Data from Epstein-Barr Virus DNA Load in Nasopharyngeal Brushings and Whole Blood in Nasopharyngeal Carcinoma Patients before and after Treatment (original) (raw)

Chapter 3 Epstein-Barr Virus ( EBV ) Serological Screening Combined with EBV DNA Load in Nasopharyngeal Brushings for Identification of Nasopharyngeal Carcinoma in Individuals with Chronic Complaints in Head and Neck

2011

Nasopharyngeal carcinoma (NPC) is the most prevalent head and neck cancer in Indonesia, and closely linked to active Epstein-Barr virus (EBV) infection. EBV-based markers are proposed for identifying early stage of NPC. We performed a clinical, serological and viral load study in subjects presenting with chronic symptoms in head and neck to define the serologic response to EBV antigens and EBV DNA load and find early onset NPC. A total of 217 individuals were recruited and underwent clinical examination. Blood samples were taken from all subjects and nasopharyngeal brushing was collected from the majority of individuals. Initial serology analysis was done by peptide-based EBV IgA ELISA and confirmed with IgG immunoblot. As many as 75 (34.6%) subjects demonstrated positive EBV IgA ELISA with 23 (10.6%) showing high response. Sixteen individuals (7.4%) had high IgG immunoblot score. EBV DNA load was determined by real-time PCR in 65 seropositive patients and 28 (43.1%) of them showed ...

The Role of Epstein-Barr Virus DNA Load and Serology as Screening Tools for Nasopharyngeal Carcinoma

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2016

Screening for nasopharyngeal carcinoma (NPC) among family members has been advocated in endemic populations in view of significantly increased risks. We aimed to compare the role of Epstein-Barr virus (EBV) DNA load and EBV IgA serology as tools for screening patients with a first-degree family history of NPC. Case-control study. Tertiary referral center. Serum samples were compared from 293 newly diagnosed NPC patients and 475 individuals with a first-degree family history of NPC. EBV DNA load was measured by real-time quantitative polymerase chain reaction, while EBV viral capsid antigen (VCA) IgA and EBV early antigen (EA) IgA titers were measured by immunofluorescence assays. NPC patients had a significantly higher median EBV DNA load as compared with unaffected family members (835.4 vs 18.8 copies/mL; P < .001). At 100 copies/mL, EBV DNA load demonstrated a sensitivity of 76.8% and a specificity of 85.6%. A positive EBV-EA IgA titer (≥1:10) gave a sensitivity of 85.0% and a ...

Evaluation of plasma Epstein-Barr virus DNA load to distinguish nasopharyngeal carcinoma patients from healthy high-risk populations in Southern China

Cancer, 2014

Introduction: Nasopharyngeal carcinoma (NPC) is an important cancer in Malaysia and is one of the major causes of cancer mortality in this country. This study evaluates the diagnostic and prognostic values in the quantitative relationship between the cell-free Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) load and the tumour burden. Methods: Blood plasma from 18 untreated NPC patients, 20 NPC patients who had been treated with radiotherapy, and 12 healthy individuals were evaluated. EBV copy number was determined following DNA extraction using real-time quantitative polymerase chain reaction. Results: The cell-free EBV DNA load was shown to be proportionately related to the presence of malignant disease. While the EBV copy number in untreated NPC patients had a median of 2,043 copies/ml, viral load in plasma of healthy controls was significantly lower (median of 0 copy/ml). A significant decrease in EBV load was observed in patients who had undergone radiotherapy while a high viral load indicated in one patient correlated to tumour relapse and presence of distant metastasis upon clinical investigation. Conclusion: The blood plasma EBV DNA load was shown to be proportionately related to the presence of malignant disease. This preliminary study underscores the prognostic value of cell-free EBV DNA quantification.

Plasma Cell-free Epstein-Barr Virus DNA Quantitation in Patients with Nasopharyngeal Carcinoma: Correlation with Clinical Staging

Annals of The New York Academy of Sciences, 2006

Nasopharyngeal carcinoma (NPC) is an important cancer in southern China and Southeast Asia. 1 In Hong Kong, nearly all NPC cases are undifferentiated or poorly differentiated and harbor Epstein-Barr virus (EBV) in tumoral tissues. The recent interest in the presence of tumor-derived DNA in the plasma and serum of cancer patients has prompted our group 2 and Mutirangura et al. to look for EBV DNA in the plasma and serum of NPC patients. Our preliminary data indicate that this approach is sensitive and specific for NPC. 2 Our core technology for EBV DNA detection is real-time quantitative PCR, 4 which is able to provide a quantitative measurement of the concentrations of EBV DNA in the plasma of NPC patients. In this communication, we report our latest results based on an expanded sample size, thus allowing a better understanding of the relationship between circulating EBV DNA and NPC staging.

Clinical utility of Epstein‐Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma

Cancer Communications, 2020

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor ubiquitously associated with the Epstein‐Barr virus (EBV), which is highly prevalent in South China, Southeast Asia, and North Africa. Despite being a highly radio‐sensitive and treatable cancer, a majority of NPC patients are diagnosed in their advanced stage, and locoregional and distant relapses following definitive treatment contribute largely to cancer‐specific mortality among these patients. Given that EBV‐driven NPC is the predominant variant seen in endemic regions, various EBV detection methods have been developed and are utilized in screening, prognostication, and post‐treatment surveillance of NPC patients. While the Immunoglobulin A (IgA) serology assay is the most extensively studied EBV detection method, the detection of plasma EBV DNA released during replication or cellular apoptosis has shown superior outcomes in endemic population screening, prognostication, and detection of distant relapse. Furthermore,...

Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer

The New England journal of medicine, 2017

Circulating cell-free Epstein-Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons. We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI). A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MR...

Noninvasive diagnosis of nasopharyngeal carcinoma: Nasopharyngeal brushings reveal high Epstein-Barr virus DNA load and carcinoma-specific viral BARF1 mRNA

International Journal of Cancer, 2006

Nasopharyngeal carcinoma (NPC) is the most prevalent ENT-tumour in Indonesia. We investigated the primary diagnostic value of Epstein-Barr virus (EBV) DNA load and mRNA detection in noninvasive nasopharyngeal (NP) brushings, obtained prospectively from consecutive Indonesian ENT-patients with suspected NPC (N = 106) and controls. A subsequent routine NP biopsy was taken for pathological examination and EBER-RISH, yielding 85 confirmed NPC and 21 non-NPC tumour patients. EBV DNA and human DNA load were quantified by real-time PCR. NP brushings from NPC patients contained extremely high EBV DNA loads compared to the 88 non-NPC controls (p < 0.0001). Using mean EBV DNA load in controls plus 3 SD as cut-off value, specificity, sensitivity, positive and negative predictive values were 98, 90, 97 and 91%, respectively. Epstein-Barr nuclear antigen 1 (EBNA1) and the carcinoma-specific BARF1 mRNA were detected by nucleic acid sequence based amplification and found in 86 and 74% of NP brushings, confirming NPC tumour cell presence. EBV RNA positivity was even higher in fresh samples stored at −80°C until RNA expression analyses (88% for both EBNA1 and BARF1). EBV RNA-negative NP brushings from proven NPC cases had the lowest EBV DNA loads, indicating erroneous sampling. No EBV mRNA was detected in NP brushings from healthy donors and non-NPC patients. In conclusion, EBV DNA load measurement combined with detection of BARF1 mRNA in simple NP brushings allows noninvasive NPC diagnosis. It reflects carcinoma-specific EBV involvement at the anatomical site of tumour development and reduces the need for invasive biopsies. This procedure may be useful for confirmatory diagnosis in large serological NPC screening programs and has potential as prognostic tool. © 2006 Wiley-Liss, Inc.

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

The International journal of biological markers

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 p...

Role of Epstein-Barr virus DNA measurement in plasma in the clinical management of nasopharyngeal carcinoma in a low risk area

Journal of Clinical Pathology, 2006

Objective: To evaluate the role of quantitative measurement of Epstein-Barr virus (EBV) DNA in the clinical management of nasopharyngeal carcinoma (NPC) in a low tumour risk area (western Europe). Methods: 22 consecutive Dutch NPC patients (11 europid) were studied. EBV DNA load in pretreatment and post-treatment plasma samples was determined. Three patients were also sampled at frequent intervals during treatment. RNA in situ hybridisation for the detection of EBV encoded RNAs (EBERs) was carried out on tumour biopsies of all cases. Results: All patients with EBER positive NPC (20/22) showed a positive EBV DNA load in plasma at the time of diagnosis (median EBV DNA level, 4.1 log 10 copies/ml). Patients with EBER negative NPC had no detectable EBV DNA in plasma. After treatment, complete remission was achieved in all cases and concurrently EBV DNA in plasma became undetectable in all patients. In the three longitudinally evaluated cases, EBV DNA load gradually declined towards undetectable levels within three weeks after start of treatment. Two patients developed a distant metastasis with concomitant increases in EBV viral load. In addition, one EBER positive patient developed an EBER negative metastasis in the neck during follow up and in this case EBV DNA load remained undetectable at the time of recurrence. Conclusions: Plasma EBV DNA load measurement appears to be useful in a low tumour risk area. However, development of local recurrences may not always coincide with raised levels of EBV DNA.