A novel biomarker derived from Epstein-Barr virus (EBV) significantly improved the diagnostic accuracy for Nasopharyngeal carcinoma, a large screening study from China showed.

Screening with P85-Ab, an anti-BNLF2b total antibody, significantly improved diagnostic performance versus a standard two-antibody test, including sensitivity (97.9% vs 72.3%), specificity (98.3% vs 97.0%), and positive predictive value (PPV; 10.0% vs 4.3%). Combining P85-Ab with the standard biomarkers increased PPV to 44.6%, associated with a 70.2% sensitivity, as reported in the New England Journal of Medicine.

“In this study, P85-Ab was identified as a novel biomarker for nasopharyngeal carcinoma screening, with improved sensitivity, specificity, and positive predictive value,” wrote Shengxiang Ge, PhD, of the State Key Laboratory of Vaccines for Infectious Diseases in Xiamen, and co-authors. “The high positive predictive value could improve the cost-effectiveness, capacity, and acceptance of nasopharyngeal carcinoma screening.”

“The combination of P85-Ab with other biomarkers could further improve the positive predictive value of nasopharyngeal carcinoma screening and eventually decrease nasopharyngeal carcinoma-associated morbidity,” they added.

EBV has a ubiquitous association with Nasopharyngeal Cancer in China, Southeast Asia, and North Africa. Screening for EBV-specific antibodies or DNA has improved early-stage diagnosis from 20% of all cases to 70%, Ge and team noted in their introduction. As the group previously reported, patients who participated in screening had significantly better survival following diagnosis of nasopharyngeal cancer. However, widespread use of screening has been limited by low PPV, even in areas where EBV is endemic.

Efforts to improve screening strategies, including combining biomarkers and multistep screening, have thus far failed to improve diagnostic results, the authors continued. Additionally, studies to identify novel biomarkers have yielded few promising candidates.

“Given the relatively low prevalence of nasopharyngeal carcinoma, the specificity should be extremely high in order to achieve a higher positive predictive value,” they noted.

The EBV genome encodes more than 80 proteins, but antibodies have been identified for only 20 or so with respect to their relationship to nasopharyngeal cancer. Ge and colleagues hypothesized that antibodies to the remaining proteins might improve diagnostic performance. They developed a peptide library of highly ranked B-cell epitopes of EBV coding sequences to identify novel biomarkers for nasopharyngeal cancer.

In a case-control study, screening with P85-Ab (anti-BNLF2b total antibody) resulted in a sensitivity of 94.4% and specificity of 99.6%. The results provided the basis for a prospective screening study to compare P85-Ab against standard two-antibody screening (EBV nuclear antigen 1-IgA and EBV-specific viral capsid antigen IgA, or EBNA1 and VCA).

Data analysis comprised 24,852 study participants, 47 of whom had nasopharyngeal cancer, including 38 diagnosed at an early stage. P85-Ab outperformed the two-antibody method for all key outcome measures:

• Sensitivity: OR 1.4 (95% CI 1.1-1.6)
• Specificity: OR 1.01 (95% CI 1.01-1.02)
• PPV: OR 2.3 (95% CI 1.8-2.8)

P85-Ab also outperformed the standard antibody test across a range of subgroup analyses.

Investigators then analyzed the performance of P85-Ab in combination with EBNA1, VCA, or both of the standard antibodies. Among all P85-Ab-positive patients at medium-to-high risk referred for endoscopic evaluation, PPV increased to 29.6% with combined-antibody screening and to 44.6% in the high-risk subgroup.

Ge and colleagues acknowledged several limitations to their study. Some cases of nasopharyngeal cancer were diagnosed via linkage to a cancer registry, rather than endoscopic evaluation. Follow-up in the prospective cohort was relatively brief (6 to 18 months). Additionally, P85-Ab was evaluated only in Zhongshan, an area that has one of the world’s highest rates of nasopharyngeal cancer.