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

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, 2.8×106 copies/swab [range 4.8×104-1.1×108] vs. 5.6×103 [range 0-3.8×106]). 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.

Epstein‐Barr virus mRNA profiles and viral DNA methylation status in nasopharyngeal brushings from nasopharyngeal carcinoma patients reflect tumor origin

“…Furthermore, changes in brush EBV DNA levels directly reflect the tumor response to treatment and can be used to identify local recurrent disease . Our data confirm and extend previous studies revealing highly elevated EBV loads in NP swabs or brushings from NPC‐patients as compared to controls . We found that the number of viral genomes per cell as well as the pattern of overall EBV latent and lytic gene expression profiles are comparable in parallel brush‐biopsy specimens, confirming the diagnostic value of NP‐brushings …”

“…The NP brushing has been proposed as an alternative for the invasive and painful biopsy in detecting the presence of NPC at the primary site of tumor development . NP brushings collected from NPC patients carry high levels of EBV DNA and carcinoma‐specific BARF1 mRNA reflecting the presence of viable tumor cells in the NP epithelium (Fig.…”

“…Molecular analysis of minimally invasive NP brushings that contain abnormal level of viral DNA and RNA provides an alternative and promising new approach for (early) NPC diagnosis . The presence of latently EBV‐infected NPC tumor cells in NP brush specimens can be visualized by cytology .…”

Multiparametric Detection of Antibodies against Different EBV Antigens to Predict Risk for Nasopharyngeal Carcinoma in a High-Risk Population of China

“…Additional MRI scanning may be helpful to depict subclinical cancers missed at endoscopy (34). However, these techniques are either invasive or expensive and, most importantly, cannot be performed by general physicians; thus, they are not suitable for mass screening programs, especially in rural areas where only limited health care facilities are available (18). The analysis of the diagnostic performance of the risk model in VCA-IgA-negative and -positive groups showed that 82.6% of VCA-IgA-negative patients with nasopharyngeal carcinoma in our study had positive Anti-EBV EUROLINE panel results (with cutoff value of 26.13%); whereas 83.3% of VCA-IgA-positive healthy people had negative Anti-EBV EUROLINE panel results.…”

“…However, the sensitivity and specificity were not satisfactory (16)(17)(18)). Hsu's research found that the sensitivity and specificity of VCA-IgA by ELISA in Chinese patients were 91.9% and 83.8%, respectively, compared with EBNA-1 IgA with sensitivity and specificity values of 80.0% and 80.0%, respectively (19).…”