
==== Front
BMC Cancer
BMC Cancer
BMC Cancer
1471-2407
BioMed Central London

12878
10.1186/s12885-024-12878-3
Research
The serological diagnostic value of EBV-related IgA antibody panels for nasopharyngeal carcinoma: a diagnostic test accuracy meta-analysis
Liu Han 1
Lei Lin 2
Song Song 1
Geng Xianyi 1
Lin Kaihao 2
Li Ni 1
Chen Wanqing 1
Peng Ji 2
Ren Jiansong ren.js@cicams.ac.cn

1
1 https://ror.org/02drdmm93 grid.506261.6 0000 0001 0706 7839 Office of Cancer Screening, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China
2 https://ror.org/05h3xe829 grid.512745.0 0000 0004 8015 6661 Department of Cancer Control and Prevention, Shenzhen Center for Chronic Disease Control, Shenzhen, 518000 China
7 9 2024
7 9 2024
2024
24 11159 5 2024
30 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

Nasopharyngeal carcinoma (NPC) is diagnosed relatively late and has a poor prognosis, requiring early detection to reduce the disease burden. This diagnostic test accuracy meta-analysis evaluated the serological diagnostic value of nine EBV-related IgA antibody panels (EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA and VCA-IgA + EA-IgA + Rta-IgG), aiming to identify suitable serological detection biomarkers for NPC screening.

Methods

PubMed, Embase, China National Knowledge Infrastructure and Chinese BioMedical Literature Database were searched from January 1st, 2000 to September 30th, 2023, with keywords nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. Articles on the diagnostic value of serum EBV-related IgA antibody panels for NPC were included. Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. Bivariate models were used for statistical analysis. The quality of included studies was evaluated through Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2).

Results

A total of 70 articles were included, involving 11 863 NPC cases and 34 995 controls. Among the nine EBV-related IgA antibody panels, EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] demonstrated higher pooled sensitivity (95%CI). In terms of diagnostic odds ratio (DOR) (95%CI), EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)] and EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] showed superior performance. Additionally, the SROC curves for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were more favorable. However, publication bias was detected for VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042).

Conclusions

In general, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among the studied panels. In the cases where fewer indicators are used, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits a comparable performance.

Trial registration

The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12885-024-12878-3.

Keywords

Nasopharyngeal carcinoma
Serum
IgA
Screening
Early detection
Meta-analysis
Sanming Project of Medicine in ShenzhenSZSM 201911015 SZSM 201911015 SZSM 201911015 SZSM 201911015 SZSM 201911015 http://dx.doi.org/10.13039/501100017610 Shenzhen Science and Technology Innovation Program KCXFZ20211020172542002 National Key R&D Program of China2023YFC2507000 National Science & Technology Fundamental Resources Investigation Program of China2019FY101105 issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcBackground

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that occurs in the nasopharynx. According to the World Health Organization (WHO), it was estimated to be 120 434 new NPC cases and 73 482 deaths in the world in 2022, mainly distributed in East Asia, Southeast Asia and North Africa [1]. Approximately 70% of NPC patients are already in advanced stages when they are diagnosed. Through comprehensive treatment, such as surgery, chemotherapy and radiotherapy, 5-year survival rate for advanced stages ranges from 51.4 to 76.0%, compared to 82.6–86.6% for early stages, so early detection is needed to reduce the disease burden [2–5].

The pathogenesis of NPC is closely related to Epstein-Barr virus (EBV) infection, and detection of EBV-related biomarkers is crucial for early detection of NPC. EBV serum antibody (antibodies are labeled as ‘anti-EBV’, or more precisely, they are antibodies against EBV-encoded antigens) detection has the characteristics of rapidity, simplicity and low cost. Enzyme-linked immunosorbent assay (ELISA) has standardized operation procedure and the interpretation of results is not subject to subjective influence of researchers.

So far, there have been a number of studies on the detection of serum EBV-related IgA antibodies or antibody panels associated with IgA by ELISA, but the results were not consistent. Although several meta-analyses have investigated the diagnostic value of relevant antibody tests for NPC, they involved only antibodies alone or in combination, and did not analyze and compare all possible IgA antibody panels simultaneously [6–9].

Regarding the above issues and preliminary search results, we used a diagnostic test accuracy meta-analysis to evaluate the serological diagnostic value of nine antibody panels of EBV-related IgA antibodies by ELISA, in order to find suitable detection biomarkers/panels and provide more evidence for NPC screening and early detection.

Methods

This meta-analysis was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and registered on the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42023426984 [10, 11].

Search strategy

1) Databases: PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Chinese BioMedical Literature Database (CBM). The first two were used for searching English literature, whereas the latter two were specifically for Chinese literature, given that a large number of related studies have been published in Chinese journals. 2) Search period: from January 1st, 2000 to September 30th, 2023. 3) Key words: nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. 4) Languages: Chinese and English. 5) References for other system reviews or meta-analyses.

Inclusion criteria

1) The case group of the study were comprised of newly diagnosed or untreated NPC patients confirmed by histopathology, and the control group were healthy individuals or general population. At least 20 cases and 20 controls were included in each study. 2) The study applied ELISA to detect serum EBV-IgA antibodies alone or in parallel, within nine antibody panels including EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA, VCA-IgA + EA-IgA + Rta-IgG. 3) If similar studies were found originated from the same population, only the most complete one was selected. If the same antibody panel in one study was tested multiple times with ELISA kits from different manufacturers, the mean value was calculated and included. 4) Only studies that provide sufficient data were included.

Exclusion criteria

1) Studies in which NPC patients in the case group also had other tumors or the control group were patients from hospital with other head and neck diseases. 2) Studies for which full texts were not available.

Study selection, data extraction and quality assessment

Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. According to the search strategy and inclusion/exclusion criteria, literature search, duplicate removal, title abstract screening, and full text screening were carried out via EndNote 20. The extracted data included first author, year of publication, journal name, funding sources, study area, number of cases, number of controls, antibody panels, and the numbers for true positive, false positive, false negative and true negative. The Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) was used to evaluate the risk of bias and applicability of the included literature. The tool is consisted of four key domains: patient selection, index test, reference standard and flow and timing. Each was assessed in terms of risk of bias based on signalling questions and the first three in terms of concerns regarding applicability. The process was conducted in RevMan5.4 [12].

Data analysis

Bivariate models were used for statistical analysis. Firstly, the Bivariate I2 value was calculated to detect heterogeneity among the included studies; if I2 > 0.5, heterogeneity was considered present. Secondly, the threshold effect was assessed using the Spearman correlation coefficient between the logarithm of sensitivity and the logarithm of (1-specificity) for each study; if P < 0.05, the threshold effect was present, only a summary receiver operating characteristic (SROC) curve was plotted; otherwise, pooled sensitivity, specificity, diagnostic odds ratio (DOR) and the corresponding 95% confidence intervals (95%CIs) were also obtained. Subsequently, the included studies were classified by study area (whether high-risk) or number of cases (whether ≤ 100). Based on the number of studies in the two categories, subgroup analysis and sensitivity analysis were performed. Additionally, meta-regression analysis was also conducted on these two factors. The difference was statistically significant when P < 0.05. All these analyses were carried out using Meta-DiSc and Meta-DiSc 2.0 [13, 14]. Finally, Deek’s asymmetry test was conducted using the midas package in Stata 12.0 to evaluate publication bias in each antibody panel; a P-value of < 0.10 indicated the presence of publication bias.

Results

Study selection

Based on the search strategy, a total of 762 articles were found. Then, 217 duplicates were removed, leaving 545 articles. According to the inclusion and exclusion criteria, 380 articles were removed due to title and abstract screening, and then 95 articles were removed by full text screening. Finally, 70 articles were included in this meta-analysis [15–84]. The literature screening process was shown in Fig. 1.

Fig. 1 Study selection flowchart

Study characteristics

Table 1 Main characteristics of the 70 included articles

Study ID	Area	Cases (n)	Controls (n)	Antibody panel	
Zhang 2002 [15]	Guangdong	266	347	c	
Cheng 2003 [16]	Guangdong	85	256	a	
Gu 2003 [17]	Guangdong	57	58	a, d	
Huang 2003 [18]	Guangdong	84	60	a	
Hu 2006 [19]	Guangdong	85	132	a, b, d	
Li 2006 [20]	Fujian	59	60	b	
Wu 2006 [21]	Guangdong	43	40	a	
Tang 2007 [22]	Hong Kong	163	98	b, c	
Liang 2008 [23]	Guangdong	195	188	a, d	
Gu 2008 [24]	Guangdong	135	130	a, b, c, e, f	
Cheng 2009 [25]	Guangxi	326	767	a	
Deng 2009 [26]	Guangdong	93	185	a, b	
Jiang 2009 [27]	Guangdong	81	89	a	
Pan 2009 [28]	Guangdong	36	58	b	
Yang 2009 [29]	Guangxi	177	90	b	
Chen 2010 [30]	Guangdong	53	40	b, c	
Hu 2010 [31]	Guangdong	300	500	b	
Tan 2010 [32]	Guangdong	123	40	b, c	
Ma 2011 [33]	Guangxi	168	174	a, b, c, d	
Wu 2011 [34]	Guangdong	42	42	b, c	
Zhang 2011 [35]	Guangdong	65	50	a, b, c	
Zhou 2011 [36]	Guangdong	152	200	c	
Zhu 2011 [37]	Guangxi	37	33	b	
Deng 2012 [38]	Guangdong	169	86	a, b, e	
Lei 2012 [39]	Hubei	102	150	b	
Wang 2012 [40]	Shanghai	206	249	a, b, e, g	
Liu 2012 [41]	Guangdong	191	197	a, b, c, d, e, f, g	
He 2013 [42]	Hunan	60	30	e	
Li 2013 [43]	Fujian	449	1 292	b, c	
Yan 2013 [44]	Beijing	51	50	b, c	
Shi 2014 [45]	Guangdong	33	30	a, b, c, d	
Xu 2014 [46]	Guangdong	75	100	b, g	
Peng 2014 [47]	Guangdong	112	138	b	
Du 2015 [48]	Guangdong	416	688	a, b, e, g	
Peng 2015 [49]	Guangdong	242	218	b	
Wu 2015 [50]	Guangdong	30	1 470	b, c	
Xu 2015 [51]	Guangdong	75	100	b, g	
Yi 2015 [52]	Fujian	96	250	b, c, f, g, i	
Zhang 2015 [53]	Fujian	155	8 884	b, c	
Gu 2016 [54]	Guangdong	60	60	a, b, d	
Pan 2016 [55]	Guangdong	100	1 000	b, c	
Wu 2016 [56]	Hainan	169	3 913	b, g	
Yu 2016 [57]	Guangdong	152	675	a, b, d	
Zheng 2016 [58]	Guangdong	300	200	b	
Lin 2016 [59]	Zhejiang	202	112	b	
Chen 2017 [60]	Guangxi	216	108	a, b, d, e, h	
Yan 2017 [61]	Beijing	68	50	b, c, f, i	
Gao 2017 [62]	Guangdong	200	200	a, b, e, h	
Lin 2017 [63]	Guangdong	129	100	b	
Gao 2018 [64]	Shaanxi	109	60	b	
Li 2018 [65]	Hubei	61	50	b, c, f	
Zhang 2018 [66]	Hunan	58	100	b, c, f, g, i	
Li 2019 [67]	Guangdong	120	380	b, c, i	
Tang 2019 [68]	Hunan	53	213	b, c, f, g, i	
Zhang 2019 [69]	Shaanxi	120	56	a, b	
Cai 2020 [70]	Guangdong	56	20	b, c	
Fang 2020 [71]	Guangdong	48	93	a, b, c	
Guo 2020 [72]	Fujian	2 155	6 957	b, c, f, g	
Liu 2020 [73]	Guangdong	106	150	a, d	
Rao 2020 [74]	Guangdong	320	320	a, b, e	
Yu 2020 [75]	Guangdong	201	1 051	a, b	
Gong 2021 [76]	Shanghai	662	731	a, b, d, e, h	
Lu 2021 [77]	Guangdong	54	100	a, b, c	
Wang 2021 [78]	Guangdong	80	70	a, b, c	
Wang2 2021 [79]	Guangdong	40	40	a, b, d, e, h	
Zhang 2021 [80]	Hunan	264	264	b, c, f, g, i	
Deng 2022 [81]	Guangdong	205	108	a, b, c, e, f, g, i	
Qu 2022 [82]	Guangdong	45	45	a, b	
Qin 2023 [83]	Shandong	163	140	b, c, i	
Xu 2023 [84]	Shandong	60	60	b, c	
n: number

a: EBNA1-IgA; b: VCA-IgA; c: EA-IgA; d: Zta-IgA; e: EBNA1-IgA+VCA-IgA; f: VCA-IgA+EA-IgA; g: VCA-IgA+Rta-IgG; h: EBNA1-IgA+VCA-IgA+Zta-IgA; i: VCA-IgA+EA-IgA+Rta-IgG

A total of 70 articles were included, published from 2002 to 2023, involving 11 863 NPC cases and 34 995 controls. All studies were conducted in China, and 50 of them were from high-risk areas (Guangdong, Guangxi, Hainan, and Hong Kong). The main characteristics of the included literature and antibody panels were shown in Tables 1 and 2.

Quality appraisal

QUADAS-2 was used to evaluate the quality of the included articles, and the results indicated that they were of high quality. The risk of bias was primarily attributed to flow and timing issues, followed by patient selection concerns. This was because the intervals between the index test and the reference standard were unclear in some studies, and it remained unclear whether subject selection in some studies involved continuous inclusion and random sampling. The quality assessment results were shown in Fig. S10.1 and Fig. S10.2 in Supplementary Materials.

Heterogeneity, threshold effect and publication bias

The heterogeneity, threshold effect and publication bias of the included studies for nine antibody panels were calculated separately. The results indicated that heterogeneity was present among all panels, whereas no significant threshold effect was observed, suggesting that the heterogeneity was primarily attributed to non-threshold factors. With the exception of VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042), no publication bias was detected in the other panels (see Table 2).

Table 2 Main characteristics, heterogeneity, threshold effect, publication bias and meta-analysis results of the nine antibody panels

Antibody panel	Studies (n)	Cases (n)	Controls (n)	Total (n)	Areas (n)	Heterogeneity (I2)	Threshold effect (P)	Publication bias (P)	Sensitivity (95%CI)	Specificity (95%CI)	DOR (95%CI)	
EBNA1-IgA	32	4 910	7 186	12 096	4	0.742	0.075	0.336	0.854 (0.828, 0.877)	0.914 (0.886, 0.935)	61.802 (41.655, 91.693)	
VCA-IgA	59	10 410	32 814	43 224	12	0.846	0.405	0.005	0.796 (0.757, 0.831)	0.903 (0.882, 0.921)	36.559 (26.927, 49.636)	
EA-IgA	31	5 718	21 839	27 557	8	0.798	0.496	0.388	0.607 (0.536, 0.675)	0.956 (0.939, 0.969)	33.893 (23.012, 49.919)	
Zta-IgA	12	1 965	2 543	4 508	3	0.675	0.245	0.694	0.819 (0.770, 0.859)	0.899 (0.864, 0.925)	40.290 (25.985, 62.469)	
EBNA1-IgA + VCA-IgA	12	2 820	2 887	5 707	4	0.781	0.331	0.042	0.928 (0.898, 0.950)	0.893 (0.839, 0.930)	107.647 (61.173, 189.430)	
VCA-IgA + EA-IgA	10	3 286	8 319	11 605	5	0.800	0.511	0.714	0.868 (0.820, 0.904)	0.899 (0.828, 0.942)	58.119 (30.676, 110.114)	
VCA-IgA + Rta-IgG	12	3 963	13 139	17 102	5	0.812	0.290	0.489	0.925 (0.890, 0.949)	0.896 (0.851, 0.928)	105.988 (60.118, 186.857)	
EBNA1-IgA + VCA-IgA + Zta-IgA	4	1 118	1 079	2 197	3	0.642	0.800	0.413	0.962 (0.909, 0.985)	0.931 (0.827, 0.974)	344.450 (136.351, 870.153)	
VCA-IgA + EA-IgA + Rta-IgG	8	1 027	1 505	2 532	5	0.667	0.320	0.731	0.945 (0.918, 0.964)	0.918 (0.771, 0.974)	193.047 (47.641, 782.251)	
n: number

Meta-analysis, subgroup analysis and sensitivity analysis

The pooled sensitivity, specificity and DOR of the nine antibody panels were presented in Table 2. Specifically, the sensitivity (95%CI) of EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] was higher. Additionally, EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)], EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] had higher DOR (95%CI). The SROC curves for each panel were depicted in Fig. 2. Observing the positions of each summary point and corresponding confidence ellipses, the results for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were better. The results of the subgroup analysis classified by study area or number of cases were shown in Fig. S11.1 and Fig. S11.2 in the Supplementary Materials. Moreover, the findings from each meta-regression analysis were not statistically significant. As demonstrated in the sensitivity analysis results presented in Table S10 of the Supplementary Materials, there was no significant change in the DOR values. Therefore, parallel detection of serum VCA-IgA and EBNA1-IgA/Rta-IgG antibodies using ELISA may constitute suitable serological detection strategies for NPC screening and early detection. However, EBNA1-IgA + VCA-IgA + Zta-IgA may potentially represent an even better panel, simply because the small number of studies or individuals included in the analysis limited its evaluation and interpretation. And the characteristics and forest plots for each panel were provided in the Supplementary Materials.

Fig. 2 SROC curves for each panel. AUC (95%CI): EBNA1-IgA=0.94 (0.91, 0.96); VCA-IgA=0.93 (0.90, 0.95); EA-IgA=0.92 (0.89, 0.94); Zta-IgA=0.93 (0.90, 0.95); EBNA1-IgA+VCA-IgA=0.97 (0.95, 0.98); VCA-IgA+EA-IgA=0.94 (0.91, 0.95); VCA-IgA+Rta-IgG=0.96 (0.94, 0.98); EBNA1-IgA+VCA-IgA+Zta-IgA=0.99 (0.97, 0.99); VCA-IgA+EA-IgA+Rta-IgG=0.96 (0.94, 0.98)

Discussion

In China, NPC is mainly distributed in Guangdong, Guangxi, Hainan and Hong Kong [85]. Given that all 70 articles included in our study were from China, we designated these regions as high-risk areas for subsequent analysis. The results of this study revealed heterogeneity among the included studies for nine antibody panels. All panels did not have threshold effects, allowing us to calculate their pooled sensitivity, specificity, and DOR. Publication bias was detected for VCA-IgA and EBNA1-IgA + VCA-IgA. In conclusion, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies by ELISA showed better pooled sensitivity and DOR among these nine panels. Under the condition that fewer indicators need to be detected, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel has comparable performance.

In addition to EBV-related antibodies serving as diagnostic markers for NPC, EBV-DNA load is also one of the common diagnostic methods. Other biomarkers, including heat shock protein 70 (HSP70), sialic acid (SA) and microRNA (miRNA), are closely associated with the development of NPC. A prospective study has shown that screening with two positive plasma EBV-DNA tests approximately four weeks apart could help in the early detection of NPC in asymptomatic individuals [86]. Another study has found and validated that P85 Ab, a novel serological biomarker for NPC screening, had good screening performance [87]. Although the results in this article are generally more accurate than those of several previous meta-analyses, the gap is not particularly significant [6–8].

This study is the first meta-analysis to determine the usefulness of EBNA1-IgA + VCA-IgA + Zta-IgA and comprehensively evaluates the performance of nine serum EBV-related IgA antibody panels detected by ELISA. The overall quality of the included studies was relatively high, and the inclusion and exclusion criteria of the article were considered comprehensively, aiming to align with the screening scenarios of a large population.

However, it also has some limitations. Since all research sources were from China, the conclusions may not be universally applicable to other regions or populations. Most of the included diagnostic trials were single-center studies, and the sample sizes of many studies were not particularly large. Due to the different designs of the included studies and the differences in sex, age, and tumor stage among the study population, the source of heterogeneity cannot be clearly explained. Although the design of this study is as close to the population screening situation as possible, the conditions still need to be verified in large-scale populations. In addition, this article focused solely on analyzing serum IgA antibodies or antibody panels detected by ELISA, and there are numerous other biomarkers and panels with promising diagnostic potential that could be explored in future research based on the current findings.

Conclusion

In summary, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among these nine panels generally. When using a reduced number of indicators, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits comparable diagnostic performance.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Author contributions

Concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: All authors. Statistical analysis: Han Liu, Song Song, Jiansong Ren. Administrative, technical, or material support: Lin Lei, Ji Peng, Jiansong Ren. Supervision: Jiansong Ren. All authors read and approved the final manuscript.

Funding

This work was supported by the National Key R&D Program of China (2023YFC2507000); National Science & Technology Fundamental Resources Investigation Program of China (2019FY101105); Sanming Project of Medicine in Shenzhen (SZSM 201911015); and Shenzhen Science and Technology Innovation Program (KCXFZ20211020172542002).

Data availability

Data is provided within the manuscript or supplementary information files.

Competing interests

The authors declare no competing interests.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Bray F Laversanne M Sung H Ferlay J Siegel RL Soerjomataram I Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin 2024 4 1 35
Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;4:1–35.
2. Wei X Yu S Wang J Xiang Z Liu L Min Y Association between time from diagnosis to treatment and survival of patients with nasopharyngeal carcinoma: a population-based cohort study Curr Probl Cancer 2024 48 101060 10.1016/j.currproblcancer.2024.101060 38211418
Wei X, Yu S, Wang J, Xiang Z, Liu L, Min Y. Association between time from diagnosis to treatment and survival of patients with nasopharyngeal carcinoma: a population-based cohort study. Curr Probl Cancer. 2024;48:101060.38211418 10.1016/j.currproblcancer.2024.101060
3. Koide Y Kodaira T Kitayama M Kawakita D Kirita T Yoshimoto S Definitive radiotherapy for nasopharyngeal carcinoma in Japan: analysis of cases in the National Head and Neck Cancer Registry from 2011 to 2014 Jpn J Clin Oncol 2024 54 1 54 61 10.1093/jjco/hyad130 37781753
Koide Y, Kodaira T, Kitayama M, Kawakita D, Kirita T, Yoshimoto S, et al. Definitive radiotherapy for nasopharyngeal carcinoma in Japan: analysis of cases in the National Head and Neck Cancer Registry from 2011 to 2014. Jpn J Clin Oncol. 2024;54(1):54–61.37781753 10.1093/jjco/hyad130
4. Huang J Yang Z-Y Wu B Ding Q Qin Y Zhang Z-J Long-term therapeutic outcome and prognostic factors of patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy: an analysis of 608 patients from low-endemic regions of China Curr Med Sci 2021 41 4 737 45 10.1007/s11596-021-2405-3 34403099
Huang J, Yang Z-Y, Wu B, Ding Q, Qin Y, Zhang Z-J, et al. Long-term therapeutic outcome and prognostic factors of patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: an analysis of 608 patients from low-endemic regions of China. Curr Med Sci. 2021;41(4):737–45.34403099 10.1007/s11596-021-2405-3
5. Xu M Zang J Luo S Wang J Li X Long-term survival outcomes and adverse effects of nasopharyngeal carcinoma patients treated with IMRT in a non-endemic region: a population-based retrospective study BMJ Open 2021 11 8 e045417 10.1136/bmjopen-2020-045417 34341036
Xu M, Zang J, Luo S, Wang J, Li X. Long-term survival outcomes and adverse effects of nasopharyngeal carcinoma patients treated with IMRT in a non-endemic region: a population-based retrospective study. BMJ Open. 2021;11(8):e045417.34341036 10.1136/bmjopen-2020-045417
6. Lian M Combining Epstein–Barr virus antibodies for early detection of nasopharyngeal carcinoma: a meta-analysis Auris Nasus Larynx 2023 50 3 430 9 10.1016/j.anl.2022.09.010 36241564
Lian M. Combining Epstein–Barr virus antibodies for early detection of nasopharyngeal carcinoma: a meta-analysis. Auris Nasus Larynx. 2023;50(3):430–9.36241564 10.1016/j.anl.2022.09.010
7. Liu W Chen G Gong X Wang Y Zheng Y Liao X The diagnostic value of EBV-DNA and EBV-related antibodies detection for nasopharyngeal carcinoma: a meta-analysis Cancer Cell Int 2021 21 1 164 10.1186/s12935-021-01862-7 33691680
Liu W, Chen G, Gong X, Wang Y, Zheng Y, Liao X, et al. The diagnostic value of EBV-DNA and EBV-related antibodies detection for nasopharyngeal carcinoma: a meta-analysis. Cancer Cell Int. 2021;21(1):164.33691680 10.1186/s12935-021-01862-7
8. Feng Y Xia W He G Ke R Liu L Xie M Accuracy evaluation and comparison of 14 diagnostic markers for nasopharyngeal carcinoma: a meta-analysis Front Oncol 2020 10 1779 10.3389/fonc.2020.01779 33072558
Feng Y, Xia W, He G, Ke R, Liu L, Xie M, et al. Accuracy evaluation and comparison of 14 diagnostic markers for nasopharyngeal carcinoma: a meta-analysis. Front Oncol. 2020;10:1779.33072558 10.3389/fonc.2020.01779
9. Chen Y Xin X Cui Z Zheng Y Guo J Chen Y Diagnostic value of serum Epstein-Barr Virus Capsid Antigen-IgA for nasopharyngeal carcinoma: a Meta-analysis based on 21 studies Clin Lab 2016 62 6 1155 66 27468579
Chen Y, Xin X, Cui Z, Zheng Y, Guo J, Chen Y, et al. Diagnostic value of serum Epstein-Barr virus capsid antigen-IgA for nasopharyngeal carcinoma: a meta-analysis based on 21 studies. Clin Lab. 2016;62(6):1155–66.27468579
10. Page MJ McKenzie JE Bossuyt PM Boutron I Hoffmann TC Mulrow CD The PRISMA 2020 statement: an updated guideline for reporting systematic reviews PLoS Med 2021 18 3 e1003583 10.1371/journal.pmed.1003583 33780438
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. PLoS Med. 2021;18(3):e1003583.33780438 10.1371/journal.pmed.1003583
11. Page MJ Moher D Bossuyt PM Boutron I Hoffmann TC Mulrow CD PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews BMJ (Clinical Res ed) 2021 372 n160
Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ (Clinical Res ed). 2021;372:n160.
12. Review Manager (RevMan). Computer program. Version 5.4. The Cochrane Collaboration.
13. Zamora J Abraira V Muriel A Khan K Coomarasamy A Meta-DiSc: a software for meta-analysis of test accuracy data BMC Med Res Methodol 2006 6 31 10.1186/1471-2288-6-31 16836745
Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol. 2006;6:31.16836745 10.1186/1471-2288-6-31
14. Plana MN Arevalo-Rodriguez I Fernández-García S Soto J Fabregate M Pérez T Meta-DiSc 2.0: a web application for meta-analysis of diagnostic test accuracy data BMC Med Res Methodol 2022 22 1 306 10.1186/s12874-022-01788-2 36443653
Plana MN, Arevalo-Rodriguez I, Fernández-García S, Soto J, Fabregate M, Pérez T, et al. Meta-DiSc 2.0: a web application for meta-analysis of diagnostic test accuracy data. BMC Med Res Methodol. 2022;22(1):306.36443653 10.1186/s12874-022-01788-2
15. Zhang CQ Zong YS Huang BZ Sun Y Ye YZ Feng KT Enhancing the efficiency of Epstein-Barr viral serologic test in the diagnosis of nasopharyngeal carcinoma Chin J Oncol 2002 24 4 356 9
Zhang CQ, Zong YS, Huang BZ, Sun Y, Ye YZ, Feng KT, et al. Enhancing the efficiency of Epstein-Barr viral serologic test in the diagnosis of nasopharyngeal carcinoma. Chin J Oncol. 2002;24(4):356–9.
16. Cheng WM Ji MF Li XL Yang JL Zong YS Screening out nasopharyngeal carcinoma by two-stage ELISA for EB virus Chin J Immunol 2003 19 12 834 6
Cheng WM, Ji MF, Li XL, Yang JL, Zong YS. Screening out nasopharyngeal carcinoma by two-stage ELISA for EB virus. Chin J Immunol. 2003;19(12):834–6.
17. Gu YL Zhang CQ Wu ZB Zong YS Liang YJ Chen YL Study on sero-diagnosis of nasopharyngeal carcinoma using a dual antibody test against recombinant Epstein-Barr Virus antigens Chin J Cancer 2003 22 9 903 6
Gu YL, Zhang CQ, Wu ZB, Zong YS, Liang YJ, Chen YL. Study on sero-diagnosis of nasopharyngeal carcinoma using a dual antibody test against recombinant Epstein-Barr virus antigens. Chin J Cancer. 2003;22(9):903–6.
18. Huang WG Lin J Chen RC Detection of diagnosis about nasopharyngeal carcinorma combined with EBVCA-IgA and EBVA-IgA in serum J Pract Med 2003 10 11 1235 6
Huang WG, Lin J, Chen RC. Detection of diagnosis about nasopharyngeal carcinorma combined with EBVCA-IgA and EBVA-IgA in serum. J Pract Med. 2003;10(11):1235–6.
19. Hu WW Zong YS Li FP Li GM Zhong BL Zhang M Comparison of 6 antibody assays detecting Epstein-Barr Virus for serodiagnosis of nasopharyngeal carcinoma Chin J Clin Oncol 2006 33 14 795 8
Hu WW, Zong YS, Li FP, Li GM, Zhong BL, Zhang M, et al. Comparison of 6 antibody assays detecting Epstein-Barr virus for serodiagnosis of nasopharyngeal carcinoma. Chin J Clin Oncol. 2006;33(14):795–8.
20. Li XL Chen Y Xu F Comparison of enzyme-linked immunosorbent assay and immunoenzymatic assay for detection of serum EB-VCA-IgA Exp Lab Med 2006 24 2 127 8
Li XL, Chen Y, Xu F. Comparison of enzyme-linked immunosorbent assay and immunoenzymatic assay for detection of serum EB-VCA-IgA. Exp Lab Med. 2006;24(2):127–8.
21. Wu XM Wei YF Analysis of EBV antibody detection by ELISA and immunoenzymatic method Med Forum 2006 10 7 631 2
Wu XM, Wei YF. Analysis of EBV antibody detection by ELISA and immunoenzymatic method. Med Forum. 2006;10(7):631–2.
22. Tang JW Rohwäder E Chu IM Tsang RK Steinhagen K Yeung AC Evaluation of Epstein-Barr virus antigen-based immunoassays for serological diagnosis of nasopharyngeal carcinoma J Clin Virol 2007 40 4 284 8 10.1016/j.jcv.2007.09.006 17977062
Tang JW, Rohwäder E, Chu IM, Tsang RK, Steinhagen K, Yeung AC, et al. Evaluation of Epstein-Barr virus antigen-based immunoassays for serological diagnosis of nasopharyngeal carcinoma. J Clin Virol. 2007;40(4):284–8.17977062 10.1016/j.jcv.2007.09.006
23. Liang YJ Zong YS Gu YL Zhang Y Feng YF Liu YD Application of enzyme-linked inununosorbent assay to the serological diagnosis of nasopharyngeal carcinoma J Pract Med 2008 24 17 3055 8
Liang YJ, Zong YS, Gu YL, Zhang Y, Feng YF, Liu YD, et al. Application of enzyme-linked inununosorbent assay to the serological diagnosis of nasopharyngeal carcinoma. J Pract Med. 2008;24(17):3055–8.
24. Gu AD Mo HY Xie YB Peng RJ Bei JX Peng J Evaluation of a multianalyte profiling assay and an enzyme-linked immunosorbent assay for serological examination of Epstein-Barr virus-specific antibody responses in diagnosis of nasopharyngeal carcinoma Clin Vaccine Immunol 2008 15 11 1684 8 10.1128/CVI.00135-08 18768669
Gu AD, Mo HY, Xie YB, Peng RJ, Bei JX, Peng J, et al. Evaluation of a multianalyte profiling assay and an enzyme-linked immunosorbent assay for serological examination of Epstein-Barr virus-specific antibody responses in diagnosis of nasopharyngeal carcinoma. Clin Vaccine Immunol. 2008;15(11):1684–8.18768669 10.1128/CVI.00135-08
25. Cheng JR Cai YL Zheng YM Li J Mo YK Detections of immunoglobulin A antibodies against different Epstein-Barr virus antigens in diagnosis of nasopharyn-geal carcinoma diagnosis Med Innov China 2009 6 27 101 3
Cheng JR, Cai YL, Zheng YM, Li J, Mo YK. Detections of immunoglobulin A antibodies against different Epstein-Barr virus antigens in diagnosis of nasopharyn-geal carcinoma diagnosis. Med Innov China. 2009;6(27):101–3.
26. Deng ZX Value of detection of serum EBNAI-IGA and EBVCA-IgA by ELISA in diagnosis of nasopharyngeal carcinoma Chin Trop Med 2009 9 9 17181797
Deng ZX. Value of detection of serum EBNAI-IGA and EBVCA-IgA by ELISA in diagnosis of nasopharyngeal carcinoma. Chin Trop Med. 2009;9(9):1718–97.
27. Jiang SQ Liu Q Application of logistic regression in combination with multiple diagnostic tests for auxiliary diagnosis of nasopharyngeal carcinoma Chin J Cancer 2009 28 2 213 6
Jiang SQ, Liu Q. Application of logistic regression in combination with multiple diagnostic tests for auxiliary diagnosis of nasopharyngeal carcinoma. Chin J Cancer. 2009;28(2):213–6.
28. Pan SX Shi ZS Evaluate the two ELISA methods and the EIA method in detecting Epstein-Barr Virus Chin J Med Guide 2009 11 11 1918 9
Pan SX, Shi ZS. Evaluate the two ELISA methods and the EIA method in detecting Epstein-Barr virus. Chin J Med Guide. 2009;11(11):1918–9.
29. Yang MC, Lu AY, Li S, Li RL, Xu MH, Li TJ et al. Comparison of IEMA and ELISA techniques for measurement of EB viral VCA-IgA. Labeled Immunoassays & Clin Med. 2009(2):93–5.
30. Chen WS Lu JX Ye SX Application of combined detection of EBV VCA-IgA and EA-IgA antibodies in the diagnosis of NPC J Trop Med 2010 10 4 434 6
Chen WS, Lu JX, Ye SX. Application of combined detection of EBV VCA-IgA and EA-IgA antibodies in the diagnosis of NPC. J Trop Med. 2010;10(4):434–6.
31. Hu B Li ZX Sheng P Li L Expression of VCA genes of Epstein-Barr virus in Pichia pastoris and clinical application Chin J Microbiol Immunol 2010 4 365 70
Hu B, Li ZX, Sheng P, Li L. Expression of VCA genes of Epstein-Barr virus in Pichia pastoris and clinical application. Chin J Microbiol Immunol. 2010;4:365–70.
32. Tan YJ SU XK Cui JH Qu WH Xue XY Comparison of detection of serum VCA-IgA, EA-IgA and EBV-DNA in nasopharygeal carcinoma patients Chongqing Med J 2010 39 6 703 704706
Tan YJ, SU XK, Cui JH, Qu WH, Xue XY. Comparison of detection of serum VCA-IgA, EA-IgA and EBV-DNA in nasopharygeal carcinoma patients. Chongqing Med J. 2010;39(6):703–6.
33. Ma DJ He XF Li YN Clinical value of immunoserological and biological detection of Epstein-Barr virus infection in nasopharyngeal carcinoma Hainan Med J 2011 22 15 105 7
Ma DJ, He XF, Li YN. Clinical value of immunoserological and biological detection of Epstein-Barr virus infection in nasopharyngeal carcinoma. Hainan Med J. 2011;22(15):105–7.
34. Wu YH Analysis of clinical effect of two different methods for detecting Epstein-Barr virus Lab Med Clin 2011 8 6 694 5
Wu YH. Analysis of clinical effect of two different methods for detecting Epstein-Barr virus. Lab Med Clin. 2011;8(6):694–5.
35. Zhang SL Li W Zeng LL Yang YQ Zhang WY Combined determination of Epstein-Barr virus-related antibodies and antigens for diagnosis of nasopharyngeal carcinoma Mil Med Jnt Log 2011 25 3 262 3
Zhang SL, Li W, Zeng LL, Yang YQ, Zhang WY. Combined determination of Epstein-Barr virus-related antibodies and antigens for diagnosis of nasopharyngeal carcinoma. Mil Med Jnt Log. 2011;25(3):262–3.
36. Zhou T, Deng YG. Correlation between three serologic tests of Epstein-Barr virus and diagnosis of nasopharyngeal carcinoma. Chin J Clin (Electronic Edition). 2011(11):3308–9.
37. Zhu HH Zhang Z Xie Y Han L M.Middeldorp J Tang CX The value of double peptide-coated ELISA test in serological diagnosis of nasopharyngeal carcinoma Chin J Oncol Prev Treat 2011 3 1 52 5
Zhu HH, Zhang Z, Xie Y, Han L, M.Middeldorp J, Tang CX, et al. The value of double peptide-coated ELISA test in serological diagnosis of nasopharyngeal carcinoma. Chin J Oncol Prev Treat. 2011;3(1):52–5.
38. Deng WW Clinical value of triple test(vca-iga,ea-igg、na1-iga)in serological diagnosis of nasopharyngeal carcinoma Mod Hosp 2012 12 4 62 4
Deng WW. Clinical value of triple test(vca-iga,ea-igg、na1-iga)in serological diagnosis of nasopharyngeal carcinoma. Mod Hosp. 2012;12(4):62–4.
39. Lei DS Yu J Tong XL Wang MW Wang K Chen H Diagnostic value of cytokeratin 19 fragment in nasopharyngeal carcinoma Chin J Pathol 2012 41 7 461 5
Lei DS, Yu J, Tong XL, Wang MW, Wang K, Chen H. Diagnostic value of cytokeratin 19 fragment in nasopharyngeal carcinoma. Chin J Pathol. 2012;41(7):461–5.
40. Wang ZJ Cao WJ Chen F Shen J Tang L Wang SZ Analysis of serum anti-epstein-barr virus antibody in patients with nasopharyngeal carcinoma in Shanghai Chin J Ophthalmol Otorhinolaryngol 2012 12 1 40 4146
Wang ZJ, Cao WJ, Chen F, Shen J, Tang L, Wang SZ. Analysis of serum anti-epstein-barr virus antibody in patients with nasopharyngeal carcinoma in Shanghai. Chin J Ophthalmol Otorhinolaryngol. 2012;12(1):40–6.
41. Liu Y Huang Q Liu W Liu Q Jia W Chang E Establishment of VCA and EBNA1 IgA-based combination by enzyme-linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two-stage design with a preliminary performance study and a mass screening in southern China Int J Cancer 2012 131 2 406 16 10.1002/ijc.26380 21866545
Liu Y, Huang Q, Liu W, Liu Q, Jia W, Chang E, et al. Establishment of VCA and EBNA1 IgA-based combination by enzyme-linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two-stage design with a preliminary performance study and a mass screening in southern China. Int J Cancer. 2012;131(2):406–16.21866545 10.1002/ijc.26380
42. He J. Study on the labeling and preliminary application of quantum dot technology for nasopharyngeal carcinoma marker EBNA1. Cent South Univ. 2013.
43. Li XL Chen Y Zheng RQ Peng W Gao YN Ye Q Application value of Epstein-Barr virus rta protein antibody IgG combined with two antibodies in the diagnosis and screening of nasopharyngeal carcinoma Lab Med Clin 2013 10 3 321 3
Li XL, Chen Y, Zheng RQ, Peng W, Gao YN, Ye Q. Application value of Epstein-Barr virus rta protein antibody IgG combined with two antibodies in the diagnosis and screening of nasopharyngeal carcinoma. Lab Med Clin. 2013;10(3):321–3.
44. Yan CE, Wang HJ, Jia DQ, Han XH, Qi J. Diagnostic value of combined measurement of serum SA 、 EA-IgA 、 VCA-IgA and CgA levels in patients with nasopharyngeal carcinoma. Chin J Med. 2013(10):27–8.
45. Shi DW Wang PP Ji MF Li YB Zhou HW Shen S Evaluation of commercial kits of detecting EBV antibodies for nasopharyngeal carcinoma diagnosis Labeled Immunoassays & Clin Med 2014 21 3 310 4
Shi DW, Wang PP, Ji MF, Li YB, Zhou HW, Shen S, et al. Evaluation of commercial kits of detecting EBV antibodies for nasopharyngeal carcinoma diagnosis. Labeled Immunoassays & Clin Med. 2014;21(3):310–4.
46. Xu Q, Zheng SH, Lin SX. To evaluate the clinical value of Epstein-Barr virus (EBV)’s Rta/IgG in the diagnosis of nasopharyngeal carcinoma (NPC) patients in Zhuhai. J Med Infrom. 2014(19):97–8.
47. Peng YH Xu YW Qiu SQ Hong CQ Zhai TT Li EM Combination of autoantibodies against NY-ESO-1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma Oncol Lett 2014 8 3 1096 102 10.3892/ol.2014.2286 25120665
Peng YH, Xu YW, Qiu SQ, Hong CQ, Zhai TT, Li EM, et al. Combination of autoantibodies against NY-ESO-1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma. Oncol Lett. 2014;8(3):1096–102.25120665 10.3892/ol.2014.2286
48. Du MX Wang WJ Diagnostic value of combined detection of Rta-IgG,EBNA1-IgA and VCA-IgA antibodies in nasopharyngeal carcinoma in Zhongshan area Int J Lab Med 2015 36 13 1856 18571860
Du MX, Wang WJ. Diagnostic value of combined detection of Rta-IgG,EBNA1-IgA and VCA-IgA antibodies in nasopharyngeal carcinoma in Zhongshan area. Int J Lab Med. 2015;36(13):1856–60.
49. Peng YH Xie CL Zhuang SS Zhang LQ Xu YW Combined analysis of autoantibodies against p53 and Epstein-BarrvirusVCA-IgA for improved diagnosis of nasopharyngeal carcinoma Cancer Prev Res (Phila) 2015 27 1 26 2934
Peng YH, Xie CL, Zhuang SS, Zhang LQ, Xu YW. Combined analysis of autoantibodies against p53 and Epstein-BarrvirusVCA-IgA for improved diagnosis of nasopharyngeal carcinoma. Cancer Prev Res (Phila). 2015;27(1):26–34.
50. Wu WQ Liao SP Lin XL Huang QF Application on the EB virus detection in the physical examination of nasopharyngeal carcinoma screening All Health 2015 9 14 18 9
Wu WQ, Liao SP, Lin XL, Huang QF. Application on the EB virus detection in the physical examination of nasopharyngeal carcinoma screening. All Health. 2015;9(14):18–9.
51. Xu Q Zheng SH Lin SX Clinical value of Rta protein antibody IgG of EB virus in diagnosis for nasopharynx cancer Int J Lab Med 2015 36 17 2500 1
Xu Q, Zheng SH, Lin SX. Clinical value of Rta protein antibody IgG of EB virus in diagnosis for nasopharynx cancer. Int J Lab Med. 2015;36(17):2500–1.
52. Yi XH. The detections of EBV-VCA-IgA, EBV-EA-Ig A and EBV-Rta-IgG in diagnosis of nasopharyngeal carcinoma. Fujian Medical Univ. 2015.
53. Zhang XL, Zhou JL, Cao YP. The value of detection of three anti-epstein-barr viral antibodies for nasopharyngeal carcinoma diagnosis. Chin J Lab Med. 2015(2):111–4.
54. Gu XM, Li YY, Lv R, Huang JS, Zhou XJ, Du GY. The correlation between serum homocysteine and EB virus three antibodies in nasopharyngeal carcinoma and the evaluation of its diagnosis performance. Chin J Health Lab Tec. 2016(2):231–3.
55. Pan JZ Huang HS Zhu YX Zhang ZD Clinical value of three kinds of EB virus antibody detection in screening of nasopharyngeal carcinoma China Med Pharm 2016 6 19 225 8
Pan JZ, Huang HS, Zhu YX, Zhang ZD. Clinical value of three kinds of EB virus antibody detection in screening of nasopharyngeal carcinoma. China Med Pharm. 2016;6(19):225–8.
56. Wu CY Qiu MH Zeng XL Du MY Yao M Chen YX VCA-IgA and Rta-IgG joint detection diagnosis and effectiveness of nasopharyngeal carcinoma Chin J Lab Med 2016 8 609 12
Wu CY, Qiu MH, Zeng XL, Du MY, Yao M, Chen YX. VCA-IgA and Rta-IgG joint detection diagnosis and effectiveness of nasopharyngeal carcinoma. Chin J Lab Med. 2016;8:609–12.
57. Yu X Ji MF Cheng WM Huang YL Li FG Assessment of EBV antibodies and EBV-DNA in the diagnosis and stages of nasopha-ryngeal carcinoma Chin J Clin Oncol 2016 43 15 650 4
Yu X, Ji MF, Cheng WM, Huang YL, Li FG. Assessment of EBV antibodies and EBV-DNA in the diagnosis and stages of nasopha-ryngeal carcinoma. Chin J Clin Oncol. 2016;43(15):650–4.
58. Zheng FJ Fu YH Chen WS Liu N Expression of Rta recombinant antigen of Epstein-Barr Virus and establishment of ELISA method for nasopharyngeal carcinoma screening J Prev Med Chin PLA 2016 34 4 464 7
Zheng FJ, Fu YH, Chen WS, Liu N. Expression of Rta recombinant antigen of Epstein-Barr virus and establishment of ELISA method for nasopharyngeal carcinoma screening. J Prev Med Chin PLA. 2016;34(4):464–7.
59. Lin X Chen S Xue X Lu L Zhu S Li W Chimerically fused antigen rich of overlapped epitopes from latent membrane protein 2 (LMP2) of Epstein-Barr virus as a potential vaccine and diagnostic agent Cell Mol Immunol 2016 13 4 492 501 10.1038/cmi.2015.29 25864917
Lin X, Chen S, Xue X, Lu L, Zhu S, Li W, et al. Chimerically fused antigen rich of overlapped epitopes from latent membrane protein 2 (LMP2) of Epstein-Barr virus as a potential vaccine and diagnostic agent. Cell Mol Immunol. 2016;13(4):492–501.25864917 10.1038/cmi.2015.29
60. Chen SC Peng L Hu JY Zhang XJ Long LN Application value of three EB virus antibody combined tests in screening of nasopharyngeal carcinoma Int J Lab Med 2017 38 14 1949 50
Chen SC, Peng L, Hu JY, Zhang XJ, Long LN. Application value of three EB virus antibody combined tests in screening of nasopharyngeal carcinoma. Int J Lab Med. 2017;38(14):1949–50.
61. Yan CE Chen F Wang QP Liu QY Li J Gao J Correlation study on serum EA-IgA、VCA-IgA、Rta-IgG、EBV-DNA levels of nasopharyngeal carcinoma Chin J Med 2017 52 8 98 100
Yan CE, Chen F, Wang QP, Liu QY, Li J, Gao J, et al. Correlation study on serum EA-IgA、VCA-IgA、Rta-IgG、EBV-DNA levels of nasopharyngeal carcinoma. Chin J Med. 2017;52(8):98–100.
62. Gao R Wang L Liu Q Zhang LF Ye YF Xie SH Evaluation of seven recombinant VCA-IgA ELISA kits for the diagnosis of nasopharyngeal carcinoma in China: a case-control trial BMJ Open 2017 7 6 e013211 10.1136/bmjopen-2016-013211 28674124
Gao R, Wang L, Liu Q, Zhang LF, Ye YF, Xie SH, et al. Evaluation of seven recombinant VCA-IgA ELISA kits for the diagnosis of nasopharyngeal carcinoma in China: a case-control trial. BMJ Open. 2017;7(6):e013211.28674124 10.1136/bmjopen-2016-013211
63. Lin LH Xu YW Huang LS Hong CQ Zhai TT Liao LD Serum proteomic-based analysis identifying autoantibodies against PRDX2 and PRDX3 as potential diagnostic biomarkers in nasopharyngeal carcinoma Clin Proteom 2017 14 1 1 10 10.1186/s12014-017-9141-5
Lin LH, Xu YW, Huang LS, Hong CQ, Zhai TT, Liao LD, et al. Serum proteomic-based analysis identifying autoantibodies against PRDX2 and PRDX3 as potential diagnostic biomarkers in nasopharyngeal carcinoma. Clin Proteom. 2017;14(1):1–10.10.1186/s12014-017-9141-5
64. Gao J Peng YP Zhang CM Liu LZ Shen JJ Diagnosis value of granulysin in patients with nasopharyngeal carcinoma Zhejiang Med J 2018 40 14 1599 16011605
Gao J, Peng YP, Zhang CM, Liu LZ, Shen JJ. Diagnosis value of granulysin in patients with nasopharyngeal carcinoma. Zhejiang Med J. 2018;40(14):1599–605.
65. Li G Xu Y The value of EB virus IgA antibody levels in nasopharyngeal carcinoma patients during radiotherapy Mod Oncol 2018 26 17 2686 9
Li G, Xu Y. The value of EB virus IgA antibody levels in nasopharyngeal carcinoma patients during radiotherapy. Mod Oncol. 2018;26(17):2686–9.
66. Zhang YN. Changes in serum levels of Rta-IgG, VCA-IgA and EA-IgA antibodies in patients with nasopharyngeal carcinoma before and after radiotherapy. University of South China. 2018.
67. Li HT Li ZH Cui MT Yang JF Yang ZZ Application and clinical significance of three EB virus antibody binding tests in screening nasopharyngeal carcinoma Int J Lab Med 2019 40 A01 126 9
Li HT, Li ZH, Cui MT, Yang JF, Yang ZZ. Application and clinical significance of three EB virus antibody binding tests in screening nasopharyngeal carcinoma. Int J Lab Med. 2019;40(A01):126–9.
68. Tang HN Li YR Tang LL Ren YP Chen YL Qin LX Study on diagnostic value of Rta-IgG combined with VCA-IgA and EA-IgA EB viral antibodies detection in nasopharyngeal carcinoma in Hunan area Lab Med Clin 2019 16 23 3396 400
Tang HN, Li YR, Tang LL, Ren YP, Chen YL, Qin LX, et al. Study on diagnostic value of Rta-IgG combined with VCA-IgA and EA-IgA EB viral antibodies detection in nasopharyngeal carcinoma in Hunan area. Lab Med Clin. 2019;16(23):3396–400.
69. Zhang HW Chen JH Correlation analysis between serum NRSN2 with epstein-Barr virus antibody and DNA in nasopharyngeal carcinoma J Chin Physician 2019 21 11 1688 92
Zhang HW, Chen JH. Correlation analysis between serum NRSN2 with epstein-Barr virus antibody and DNA in nasopharyngeal carcinoma. J Chin Physician. 2019;21(11):1688–92.
70. Cai XP Cai WP Comparison of Epstein-Barr virus serum antibody kits from different manufacturers in the detection of nasopharyngeal carcinoma Front Med 2020 10 20 242 3
Cai XP, Cai WP. Comparison of Epstein-Barr virus serum antibody kits from different manufacturers in the detection of nasopharyngeal carcinoma. Front Med. 2020;10(20):242–3.
71. Fang QM Cai WP Wang Y Zhong SY Luo XH Application value of combined detection of 4 EB Virus antibodies in diagnosis and treatment of nasopharyngeal carcinoma Lingnan J Emerg Med 2020 25 3 279 82
Fang QM, Cai WP, Wang Y, Zhong SY, Luo XH. Application value of combined detection of 4 EB Virus antibodies in diagnosis and treatment of nasopharyngeal carcinoma. Lingnan J Emerg Med. 2020;25(3):279–82.
72. Guo J Cui Z Zheng Y Li X Chen Y Comparison of Epstein-Barr Virus serological tools for the screening and risk assessment of nasopharyngeal carcinoma: a large population-based study Pathol Oncol Res 2020 26 4 2185 90 10.1007/s12253-020-00808-0 32222897
Guo J, Cui Z, Zheng Y, Li X, Chen Y. Comparison of Epstein-Barr virus serological tools for the screening and risk assessment of nasopharyngeal carcinoma: a large population-based study. Pathol Oncol Res. 2020;26(4):2185–90.32222897 10.1007/s12253-020-00808-0
73. Liu W Li H Sheng H Liu X Chi P Wang X A randomized controlled trial on evaluation of plasma Epstein-Barr Virus biomarker for early diagnosis in patients with nasopharyngeal carcinoma Adv Ther 2020 37 10 4280 90 10.1007/s12325-020-01461-4 32780356
Liu W, Li H, Sheng H, Liu X, Chi P, Wang X, et al. A randomized controlled trial on evaluation of plasma Epstein-Barr virus biomarker for early diagnosis in patients with nasopharyngeal carcinoma. Adv Ther. 2020;37(10):4280–90.32780356 10.1007/s12325-020-01461-4
74. Rao D Fu M Chen Y Liu Q Xiao L Zhang X A combination of two ELISA tests for nasopharyngeal carcinoma screening in endemic areas based on a case-control study PeerJ 2020 8 e10254 10.7717/peerj.10254 33240616
Rao D, Fu M, Chen Y, Liu Q, Xiao L, Zhang X, et al. A combination of two ELISA tests for nasopharyngeal carcinoma screening in endemic areas based on a case-control study. PeerJ. 2020;8:e10254.33240616 10.7717/peerj.10254
75. Yu X Li F Cheng W Wu B Fang H Xia F Efficacy of chemiluminescence immunoassays on VCA-IgA and EBNA1-IgA antibodies of Epstein-Barr virus in diagnosing nasopharyngeal carcinoma J Cancer 2020 11 24 7176 83 10.7150/jca.47260 33193880
Yu X, Li F, Cheng W, Wu B, Fang H, Xia F, et al. Efficacy of chemiluminescence immunoassays on VCA-IgA and EBNA1-IgA antibodies of Epstein-Barr virus in diagnosing nasopharyngeal carcinoma. J Cancer. 2020;11(24):7176–83.33193880 10.7150/jca.47260
76. Gong YF Tang BH Song XM Tang L Wang ZJ Cao WJ Application of serological detection of EB virus immunoglobin A in nasopharyngeal carcinoma screening Chin J Ophthalmol Otorhinolaryngol 2021 21 6 431 4
Gong YF, Tang BH, Song XM, Tang L, Wang ZJ, Cao WJ. Application of serological detection of EB virus immunoglobin A in nasopharyngeal carcinoma screening. Chin J Ophthalmol Otorhinolaryngol. 2021;21(6):431–4.
77. Lu SJ Wu XH Yang XY Guo ZH Study on the diagnostic value of serum EBNA1-IgA,VCA-IgA and VEA-IgA in nasopharyngeal carcinoma Exp Lab Med 2021 39 1 142 4
Lu SJ, Wu XH, Yang XY, Guo ZH. Study on the diagnostic value of serum EBNA1-IgA,VCA-IgA and VEA-IgA in nasopharyngeal carcinoma. Exp Lab Med. 2021;39(1):142–4.
78. Wang CY Zhang SC Xie ZJ An L Zhao CP Wang CH Value study of EB Virus antibody and SCCA combined examination on the early diagnosis and prognosis prediction for nasopharyngeal carcinoma patients Smart Healthc 2021 7 20 10 1215
Wang CY, Zhang SC, Xie ZJ, An L, Zhao CP, Wang CH. Value study of EB virus antibody and scca combined examination on the early diagnosis and prognosis prediction for nasopharyngeal carcinoma patients. Smart Healthc. 2021;7(20):10–15.
79. Wang J Xue SW Detection and analysis of three antibodies of Eb Virus NA,ZTA and VCA Smart Healthc 2021 7 24 1 3
Wang J, Xue SW. Detection and analysis of three antibodies of Eb virus NA,ZTA and VCA. Smart Healthc. 2021;7(24):1–3.
80. Zhang J Gu XM Deng HY Shen HM Ding JX Tang FQ Diagnostic significance of combined detection of Epstein-Barr virus antibodies,EA-IgA,VCA-IgA and Rta-IgG in serum for nasopharyngeal carcinoma Pract Prev Med 2021 28 1 44 7
Zhang J, Gu XM, Deng HY, Shen HM, Ding JX, Tang FQ, et al. Diagnostic significance of combined detection of Epstein-Barr virus antibodies,EA-IgA,VCA-IgA and Rta-IgG in serum for nasopharyngeal carcinoma. Pract Prev Med. 2021;28(1):44–7.
81. Deng RH Liu LY Xie WK Liu ML Zhang GR Screening value of combined detection of four EB virus antibodies in nasopharyngeal carcinoma Chin J Otorhinolaryngol Integ Med 2022 30 2 88 91
Deng RH, Liu LY, Xie WK, Liu ML, Zhang GR. Screening value of combined detection of four EB virus antibodies in nasopharyngeal carcinoma. Chin J Otorhinolaryngol Integ Med. 2022;30(2):88–91.
82. Qu HL Ye PJ Liu JH Lv WB Yao J The prognostic value of epstein-barr virus antibodies in nasopharyngeal carcinoma J Trop Med 2022 22 1 41 4
Qu HL, Ye PJ, Liu JH, Lv WB, Yao J. The prognostic value of epstein-barr virus antibodies in nasopharyngeal carcinoma. J Trop Med. 2022;22(1):41–4.
83. Qin N Wang S Liu W Value of combined measurement of serum epstein-barr virus antibodies and epstein-barr virus DNA in the diagnosis of nasopharyngeal carcinoma J Qingdao Univ Med Sci 2023 59 1 64 7
Qin N, Wang S, Liu W. Value of combined measurement of serum epstein-barr virus antibodies and epstein-barr virus DNA in the diagnosis of nasopharyngeal carcinoma. J Qingdao Univ Med Sci. 2023;59(1):64–7.
84. Xu FX Clinical value of Epstein-Barr virus antibody detection in the diagnosis of nasopharyngeal carcinoma Chin Med Digest(Otorhinolaryngology) 2023 38 2 49 52
Xu FX. Clinical value of Epstein-Barr virus antibody detection in the diagnosis of nasopharyngeal carcinoma. Chin Med Digest(Otorhinolaryngology). 2023;38(2):49–52.
85. Zheng RS Chen R Han BF Wang SM Li L Sun KX Cancer incidence and mortality in China, 2022 Chin J Cancer 2024 00 221 31
Zheng RS, Chen R, Han BF, Wang SM, Li L, Sun KX, et al. Cancer incidence and mortality in China, 2022. Chin J Cancer. 2024;00:221–31.
86. Chan KCA Woo JKS King A Zee BCY Lam WKJ Chan SL Analysis of plasma Epstein-Barr Virus DNA to screen for nasopharyngeal Cancer N Engl J Med 2017 377 6 513 22 10.1056/NEJMoa1701717 28792880
Chan KCA, Woo JKS, King A, Zee BCY, Lam WKJ, Chan SL, et al. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017;377(6):513–22.28792880 10.1056/NEJMoa1701717
87. Li T Li F Guo X Hong C Yu X Wu B Anti-epstein-barr Virus BNLF2b for Mass Screening for Nasopharyngeal Cancer N Engl J Med 2023 389 9 808 19 10.1056/NEJMoa2301496 37646678
Li T, Li F, Guo X, Hong C, Yu X, Wu B, et al. Anti-epstein-barr virus BNLF2b for mass screening for nasopharyngeal cancer. N Engl J Med. 2023;389(9):808–19.37646678 10.1056/NEJMoa2301496
