Epstein-Barr Virus DNA In Patients Research Articles

Association of Plasma Epstein-Barr Virus DNA With Outcomes for Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma Receiving Anti–Programmed Cell Death 1 Immunotherapy

Anti-programmed cell death 1 (anti-PD-1) immunotherapy features a durable response and improved survival in a small subset of patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). The association between plasma Epstein-Barr virus (EBV) DNA titer dynamics and efficacy of anti-PD-1 monotherapy has been reported, while its value in predicting long-term outcomes and monitoring disease progression is unclear for patients with RM-NPC who are receiving anti-PD-1 monotherapy. To evaluate the role of plasma EBV DNA titers in prognosis prediction and surveillance of disease progression for patients with RM-NPC who are receiving anti-PD-1 monotherapy. Patients with RM-NPC from the POLARIS-02 prospective clinical trial, the largest cohort to receive anti-PD-1 monotherapy, were included in this study. From December 22, 2016, to February 19, 2019, 17 participating centers in China screened 279 patients with RM-NPC; 190 patients were enrolled and followed up until February 19, 2020. Plasma EBV DNA was detected before treatment and every 4 weeks until disease progression. Plasma EBV DNA as a predictor for progression-free survival (PFS), overall survival (OS), durable clinical benefit (defined as PFS of ≥6 months), and disease progression. Of 179 patients with RM-NPC receiving anti-PD-1 therapy, 148 (82.7%) were men, and the median age was 46 years (range, 22-71 years). A higher baseline EBV DNA titer was associated with shorter median OS (hazard ratio, 1.88; 95% CI, 1.22-2.89; P = .004). Patients with a ratio of the EBV DNA titer at week 4 to that at baseline (W4 to baseline ratio) greater than 0.5 had shorter median OS (hazard ratio, 2.18; 95% CI, 1.30-3.65; P < .001) than those with a W4 to baseline ratio of 0.5 or less. Patients with higher baseline EBV DNA titers had a lower durable clinical benefit rate than those with lower baseline EBV DNA titers (19 of 97 [19.6%] vs 27 of 71 [38.0%]; P = .01). Similarly, patients with a W4 to baseline ratio greater than 0.5 had a lower durable clinical benefit rate than those with a W4 to baseline ratio of 0.5 or less (9 of 86 [10.5%] vs 32 of 54 [59.3%]; P < .001). In addition, a significant EBV DNA titer increase was present at a median of 2.6 months (IQR, 0.9-4.5 months) prior to radiographic progression. This study of plasma EBV DNA in patients with RM-NPC who are receiving anti-PD-1 monotherapy suggests that plasma EBV DNA could be a useful biomarker for outcomes and monitoring disease progression.

Markers of Epstein–Barr virus in clinical assessment of Russian patients with nasopharyngeal cancer

Introduction. Epstein–Barr virus (EBV) is equally widespread in the endemic and non-endemic world regions for nasopharyngeal cancer (NPC). High incidence of NPC in endemic countries and low in non-endemic countries suggest there are different mechanisms and conditions for tumor occurrence and, possibly, different clinical significance of EBV-associated markers. However, significance of these markers for determining NPC in non-endemic regions is still poorly understood. Objective – to determine clinical significance of titers of IgG/IgA antibodies to EBV capsid antigen and concentrations of the viral DNA in patients’ blood plasma as diagnostic and monitoring markers for NPC in a non-endemic region of Russia. Materials and methods. Titers of EB-specific antibodies were determined by indirect immunofluorescence, and concentration of the viral DNA in plasma was measured using a quantitative polymerase chain reaction in real time. Study group included patients with NPC (n = 96), and control group – blood donors (n = 171) and patients with other head and neck tumors (n = 33).Results. Titers of IgG/IgA antibodies to EBV capsid antigen, being an important diagnostic marker of nasopharyngeal cancer, did not always correlate with patients’ clinical condition. Humoral response to emerging events often delayed due to inertia of the immune system. Concentration of EBV DNA in patients’ blood plasma clearly reflected the dynamics of the pathological process: it decreased to background values in remission and increased while the disease progressed. In contrast to endemic regions, we did not find any correlation between the studied EBV markers and clinical manifestations of the disease, evaluated in accordance with the TNM classification (Tumor, Nodus and Metastasis).Conclusion. In non-endemic countries, such as Russia, serological and molecular markers of EBV can be successfully used for the primary diagnosis of NPC. However, for the disease monitoring, it is preferable to use the value of the concentrations of circulating EBV DNA, which, in contrast to the values of IgG/IgA antibody titers to VCA EBV, more accurately reflect the patient’s clinical condition.

CpG methylation in cell-free Epstein-Barr virus DNA in patients with EBV-Hodgkin lymphoma

AbstractEpstein-Barr virus (EBV) is associated with a variety of tumors and nonmalignant conditions. Latent EBV genomes in cells, including tumor cells, are often CpG methylated, whereas virion DNA is not CpG methylated. We demonstrate that methyl CpG binding magnetic beads can be used to fractionate among sources of EBV DNA (DNA extracted from laboratory-purified virions vs DNA extracted from latently infected cell lines). We then applied the technique to plasma specimens and showed that this technique can distinguish EBV DNA from patients with EBV-associated tumors (nasopharyngeal carcinoma, Hodgkin lymphoma) and viral DNA from patients without EBV-associated tumors, including immunocompromised patients and patients with EBV(−) Hodgkin lymphoma.

Plasma Epstein–Barr virus DNA as an archetypal circulating tumour DNA marker

Analysis of circulating tumour DNA (ctDNA), as one type of ‘liquid biopsy’, has recently attracted great attention. Researchers are exploring many potential applications of liquid biopsy in many different types of cancer. In particular, it is of biological interest and clinical relevance to study the molecular characteristics of ctDNA. For such purposes, plasma Epstein–Barr virus (EBV) DNA from patients with nasopharyngeal carcinoma (NPC) would provide a good model to understand the biological properties and clinical applications of ctDNA in general. The strong association between EBV and NPC in endemic regions has made plasma EBV DNA a robust biomarker for this cancer. There are many clinical utilities of plasma EBV DNA analysis in NPC diagnostics. Its role in prognostication and surveillance of recurrence is well established. Plasma EBV DNA has also been validated for screening NPC in a recent large‐scale prospective study. Indeed, plasma EBV DNA could be regarded as an archetypal ctDNA marker. In this review, we discuss the biological properties of plasma EBV DNA from NPC samples and also the clinical applications of plasma EBV DNA analysis in the management of NPC. Of note, the recently reported size analysis of plasma EBV DNA in patients with NPC has highlighted size as an important analytical parameter of ctDNA and demonstrated clinical value in improving the diagnostic performance of an EBV DNA‐based NPC screening test. Such insights into ctDNA analysis (including size profiling) may help its full potential in cancer diagnostics for other types of cancer to be realised. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Abstract 3051: Prognostic value of 18F-FDG PET/CT parameters in patients with primary pulmonary lymphoepithelioma-like carcinoma

Abstract Introduction Pretreatment tumor metabolic burden, which measured by fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) have been shown to predict outcomes in various malignancies. Epstein-Barr virus (EBV) serology titer in pulmonary LELC is correlated to stage. However, the prognostic value of 18F-FDG PET/CT in patients with pulmonary lymphoepithelioma-like carcinoma (LELC) and the relationship between EBV viral load remained unknown. The current study aims to investigate the prognostic value and association between functional parameters of 18F-FDG PET/CT and serum EBV DNA in patients with pulmonary LELC. Methods This retrospective study comprised 32 patients with pulmonary LELC who underwent pretreatment 18F-FDG PET/CT between January 2008 and December 2016. The EBV viral load and the functional parameters of 18F-FDG PET/CT were used for survival analysis. Results The value of pre-treatment serum EBV DNA had significantly positive correlation with whole MTV (r = 0.63, P = 0.0337) and whole TLG (r = 0.77, P = 0.0093). Advanced tumor stage (≥III) and high whole MTV (≥72.58) significantly predicted poor PFS. Multivariate survival analysis for PFS showed that there was a trend toward a lower risk of recurrence in patients with early tumor stage (≤II) (HR = 0.112, 95% CI =0.011-1.117, P = 0.062, Table 3), albeit not significantly so. Advanced tumor stage (≥III), high whole MTV (≥72.58) and high whole TLG (≥278.4) were predictors of poor OS. However, in multivariate survival analysis, none of them were independent predictors for OS. EBV viral load was not prognostic factor for both PFS and OS. Conclusion Greater whole MTV and whole TLG predicted poorer OS in patients with primary pulmonary LELC. Functional parameter of 18F-FDG PET/CT may provide useful prognostic information. Serum EBV DNA was closely related to whole MTV and TLG, but not a prognostic factor. Citation Format: Yueh-Fu Fang, Chun-Yu Lin. Prognostic value of 18F-FDG PET/CT parameters in patients with primary pulmonary lymphoepithelioma-like carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3051.

Relationship between dynamic changes of Epstein-Barr virus and efficacy of lymphoma

Objective To observe the relationship between the dynamic changes of Epstein-Barr virus (EBV) and the clinical efficacy of lymphoma. Methods The retrospective study was performed on 51 lymphoma patients with EBV-positive in Anhui Provincial Cancer Hospital from September 2015 to August 2017. The treatment effect of lymphoma was evaluated by the changes of EBV DNA, lactic dehydrogenase (LDH) and lymph nodes. Results Among the 51 lymphoma patients, EBV DNA elevated in 18 patients when the LDH was elevated, 23 cases presented with EBV DNA decrease and the LDH also decreased. EBV DNA decreased in 2 patients when the LDH was elevated. Eight patients were elevated when LDH was reduced. The quantification of EBV DNA and LDH had high consistency (κ= 0.609, P= 0.000). Among the 51 lymphoma patients, 20 patients with elevated EBV DNA were elevated with lymph nodeen largement, the lymph nodes in 22 cases with EBV DNA decrease were also decreased. EBV DNA decreased in 3 patients when the lymph nodes were enlarged. Six patients were elevated when lymph nodes were reduced. The quantification of EBV and lymph nodes had high consistency (κ= 0.648, P= 0.000). Patients with elevated EBV DNA during the course of treatment showed an increase in the mean value of LDH, and the patients with reduced EBV DNA during treatment also had lower average LDH. LDH levels were positively correlated with EBV DNA in patients with EBV-positive lymphoma (r= 0.627, P= 0.000). Conclusion Dynamic detection of EBV DNA and LDH can be used as the evaluation index of therapeutic effect and follow-up in patients with EBV-positive lymphoma. Key words: Herpesvirus 4, human; Lymphoma; Lactate dehydrogenases; Lymph nodes

Clinical Significance of Plasma Epstein-Barr Virus DNA in Pulmonary Lymphoepithelioma-like Carcinoma (LELC) Patients

Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a histologically distinctive subtype of NSCLC and an Epstein-Barr virus (EBV)-associated epithelial neoplasm. We investigated the clinical significance of plasma concentrations of EBV DNA in patients with pulmonary LELC. Two independent sets of plasma samples from a total of 429 patients with patients with pulmonary LELC (287 initial and 142 confirmatory) were available for EBV DNA determination. Plasma samples from the patients were subjected to a real-time quantitative polymerase chain reaction before treatment and 3 months after radical resection. Cutoff points were determined for pretreatment plasma EBV DNA concentration (low <4000 copies/mL versus high ≥4000 copies/mL) on the basis of a measure of heterogeneity with the log-rank test statistic with respect to overall survival (OS). The Kaplan-Meier method and Cox regression were used to evaluate the relationship between plasma EBV DNA concentrations and clinical outcome. Among patients with advanced-stage pulmonary LELC who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in EBV DNA concentrations by using nonparametric tests. High EBV DNA concentration was associated with shorter OS in the initial, confirmatory, and combined data sets (combined data set hazard ratio= 3.67, 95% confidence interval: 2.72-4.38, p < 0.001). These findings persisted after multivariable adjustment. Compared with low EBV DNA concentration, high EBV DNA concentration was associated with shorter OS in patients with any stage of disease. High EBV DNA concentration was also associated with shorter disease-free survival (DFS) in patients with stage I/II disease. Patients with persistently detectable plasma EBV DNA had significantly poorer OS (p < 0.001) and DFS (p < 0.001) than did patients with undetectable EBV DNA 3 months after radical resection. In patients who underwent sequential evaluation of EBV DNA, an association was identified between an increase in EBV DNA concentration and a poor response to treatment and disease progression of pulmonary LELC. High baseline EBV DNA concentration is an independent poor prognostic marker in patients with pulmonary LELC. These results should be confirmed in larger prospective trials.

The prognostic significance of plasma Epstein-Barr virus DNA in patients with diffuse large B cell lymphoma

To retrospectively analyze the prognostic significance of plasma Epstein-Barr virus (EBV) DNA in 122 patients with diffuse large B cell lymphoma (DLBCL). Plasma EBV DNA positivity was related to advanced disease stage (P=0.030), B symptoms (P=0.004) and elevated serum lactic dehydrogenase (LDH) (P=0.001). Furthermore, univariate analysis indicated that plasma EBV DNA level was associated with worse overall survival (OS) (HR=0.223, 95%CI 0.096-0.518, P<0.001) and worse progression free survival (PFS) (HR=4.417, 95%CI 1.911-10.208, P<0.001), whereas multivariate analysis showed plasma EBV DNA as a probable independent prognostic factor of clinical outcome(HR=0.409, 95%CI 0.166-1.008, P=0.052).

Clinical utility of circulating cell-free Epstein-Barr virus DNA in patients with gastric cancer.

Recent comprehensive molecular subtyping of gastric cancer (GC) identified Epstein–Barr virus (EBV)-positive tumors as a subtype with distinct salient molecular and clinical features. In this study, we aimed to determine the potential utility of circulating cell-free EBV DNA as a biomarker for the detection and/or monitoring of therapeutic response in patients with EBV-associated gastric carcinoma (EBVaGC). The EBV genes-to-ribonuclease P RNA component H1 ratios (EBV ratios) in the GC tumors and plasma samples were determined by quantitative real-time polymerase chain reaction in 153 patients with GC, including 14 patients with EBVaGC diagnosed by the conventional method. Circulating cell-free EBV DNA was detected in 14 patients with GC: the sensitivity and specificity of detection were 71.4% (10/14) and 97.1% (135/139), respectively. Plasma EBV ratios were significantly correlated with the size of EBVaGC tumors, and the plasma EBV DNA detected before surgery in EBVaGC cases disappeared after surgery. Patients with EBVaGC may have a better prognosis, but circulating cell-free EBV DNA had no or little impact on prognosis. In addition, repeated assessment of the plasma EBV ratio in EBVaGC showed a decrease and increase in plasma EBV DNA after treatment and during tumor progression/recurrence, respectively. These results suggest the potential utility of circulating cell-free DNA to reveal EBV DNA for the identification of the EBVaGC subtype and/or for real-time monitoring of tumor progression as well as treatment response in patients with EBVaGC.

Prognostic Correlations between ABO Blood Group and Pre-Treatment Plasma Epstein-Barr Virus DNA in Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

PurposeThe objective of this study is to assess the prognostic value of ABO blood group in nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT).Patients and MethodsWe retrospectively reviewed the data on 1397 patients with non-metastatic, newly diagnosed NPC treated using IMRT. Patient survival between different ABO blood groups were compared using log-rank test. Cox hazards model was adopted to establish independent prognostic factors.ResultsIn our study, the distribution of the A, B, AB and O blood groups was 26.6% (372/1397), 26.2% (366/1397), 5.2% (73/1397) and 42.0% (586/1397), respectively. The cut-off value of pre-treatment Epstein-Barr virus (EBV) DNA based on disease-free survival (DFS) was 1355 copies/ml (area under curve [AUC], 0.649; sensitivity, 0.76; specificity, 0.496) for the whole cohort. Estimated four-year DFS, overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates were 81.7%, 89.2%, 89.4% and 92.3% for blood group A; 82.1%, 89.3%, 89.0% and 92.0% for group B; 83.3%, 88.1%, 86.2% and 95.5% for group AB, 80.9%, 90.7%, 88.4% and 90.2% for group O (P > 0.05 for all rates). Multivariate analysis revealed ABO blood group was not an independent prognostic factor for DFS, OS, DMFS or LRRFS (P > 0.05 for all rates) after adjusting for plasma EBV DNA in either the whole cohort or subgroup analysis by gender.ConclusionsThe prognostic value of ABO blood group may be limited for patients with NPC in the era of IMRT, and no substantial correlation between ABO blood group and plasma EBV DNA was observed.

Prognostic efficacy of combining tumor volume with Epstein-Barr virus DNA in patients treated with intensity-modulated radiotherapy for nasopharyngeal carcinoma

ObjectivesTo evaluate the prognostic effect of combining tumor volume with pre-treatment plasma Epstein-Barr virus DNA (EBV DNA) in patients treated with intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Materials and methodsA total of 180 consecutive NPC patients enrolled in this observational, prospective study and underwent IMRT. Tumor volume was delineated with IMRT planning system and plasma EBV DNA level was quantified by polymerized chain-reaction assay. The effects of tumor volume and EBV DNA level, either alone or in combination, on 5-year overall survival (OS) were cross-compared. ResultsThe 5-year OS in patients with gross tumor volume of nasopharynx (GTVnx)⩽20cc and >20cc was significantly different (P=0.001). The 5-year OS in patients with EBV DNA <6800copies/mL and ⩾6800copies/mL was also significantly different (P<0.001). Based on the combination of GTVnx with EBV DNA, the 5-year OS in different subgroups was: low-risk (100%), intermediate-risk (87.8%, 95% CI: 70.6–95.2%) and high-risk (61.3%, 95% CI: 47.9–72.2%). Patients with small tumor volume and high EBV DNA level had a worse prognosis than those with large tumor and low EBV DNA level. Patients with low EBV DNA levels, and either small or large tumor volumes, had favorable prognosis. According to small or large tumor volume, patients with high EBV DNA level were divided into intermediaterisk and high-risk subgroups. ConclusionCombining tumor volume with pre-treatment plasma EBV DNA level altered survival-risk definition for subgroups of NPC patients and this combination, more than individual factors alone, improved the accuracy of prognostic evaluation.

Prognostic Impact of Plasma Epstein-Barr Virus DNA in Patients with Nasopharyngeal Carcinoma Treated using Intensity-Modulated Radiation Therapy.

The prognostic value of plasma Epstein-Barr virus (EBV) DNA remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 584 newly diagnosed patients with nonmetastatic and biopsy-proven NPC treated using IMRT. Plasma EBV DNA concentration was measured before therapy (pre-DNA) and within 1 month of completing therapy (post-DNA) using real-time quantitative polymerase chain reaction. Receiver operating characteristic (ROC) curves were generated to identify pre-DNA and post-DNA cut-off values. Prognostic value was assessed using a multivariate Cox proportional hazards model .Three-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free (DMFS) for pre-DNA >2010 vs.≤2010 were 78.1% vs. 93.6% (P < 0.001), 92.3% vs. 98.9% (P < 0.001), 90.9% vs. 96.6% (P = 0.004) and 85.5% vs. 96.6% (P < 0.001), respectively. Three-year DFS, OS, LRRFS and DMFS for post-DNA >0 vs. = 0 were 49.9% vs. 88.5% (P < 0.001), 72.1% vs. 97.5% (P < 0.001), 86.6% vs. 94.3% (P = 0.019), and 60.5% vs. 93.3% (P < 0.001), respectively. Plasma EBV DNA remains a prognostic factor in IMRT era and should be incorporated into TNM staging to guide individualized treatment strategies in NPC.

A Prognostic Analysis on Using the Combination of Tumor Volume and Epstein-Barr Virus DNA in Patients With Nasopharyngeal Carcinoma Treated With IMRT

A Prognostic Analysis on Using the Combination of Tumor Volume and Epstein-Barr Virus DNA in Patients With Nasopharyngeal Carcinoma Treated With IMRT

Higher Prevalence of Epstein–Barr Virus DNA in Deeper Periodontal Pockets of Chronic Periodontitis in Japanese Patients

Periodontitis, a complex chronic inflammatory disease caused by subgingival infection, is among the most prevalent microbial diseases in humans. Although traditional microbiological research on periodontitis has focused on putative bacteria such as Porphyromonas gingivalis, the herpes virus is proposed to be involved in the pathogenesis of periodontitis because bacterial etiology alone does not adequately explain various clinical aspects. In this study, we established for the first time, more Epstein–Barr virus (EBV) DNA is found deeper in periodontal pockets of chronic periodontitis in Japanese patients. Subgingival samples were collected from 85 patients with chronic periodontitis having two periodontal sites with probing depths (PD) of ≤3 mm (shallow) or ≥5 mm (deep) and were subjected to a nested polymerase chain reaction. EBV DNA was more frequently detected in patients with deeper PD sites (66%) than in those with shallow PD sites (48%) or healthy controls (45%). Coexistence of EBV DNA and P. gingivalis was significantly higher in patients with deeper PD sites (40%) than in those with shallow PD sites (14%) or healthy controls (13%). Although no difference in clinical index for periodontitis, the odds ratio of EBV DNA in patients with deeper PD sites was 2.36, which was 2.07-fold higher than that in those with shallow PD sites. Interestingly, the odds of acquiring chronic periodontitis (PD ≥5 mm) were higher in the presence of both EBV DNA and P. gingivalis compared with either EBV DNA or P. gingivalis only. In addition, we also observed that EBV-encoded small RNA (EBER) in positive cells of human gingival tissues. These results would suggest that EBV DNA may serve as a pathogenic factor leading to chronic periodontitis among Japanese patients.

Quantification of Epstein-Barr virus DNA in patients with idiopathic orbital inflammatory pseudotumor.

Inflammatory pseudotumors (IPT) are soft tissue tumors that include a diverse group of lesions characterized by inflammatory cell infiltration and variable fibrotic responses. Idiopathic orbital inflammatory pseudotumors (IOIP) are IPTs of unknown etiology that develop in the orbit. Due to the lack of well-defined pathogenic mechanisms, diagnosis and treatment of this disease remain a significant challenge. Epstein-Barr virus (EBV) infection, which causes significant lymphocyte infiltration, has been proposed to be involved in IOIP. This study tries to validate the relationship between EBV infection and the development of IOIP. Sixteen IOIP tissue samples were obtained from patients during surgical resection of the lesion. One Graves' ophthalmopathy tissue sample and 20 normal donors' plasma serves as controls. The plasma level of five EBV antibodies, including VCA-IgG, VCA-IgA, VCA-IgM, EA-IgG and EBNA1-IgG were examined. All plasma samples were EB-VCA-IgG positive and EB-VCA-IgM negative, suggesting that all people tested had been infected with EBV but not in the acute infection stage. EBV-DNA was detected in 15/16 (94%) of IOIP tissue samples despite different levels of lymphocyte infiltration and 5/16 plasma samples (31%) were detected EBV DNA positive which is higher than the normal controls (10%). Percent of positive plus suspected positive samples with one or more of the three important risk markers (VCA-IgA, EA-IgG, EBV-DNA) is 50% of the patients (8/16) which is much higher compare with the normal controls (20%). The results further reveal the relationship between IOIP and EBV infection.

Clinical Significance of Quantitative Analysis of Plasma Epstein-Barr Virus DNA in Patients of Xinjiang Uygur Nationality with Hodgkin's Lymphoma

To investigate the relationship between plasma EBV-DNA concentration and clinicopathologic features of Hodgkin's lymphoma cases. At first, the positive rate of plasma EBV-DNA was determined with a nested-PCR method using 45 specimens from Uygur HL patients, as well as 110 healthy people sampled as normal controls. Secondly, using fluorescent quantitative nested-PCR, EBV viral load was assessed in the EBV-DNA positive plasma samples. Then, relationships between plasma EBV viral load and clinicopathologic features of HL patients were analyzed. The positive rate of plasma EBV-DNA of HL patients was significantly higher than that of normal controls (53.3%vs26.4%, P=0.001). There was no significant difference about plasma EBV viral load between EBV-associated HL and EBV-DNA positive normal people (P=0.490). Looking at patients' characteristics, plasma EBV viral load in 10-20 years EBV-associated HL was higher than in EBV cases which were less than 10 years or more than 35 years (P=0.025). Furthermore, in EBV-associated HL, concentration of plasma EBV-DNA was significantly higher in advanced stage disease (stages III-IV; P=0.013), and with B-symptoms (P=0.020). EBV-DNA levels were associated with part of clinicopathologic features of cases. It was of practical use to screen HL. Further etiological studies appear warranted.

Nasopharyngeal cancer: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Nasopharyngeal cancer: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up

5504 ORAL Quantification of plasma Epstein-Barr virus DNA in patients with nasopharyngeal carcinoma: results of a prospective study

5504 ORAL Quantification of plasma Epstein-Barr virus DNA in patients with nasopharyngeal carcinoma: results of a prospective study

Quantification of plasma epstein-barr virus dna in patients with nasopharyngeal carcinoma: Preliminary results of a prospective study

Quantification of plasma epstein-barr virus dna in patients with nasopharyngeal carcinoma: Preliminary results of a prospective study

Quantitative analysis of plasma cell-free Epstein-Barr virus DNA in nasopharyngeal carcinoma after salvage nasopharyngectomy: a prospective study.

The quantity of circulating cell-free Epstein-Barr virus (EBV) DNA in patients with nasopharyngeal carcinoma (NPC) managed by radiotherapy has prognostic relevance. We measured the copy number of EBV DNA in patients with early recurrent NPC before and after salvage nasopharyngectomy. Nasopharyngectomy with the maxillary swing approach was performed for 28 patients. Serum blood samples were taken prospectively before nasopharyngectomy and on postoperative day 7. Plasma cell-free EBV DNA copies were measured with a real-time quantitative polymerase chain reaction for the BamHI-W fragment of the EBV genome. Cell-free EBV DNA was detected in 17 patients before nasopharyngectomy. Surgical resection reduced the copy number of EBV DNA significantly (p = .016). Negative surgical margins achieved during nasopharyngectomy is associated with a zero EBV DNA copy postoperatively (p = .022). Cell-free EBV DNA was detected in 61% of patients with recurrent NPC, and its quantity postoperatively reflects whether the salvage nasopharyngectomy has achieved a negative surgical margin.