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Nasopharyngeal Epstein-Barr Virus Load: An Efficient Supplementary Method for Population-Based Nasopharyngeal Carcinoma Screening.

Chen Y, Zhao W, Lin L, Xiao X, Zhou X, Ming H, Huang T, Liao J, Li Y, Zeng X, Huang G, Ye W, Zhang Z - PLoS ONE (2015)

Bottom Line: The EBV loads of 8 NPCs were significantly higher than those of 897 NPC-free subjects (mean, 2.8 × 10(6) copies/swab [range 4.8 × 10(4)-1.1 × 10(8)] vs. 5.6 × 10(3) [range 0-3.8 × 10(6)]).Using mean EBV load in NPC-free population plus two standard deviations as cut-off value, a higher diagnostic performance was obtained for EBV load test than serum VCA/IgA test (area under ROC, 0.980 vs 0.895).In conclusion, in a prospective and population-based study we demonstrated that an additional assay of EBV load in the nasopharynx among high-risk individuals may reduce the number of subjects needed to be closely followed up and could serve as part of a NPC screening program in high-risk populations.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China; Department of Epidemiology, School of public health, Guangxi Medical University, Nanning, Guangxi, China.

ABSTRACT
Serological detection of Epstein-Barr virus (EBV) antibodies is frequently used in nasopharyngeal carcinoma (NPC) mass screening. However, the large number of seropositive subjects who require close follow-up is still a big burden. The present study aimed to detect the nasopharyngeal EBV load in a high-risk population seropositive for antibodies against EBV, as well as to examine whether assay for nasopharyngeal EBV DNA load might reduce the number of high-risk subjects for follow-up and improve early detection of NPC. A prospective and population-based cohort study was conducted in southern China from 2006 through 2013. Among 22,186 participants, 1045 subjects with serum immunoglobulin A (IgA) antibodies against viral capsid antigen (VCA) titers ≥ 1:5 were defined as high-risk group, and were then followed-up for NPC occurrence. Qualified nasopharyngeal swab specimens were available from 905 participants and used for quantitative PCR assay. Our study revealed that 89% (802/905) subjects showed positive EBV DNA in nasopharyngeal swab. The nasopharyngeal EBV load in females was higher than that in males. The nasopharyngeal EBV load increased with increasing serum VCA/IgA titers. Eight cases of newly diagnosed NPC showed an extremely elevated EBV load, and 87.5% (7 of 8 patients) were early-stage NPCs. The EBV loads of 8 NPCs were significantly higher than those of 897 NPC-free subjects (mean, 2.8 × 10(6) copies/swab [range 4.8 × 10(4)-1.1 × 10(8)] vs. 5.6 × 10(3) [range 0-3.8 × 10(6)]). Using mean EBV load in NPC-free population plus two standard deviations as cut-off value, a higher diagnostic performance was obtained for EBV load test than serum VCA/IgA test (area under ROC, 0.980 vs 0.895). In conclusion, in a prospective and population-based study we demonstrated that an additional assay of EBV load in the nasopharynx among high-risk individuals may reduce the number of subjects needed to be closely followed up and could serve as part of a NPC screening program in high-risk populations.

No MeSH data available.


Related in: MedlinePlus

Diagnostic performance of EBV load and VCA/IgA titers.Cut-off values (COV) and areas under receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic performance of EBV load and VCA/IgA titers. (a) The optimal COV for EBV load was mean plus 2 standard deviations (i.e. 4.7×105 copies/swab); (b) The best COV for VCA/IgA titers was mean plus standard deviation (i.e. 1:20); (c) The ROC curve indicated that EBV load had a better diagnostic value than VCA/IgA titers; the area under the curve of EBV load was larger than VCA/IgA titers.
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pone.0132669.g003: Diagnostic performance of EBV load and VCA/IgA titers.Cut-off values (COV) and areas under receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic performance of EBV load and VCA/IgA titers. (a) The optimal COV for EBV load was mean plus 2 standard deviations (i.e. 4.7×105 copies/swab); (b) The best COV for VCA/IgA titers was mean plus standard deviation (i.e. 1:20); (c) The ROC curve indicated that EBV load had a better diagnostic value than VCA/IgA titers; the area under the curve of EBV load was larger than VCA/IgA titers.

Mentions: During follow-up, 8 individuals were diagnosed with NPC by pathological examination in the 905 NPC high-risk subjects (Table 5). Seven of the 8 cases were early-stage NPCs, and the early diagnosis rate was 87.5%. All the 8 NPC cases were undifferentiated and non-keratinizing carcinoma. Six of them were males and two were females, and the cumulative incidence rates among males was 1.69% (6/356), and among females 0.36% (2/549) (male vs female, RR = 4.69, 95%CI: 0.94–23.36). The mean EBV load among the NPCs was significantly higher than that of NPC-free high-risk individuals (mean, 2.8×106 copies/swab [range 4.8×104−1.1×108] vs 5.6×103 copies/swab [range 0–3.8×106]; Z = -4.688, P < 0.001, Mann-Whitney U test) (Fig 3A). The mean titer of VCA/IgA was also significantly higher in NPCs than that of NPC-free subjects (NPC vs NPC-free = 1:33.9 vs 1:9.1; Z = -4.097, P < 0.001, Mann-Whitney U test) (Fig 3B). Both the EBV load and VCA/IgA titer of the NPC patients showed no correlation with the clinical stage (Spearman’s correlation coefficient = 0.385, P = 0.346 and 0.193, P = 0.648, respectively).


Nasopharyngeal Epstein-Barr Virus Load: An Efficient Supplementary Method for Population-Based Nasopharyngeal Carcinoma Screening.

Chen Y, Zhao W, Lin L, Xiao X, Zhou X, Ming H, Huang T, Liao J, Li Y, Zeng X, Huang G, Ye W, Zhang Z - PLoS ONE (2015)

Diagnostic performance of EBV load and VCA/IgA titers.Cut-off values (COV) and areas under receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic performance of EBV load and VCA/IgA titers. (a) The optimal COV for EBV load was mean plus 2 standard deviations (i.e. 4.7×105 copies/swab); (b) The best COV for VCA/IgA titers was mean plus standard deviation (i.e. 1:20); (c) The ROC curve indicated that EBV load had a better diagnostic value than VCA/IgA titers; the area under the curve of EBV load was larger than VCA/IgA titers.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495031&req=5

pone.0132669.g003: Diagnostic performance of EBV load and VCA/IgA titers.Cut-off values (COV) and areas under receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic performance of EBV load and VCA/IgA titers. (a) The optimal COV for EBV load was mean plus 2 standard deviations (i.e. 4.7×105 copies/swab); (b) The best COV for VCA/IgA titers was mean plus standard deviation (i.e. 1:20); (c) The ROC curve indicated that EBV load had a better diagnostic value than VCA/IgA titers; the area under the curve of EBV load was larger than VCA/IgA titers.
Mentions: During follow-up, 8 individuals were diagnosed with NPC by pathological examination in the 905 NPC high-risk subjects (Table 5). Seven of the 8 cases were early-stage NPCs, and the early diagnosis rate was 87.5%. All the 8 NPC cases were undifferentiated and non-keratinizing carcinoma. Six of them were males and two were females, and the cumulative incidence rates among males was 1.69% (6/356), and among females 0.36% (2/549) (male vs female, RR = 4.69, 95%CI: 0.94–23.36). The mean EBV load among the NPCs was significantly higher than that of NPC-free high-risk individuals (mean, 2.8×106 copies/swab [range 4.8×104−1.1×108] vs 5.6×103 copies/swab [range 0–3.8×106]; Z = -4.688, P < 0.001, Mann-Whitney U test) (Fig 3A). The mean titer of VCA/IgA was also significantly higher in NPCs than that of NPC-free subjects (NPC vs NPC-free = 1:33.9 vs 1:9.1; Z = -4.097, P < 0.001, Mann-Whitney U test) (Fig 3B). Both the EBV load and VCA/IgA titer of the NPC patients showed no correlation with the clinical stage (Spearman’s correlation coefficient = 0.385, P = 0.346 and 0.193, P = 0.648, respectively).

Bottom Line: The EBV loads of 8 NPCs were significantly higher than those of 897 NPC-free subjects (mean, 2.8 × 10(6) copies/swab [range 4.8 × 10(4)-1.1 × 10(8)] vs. 5.6 × 10(3) [range 0-3.8 × 10(6)]).Using mean EBV load in NPC-free population plus two standard deviations as cut-off value, a higher diagnostic performance was obtained for EBV load test than serum VCA/IgA test (area under ROC, 0.980 vs 0.895).In conclusion, in a prospective and population-based study we demonstrated that an additional assay of EBV load in the nasopharynx among high-risk individuals may reduce the number of subjects needed to be closely followed up and could serve as part of a NPC screening program in high-risk populations.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China; Department of Epidemiology, School of public health, Guangxi Medical University, Nanning, Guangxi, China.

ABSTRACT
Serological detection of Epstein-Barr virus (EBV) antibodies is frequently used in nasopharyngeal carcinoma (NPC) mass screening. However, the large number of seropositive subjects who require close follow-up is still a big burden. The present study aimed to detect the nasopharyngeal EBV load in a high-risk population seropositive for antibodies against EBV, as well as to examine whether assay for nasopharyngeal EBV DNA load might reduce the number of high-risk subjects for follow-up and improve early detection of NPC. A prospective and population-based cohort study was conducted in southern China from 2006 through 2013. Among 22,186 participants, 1045 subjects with serum immunoglobulin A (IgA) antibodies against viral capsid antigen (VCA) titers ≥ 1:5 were defined as high-risk group, and were then followed-up for NPC occurrence. Qualified nasopharyngeal swab specimens were available from 905 participants and used for quantitative PCR assay. Our study revealed that 89% (802/905) subjects showed positive EBV DNA in nasopharyngeal swab. The nasopharyngeal EBV load in females was higher than that in males. The nasopharyngeal EBV load increased with increasing serum VCA/IgA titers. Eight cases of newly diagnosed NPC showed an extremely elevated EBV load, and 87.5% (7 of 8 patients) were early-stage NPCs. The EBV loads of 8 NPCs were significantly higher than those of 897 NPC-free subjects (mean, 2.8 × 10(6) copies/swab [range 4.8 × 10(4)-1.1 × 10(8)] vs. 5.6 × 10(3) [range 0-3.8 × 10(6)]). Using mean EBV load in NPC-free population plus two standard deviations as cut-off value, a higher diagnostic performance was obtained for EBV load test than serum VCA/IgA test (area under ROC, 0.980 vs 0.895). In conclusion, in a prospective and population-based study we demonstrated that an additional assay of EBV load in the nasopharynx among high-risk individuals may reduce the number of subjects needed to be closely followed up and could serve as part of a NPC screening program in high-risk populations.

No MeSH data available.


Related in: MedlinePlus