Received on May 28, 2003
Accepted on November 26, 2003

Cancer Diagnostics

Improved Accuracy of Detection of Nasopharyngeal Carcinoma by Combined Application of Circulating Epstein-Barr Virus DNA and Anti-Epstein-Barr Viral Capsid Antigen IgA Antibody

¹ Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong SAR, Peoples Republic of China
² Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, Peoples Republic of China
³ Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong SAR, Peoples Republic of China
⁴ Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR, Peoples Republic of China
⁵ The Chinese University of Hong Kong, Hong Kong SAR, Peoples Republic of China
⁶ Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, Peoples Republic of China

^* To whom correspondence should be addressed. E-mail: singfaileung{at}cuhk.edu.hk.

Background: Circulating Epstein-Barr viral (EBV) DNA and anti-EBV capsid antigen IgA (IgA VCA) represent two of the most sensitive peripheral blood markers of nasopharyngeal carcinoma (NPC), but direct comparative studies of these two markers are lacking.

Methods: The sensitivities and specificities of IgA-VCA and EBV DNA for diagnosis of NPC were determined in 139 new cases of NPC and 178 healthy individuals, respectively. EBV DNA was also assessed in 36 healthy family members identified to have false-positive IgA-VCA results at a screening clinic. EBV DNA was measured by a real-time quantitative PCR assay with a detection limit of 60 copies/mL. IgA-VCA was measured by semiquantitative indirect immunofluorescent method; a titer 1/10 was taken as positive.

Results: The sensitivities of EBV DNA and IgA-VCA for diagnosis of NPC were 95% (95% confidence interval, 91-98%) and 81% (73-87%), respectively. The combined marker panel had an overall sensitivity (positive result by either marker) of 99%. The concentrations of both markers showed dependence on cancer stage. The specificities of EBV DNA and IgA-VCA were 98% (96-99%) and 96% (91-98%), respectively. Among 36 healthy family members with false-positive IgA-VCA results, three-fourths had undetectable EBV DNA, whereas the others had increased EBV DNA concentrations that were significantly lower than in NPC patients.

Conclusions: For diagnosis of NPC, EBV DNA identifies almost all false-negative IgA-VCA cases and gives a 99% diagnostic sensitivity when combined with IgA-VCA. In the screening setting, EBV DNA identifies three-fourths of false-positive IgA-VCA cases. The selective application of EBV DNA in an IgA-VCA-based screening protocol could improve screening accuracy with only moderate increases in cost.