Use of Plasma Epstein-Barr virus DNA Monitoring as a Tumor Marker in follow-up of Patients with Nasopharyngeal Carcinoma: Preliminary Results and Report of two Cases

2007 ◽  
Vol 22 (3) ◽  
pp. 194-199 ◽  
Author(s):  
E. Özyar ◽  
M. Gültekin ◽  
A. Alp ◽  
G. Hasçelik ◽  
Ö. Ugur ◽  
...  

Recent studies suggest that plasma Epstein-Barr virus (EBV) DNA may reflect tumor burden in patients with nasopharyngeal cancer. A prospective study was initiated to investigate this correlation in 125 patients (34 pretreatment [Group A], 78 in remission [Group B] and 13 relapsed [Group C]) and 19 healthy controls. In group A, EBV DNA was detected in plasma samples of 24 (70%) patients. In Group B, EBV DNA was detected in 7 patients (range 77–13,731 copies/mL) and further imaging in all but one of these patients revealed active disease confirmed by ultrasound-guided fine-needle biopsy. There was only one false-positive case; this patient is currently under follow-up. Here we describe 2 of the 7 patients with detectable plasma EBV DNA in whom recurrence was documented by PET scan during follow-up. Our results showed that in group B the positive predictive value of quantitative analysis of plasma EBV DNA was 85%. Quantitative analysis of EBV DNA in plasma seems to become an integral part of screening, staging, monitoring, and prediction of relapse in patients with nasopharyngeal carcinoma. However, previous studies cannot be considered definitive and more reports on the use of this technique are urgently needed from both endemic and non-endemic regions.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen-Jie Chen ◽  
Wen-Na Xu ◽  
Hai-Yun Wang ◽  
Xiao-Xia Chen ◽  
Xue-Qi Li ◽  
...  

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.


2020 ◽  
Author(s):  
Sha-sha He ◽  
Yun-ying Yang ◽  
Yan Wang ◽  
Yu-feng Ren ◽  
Cheng-tao Wang ◽  
...  

Abstract PURPOSE Epstein Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma, while the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival. METHODS We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan–Meier estimates. 12 and 24-month landmark analyses for OS data were performed according to the EBV groups. RESULTS Patients with post-EBV < 2,500 copies/mL achieved better survival than the higher ones. Furthermore, patients with continuously elevated EBV DNA had significantly poorer OS (HR: 2.542, 95%CI: 2.077–3.111, P < 0.001), DMFS (HR: 2.970, 95%CI: 2.392–3.687, P < 0.001), LRFS (HR: 1.699, 95%CI: 1.072–2.692, P = 0.013), and PFS (HR:2.535, 95%CI: 1.987–3.233, P < 0.001) than patients with continuously normal EBV or those with elevated levels at any time-point. The 5-year OS with elevated EBV was lower than the remission group by the 12 and 24-month landmark analysis. CONCLUSIONS Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis and unfavorable prognosis for NPC. In addition, EBV DNA was predictable no matter how long the follow-up time.


2018 ◽  
Vol 11 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Paolo Gamba ◽  
Luigina Rota ◽  
C. Abeni ◽  
Alessandra Huscher ◽  
Gabriele Saldi ◽  
...  

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.


2020 ◽  
Author(s):  
Sha-sha He ◽  
Yun-ying Yang ◽  
Yan Wang ◽  
Yu-feng Ren ◽  
Cheng-tao Wang ◽  
...  

Abstract Background: Epstein Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma, while the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival.Methods: We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan–Meier estimates. 12 and 24-month landmark analyses for OS data were performed according to the EBV groups.Results: Patients with post-EBV < 2,500 copies/mL achieved better survival than the higher ones. Furthermore, patients with continuously elevated EBV DNA had significantly poorer OS (HR: 2.542, 95%CI: 2.077–3.111, P < 0.001), DMFS (HR: 2.970, 95%CI: 2.392–3.687, P < 0.001), LRFS (HR: 1.699, 95%CI: 1.072–2.692, P = 0.013), and PFS (HR:2.535, 95%CI: 1.987–3.233, P < 0.001) than patients with continuously normal EBV or those with elevated levels at any time-point. The 5-year OS with elevated EBV was lower than the remission group by the 12 and 24-month landmark analysis.Conclusions: Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis and unfavorable prognosis for NPC. In addition, EBV DNA was predictable in the long follow-up time.


2020 ◽  
Vol 2 (1) ◽  
pp. 61-68
Author(s):  
Ria Wahyu Januarti

Nasopharyngeal carcinoma is a type of cancer that has a considerable prevalence in Indonesia. Nasopharyngeal cancer is associated with Epstein-Barr virus infection, which also correlates with other factors. These factors are age, genetic, environmental and oral hygiene. Usually, nasopharyngeal cancer is late for diagnosis, so it is always found at an advanced stage. In individuals in risky communities, early detection of nasopharyngeal cancer can be done, without being invasive. The examination that can be done is EBV virus serology analysis and EBV DNA examination. The examination can use simple samples such as nasopharyngeal smear and saliva. This convenience allows early detection of nasopharyngeal cancer so that it can reduce morbidity and mortality.


2000 ◽  
Vol 111 (1) ◽  
pp. 239-246 ◽  
Author(s):  
Kenny I. K. Lei ◽  
Lisa Y.S. Chan ◽  
Wing Y. Chan ◽  
Philip J. Johnson ◽  
Y. M. Dennis Lo

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Amina Gihbid ◽  
Raja Benzeid ◽  
Abdellah Faouzi ◽  
Jalal Nourlil ◽  
Nezha Tawfiq ◽  
...  

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.


2021 ◽  
Vol 12 (1) ◽  
pp. 150-156
Author(s):  
Soehartati A. Gondhowiardjo ◽  
Handoko ◽  
Marlinda Adham ◽  
Lisnawati Rachmadi ◽  
Henry Kodrat ◽  
...  

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm3. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.


Blood ◽  
2013 ◽  
Vol 121 (18) ◽  
pp. 3547-3553 ◽  
Author(s):  
Jennifer A. Kanakry ◽  
Hailun Li ◽  
Lan L. Gellert ◽  
M. Victor Lemas ◽  
Wen-son Hsieh ◽  
...  

Key Points Plasma EBV-DNA is highly concordant with EBV tumor status in Hodgkin lymphoma. Plasma EBV-DNA has prognostic significance in Hodgkin lymphoma, both before therapy and at month 6 of follow-up.


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