Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches

Pei Jen Lou; W. K. Jacky Lam; Wan Lun Hsu; Ruth M. Pfeiffer; Kelly J. Yu; Charles M.L. Chan; Vicky C.T. Lee; Tseng Cheng Chen; Shyuang Der Terng; Yung An Tsou; Yi Shing Leu; Li Jen Liao; Yen Liang Chang; Yin Chu Chien; Cheng Ping Wang; Ching Yuan Lin; Chun Hung Hua; Jehn Chuan Lee; Tsung Lin Yang; Chu Hsing Hsiao; Ming Shiang Wu; Ming Hsui Tsai; Hung Chun Cheng; Allan Hildesheim; Chien Jen Chen; K. C.Allen Chan; Zhiwei Liu; Wan Lun Hsu; Yin Chu Chien; Chien Jen Chen; Allan Hildesheim; Ruth M. Pfeiffer; Zhiwei Liu; Kelly J. Yu; Cheng Ping Wang; Tsung Lin Yang; Pei Jen Lou; Chun Nan Chen; Tseng Cheng Chen; Chih Feng Lin; James Jer Min Jian; Skye Hongiun Cheng; Yu Chen Tsai; Yih Lin Chung; Jia Shing Wu; Ming Jiung Liu; Kuei Kang Huang; Mei Hua Tsou; Hsin Hsuan Chen; Ching Yuan Lin; Shyuang Der Terng; Fang Yin Lin; Hsin I. Huang; Hung Chun Cheng; Yung An Tsou; Chun Hung Hua; Ming-Hsui Tsai; Yi Shing Leu; Jehn Chuan Lee; Li Jen Liao; Yen Liang Chang; Chu Hsing Hsiao; Ming Shiang Wu

doi:10.1200/JCO.22.01979

Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches

Pei Jen Lou, W. K. Jacky Lam, Wan Lun Hsu, Ruth M. Pfeiffer, Kelly J. Yu, Charles M.L. Chan, Vicky C.T. Lee, Tseng Cheng Chen, Shyuang Der Terng, Yung An Tsou, Yi Shing Leu, Li Jen Liao, Yen Liang Chang, Yin Chu Chien, Cheng Ping Wang, Ching Yuan Lin, Chun Hung Hua, Jehn Chuan Lee, Tsung Lin Yang, Chu Hsing HsiaoMing Shiang Wu, Ming Hsui Tsai, Hung Chun Cheng, Allan Hildesheim, Chien Jen Chen, K. C.Allen Chan^*, Zhiwei Liu, Wan Lun Hsu, Yin Chu Chien, Chien Jen Chen, Allan Hildesheim, Ruth M. Pfeiffer, Zhiwei Liu, Kelly J. Yu, Cheng Ping Wang, Tsung Lin Yang, Pei Jen Lou, Chun Nan Chen, Tseng Cheng Chen, Chih Feng Lin, James Jer Min Jian, Skye Hongiun Cheng, Yu Chen Tsai, Yih Lin Chung, Jia Shing Wu, Ming Jiung Liu, Kuei Kang Huang, Mei Hua Tsou, Hsin Hsuan Chen, Ching Yuan Lin, Shyuang Der Terng, Fang Yin Lin, Hsin I. Huang, Hung Chun Cheng, Yung An Tsou, Chun Hung Hua, Ming-Hsui Tsai, Yi Shing Leu, Jehn Chuan Lee, Li Jen Liao, Yen Liang Chang, Chu Hsing Hsiao, Ming Shiang Wu

^*Corresponding author for this work

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

17 Scopus citations

Abstract

PURPOSETwo Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population.METHODSWe tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm).RESULTSEBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10-4) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10-7). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (P =.514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively.CONCLUSIONWe demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

Original language	English
Pages (from-to)	4257-4266
Number of pages	10
Journal	Journal of Clinical Oncology
Volume	41
Issue number	26
DOIs	https://doi.org/10.1200/JCO.22.01979
State	Published - 10 09 2023
Externally published	Yes

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Publisher Copyright:
© American Society of Clinical Oncology.

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10.1200/JCO.22.01979

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Lou, P. J., Jacky Lam, W. K., Hsu, W. L., Pfeiffer, R. M., Yu, K. J., Chan, C. M. L., Lee, V. C. T., Chen, T. C., Terng, S. D., Tsou, Y. A., Leu, Y. S., Liao, L. J., Chang, Y. L., Chien, Y. C., Wang, C. P., Lin, C. Y., Hua, C. H., Lee, J. C., Yang, T. L., ... Wu, M. S. (2023). Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches. Journal of Clinical Oncology, 41(26), 4257-4266. https://doi.org/10.1200/JCO.22.01979

@article{58ee565d5f934c608a6a79ef1b8af92b,

title = "Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches",

abstract = "PURPOSETwo Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population.METHODSWe tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm).RESULTSEBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10-4) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10-7). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (P =.514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively.CONCLUSIONWe demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.",

author = "Lou, {Pei Jen} and {Jacky Lam}, {W. K.} and Hsu, {Wan Lun} and Pfeiffer, {Ruth M.} and Yu, {Kelly J.} and Chan, {Charles M.L.} and Lee, {Vicky C.T.} and Chen, {Tseng Cheng} and Terng, {Shyuang Der} and Tsou, {Yung An} and Leu, {Yi Shing} and Liao, {Li Jen} and Chang, {Yen Liang} and Chien, {Yin Chu} and Wang, {Cheng Ping} and Lin, {Ching Yuan} and Hua, {Chun Hung} and Lee, {Jehn Chuan} and Yang, {Tsung Lin} and Hsiao, {Chu Hsing} and Wu, {Ming Shiang} and Tsai, {Ming Hsui} and Cheng, {Hung Chun} and Allan Hildesheim and Chen, {Chien Jen} and Chan, {K. C.Allen} and Zhiwei Liu and Hsu, {Wan Lun} and Chien, {Yin Chu} and Chen, {Chien Jen} and Allan Hildesheim and Pfeiffer, {Ruth M.} and Zhiwei Liu and Yu, {Kelly J.} and Wang, {Cheng Ping} and Yang, {Tsung Lin} and Lou, {Pei Jen} and Chen, {Chun Nan} and Chen, {Tseng Cheng} and Lin, {Chih Feng} and Jian, {James Jer Min} and Cheng, {Skye Hongiun} and Tsai, {Yu Chen} and Chung, {Yih Lin} and Wu, {Jia Shing} and Liu, {Ming Jiung} and Huang, {Kuei Kang} and Tsou, {Mei Hua} and Chen, {Hsin Hsuan} and Lin, {Ching Yuan} and Terng, {Shyuang Der} and Lin, {Fang Yin} and Huang, {Hsin I.} and Cheng, {Hung Chun} and Tsou, {Yung An} and Hua, {Chun Hung} and Ming-Hsui Tsai and Leu, {Yi Shing} and Lee, {Jehn Chuan} and Liao, {Li Jen} and Chang, {Yen Liang} and Hsiao, {Chu Hsing} and Wu, {Ming Shiang}",

note = "Publisher Copyright: {\textcopyright} American Society of Clinical Oncology.",

year = "2023",

month = sep,

day = "10",

doi = "10.1200/JCO.22.01979",

language = "英语",

volume = "41",

pages = "4257--4266",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "Lippincott Williams and Wilkins",

number = "26",

}

Lou, PJ, Jacky Lam, WK, Hsu, WL, Pfeiffer, RM, Yu, KJ, Chan, CML, Lee, VCT, Chen, TC, Terng, SD, Tsou, YA, Leu, YS, Liao, LJ, Chang, YL, Chien, YC, Wang, CP, Lin, CY, Hua, CH, Lee, JC, Yang, TL, Hsiao, CH, Wu, MS, Tsai, MH, Cheng, HC, Hildesheim, A, Chen, CJ, Chan, KCA, Liu, Z, Hsu, WL, Chien, YC, Chen, CJ, Hildesheim, A, Pfeiffer, RM, Liu, Z, Yu, KJ, Wang, CP, Yang, TL, Lou, PJ, Chen, CN, Chen, TC, Lin, CF, Jian, JJM, Cheng, SH, Tsai, YC, Chung, YL, Wu, JS, Liu, MJ, Huang, KK, Tsou, MH, Chen, HH, Lin, CY, Terng, SD, Lin, FY, Huang, HI, Cheng, HC, Tsou, YA, Hua, CH, Tsai, M-H, Leu, YS, Lee, JC, Liao, LJ, Chang, YL, Hsiao, CH & Wu, MS 2023, 'Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches', Journal of Clinical Oncology, vol. 41, no. 26, pp. 4257-4266. https://doi.org/10.1200/JCO.22.01979

Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches. / Lou, Pei Jen; Jacky Lam, W. K.; Hsu, Wan Lun et al.
In: Journal of Clinical Oncology, Vol. 41, No. 26, 10.09.2023, p. 4257-4266.

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

TY - JOUR

T1 - Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma

T2 - Direct Comparison of Two Alternative Approaches

AU - Lou, Pei Jen

AU - Jacky Lam, W. K.

AU - Hsu, Wan Lun

AU - Pfeiffer, Ruth M.

AU - Yu, Kelly J.

AU - Chan, Charles M.L.

AU - Lee, Vicky C.T.

AU - Chen, Tseng Cheng

AU - Terng, Shyuang Der

AU - Tsou, Yung An

AU - Leu, Yi Shing

AU - Liao, Li Jen

AU - Chang, Yen Liang

AU - Chien, Yin Chu

AU - Wang, Cheng Ping

AU - Lin, Ching Yuan

AU - Hua, Chun Hung

AU - Lee, Jehn Chuan

AU - Yang, Tsung Lin

AU - Hsiao, Chu Hsing

AU - Wu, Ming Shiang

AU - Tsai, Ming Hsui

AU - Cheng, Hung Chun

AU - Hildesheim, Allan

AU - Chen, Chien Jen

AU - Chan, K. C.Allen

AU - Liu, Zhiwei

AU - Hsu, Wan Lun

AU - Chien, Yin Chu

AU - Chen, Chien Jen

AU - Hildesheim, Allan

AU - Pfeiffer, Ruth M.

AU - Liu, Zhiwei

AU - Yu, Kelly J.

AU - Wang, Cheng Ping

AU - Yang, Tsung Lin

AU - Lou, Pei Jen

AU - Chen, Chun Nan

AU - Chen, Tseng Cheng

AU - Lin, Chih Feng

AU - Jian, James Jer Min

AU - Cheng, Skye Hongiun

AU - Tsai, Yu Chen

AU - Chung, Yih Lin

AU - Wu, Jia Shing

AU - Liu, Ming Jiung

AU - Huang, Kuei Kang

AU - Tsou, Mei Hua

AU - Chen, Hsin Hsuan

AU - Lin, Ching Yuan

AU - Terng, Shyuang Der

AU - Lin, Fang Yin

AU - Huang, Hsin I.

AU - Cheng, Hung Chun

AU - Tsou, Yung An

AU - Hua, Chun Hung

AU - Tsai, Ming-Hsui

AU - Leu, Yi Shing

AU - Lee, Jehn Chuan

AU - Liao, Li Jen

AU - Chang, Yen Liang

AU - Hsiao, Chu Hsing

AU - Wu, Ming Shiang

PY - 2023/9/10

Y1 - 2023/9/10

N2 - PURPOSETwo Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population.METHODSWe tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm).RESULTSEBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10-4) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10-7). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (P =.514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively.CONCLUSIONWe demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

AB - PURPOSETwo Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population.METHODSWe tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm).RESULTSEBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10-4) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10-7). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (P =.514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively.CONCLUSIONWe demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

UR - http://www.scopus.com/inward/record.url?scp=85170111391&partnerID=8YFLogxK

U2 - 10.1200/JCO.22.01979

DO - 10.1200/JCO.22.01979

M3 - 文章

C2 - 37478397

AN - SCOPUS:85170111391

SN - 0732-183X

VL - 41

SP - 4257

EP - 4266

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 26

ER -

Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches

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