scholarly journals Negative plasma Epstein-Barr virus DNA nasopharyngeal carcinoma in an endemic region and its influence on liquid biopsy screening programmes

2019 ◽  
Vol 121 (8) ◽  
pp. 690-698
Author(s):  
John Malcolm Nicholls ◽  
Victor Ho-Fun Lee ◽  
Sik-Kwan Chan ◽  
Ka-Chun Tsang ◽  
Cheuk-Wai Choi ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Early Stage ◽  
Primary Tumour ◽  
Cancer Specific Survival ◽  
Early Stage Disease ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment

Abstract Background Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA. Methods We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0–20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared. Results Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p < 0.001). Though EBV DNA-negative patients had more early-stage disease (p < 0.001) and smaller volumes of the primary tumour and the positive neck nodes (p < 0.001), they had similar 5-year overall survival and cancer-specific survival to those EBV DNA-positive counterparts by stage. Similar results were also seen when plasma EBV DNA cut-off was set at 0 copy/ml. Conclusions Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions. Clinical trial registration Clinicaltrials.gov Identifier: NCT02476669.

scholarly journals Circulating cell‐free epstein–barr virus DNA levels and clinical features in Moroccan patients with nasopharyngeal carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Amina Gihbid ◽  
Raja Benzeid ◽  
Abdellah Faouzi ◽  
Jalal Nourlil ◽  
Nezha Tawfiq ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Disease Stage ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment ◽  
Moroccan Patients

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.

scholarly journals Integrated Diagnostic Model That Incorporates Epstein-Barr Virus DNA, Imaging, and Nasal Endoscopy to Stratify Primary Tumor and Lymph Nodes in a Patient with N1 Nasopharyngeal Carcinoma: Multidisciplinary Management

2018 ◽  
Vol 11 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Paolo Gamba ◽  
Luigina Rota ◽  
C. Abeni ◽  
Alessandra Huscher ◽  
Gabriele Saldi ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Early Stage ◽  
Distant Metastases ◽  
Disease Stage ◽  
Diagnostic Model ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, with a high metastatic potential. Epstein-Barr virus (EBV) infection plays a fundamental role, even if it is not well understood. The diagnosis of the disease in its early stage is infrequent. Imaging studies, positron emission tomography scans in addition to clinical examination, endoscopic examination, and biopsy provide information on the extent of the disease. The application of neoadjuvant chemotherapy followed by concomitant chemoradiation can improve the control of NPC. In March 2016, a 54-year-old male with NPC cT1 cN2 cM0, stage III (8th edition of American Joint Committee on Cancer (AJCC) staging system) underwent to a two-step treatment: induction chemotherapy by TPF regimen (docetaxel, cisplatin, 5-fluorouracil), followed by concomitant chemoradiotherapy (weekly cisplatin). The quantity of free plasma EBV-DNA can be related to the disease stage, and the detection of EBV-DNA during follow-up can be predictive of distant metastases. Especially, either plasma or serum EBV-DNA titer is estimated to reflect tumor volume. Biologically, such EBV-DNA reflects reproduced or released DNA from dead or dying tumor cells. On the other hand, EBV-specific DNA released as exosome may reflect the biological feature of the alive NPC tumor cell. The follow-up is ongoing after 21 months from a complete response.

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

BMC Cancer ◽  
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.

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

2014 ◽  
Vol 66 (2) ◽  
pp. 537-544 ◽  
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.

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

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.

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

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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