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4. Kinetics of EBV antibody‐based NPC risk scores in Taiwan NPC multiplex families.

Author

Hsu, Wan‐Lun, Tao, Jun, Fu, Sheng, Yu, Kelly J., Simon, Julia, Chen, Tseng‐Cheng, Chen, Chien‐Jen, Goldstein, Alisa M., Yu, Kai, Hildesheim, Allan, Waterboer, Tim, Wang, Cheng‐Ping, and Liu, Zhiwei

Subjects
DISEASE risk factors, VIRAL antibodies, NASOPHARYNX cancer, EARLY detection of cancer, ANTIBODY formation
Abstract

Nasopharyngeal carcinoma (NPC) risk prediction models based on Epstein–Barr virus (EBV)‐antibody testing have shown potential for screening of NPC; however, the long‐term stability is unclear. Here, we investigated the kinetics of two EBV‐antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2‐marker enzyme‐linked immunosorbent assay score and 13‐marker multiplex serology score using the intra‐class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20‐year follow‐up, the 2‐marker score showed high stability over time, whereas the 13‐marker score was more variable (p <.05). Case–control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2‐marker score than the 13‐marker score (p <.05). The 2‐marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13‐marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high‐risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high‐risk regions. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Association Between Antibodies That Bind Epstein-Barr Virus (EBV) gp350 and gH/gL and Shedding of EBV in Saliva From Nasopharyngeal Carcinoma Multiplex Family Members in Taiwan.

Author

Liu, Kai-Lin, Hsu, Wan-Lun, Bu, Wei, Yu, Kelly J, Wang, Cheng-Ping, Chien, Yin-Chu, Chen, Tseng-Cheng, Chen, Chien-Jen, Hildesheim, Allan, Middeldorp, Jaap M, Waterboer, Tim, Cohen, Jeffrey I, Coghill, Anna E, and Liu, Zhiwei

Subjects
*EPSTEIN-Barr virus, *VIRAL DNA, *NASOPHARYNX cancer, *GLYCOPROTEINS, *ODDS ratio
Abstract

Elevated levels of Epstein-Barr virus (EBV) gp350 and gH/gL antibodies have been associated with a lower risk of developing nasopharyngeal carcinoma (NPC), although the evidence remains inconclusive and unexplained. We conducted a longitudinal study within a high-risk Taiwanese cohort, analyzing total immunoglobulin against EBV-gp350 and -gH/gL in blood and EBV DNA shedding in saliva. Contrary to our hypothesis—that elevated levels of antibodies previously shown to be associated with a lower NPC risk should result in a decrease in EBV shedding in saliva—higher anti-gp350 antibodies at baseline were significantly associated with detectable EBV DNA in saliva at follow-up (odds ratio [OR], 1.99 [95% confidence interval {CI}, 1.03–3.97]; P =.04). Higher anti-EBV-gH/gL antibodies at baseline were not significantly associated with risk of detectable EBV DNA at follow-up (OR, 0.69 [95% CI,.35–1.32]; P =.26). These findings underscore the complexity of virus–host interactions and emphasize the need for further investigations into their role in EBV-associated diseases. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Epidemiology of Virus Infection and Human Cancer

Author

Chen, Chien-Jen, You, San-Lin, Hsu, Wan-Lun, Yang, Hwai-I, Lee, Mei-Hsuan, Chen, Hui-Chi, Chen, Yun-Yuan, Liu, Jessica, Hu, Hui-Han, Lin, Yu-Ju, Chu, Yu-Ju, Huang, Yen-Tsung, Chiang, Chun-Ju, Chien, Yin-Chu, Krämer, Alwin, Series Editor, Lu, Jiade J., Series Editor, Wu, T.-C., editor, Chang, Mei-Hwei, editor, and Jeang, Kuan-Teh, editor

Published
2021
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8. Impact of oral hygiene on head and neck cancer risk in a Chinese population

Author

Kawakita, Daisuke, Lee, Yuan‐Chin Amy, Li, Qian, Chen, Yuji, Chen, Chien‐Jen, Hsu, Wan‐Lun, Lou, Pei‐Jen, Zhu, Cairong, Pan, Jian, Shen, Hongbing, Ma, Hongxia, Cai, Lin, He, Baochang, Wang, Yu, Zhou, Xiaoyan, Ji, Qinghai, Zhou, Baosen, Wu, Wei, Ma, Jie, Boffetta, Paolo, Zhang, Zuo‐Feng, Dai, Min, and Hashibe, Mia

Subjects
Rare Diseases, Cancer, Dental/Oral and Craniofacial Disease, Clinical Research, Prevention, Oral and gastrointestinal, Adult, Age Distribution, Aged, Aged, 80 and over, Carcinoma, Squamous Cell, Case-Control Studies, China, Confidence Intervals, Female, Head and Neck Neoplasms, Humans, Incidence, Logistic Models, Male, Middle Aged, Multivariate Analysis, Neoplasm Invasiveness, Neoplasm Staging, Odds Ratio, Oral Hygiene, Risk Assessment, Sex Distribution, Young Adult, Chinese, dental care, head and neck cancer, oral hygiene, risk, Clinical Sciences, Dentistry, Otorhinolaryngology
Abstract

BackgroundAlthough the impact of oral hygiene on head and neck cancer risk has been investigated, few studies have been conducted among the Asian population.MethodsWe conducted a multicenter case-control study to investigate this potential association. We performed unconditional multiple logistic regression models adjusted by potential confounders.ResultsWe observed an inverse association of frequency of dental visits with head and neck cancer risk, with an adjusted odds ratio (OR) of 3.70 (95% CI 2.51-5.45) for never dental visits compared with ≥1 time/year (Ptrend < .001). We also observed a positive association between the number of missing teeth and head and neck cancer risk, with an adjusted OR for ≥5 missing teeth compared with

Published
2017

9. Secular Increasing Trends in Female Thyroid Cancer Incidence in Taiwan.

Author

Wu, Jiun-Yan, Shyu, Yuh-Kae, Lee, Yu-Kwang, Wang, Yu-Chiao, Chiang, Chun-Ju, You, San-Lin, Liao, Li-Jen, Hsu, Wan-Lun, and Chen, Yong-Chen

Subjects
THYROID cancer, OVERTREATMENT of cancer, COHORT analysis, AGE groups, FERTILITY
Abstract

Background: Thyroid cancer incidence has increased globally in recent decades, especially in females, although its trends in Taiwan have not been studied extensively. This study aimed to investigate changes in female incidence and possible causes of thyroid cancer in Taiwan. Methods: Using the Taiwan Cancer Registry (TCR) Database, age-standardized incidence rates, age-specific incidence rates and birth cohorts were calculated. Correlation between female thyroid cancer incidence and cohort fertility rates were examined. Results: Thyroid cancer incidence increased in Taiwanese female, with age-adjusted rates per 100,000 people increasing from 7.37 during 1995–1999 to 20.53 during 2015–2019; the annual percentage change (APC) was 5.9% (95% CI, 5.3–6.5). Age-specific incidence rates increased with age, with peak rates occurring at younger ages. The APCs in the 50–54 age group were the highest (6.8%, 95% CI, 6.1–7.5). Incidence rates also increased with later birth cohorts. We observed a significant negative correlation between thyroid cancer incidence and fertility rates in the same birth cohort. Conclusions: We hypothesize that overdiagnosis may be a main reason for the rapidly increasing thyroid cancer incidence in Taiwanese females. Notably, we observed a strong negative correlation between fertility and thyroid cancer incidence. However, our study is limited by the absence of individual-level cancer data in the TCR database. These associations with fertility will be an important subject for future thyroid cancer research. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Epidemiology of Virus Infection and Human Cancer

Author

Chen, Chien-Jen, primary, You, San-Lin, additional, Hsu, Wan-Lun, additional, Yang, Hwai-I, additional, Lee, Mei-Hsuan, additional, Chen, Hui-Chi, additional, Chen, Yun-Yuan, additional, Liu, Jessica, additional, Hu, Hui-Han, additional, Lin, Yu-Ju, additional, Chu, Yu-Ju, additional, Huang, Yen-Tsung, additional, Chiang, Chun-Ju, additional, and Chien, Yin-Chu, additional

Published
2020
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20. Data from Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies

Author

Argirion, Ilona, primary, Pfeiffer, Ruth M., primary, Proietti, Carla, primary, Coghill, Anna E., primary, Yu, Kelly J., primary, Middeldorp, Jaap M., primary, Sarathkumara, Yomani D., primary, Hsu, Wan-Lun, primary, Chien, Yin-Chu, primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Rothman, Nathaniel, primary, Lan, Qing, primary, Chen, Chien-Jen, primary, Mbulaiteye, Sam M., primary, Jarrett, Ruth F., primary, Glimelius, Ingrid, primary, Smedby, Karin E., primary, Hjalgrim, Henrik, primary, Hildesheim, Allan, primary, Doolan, Denise L., primary, and Liu, Zhiwei, primary

Published
2023
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21. Supplementary Table S2 from Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies

Author

Argirion, Ilona, primary, Pfeiffer, Ruth M., primary, Proietti, Carla, primary, Coghill, Anna E., primary, Yu, Kelly J., primary, Middeldorp, Jaap M., primary, Sarathkumara, Yomani D., primary, Hsu, Wan-Lun, primary, Chien, Yin-Chu, primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Rothman, Nathaniel, primary, Lan, Qing, primary, Chen, Chien-Jen, primary, Mbulaiteye, Sam M., primary, Jarrett, Ruth F., primary, Glimelius, Ingrid, primary, Smedby, Karin E., primary, Hjalgrim, Henrik, primary, Hildesheim, Allan, primary, Doolan, Denise L., primary, and Liu, Zhiwei, primary

Published
2023
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22. Supplementary Methods S1 from Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies

Author

Argirion, Ilona, primary, Pfeiffer, Ruth M., primary, Proietti, Carla, primary, Coghill, Anna E., primary, Yu, Kelly J., primary, Middeldorp, Jaap M., primary, Sarathkumara, Yomani D., primary, Hsu, Wan-Lun, primary, Chien, Yin-Chu, primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Rothman, Nathaniel, primary, Lan, Qing, primary, Chen, Chien-Jen, primary, Mbulaiteye, Sam M., primary, Jarrett, Ruth F., primary, Glimelius, Ingrid, primary, Smedby, Karin E., primary, Hjalgrim, Henrik, primary, Hildesheim, Allan, primary, Doolan, Denise L., primary, and Liu, Zhiwei, primary

Published
2023
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27. Supplementary Figure 2 from Epstein–Barr Virus Serology as a Potential Screening Marker for Nasopharyngeal Carcinoma among High-Risk Individuals from Multiplex Families in Taiwan

Author

Coghill, Anna E., primary, Hsu, Wan-Lun, primary, Pfeiffer, Ruth M., primary, Juwana, Hedy, primary, Yu, Kelly J., primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Chen, Jen-Yang, primary, Chen, Chien-Jen, primary, Middeldorp, Jaap M., primary, and Hildesheim, Allan, primary

Published
2023
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28. Figure S3 from Identification of a Novel, EBV-Based Antibody Risk Stratification Signature for Early Detection of Nasopharyngeal Carcinoma in Taiwan

Author

Coghill, Anna E., primary, Pfeiffer, Ruth M., primary, Proietti, Carla, primary, Hsu, Wan-Lun, primary, Chien, Yin-Chu, primary, Lekieffre, Lea, primary, Krause, Lutz, primary, Teng, Andy, primary, Pablo, Jocelyn, primary, Yu, Kelly J., primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Liu, Zhiwei, primary, Chen, Chien-Jen, primary, Middeldorp, Jaap, primary, Mulvenna, Jason, primary, Bethony, Jeff, primary, Hildesheim, Allan, primary, and Doolan, Denise L., primary

Published
2023
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29. Tables S2-S4 from Identification of a Novel, EBV-Based Antibody Risk Stratification Signature for Early Detection of Nasopharyngeal Carcinoma in Taiwan

Author

Coghill, Anna E., primary, Pfeiffer, Ruth M., primary, Proietti, Carla, primary, Hsu, Wan-Lun, primary, Chien, Yin-Chu, primary, Lekieffre, Lea, primary, Krause, Lutz, primary, Teng, Andy, primary, Pablo, Jocelyn, primary, Yu, Kelly J., primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Liu, Zhiwei, primary, Chen, Chien-Jen, primary, Middeldorp, Jaap, primary, Mulvenna, Jason, primary, Bethony, Jeff, primary, Hildesheim, Allan, primary, and Doolan, Denise L., primary

Published
2023
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32. Supplemental Figure 1S from A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry

Author

Bei, Jin-Xin, primary, Su, Wen-Hui, primary, Ng, Ching-Ching, primary, Yu, Kai, primary, Chin, Yoon-Ming, primary, Lou, Pei-Jen, primary, Hsu, Wan-Lun, primary, McKay, James D., primary, Chen, Chien-Jen, primary, Chang, Yu-Sun, primary, Chen, Li-Zhen, primary, Chen, Ming-Yuan, primary, Cui, Qian, primary, Feng, Fu-Tuo, primary, Feng, Qi-Shen, primary, Guo, Yun-Miao, primary, Jia, Wei-Hua, primary, Khoo, Alan Soo-Beng, primary, Liu, Wen-Sheng, primary, Mo, Hao-Yuan, primary, Pua, Kin-Choo, primary, Teo, Soo-Hwang, primary, Tse, Ka-Po, primary, Xia, Yun-Fei, primary, Zhang, Hongxin, primary, Zhou, Gang-Qiao, primary, Liu, Jian-Jun, primary, Zeng, Yi-Xin, primary, and Hildesheim, Allan, primary

Published
2023
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33. Supplementary Tables S1-S2 from Prognostic Utility of Anti-EBV Antibody Testing for Defining NPC Risk among Individuals from High-Risk NPC Families

Author

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

Published
2023
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35. Supplemental Methods from Identification of a Novel, EBV-Based Antibody Risk Stratification Signature for Early Detection of Nasopharyngeal Carcinoma in Taiwan

Author

Coghill, Anna E., primary, Pfeiffer, Ruth M., primary, Proietti, Carla, primary, Hsu, Wan-Lun, primary, Chien, Yin-Chu, primary, Lekieffre, Lea, primary, Krause, Lutz, primary, Teng, Andy, primary, Pablo, Jocelyn, primary, Yu, Kelly J., primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Liu, Zhiwei, primary, Chen, Chien-Jen, primary, Middeldorp, Jaap, primary, Mulvenna, Jason, primary, Bethony, Jeff, primary, Hildesheim, Allan, primary, and Doolan, Denise L., primary

Published
2023
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37. Supplementary Figure Legends from Epstein–Barr Virus Serology as a Potential Screening Marker for Nasopharyngeal Carcinoma among High-Risk Individuals from Multiplex Families in Taiwan

Author

Coghill, Anna E., primary, Hsu, Wan-Lun, primary, Pfeiffer, Ruth M., primary, Juwana, Hedy, primary, Yu, Kelly J., primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Chen, Jen-Yang, primary, Chen, Chien-Jen, primary, Middeldorp, Jaap M., primary, and Hildesheim, Allan, primary

Published
2023
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38. Supplementary Table 1 from Epstein–Barr Virus Serology as a Potential Screening Marker for Nasopharyngeal Carcinoma among High-Risk Individuals from Multiplex Families in Taiwan

Author

Coghill, Anna E., primary, Hsu, Wan-Lun, primary, Pfeiffer, Ruth M., primary, Juwana, Hedy, primary, Yu, Kelly J., primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Chen, Jen-Yang, primary, Chen, Chien-Jen, primary, Middeldorp, Jaap M., primary, and Hildesheim, Allan, primary

Published
2023
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39. Supplemental Tables 1S-2S from A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry

Author

Bei, Jin-Xin, primary, Su, Wen-Hui, primary, Ng, Ching-Ching, primary, Yu, Kai, primary, Chin, Yoon-Ming, primary, Lou, Pei-Jen, primary, Hsu, Wan-Lun, primary, McKay, James D., primary, Chen, Chien-Jen, primary, Chang, Yu-Sun, primary, Chen, Li-Zhen, primary, Chen, Ming-Yuan, primary, Cui, Qian, primary, Feng, Fu-Tuo, primary, Feng, Qi-Shen, primary, Guo, Yun-Miao, primary, Jia, Wei-Hua, primary, Khoo, Alan Soo-Beng, primary, Liu, Wen-Sheng, primary, Mo, Hao-Yuan, primary, Pua, Kin-Choo, primary, Teo, Soo-Hwang, primary, Tse, Ka-Po, primary, Xia, Yun-Fei, primary, Zhang, Hongxin, primary, Zhou, Gang-Qiao, primary, Liu, Jian-Jun, primary, Zeng, Yi-Xin, primary, and Hildesheim, Allan, primary

Published
2023
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40. Supplementary Figure 1 from Epstein–Barr Virus Serology as a Potential Screening Marker for Nasopharyngeal Carcinoma among High-Risk Individuals from Multiplex Families in Taiwan

Author

Coghill, Anna E., primary, Hsu, Wan-Lun, primary, Pfeiffer, Ruth M., primary, Juwana, Hedy, primary, Yu, Kelly J., primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Chen, Jen-Yang, primary, Chen, Chien-Jen, primary, Middeldorp, Jaap M., primary, and Hildesheim, Allan, primary

Published
2023
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41. Data from Epstein–Barr Virus Serology as a Potential Screening Marker for Nasopharyngeal Carcinoma among High-Risk Individuals from Multiplex Families in Taiwan

Author

Coghill, Anna E., primary, Hsu, Wan-Lun, primary, Pfeiffer, Ruth M., primary, Juwana, Hedy, primary, Yu, Kelly J., primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Chen, Jen-Yang, primary, Chen, Chien-Jen, primary, Middeldorp, Jaap M., primary, and Hildesheim, Allan, primary

Published
2023
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43. Table S1 from Identification of a Novel, EBV-Based Antibody Risk Stratification Signature for Early Detection of Nasopharyngeal Carcinoma in Taiwan

Author

Coghill, Anna E., primary, Pfeiffer, Ruth M., primary, Proietti, Carla, primary, Hsu, Wan-Lun, primary, Chien, Yin-Chu, primary, Lekieffre, Lea, primary, Krause, Lutz, primary, Teng, Andy, primary, Pablo, Jocelyn, primary, Yu, Kelly J., primary, Lou, Pei-Jen, primary, Wang, Cheng-Ping, primary, Liu, Zhiwei, primary, Chen, Chien-Jen, primary, Middeldorp, Jaap, primary, Mulvenna, Jason, primary, Bethony, Jeff, primary, Hildesheim, Allan, primary, and Doolan, Denise L., primary

Published
2023
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46. Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies

Author

Argirion, Ilona, primary, Pfeiffer, Ruth M., additional, Proietti, Carla, additional, Coghill, Anna E., additional, Yu, Kelly J., additional, Middeldorp, Jaap M., additional, Sarathkumara, Yomani D., additional, Hsu, Wan-Lun, additional, Chien, Yin-Chu, additional, Lou, Pei-Jen, additional, Wang, Cheng-Ping, additional, Rothman, Nathaniel, additional, Lan, Qing, additional, Chen, Chien-Jen, additional, Mbulaiteye, Sam M., additional, Jarrett, Ruth F., additional, Glimelius, Ingrid, additional, Smedby, Karin E., additional, Hjalgrim, Henrik, additional, Hildesheim, Allan, additional, Doolan, Denise L., additional, and Liu, Zhiwei, additional

Published
2023
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48. Recommendations for Epstein-Barr virus–based screening for nasopharyngeal cancer in high- and intermediate-risk regions

Author

Lam, W K Jacky, primary, King, Ann D, additional, Miller, Jacob A, additional, Liu, Zhiwei, additional, Yu, Kelly J, additional, Chua, Melvin L K, additional, Ma, Brigette B Y, additional, Chen, Ming Yuan, additional, Pinsky, Benjamin A, additional, Lou, Pei-Jen, additional, Woo, John K S, additional, Hsu, Wan-Lun, additional, Simon, Julia, additional, Doolan, Denise L, additional, Waterboer, Tim, additional, Hui, Edwin P, additional, Li, Hui, additional, Tsang, Raymond K, additional, Wong, Kenneth C W, additional, Goh, Julian P, additional, Vlantis, Alexander C, additional, Ai, Qi Yong, additional, Wong, Lun M, additional, Abdullah, Victor, additional, Lin, Jin Ching, additional, Chen, Chien-Jen, additional, Pfeiffer, Ruth M, additional, Le, Quynh-Thu, additional, Lee, Anne W M, additional, Ji, Mingfang, additional, Cao, Sumei, additional, Ma, Jun, additional, Chan, Anthony T C, additional, Chan, K C Allen, additional, and Hildesheim, Allan, additional

Published
2023
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49. Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies

Author

Argirion, Ilona, Pfeiffer, Ruth M., Proietti, Carla, Coghill, Anna E., Yu, Kelly J., Middeldorp, Jaap M., Sarathkumara, Yomani D., Hsu, Wan-Lun, Chien, Yin-Chu, Lou, Pei-Jen, Wang, Cheng-Ping, Rothman, Nathaniel, Lan, Qing, Chen, Chien-Jen, Mbulaiteye, Sam M., Jarrett, Ruth F., Glimelius, Ingrid, Smedby, Karin E., Hjalgrim, Henrik, Hildesheim, Allan, Doolan, Denise L., Liu, Zhiwei, Argirion, Ilona, Pfeiffer, Ruth M., Proietti, Carla, Coghill, Anna E., Yu, Kelly J., Middeldorp, Jaap M., Sarathkumara, Yomani D., Hsu, Wan-Lun, Chien, Yin-Chu, Lou, Pei-Jen, Wang, Cheng-Ping, Rothman, Nathaniel, Lan, Qing, Chen, Chien-Jen, Mbulaiteye, Sam M., Jarrett, Ruth F., Glimelius, Ingrid, Smedby, Karin E., Hjalgrim, Henrik, Hildesheim, Allan, Doolan, Denise L., and Liu, Zhiwei

Abstract

Background: Epstein-Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL). Methods: Anti-EBV IgG and IgA antibody responses target-ing 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case-control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their associ-ation with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies repre-senting the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models. Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glyco-protein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types.Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis. Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.

Published
2023
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