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

Int J Cancer. 2012 Jul 15;131(2):406-16. doi: 10.1002/ijc.26380. Epub 2011 Nov 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology*
  • Capsid / immunology
  • Capsid Proteins / immunology*
  • Carcinoma
  • China
  • Early Detection of Cancer / methods
  • Enzyme-Linked Immunosorbent Assay
  • Epstein-Barr Virus Infections / diagnosis*
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Nuclear Antigens / immunology*
  • Female
  • Fluorescent Antibody Technique
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunoglobulin A / blood*
  • Immunoglobulin A / immunology
  • Male
  • Mass Screening / methods
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / diagnosis*
  • Nasopharyngeal Neoplasms / immunology


  • Antibodies, Viral
  • Antigens, Viral
  • Capsid Proteins
  • Epstein-Barr Virus Nuclear Antigens
  • Epstein-Barr viral capsid antigen
  • Immunoglobulin A
  • EBV-encoded nuclear antigen 1