Distribution of Epstein-Barr viral load in serum of individuals from nasopharyngeal carcinoma high-risk families in Taiwan.
The utility of EBV load as a tumor marker in nasopharyngeal carcinoma (NPC) patients suggests that it might also serve as a screening test for individuals who are at high risk for developing NPC. We previously demonstrated that unaffected individuals from high-risk families had elevated anti-EBV antibody levels compared to community controls. In this study, we measured EBV load using 2 different real-time PCR assays (targeting BamH1W and polymerase gene sequences, respectively) carried out in 2 independent research labs in serum samples from 19 untreated NPC cases, 11 healthy community controls and 100 unaffected individuals from families in which 2 or more individuals were affected with NPC. EBV genomes were detectable in 68% of NPC cases by the EBV BamH1W assay and in 74% by the EBV polymerase assay (kappa = 0.64). Patients with stage III or IV disease had significantly higher EBV load compared to those with stage I or II disease (p = 0.008). EBV DNA was detected in a single community control sample by the EBV BamH1W assay and in none of the samples by the EBV polymerase assay. Only one of 100 unaffected family members tested positive by both assays. An additional 14 were positive by only one of the 2 EBV load assays used and usually in only one of the duplicate wells tested, all with very low viral loads (3-50 copies/ml). In addition, EBV load did not correlate with EBV serology results (anti-VCA, anti-DNase, anti-EBNA-1) among these unaffected family members. In conclusion, our study suggests limited clinical utility of the EBV load test, in its current configuration, to screen individuals from high-risk families. Should a more sensitive or specific molecular assay be developed that is capable of detecting and distinguishing tumor-derived EBV genomes or gene products from true negatives, it could be evaluated as a possible screening tool for asymptomatic and early-stage NPC.
Yang
Xiaohong
X
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20852, USA. royang@mail.nih.gov
Goldstein
Alisa M
AM
Chen
Chien-Jen
CJ
Rabkin
Charles S
CS
Chen
Jen-Yang
JY
Cheng
Yu-Juen
YJ
Hsu
Wan-Lun
WL
Sun
Brenda
B
Diehl
Scott R
SR
Liu
Mei-Ying
MY
Walters
Michael
M
Shao
Wen
W
Ortiz-Conde
Betty A
BA
Whitby
Denise
D
Elmore
Sandra H
SH
Gulley
Margaret L
ML
Hildesheim
Allan
A
D000914:Antibodies, Viral / Q000032:analysis*; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology / Q000276:immunology*; D005190:Family; D020022:Genetic Predisposition to Disease; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000821:virology*; D012306:Risk; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D013624:Taiwan / Q000453:epidemiology; D019562:Viral Load
D000914:Antibodies, Viral