Epstein-Barr virus serology as a potential screening marker for nasopharyngeal carcinoma among high-risk individuals from multiplex families in Taiwan.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of approximately 90%. However, NPC is typically diagnosed at advanced stages, in which disease-free survival is <50%. There is, therefore, a need for clinical tools to assist in early NPC detection, particularly among high-risk individuals.


METHODS
We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (N = 21) and age- and sex-matched controls (N = 84) were selected. Serum collected before NPC diagnosis was tested for ELISA-based IgA antibodies against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated.


RESULTS
EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected.


CONCLUSIONS
EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives.


CONCLUSIONS
Results from this study could inform decisions about screening biomarkers and referral thresholds for future NPC early-detection program evaluations.
Authors' Affiliations: Division of Cancer Epidemiology and Genetics; anna.coghill@nih.gov.
Anna E
AE
Coghill
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University; Genomics Research Center, Academia Sinica;
Wan-Lun
WL
Hsu
Authors' Affiliations: Division of Cancer Epidemiology and Genetics;
Ruth M
RM
Pfeiffer
Department of Pathology, Vrije University Medical Center, Amsterdam, the Netherlands.
Hedy
H
Juwana
Authors' Affiliations: Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland;
Kelly J
KJ
Yu
Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei;
Pei-Jen
PJ
Lou
Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei;
Cheng-Ping
CP
Wang
National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan; and.
Jen-Yang
JY
Chen
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University; Genomics Research Center, Academia Sinica;
Chien-Jen
CJ
Chen
Department of Pathology, Vrije University Medical Center, Amsterdam, the Netherlands.
Jaap M
JM
Middeldorp
Authors' Affiliations: Division of Cancer Epidemiology and Genetics;
Allan
A
Hildesheim
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D019540:Area Under Curve; D002277:Carcinoma; D055088:Early Detection of Cancer / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications; D019309:Epstein-Barr Virus Nuclear Antigens / Q000097:blood; D005189:False Positive Reactions; D006801:Humans; D007070:Immunoglobulin A; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood* / Q000821:virology; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013624:Taiwan
D000914:Antibodies, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D007070:Immunoglobulin A; C417029:EBV-encoded nuclear antigen 1