title: Complementary serum test of antibodies to Epstein-Barr virus nuclear antigen-1 and early antigen: a possible alternative for primary screening of nasopharyngeal carcinoma.
abstract: This hospital-based cohort study evaluated the efficacy of three Epstein-Barr virus (EBV) - associated assays for nasopharyngeal carcinoma (NPC) primary screening and monitoring treatment outcome. Five hundred and seventeen consecutive subjects, including 156 NPC patients, 264 healthy volunteers and 97 patients with head and neck squamous cell carcinoma (HNSCC) were enrolled. The sensitivity and specificity of EBV IgAs to viral capsid antigen (VCA), complementary EBV IgAs to early antigen and nuclear antigen-1 (EA+EBNA-1), and EBV DNA load were examined by immunofluorescent assays, enzyme-linked immunosorbent assays, and quantitative real-time PCR, respectively. After constructing the receiver operating characteristics to demonstrate screening efficacy, EBV EA+EBNA-1 IgA (AUC: 0.952; 95% CI, 0.930-0.974) was proved superior to EBV VCA IgA (AUC: 0.888; 95% CI, 0.854-0.922) or EBV DNA load (AUC: 0.893; 95% CI, 0.854-0.932) in differentiating NPC patients from controls. Comparison of screening efficacy between NPC patients and HNSCC patients revealed EBV EA+EBNA-1 IgA (AUC: 0.964; 95% CI, 0.943-0.985) still outperformed EBV VCA IgA (AUC: 0.884; 95% CI, 0.845-0.923). In subjects with higher serum titer or level equal to or above 1:80 and 6 EU/ml for EBV VCA IgA and EA+EBNA-1 IgA, the specificity reached as high as 99.2% and 95.1%, respectively, in the control groups. However, correlation of these three assays with clinicopathological manifestations of NPC, revealed only EBV DNA load significantly associated with N stage and overall stage in NPC patients. Additionally, EBV DNA load could be used to further raise the specificity of EBV EA+EBNA-1 IgA assays and was also the only assay to be consistently predictive of tumor relapse in post-treatment patients according to serial test results by time frame. Consequently, an EBV EA+EBNA-1 IgA-based protocol is recommended for mass screening, but EBV DNA load should be used solely for post-treatment monitoring for NPC in endemic areas.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan.
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: Cheng-Lung
authors.initials: CL
authors.lastname: Hsu
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Chang
authors.forename: Ngan-Ming
authors.initials: NM
authors.lastname: Tsang
authors.forename: Chin-Kuo
authors.initials: CK
authors.lastname: Chen
authors.forename: Ta-Jen
authors.initials: TJ
authors.lastname: Lee
authors.forename: Kuo-Chien
authors.initials: KC
authors.lastname: Tsao
authors.forename: Chung-Guei
authors.initials: CG
authors.lastname: Huang
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
authors.forename: Sheng-Po
authors.initials: SP
authors.lastname: Hao
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000097:blood*; D036022:Capsid Proteins / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D019309:Epstein-Barr Virus Nuclear Antigens / Q000097:blood*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014412:Tumor Virus Infections / Q000097:blood / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; C041788:Epstein-Barr viral capsid antigen; C033305:Epstein-Barr virus early antigen; D007070:Immunoglobulin A