Amplification of Epstein-Barr virus (EBV) DNA by superinfection with a strain of EBV derived from nasopharyngeal carcinoma.

Abstract Background The identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC. Methods The present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR. Results Overall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients’ age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients. Conclusions The results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.

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Plasma Epstein-Barr virus DNA and risk of nasopharyngeal carcinoma in a prospective seropositive population

BMC Cancer ◽

10.1186/s12885-021-08408-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wen-Jie Chen ◽

Wen-Na Xu ◽

Hai-Yun Wang ◽

Xiao-Xia Chen ◽

Xue-Qi Li ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Screening Program ◽

Southern China ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr

Abstract Objective Plasma Epstein-Barr virus (EBV) DNA is considered a biomarker for nasopharyngeal carcinoma (NPC). However, its long-term role in NPC development is unclear. Materials and methods A total of 1363 participants seropositive for EBV VCA-IgA and EBNA1-IgA in a community-based NPC screening program in southern China were tested for plasma EBV DNA levels by real-time qPCR between 2008 and 2015. New NPC cases were confirmed by active follow-up approach and linkage to local cancer registry through the end of 2016. Cox proportional hazards regression analysis was performed to calculate the hazard ratios (HRs) for NPC risk with plasma EBV DNA. Results Thirty patients were newly diagnosed during a median 7.5 years follow-up. NPC incidence increased with the plasma EBV DNA load ranging from 281.46 to 10,074.47 per 100,000 person-years in participants with undetectable and ≥ 1000 copies/ml levels; the corresponding cumulative incidence rates were 1.73 and 50%. Furthermore, plasma EBV DNA loads conferred an independent risk for NPC development after adjustment for other risk factors, with HRs of 7.63 for > 3–999 copies/ml and 39.79 for ≥1000 copies/ml. However, the HRs decreased gradually after excluding NPC cases detected in the first 2 to 3 years and became statistically nonsignificant by excluding cases detected during the first 4 years. Conclusion Elevated plasma EBV DNA can predict NPC risk over 3 years. Monitoring plasma EBV DNA can be used as a complementary approach to EBV serological antibody-based screening for NPC.

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Comparison of plasma Epstein–Barr virus(EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma

Cancer ◽

10.1002/cncr.20099 ◽

2004 ◽

Vol 100 (6) ◽

pp. 1162-1170 ◽

Cited By ~ 126

Author(s):

Jian-Yong Shao ◽

Yu-Hong Li ◽

Hong-Yi Gao ◽

Qiu-Liang Wu ◽

Nian-Ji Cui ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Immunoglobulin A ◽

Virus Capsid ◽

Barr Virus ◽

Antibody Titers ◽

Ebv Dna ◽

Epstein Barr ◽

Antigen Antibody ◽

Virus Capsid Antigen

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Prevalence of Epstein Barr Virus in biopsy specimens of nasopharyngeal carcinoma from Serbian patients

Archives of Biological Sciences ◽

10.2298/abs1402537b ◽

2014 ◽

Vol 66 (2) ◽

pp. 537-544 ◽

Cited By ~ 1

Author(s):

Ana Banko ◽

Ivana Lazarevic ◽

M. Folic ◽

Maja Cupic ◽

Tanja Jovanovic

Keyword(s):

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Barr Virus ◽

Biopsy Specimens ◽

C Terminus ◽

Geographical Regions ◽

Significant Difference ◽

Ebv Dna ◽

Epstein Barr

The development of nasopharyngeal carcinoma (NPC) is the result of interaction between Epstein-Barr Virus (EBV) and many non-viral factors. The aims of this study were to determine the prevalence of EBV in NPC biopsies from Serbian patients and to investigate the correlation between EBV presence and demographic, anamnestic and clinical data. Ninety-three tissue blocks were included. For detection of EBV DNA, the C terminus of the LMP1 gene was amplified by nested-PCR. Twenty-eight biopsies were EBV-DNA-positive (30.1%), with a statistically significant difference in EBV DNA presence between geographical regions (p=0.02) and between the stages of tumor-node-metastasis (TNM) (p=0.02). A correlation was also found with the presence of EBV DNA and smoking (p=0.02). The correlation of EBV DNA presence, with or without smoking and the promising outcome of the disease was statistically significant (p=0.02; p=0.01). The EBV DNA findings from this study confirm the role of EBV in NPC carcinogenesis, and show the different distribution among TNM stages and correlation between the virus and outcome of disease.

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Diagnostic and prognostic performance of circulating levels of the Epstein-Barr virus microRNAs BART 7-3p and BART 13-3p in nasopharyngeal carcinoma

10.21203/rs.2.22593/v1 ◽

2020 ◽

Author(s):

Tianzhu Lu ◽

Qiaojuan Guo ◽

Keyu Lin ◽

Honglin Chen ◽

Yixin Chen ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Distant Metastasis ◽

Plasma Levels ◽

Epstein Barr Virus ◽

Cox Regression ◽

Prognostic Performance ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr ◽

Circulating Levels

Abstract Background Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. EBV BamHI A rightward transcripts (BART) encode microRNAs (EBV-miR-BARTs) abnormally highly expressed and play an essential role in NPC. Our previous study indicated that circulating EBV-miR-BARTs was potentially severed as a biomarker of NPC. This study aims to investigate the diagnostic and prognostic performance of miR-BART7-3p and miR-BART13-3p. Methods Plasma levels of EBV DNA, miR-BART7-3p, and miR-BART13-3p were examined by quantitative PCR in 483 treatment-naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow-up. Results Plasma EBV DNA was detected in 93.7% of NPC subjects vs. 8.6% of controls. The microRNAs BART7-3p and miR-BART13-3p were detected in 96.1% and 97.9% of NPC subjects vs. 3.39% and 3.3% of controls. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for miR-BART7-3p, 0.973 for miR-BART13-3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above-median miR-BART7-3p and EBV-DNA were independent risk for shorter distant metastasis-free survival (DMFS) (HR=2.94, 95%CI: 1.44-5.97, p=0.003; HR=2.27, 95%CI:1.26-4.10, p=0.006) in multivariate Cox regression. In the 245 patients who received radiotherapy, EBV DNA, miR-BART7-3p, and miR-BART13-3p were detectable immediately afterward in, respectively, 28.6%, 17.6%, and 54.7% of patients. Four-year DMFS rate was lower in patients with detectable miR-BART7-3p (73.0% vs. 89.7%, p<0.001), miR-BART13-3p (61.4% vs. 90.0%, p<0.001), and EBV-DNA (82.7% vs. 89.5%, p=0.035) after radiotherapy. In multivariate Cox regression, detectable miR-BART7-3p and EBV-DNA were independent risks for shorter DMFS (HR=4.13, 95%CI: 1.89-9.01, p<0.001; HR = 2.14, 95%CI: 1.04-4.42, p=0.039). Four-years DMFS rate was 92.0% in subjects (n=156) with neither detectable miR-BART7-3p nor EBV-DNA after radiotherapy, 80.0% in subjects (n=65) with either detectable miR-BART7-3p or EBV-DNA after radiotherapy, and 52.9% in subjects (n=24) with both detectable miR-BART7-3p and EBV-DNA after radiotherapy (p<0.001). Conclusions Circulating levels of miR-BART7-3p and miR-BART13-3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR-BART7-3p and EBV DNA at diagnosis and after radiotherapy may help stratify patients by risk of poor DMFS.

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Abstract 3153: A new circulating plasma/serum Epstein-Barr virus (EBV) DNA test by locked nucleic acid (LNA) PCR technique with enhanced sensitivity in diagnosis & monitoring of patients suffering from nasopharyngeal carcinoma (NPC) and other EBV associated malignancies

10.1158/1538-7445.am2016-3153 ◽

2016 ◽

Author(s):

Timothy T.C. Yip ◽

Hazel Y.Y. Kwok ◽

Sharon S.Y. You ◽

Dora L.W. Kwong ◽

Alvin H.W. Fong ◽

...

Keyword(s):

Nucleic Acid ◽

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Locked Nucleic Acid ◽

Dna Test ◽

Barr Virus ◽

Enhanced Sensitivity ◽

Ebv Dna ◽

Epstein Barr

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Plasma Macrophage Inhibitory Cytokine-1 as a Complement of Epstein-Barr Virus Related Markers in Identifying Nasopharyngeal Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820956991 ◽

2020 ◽

Vol 19 ◽

pp. 153303382095699

Author(s):

Shan Xing ◽

Huilan Li ◽

Yingqi Pi ◽

Tao Zeng ◽

Qi Huang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Copy Number ◽

Epstein Barr Virus ◽

Normal Subjects ◽

Diagnostic Value ◽

Healthy Controls ◽

Barr Virus ◽

Healthy Donors ◽

Ebv Dna ◽

Epstein Barr

Background: We evaluated the diagnostic value of plasma Macrophage inhibitory cytokine-1 (MIC-1) in distinguishing patients with nasopharyngeal carcinoma (NPC) and explored its complementary role with widely used Epstein-Barr virus (EBV) related markers, EBV capsid antigen-specific IgA (VCA-IgA) and EBV copy number. Methods: ELISA was used to analyze the plasma MIC-1 levels in 190 NPC patients, 72 VCA-IgA-positive healthy donors (VP), and 219 normal subjects with negative VCA-IgA (VN). 10 pairs of plasma samples before and after radiotherapy were also included. Results: The plasma MIC-1 levels were significantly higher in NPC patients (Median: 678.39 ng/mL) than those in VN and VP (310.29 and 294.59, p < 0.001). Receiver operating characteristic (ROC) curves of the MIC-1 concentrations revealed that the area under the ROC curve (AUC) was 0.790 (95% confidence interval [CI]: 0.748-0.832), with a sensitivity of 63.7%, and a specificity of 85.9% respectively, for distinguishing NPC patients from the healthy donors. Similarly, between NPC and VP, ROC was 0.796 (0.738-0.853) with sensitivity of 63.7%, and specificity of 88.9%. In addition, between NPC and VN, ROC was 0.788(0.744-0.832) with sensitivity of 63.7%, and specificity of 84.9%. Further, we found that MIC-1 could complement VCA-IgA and EBV DNA markers, with a negative rate of 88.9% in VCA-IgA-positive healthy controls, and a positive rate of 59.0% in EBV DNA negative NPC patients, respectively. Also, the MIC-1 plasma concentration dropped significantly after radiotherapy ( p = 0.027). Conclusions: MIC-1 can complement VCA-IgA titers and EBV DNA copy number tests in NPC detection, improve identification of EBV DNA-negative NPC patients, and distinguish NPC from VCA -IgA positive healthy controls.

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Distribution of Cell-Free and Cell-Associated Epstein–Barr Virus (EBV) DNA in the Blood of Patients with Nasopharyngeal Carcinoma and EBV-Associated Lymphoma

Clinical Chemistry ◽

10.1373/clinchem.2004.036640 ◽

2004 ◽

Vol 50 (10) ◽

pp. 1842-1845 ◽

Cited By ~ 11

Author(s):

Lydia C W Lit ◽

K C Allen Chan ◽

Sing-Fai Leung ◽

Kenny I K Lei ◽

Lisa Y S Chan ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Epstein Barr Virus ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr

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Phase II Study of Neoadjuvant Carboplatin and Paclitaxel Followed by Radiotherapy and Concurrent Cisplatin in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: Therapeutic Monitoring With Plasma Epstein-Barr Virus DNA

Journal of Clinical Oncology ◽

10.1200/jco.2004.05.178 ◽

2004 ◽

Vol 22 (15) ◽

pp. 3053-3060 ◽

Cited By ~ 89

Author(s):

Anthony T.C. Chan ◽

Brigette B.Y. Ma ◽

Y.M. Dennis Lo ◽

S.F. Leung ◽

W.H. Kwan ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Treatment Response ◽

Epstein Barr Virus ◽

Quantitative Polymerase Chain Reaction ◽

Therapeutic Monitoring ◽

Tumor Control ◽

Weekly Cycle ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr

Purpose To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. Patients and Methods Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. Conclusion This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.

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