Epstein-Barr virus biomarkers for nasopharyngeal carcinoma in non-endemic regions.

The Epstein-Barr virus (EBV) plays a key role in the development of undifferentiated nasopharyngeal carcinoma (uNPC). In uNPC endemic regions EBV-specific antibodies and plasma EBV DNA load are used as markers for the early detection of uNPC and monitoring of the disease. In non-endemic regions, such studies were practically not conducted. The aim of this study was to compare the clinical significance of EBV serological markers and plasma EBV DNA levels for uNPC patients in a non-endemic region, Russia. The results obtained indicate that both viral capsid antigen/immunoglobulin A (VCA/IgA) antibodies and plasma EBV DNA copies can effectively be used for nasopharyngeal carcinoma (NPC) diagnosis. Besides, plasma EBV DNA load was found to be a more sensitive marker of uNPC than VCA/IgA antibody titres, as it reflected the effect of the therapy in stages of remission and relapse of the disease more precisely. Our study, for the first time, demonstrates that the simultaneous use of plasma EBV DNA loads and VCA/IgA antibody levels are indispensable markers for uNPC in non-endemic regions: a serological marker can be more effectively used for NPC screening, but EBV DNA copies are better for monitoring the disease. However, both markers turned out to be practically unsuitable for assessing the clinical status of patients. Serological markers did not correlate with any signs of the tumour process estimated by tumour, node and metastasis (TNM) classification and the plasma EBV DNA loads correlated only with the size of the pathologically altered lymph nodes (N). Additional study is required to confirm these findings.

Diagnostic value of the Epstein-Barr virus serological markers in patients with nasopharyngeal carcinoma in cases of undetectable primary tumor location.

The goal of this work was to describe a method for diagnosis of the non-keratinizing nasopharyngeal carcinoma (nNPC) in cases of the undetectable primary tumor location. The method is based on evaluation of IgG and IgA antibody levels to the capsid (VCA) and early antigens (EA) of the Epstein-Barr virus (EBV). The diagnosis of nNPC is established by a so-called decision rule. The latter was created by mathematical processing of the method of multifactor analysis of the results of anti-EBV antibody testing of 72 patients with clinically and morphologically confirmed nNPC and 72 patients with other head and neck benign tumors (OHNT) not associated with EBV, which were tested as a control group. The diagnostic value of the decision rule which was tested in the group of 77 patients with confirmed nNPC and 231 patients of a control group was high. The numbers of false negative and false positive cases were equal to 5.2% (4/77) and 6.5% (17/231), respectively. Among 32 patients with undetectable primary tumors the decision rule was able to identify 11 cases of nNPC. This diagnosis later was confirmed by morphological and instrumental methods of study. Only in two cases, false negative result was obtained (2/32; 6.3%) indicating that the serological diagnostics of nNPC with the decision rule is highly specific but not exact. Thus, the data obtained allowed us to conclude that the serological testing of EBV specific antibody evaluated by the decision rule can be recommended as an important test supplementing the standard methods of pdNPC diagnostics including cases with undetected primary tumor location.

EPSTEIN-BARR VIRUS AND NASOPHARYNGEAL CARCINOMA: VIRAL MARKERS FOR DIAGNOSTICS AND ASSESSMENT OF CLINICAL STATUS OF PATIENTS.

The etiological role of the Epstein-Barr virus (EBV) in the development of an undifferentiated histological variant of nasopharyngeal carcinoma (uNPC) found for the first time in regions with a high incidence of this pathology, the Southern provinces of China and the countries of Southeast Asia, and later in the rest of the world, has served as a basis for the widespread use of EBV serological markers for the diagnosis of this form of tumor. In recent years, the use of a test based on the quantitative determination of the EBV DNA concentration in the blood plasma of uNPC patients for early detection and monitoring of the disease has become widespread in endemic regions. In non-endemic regions, such studies virtually have not been carried out, and moreover, the comparative evaluation of the significance of two viral markers, serological and EBV DNA load in the bloodstream of uNPC patients, for diagnostics and evaluation of the therapeutic effect was not investigated. The aim of this study was to compare the clinical value of two serological markers and plasma EBV DNA load in uNPC patients from non-endemic region (Russia). The obtained results indicate that IgA antibodies to the viral capsid antigen (IgA/VCA) and plasma EBV DNA concentration can be successfully used for the diagnosis of uNPC, while IgG/VCA antibodies have no practical significance as an uNPC marker. In addition, it was found that plasma EBV DNA load is more sensitive marker of uNPC than IgA/VCA titers because DNA copy numbers reflect more accurately the effect of the therapy and the clinical state of patients at the stages of remission or relapse. It was shown for the first time that in the non-endemic region the simultaneous evaluation of IgA/VCA antibody levels and the plasma EBV DNA loads are the most effective markers for the diagnostics of uNPC. However, we believe, that it is more practical to use IgA/VCA antibody levels for uNPC screening, and plasma EBV DNA copies - for monitoring of the disease.