Establishment of VCA and EBNA1 IgA‐based combination by enzyme‐linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two‐stage design with a preliminary performance study and a mass screening in southern China

Abstract

A two-stage study was conducted in southern China to determine and validate an optimal combination of Epstein-Barr virus (EBV)-related seromarkers for nasopharyngeal carcinoma (NPC) screening. In the first stage, six seromarkers [VCA-IgA, EA-IgA, Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), EBNA1-IgG, Zta-IgA and Rta-IgG] were detected by enzyme-linked immunosorbent assay (ELISA) and two traditional NPC screening seromarkers (VCA-IgA and EA-IgA) were detected by immunofluorescence assay (IFA) in serum samples from 191 NPC patients and 337 controls. An optimal combination of seromarkers for NPC diagnosis was selected using logistic regression models. Results showed that the diagnostic performances of VCA-IgA and EA-IgA tested by ELISA were superior to the performances of the same seromarkers by IFA. VCA-IgA combined with EBNA1-IgA by ELISA was identified as the optimal combination, with an area under the receiver operating characteristic (ROC) curve (AUC) up to 0.97, a sensitivity of 95.3% and a specificity of 94.1% for classification of NPCs vs. controls. In the second stage, 5,481 participants aged 30-59 years and without clinical evidence of NPC were recruited into a population-based NPC screening program from May 2008 to February 2009 in Sihui City, China. Their sera were tested simultaneously by both the new and the traditional screening schemes and eight early stage NPC patients were subsequently histopathologically confirmed. The traditional and the new screening schemes had comparable specificity (estimated as 98.5%), but the sensitivity of the new scheme (75.0%) was significantly higher than that of the traditional one (25.0%). The combination of VCA-IgA and EBNA1-IgA by ELISA outperforms the traditional NPC screening scheme and could become the preferred serodiagnostic strategy for NPC screening in high-incidence areas.

Diagnostic Significance of Combined Detection of Epstein-Barr Virus Antibodies, VCA/IgA, EA/IgA, Rta/IgG and EBNA1/IgA for Nasopharyngeal Carcinoma

“…At the aspect of diagnostic value of EBV antibody independently, the sensitivity of VCA/IgA and the specificity of EA/IgA were the highest; these results were similar to our team previous studies Zhan et al, 2009) and were superior to the performances of the same seromarkers by IFA reported by (Yu et al, 2011;Liu et al, 2012). It suggests that on the current technological condition, VCA/IgA and EA/IgA detected by immunoenzymatic assay still play important roles in NPC screening and diagnosis.…”

Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma

“…A cut-off level of 4000 copies/ml was chosen to define low and high EBV DNA levels because this threshold has previously been shown to be prognostic in NPC patients using the same measurement system [10, 29]. EBV-specific VCA/IgA antibodies and EBV-specific EA/IgA antibodies were measured using a previously described immunoenzymatic assay [30]. …”

Hepatitis B Virus Infection and Risk of Nasopharyngeal Carcinoma in Southern China

“…The healthy population controls were selected from individuals that participated in a population-based NPC screening program in Sihui county, Guangdong Province, China (34). In total, 5481 eligible individuals at the age of 30 to 59 years in Sihui were recruited in 2008 to the screening program.…”