Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma

// Rui-Chen Li 1,2,5,* , Yong Du 2,* , Qiu-Yao Zeng 3,* , Lin-Quan Tang 2,4 , Hua Zhang 2 , Yan Li 2 , Wan-Li Liu 3 , Qian Zhong 2 , Mu-Sheng Zeng 2 and Xiao-Ming Huang 1 1 Department of Otorhinolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, P. R. China 2 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China 3 Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 4 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 5 Department of Otorhinolaryngology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, P. R. China * These authors have contributed equally to this work Correspondence to: Mu-Sheng Zeng, email: // Xiao-Ming Huang, email: // Keywords : nasopharyngeal carcinoma, Epstein-Barr virus, biomarker, gH/gL, viral capsid antigen Received : July 19, 2015 Accepted : February 05, 2016 Published : February 24, 2016 Abstract To determine whether measuring antibodies against Epstein-Barr virus (EBV) glycoprotein gH/gL in serum could improve diagnostic accuracy in nasopharyngeal carcinoma (NPC) cases, gH/gL expressed in a recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in two independent cohorts. Binary logistic regression analyses were performed using results from a training cohort ( n = 406) to establish diagnostic mathematical models, which were validated in a second independent cohort ( n = 279). Levels of serum gH/gL antibodies were higher in NPC patients than in healthy controls ( p < 0.001). In the training cohort, the IgA-gH/gL ELISA had a sensitivity of 83.7%, specificity of 82.3% and area under the curve (AUC) of 0.893 (95% CI, 0.862-0.924) for NPC diagnosis. Furthermore, gH/gL maintained diagnostic capacity in IgA-VCA negative NPC patients (sensitivity = 78.1%, specificity = 82.3%, AUC = 0.879 [95% CI, 0.820 - 0.937]). Combining gH/gL and viral capsid antigen (VCA) detection improved diagnostic capacity as compared to individual tests alone in both the training cohort (sensitivity = 88.5%, specificity = 97%, AUC = 0.98 [95% CI, 0.97 - 0.991]), and validation cohort (sensitivity = 91.2%, specificity = 96.5%, AUC = 0.97 [95% CI, 0.951-0.988]). These findings suggest that EBV gH/gL detection complements VCA detection in the diagnosis of NPC and aids in the identification of patients with VCA-negative NPC.