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.
A two-stage study was conducted in southern China to determine and validate an optimal combination of Epstein-Barr virus (EBV)-related seromarkers for nasopharyngeal carcinoma (NPC) screening. In the first stage, six seromarkers [VCA-IgA, EA-IgA, Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), EBNA1-IgG, Zta-IgA and Rta-IgG] were detected by enzyme-linked immunosorbent assay (ELISA) and two traditional NPC screening seromarkers (VCA-IgA and EA-IgA) were detected by immunofluorescence assay (IFA) in serum samples from 191 NPC patients and 337 controls. An optimal combination of seromarkers for NPC diagnosis was selected using logistic regression models. Results showed that the diagnostic performances of VCA-IgA and EA-IgA tested by ELISA were superior to the performances of the same seromarkers by IFA. VCA-IgA combined with EBNA1-IgA by ELISA was identified as the optimal combination, with an area under the receiver operating characteristic (ROC) curve (AUC) up to 0.97, a sensitivity of 95.3% and a specificity of 94.1% for classification of NPCs vs. controls. In the second stage, 5,481 participants aged 30-59 years and without clinical evidence of NPC were recruited into a population-based NPC screening program from May 2008 to February 2009 in Sihui City, China. Their sera were tested simultaneously by both the new and the traditional screening schemes and eight early stage NPC patients were subsequently histopathologically confirmed. The traditional and the new screening schemes had comparable specificity (estimated as 98.5%), but the sensitivity of the new scheme (75.0%) was significantly higher than that of the traditional one (25.0%). The combination of VCA-IgA and EBNA1-IgA by ELISA outperforms the traditional NPC screening scheme and could become the preferred serodiagnostic strategy for NPC screening in high-incidence areas.
Liu Y
，Huang Q
，Liu W
，Liu Q
，Jia W
，Chang E
，Chen F
，Liu Z
，Guo X
，Mo H
，Chen J
，Rao D
，Ye W
，Cao S
，Hong M
... -
《-》
Evaluation of a semi-quantitative ELISA for IgA antibody against Epstein-Barr virus capsid antigen in the serological diagnosis of nasopharyngeal carcinoma.
This study was designed to establish an ELISA method, as well as the cut-off value, for IgA against Epstein-Barr virus (EBV) viral capsid antigen (VCA), as a screening assay for nasopharyngeal carcinoma (NPC) in southern China. In addition, the correlation between relative optical density (rOD) values from ELISA and titers from the immunoenzymatic assay (IEA) was also evaluated.
Two hundred and fifty-eight NPC cases, 33 non-NPC head and neck cancer patients, and 1156 healthy controls were recruited for this study. VCA-IgA and early antigen (EA)-IgA were measured by ELISA kits and IEA in parallel.
The total precision of the VCA-IgA ELISA achieved a level of <13.0% coefficient of variation. An rOD value of 1.60 for the VCA-IgA ELISA was determined as the cut-off point for southern China, and the sensitivity and specificity for NPC diagnosis when using this cut-off value were 93.0% and 92.4%, respectively. The area under the receiver operating characteristic curve (ROC-AUC) value was 0.969. The correlation coefficient between titers and rOD values was 0.957. rOD values were correlated with NPC overall stage and lymph node involvement.
The cut-off level established in our study could be used to facilitate more accurate diagnosis of NPC in southern China. The rOD value might be an index for NPC prognosis, since it shows a good correlation with the titer from IEA.
Chen H
，Chi P
，Wang W
，Li L
，Luo Y
，Fu J
，Zhang L
，Liu W
... -
《-》
The serological diagnostic value of EBV-related IgA antibody panels for nasopharyngeal carcinoma: a diagnostic test accuracy meta-analysis.
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.
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).
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).
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.
The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023.
Liu H
，Lei L
，Song S
，Geng X
，Lin K
，Li N
，Chen W
，Peng J
，Ren J
... -
《BMC CANCER》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
