Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs

Geng Hang Chen; Zhiwei Liu; Kelly J. Yu; Anna E. Coghill; Xiao Xia Chen; Shang Hang Xie; Dong Feng Lin; Qi Hong Huang; Yu Qiang Lu; Wei Ling; Chu Yang Lin; Zi Jian Lu; Yu Ying Fan; Lin Quan Tang; Joshua N. Sampson; Hui Li; Ann D. King; Jaap M. Middeldorp; Allan Hildesheim; Su Mei Cao

doi:https://doi.org/10.1093/clinchem/hvac032

Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs

Geng Hang Chen, Zhiwei Liu, Kelly J. Yu, Anna E. Coghill, Xiao Xia Chen, Shang Hang Xie, Dong Feng Lin, Qi Hong Huang, Yu Qiang Lu, Wei Ling, Chu Yang Lin, Zi Jian Lu, Yu Ying Fan, Lin Quan Tang, Joshua N. Sampson, Hui Li, Ann D. King, Jaap M. Middeldorp, Allan Hildesheim, Su Mei Cao

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.

Original language	English
Pages (from-to)	953-962
Number of pages	10
Journal	Clinical Chemistry
Volume	68
Issue number	7
DOIs	https://doi.org/10.1093/clinchem/hvac032
Publication status	Published - 1 Jul 2022

Keywords

cancer
epidemiology studies
molecular diagnostics

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Chen, G. H., Liu, Z., Yu, K. J., Coghill, A. E., Chen, X. X., Xie, S. H., Lin, D. F., Huang, Q. H., Lu, Y. Q., Ling, W., Lin, C. Y., Lu, Z. J., Fan, Y. Y., Tang, L. Q., Sampson, J. N., Li, H., King, A. D., Middeldorp, J. M., Hildesheim, A., & Cao, S. M. (2022). Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs. Clinical Chemistry, 68(7), 953-962. https://doi.org/10.1093/clinchem/hvac032

@article{2102aafbb7b94b42bd6ab5473309662c,

title = "Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs",

abstract = "BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.",

keywords = "cancer, epidemiology studies, molecular diagnostics",

author = "Chen, {Geng Hang} and Zhiwei Liu and Yu, {Kelly J.} and Coghill, {Anna E.} and Chen, {Xiao Xia} and Xie, {Shang Hang} and Lin, {Dong Feng} and Huang, {Qi Hong} and Lu, {Yu Qiang} and Wei Ling and Lin, {Chu Yang} and Lu, {Zi Jian} and Fan, {Yu Ying} and Tang, {Lin Quan} and Sampson, {Joshua N.} and Hui Li and King, {Ann D.} and Middeldorp, {Jaap M.} and Allan Hildesheim and Cao, {Su Mei}",

note = "Funding Information: This work was supported by National Key R&D Program of China (2020YFC1316905, to S.C.); National Natural Science Foundation of China (81872700, 82073625, to S.C.); Planned Science and Technology Project of Guangdong Province (2019B020230002, to S.C.); Heath&Medical Collaborate Innovation Project of Guangzhou City, China (201803040003, to S.C.); Sun Yat-Sen University Clinical Research 5010 Program (2013012, to S.C.); Intramural Research Program of National Cancer Institute (NCI), USA (to A.H. and S.C.). Publisher Copyright: {\textcopyright} 2022 American Association for Clinical Chemistry. All rights reserved.",

year = "2022",

month = jul,

day = "1",

doi = "https://doi.org/10.1093/clinchem/hvac032",

language = "English",

volume = "68",

pages = "953--962",

journal = "Clinical Chemistry",

issn = "0009-9147",

publisher = "American Association for Clinical Chemistry Inc.",

number = "7",

}

Chen, GH, Liu, Z, Yu, KJ, Coghill, AE, Chen, XX, Xie, SH, Lin, DF, Huang, QH, Lu, YQ, Ling, W, Lin, CY, Lu, ZJ, Fan, YY, Tang, LQ, Sampson, JN, Li, H, King, AD, Middeldorp, JM, Hildesheim, A & Cao, SM 2022, 'Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs', Clinical Chemistry, vol. 68, no. 7, pp. 953-962. https://doi.org/10.1093/clinchem/hvac032

TY - JOUR

T1 - Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs

AU - Chen, Geng Hang

AU - Liu, Zhiwei

AU - Yu, Kelly J.

AU - Coghill, Anna E.

AU - Chen, Xiao Xia

AU - Xie, Shang Hang

AU - Lin, Dong Feng

AU - Huang, Qi Hong

AU - Lu, Yu Qiang

AU - Ling, Wei

AU - Lin, Chu Yang

AU - Lu, Zi Jian

AU - Fan, Yu Ying

AU - Tang, Lin Quan

AU - Sampson, Joshua N.

AU - Li, Hui

AU - King, Ann D.

AU - Middeldorp, Jaap M.

AU - Hildesheim, Allan

AU - Cao, Su Mei

N1 - Funding Information: This work was supported by National Key R&D Program of China (2020YFC1316905, to S.C.); National Natural Science Foundation of China (81872700, 82073625, to S.C.); Planned Science and Technology Project of Guangdong Province (2019B020230002, to S.C.); Heath&Medical Collaborate Innovation Project of Guangzhou City, China (201803040003, to S.C.); Sun Yat-Sen University Clinical Research 5010 Program (2013012, to S.C.); Intramural Research Program of National Cancer Institute (NCI), USA (to A.H. and S.C.). Publisher Copyright: © 2022 American Association for Clinical Chemistry. All rights reserved.

PY - 2022/7/1

Y1 - 2022/7/1

N2 - BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.

AB - BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.

KW - cancer

KW - epidemiology studies

KW - molecular diagnostics

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U2 - https://doi.org/10.1093/clinchem/hvac032

DO - https://doi.org/10.1093/clinchem/hvac032

M3 - Article

C2 - 35325087

SN - 0009-9147

VL - 68

SP - 953

EP - 962

JO - Clinical Chemistry

JF - Clinical Chemistry

IS - 7

ER -

Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs

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