Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families

Kelly J. Yu, Wan Lun Hsu, Ruth M. Pfeiffer, Chun Ju Chiang, Cheng Ping Wang, Pei Jen Lou, Yu Juen Cheng, Patti Gravitt, Scott R. Diehl, Alisa M. Goldstein, Chien Jen Chen, Allan Hildesheim

Research output: Contribution to journalArticle

Abstract

Purpose: Epstein-Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families. Experimental Design: We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/ specificity and receiver operating characteristic (ROC) curves were calculated. Results: A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4-16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5-61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker. Conclusions: Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity.

Original languageEnglish (US)
Pages (from-to)1906-1914
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number7
DOIs
StatePublished - Apr 1 2011

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Human Herpesvirus 4
Antibodies
Epstein-Barr Virus Nuclear Antigens
Immunoglobulin A
Nasopharyngeal carcinoma
Sensitivity and Specificity
ROC Curve
Epstein-Barr Virus Infections
Deoxyribonucleases
Viral Antigens
Capsid
Serology
Taiwan
Registries
Research Design
Biomarkers

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yu, K. J., Hsu, W. L., Pfeiffer, R. M., Chiang, C. J., Wang, C. P., Lou, P. J., ... Hildesheim, A. (2011). Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families. Clinical Cancer Research, 17(7), 1906-1914. https://doi.org/10.1158/1078-0432.CCR-10-1681

Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families. / Yu, Kelly J.; Hsu, Wan Lun; Pfeiffer, Ruth M.; Chiang, Chun Ju; Wang, Cheng Ping; Lou, Pei Jen; Cheng, Yu Juen; Gravitt, Patti; Diehl, Scott R.; Goldstein, Alisa M.; Chen, Chien Jen; Hildesheim, Allan.

In: Clinical Cancer Research, Vol. 17, No. 7, 01.04.2011, p. 1906-1914.

Research output: Contribution to journalArticle

Yu, KJ, Hsu, WL, Pfeiffer, RM, Chiang, CJ, Wang, CP, Lou, PJ, Cheng, YJ, Gravitt, P, Diehl, SR, Goldstein, AM, Chen, CJ & Hildesheim, A 2011, 'Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families', Clinical Cancer Research, vol. 17, no. 7, pp. 1906-1914. https://doi.org/10.1158/1078-0432.CCR-10-1681
Yu, Kelly J. ; Hsu, Wan Lun ; Pfeiffer, Ruth M. ; Chiang, Chun Ju ; Wang, Cheng Ping ; Lou, Pei Jen ; Cheng, Yu Juen ; Gravitt, Patti ; Diehl, Scott R. ; Goldstein, Alisa M. ; Chen, Chien Jen ; Hildesheim, Allan. / Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 7. pp. 1906-1914.
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abstract = "Purpose: Epstein-Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families. Experimental Design: We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95{\%} CI. Associated sensitivity/ specificity and receiver operating characteristic (ROC) curves were calculated. Results: A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95{\%} CI: 1.4-16) and 166/100,000 person-years with a 6.6-fold increase (95{\%} CI: 1.5-61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7{\%} and 51.2{\%}, respectively. It is estimated that active evaluation of 49{\%} of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86{\%} of NPC cases. Risks associated with the other three EBV markers were weaker. Conclusions: Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity.",
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AU - Chiang, Chun Ju

AU - Wang, Cheng Ping

AU - Lou, Pei Jen

AU - Cheng, Yu Juen

AU - Gravitt, Patti

AU - Diehl, Scott R.

AU - Goldstein, Alisa M.

AU - Chen, Chien Jen

AU - Hildesheim, Allan

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N2 - Purpose: Epstein-Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families. Experimental Design: We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/ specificity and receiver operating characteristic (ROC) curves were calculated. Results: A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4-16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5-61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker. Conclusions: Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity.

AB - Purpose: Epstein-Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families. Experimental Design: We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/ specificity and receiver operating characteristic (ROC) curves were calculated. Results: A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4-16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5-61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker. Conclusions: Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity.

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