The use of a tandem serial measurement of circulating EBV DNA for the outpatient screening of EBV associated nasophayngeal carcinoma

Abstract

9617 Background: Epstein Barr virus (EBV) DNA has been found in the plasma of patients with nasopharyngeal carcinoma (NPC). The presence and quantity of EBV DNA has been used for the diagnosis, prognosis and monitoring of NPC patients. However, low copies of EBV DNA may also been found in a small percentage (1–3%) of normal individuals. This phenomenon may be due to the episodic lytic reactivations of the virus. The present study is to find out, by the use of a tandem and serial measurement of circulating EBV DNA in plasma, the positive and negative predictive value of this test for EBV positive nasopharyngeal carcinoma. Methods: Normal adults recruited during routine physicals and those with outpatient ear, nose and throat symptoms but with no confirmed diagnosis of cancer and age over 18 were admitted to the study. The quantity of circulating EBV DNA extracted from plasma was determined by a well described real-time PCR method using ABI Prism 7900 HT with specific primers and probe against the W1 fragment from the EBNA-LP region of the EBV genome. A second measurement of any positive case was offered to that individual 4–12 weeks after the first. All cases were followed for one year. Results: In this study group, 74 out of 3987 cases were determined as having positive EBV DNA values. Among the 74 positive EBV DNA cases, 27 cases returned to have second measurements within a 4 to 12 week period from the first. All except one saw their EBV DNA titers reduced to zero at the second measurement. The one that still showed a positive EBV DNA had a 50% reduction of its quantity compared with the first. He was given a third measurement 6 weeks later and the result was then negative. No EBV associated nasopharyngeal carcinoma case was identified in this study group. Conclusions: The negative predictive value using a tandem measurement of plasma circulating EBV DNA with the second measurement done within 4–12 week from the first has been close to perfect for a group of normal individuals and those with outpatient ear, nose and throat symptoms. The study is still ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Plasmagene Biosciences Ltd. Plasmagene Biosciences Ltd.