title: The Role of Epstein-Barr Virus DNA Load and Serology as Screening Tools for Nasopharyngeal Carcinoma.
abstract: Screening for nasopharyngeal carcinoma (NPC) among family members has been advocated in endemic populations in view of significantly increased risks. We aimed to compare the role of Epstein-Barr virus (EBV) DNA load and EBV IgA serology as tools for screening patients with a first-degree family history of NPC.
  
  
  
  Case-control study.
  
  
  
  Tertiary referral center.
  
  
  
  Serum samples were compared from 293 newly diagnosed NPC patients and 475 individuals with a first-degree family history of NPC. EBV DNA load was measured by real-time quantitative polymerase chain reaction, while EBV viral capsid antigen (VCA) IgA and EBV early antigen (EA) IgA titers were measured by immunofluorescence assays.
  
  
  
  NPC patients had a significantly higher median EBV DNA load as compared with unaffected family members (835.4 vs 18.8 copies/mL; P < .001). At 100 copies/mL, EBV DNA load demonstrated a sensitivity of 76.8% and a specificity of 85.6%. A positive EBV-EA IgA titer (≥1:10) gave a sensitivity of 85.0% and a specificity of 96.4%. There was good correlation between EBV DNA load and EBV serology titers (Spearman's ρ = .536 and .594 for EBV-VCA IgA and EBV-EA IgA, respectively; P < .001). Receiver operating characteristic analysis demonstrated that EBV-VCA IgA and EBV-EA IgA were better classifiers than EBV DNA load (areas under the curve: 0.942, 0.926, and 0.880, respectively) in distinguishing NPC patients and unaffected family members.
  
  
  
  EBV DNA load and EBV IgA serology demonstrate good sensitivity and specificity as screening tools. EBV-EA IgA gave the best sensitivity and specificity profile as a screening tool for NPC among high-risk family members.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System, Singapore Department of Cancer Biology, Stanford University School of Medicine, Stanford, California, USA joshua_tay@nuhs.edu.sg.
authors.forename: Joshua K
authors.initials: JK
authors.lastname: Tay
authors.affiliation: Department of Microbiology, National University of Singapore, Singapore World Health Organisation Immunology and Training Research Centre, Singapore.
authors.forename: Soh Ha
authors.initials: SH
authors.lastname: Chan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System, Singapore.
authors.forename: Chwee Ming
authors.initials: CM
authors.lastname: Lim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System, Singapore.
authors.forename: Chor Hiang
authors.initials: CH
authors.lastname: Siow
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System, Singapore.
authors.forename: Han Lee
authors.initials: HL
authors.lastname: Goh
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System, Singapore.
authors.forename: Kwok Seng
authors.initials: KS
authors.lastname: Loh
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000821:virology*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D005455:Fluorescent Antibody Technique; D020022:Genetic Predisposition to Disease; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D004279:DNA, Viral; D007070:Immunoglobulin A
keywords: DNA load; Epstein-Barr virus; family screen; nasopharyngeal carcinoma; serology