filial FGBU NMIRTs Minzdrava Rossii; 2017. (In Russ.)
Micheau C, Rilke F, Pilotti S. Proposal for a new histopathological classification of the carcinomas of the nasopharynx. Tumori. 1978;64(5):513-518.
Tsao S, Tsang C, To K, Lo K. The role of Epstein—Barr virus in epithelial malignancies. J Pathol. 2014;235(2):323-333. https://doi.org/10.1002/path.4448
Raab-Traub N. Epstein—Barr virus in the pathogenesis of NPC. Semin Cancer Biol. 2002;12(6):431-441. https://doi.org/10.1016/s1044579x0200086x
Thompson LD. Update on nasopharyngeal carcinoma. Head Neck Pathol. 2007;1(1):81-86. https://doi.org/10.1007/s12105-007-0012-7
Gu AD, Lu LX, Xie YB, Chen LZ, Feng QS, Kang T, et al. Clinical values of multiple Epstein—Barr virus (EBV) serological biomarkers detected by xMAP technology. J Transl Med. 2009;7:73. https://doi.org/10.1186/1479-5876-7-73
Moody CA, Scott RS, Su T, Sixbey JW. Length of Epstein—Barr virus termini as a determinant of epithelial cell clonal emergence. J Virol. 2003;77(15):8555-8561. https://doi.org/10.1128/jvi.77.15.8555-8561.2003
Hu LF, Qiu QH, Fu SM, Sun D, Magnusson K, He B, et al. A genome-wide scan suggests a susceptibility locus on 5p 13 for nasopharyngeal carcinoma. Eur J Hum Genet. 2008;16(3):343-349. https://doi.org/10.1038/sj.ejhg.5201951
Lo KW, Huang DP. Genetic and epigenetic changes in nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12(6):451-462. https://doi.org/10.1016/s1044579x02000883
Tulalamba W, Janvilisri T. Nasopharyngeal carcinoma signaling pathway: an update on molecular biomarkers. Int J Cell Biol. 2012;2012:594681. https://doi.org/10.1155/2012/594681
Zeng Z, Huang H, Huang L, Sun M, Yan Q, Song Y, et al. Regulation network and expression profiles of Epstein—Barr virus-encoded microRNAs and their potential target host genes in nasopharyn-geal carcinomas. Sci China Life Sci. 2014;57(3):315-326. https://doi.org/10.1007/s11427-013-4577-y
Zhang J, Huang T, Zhou Y, Cheng ASL, Yu J, To KF, et al. The oncogenic role of Epstein—Barr virus‐encoded microRNAs in Epstein—Barr virus‐associated gastric carcinoma. J Cell Mol Med. 2018;22(1):38-45. https://doi.org/10.1111/jcmm.13354
Verhoeven RJA, Tong S, Zhang G, Zong J, Chen Y, Jin D-Y, et al. NF-B signaling regulates expression of Epstein—Barr virus BART microRNAs and long noncoding RNAs in nasopharyngeal carcinoma. J Virol. 2016;90(14):6475-6488. https://doi.org/10.1128/JVI.00613-16
Gourzones C, Gelin A, Bombik I, Klibi J, Vérillaud B, Guigay J, et al. Extra‐cellular release and blood diffusion of BART viral micro‐RNAs produced by EBV‐infected nasopharyngeal carcinoma cells. Virol J. 2010;7:271. https://doi.org/10.1186/1743-422X-7-271
Zheng XH, Lu LX, Cui C, Chen MY, Li XZ, Jia WH. Epstein—Barr virus mir‐bart1‐5p detection via nasopharyngeal brush sampling is effective for diagnosing nasopharyngeal carcinoma. Oncotarget. 2016;7(4):4972-4980. https://doi.org/10.18632/oncotarget.6649
Hirai N, Wakisaka N, Kondo S, Aga M, Moriyama-Kita M, Ueno T, et al. Potential interest in circulating miR‐BART17‐5p as a post‐treatment biomarker for prediction of recurrence in Epstein—Barr virus‐related nasopharyngeal carcinoma. PLoS One. 2016;11(9):e0163609. https://doi.org/10.1371/journal.pone.0163609
Chow YP, Tan LP, Chai SJ, Abdul Aziz N, Choo SW, Lim PV, et al. Exome sequencing identifies potentially druggable mutations in nasopharyngeal carcinoma. Sci Rep. 2017;7:42980. https://doi.org/10.1038/srep42980
Old LJ, Boyse EA, Oettgen HF, Harven ED, Geering G, Williamson B, et al. Precipitating antibody in human serum to an antigen present in cultured Burkitt’s lymphoma cells. Proc Natl Acad Sci USA. 1966;56(6):1699-1704. https://doi.org/10.1073/pnas.56.6.1699
Gu AD, Xie YB, Mo HY, Jia WH, Li MY, Li M, et al. Antibodies against Epstein—Barr virus gp78 antigen: A novel marker for serological diagnosis of nasopharyngeal carcinoma detected by xMAP technology. J Gen Virol. 2008;89(Pt 5):1152-1158. https://doi.org/10.1099/vir.0.83686-0
Tzellos S, Farrell PJ. Epstein—Barr virus sequence variation-biology and disease. Pathogens. 2012;1(2):156-174. https://doi.org/10.3390/pathogens1020156
Mutirangura A, Pornthanakasem W, Theamboonlers A, Sriuranpong V, Lertsanguansinchi P, Yenrudi S, et al. Epstein—Barr viral DNA in serum of patients with nasopharyngeal carcinoma. Clin Cancer Res. 1998;4(3):665-669.
Liu S, Li H, Chen L, Yang L, Li L, Tao Y, et al. (-)-Epigallocatechin-3-gallate inhibition of Epstein—Barr virus spontaneous lytic infection involves ERK1/2 and PI3-K/Akt signaling in EBV-positive cells. Carcinogenesis. 2013;34(3):627-637. https://doi.org/10.1093/carcin/bgs364
Lit LC, Chan KC, Leung SF, Lei KI, Chan LY, Chow KC, et al. Distribution of cell-free and cell-associated Epstein—Barr virus (EBV) DNA in the blood of patients with nasopharyngeal carcinoma and EBV-associated lymphoma. Clin Chem. 2004;50(10):1842-1845. https://doi.org/10.1373/clinchem.2004.036640
Lo YM, Chan LY, Lo KW, Leung SF, Zhang J, Chan AT, et al. Quantitative analysis of cell-free Epstein—Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res. 1999;59(6):1188-1191.
Le QT, Jones CD, Yau TK, Shirazi HA, Wong PH, Thomas EN, et al. A comparison study of different PCR assays in measuring circulating plasma Epstein—Barr virus DNA levels in patients with nasopharyngeal carcinoma. Clin Cancer Res. 2005;11(16):5700-5707. https://doi.org/10.1158/1078-0432.ccr-05-0648
Chan KCA, Woo JKS, King A, Zee BCY, Lam WKJ, Chan SL, et al. Analysis of plasma Epstein—Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017;377(6):513-522. https://doi.org/10.1056/NEJMoa1701717
Wei W, Huanga Z, Li Sh, Chen H, Zhang G, Li Shuxia, et al. Pretreatment Epstein—Barr virus DNA load and cumulative cisplatin dose intensity affect long-term outcome of nasopharyngeal carcinoma treated with concurrent chemotherapy: Experience of an Institute in an Endemic Area. Oncol Res Treat. 2014;37:88-95.
Lee AW, Ma BB, Ng WT, Chan AT. Management of nasopharyngeal carcinoma: current practice and future perspective. J Clin Oncol. 2015;33(29):3356-3364. https://doi.org/10.1200/JCO.2015.60.9347
To EW, Chan KCA, Leung SF, Chan LY, To KF, Chan AT, et al. Rapid clearance of plasma Epstein—Barr virus DNA after surgical treatment of nasopharyngeal carcinoma. Clin Cancer Res. 2003,9:3254-3259.
Zhang J, Shu C, Song Y, Li Q, Huang J, Ma X. Epstein—Barr virus DNA level as a novel prognostic factor in nasopharyngeal carcinoma: a metaanalysis. Medicine (Baltimore). 2016;95(40):e5130. https://doi.org/10.1097/md.0000000000005130
Lee VH, Kwong DL, Leung TW, Choi CW, Lai V, Ng L, et al. Prognostication of serial undetectable plasma EBV DNA for nasopharyngeal carcinoma. Oncotarget. 2017;8(3):5292-5308. https://doi.org/10.18632/oncotarget.14137
Jin Y, Cai XY, Cai YC, Cao Y, Xia Q, Tan YT, et al. To build a prognostic score model containing indispensible tumour markers for metastatic nasopharyngeal carcinoma in an epidemic area. Eur J Cancer. 2012;48(6):882-888. https://doi.org/10.1016/j.ejca.2011.09.004
Le QT, Zhang Q, Cao H, Cheng AJ, Pinsky BA, Hong RL, et al. An International collaboration to harmonize the quantitative plasma Epstein—Barr Virus (EBV) DNA assay for future biomarker-guided trials in nasopharyngeal carcinoma. Clin Cancer Res. 2013;19(8):2208-2215. https://doi.org/10.1158/1078-0432.CCR-12-3702
Chan AT, Grégoire V, Lefebvre JL, Licitra L, Hui EP, Leung SF, et al. Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl.7):vii83-vii85. https://doi.org/10.1093/annonc/mds266