A large-scale population-based study reveals that gp42-IgG antibody is protective against Epstein-Barr virus-associated nasopharyngeal carcinoma.

Background: Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), but the existence of NPC protective antibody against EBV-associated antigens remains inconclusive.

Methods: NPC cases and matched controls were identified from prospective cohorts comprising 75,481 participants in southern China. ELISA and conditional logistic regression were applied to assess effects of gp42-IgG on NPC. The expression of HLA-II, the gp42 receptor, in nasopharyngeal atypical dysplasia and its impact on EBV infecting epithelial cells were evaluated.

Findings: gp42-IgG titers were significantly lower in NPC cases compared to controls across various follow-up years before NPC diagnosis (P<0.05). Individuals in the highest quartile of gp42-IgG titers had a 71% NPC risk reduction comparing to those in the lowest quartile (odds ratios [OR]Q4vsQ1=0.29, 95% confidence intervals [CIs]=0·15 to 0·55, P<0.001). Each unit antibody titer increase was associated with 34% lower risk of NPC (OR=0.66, 95% CI=0.54 to 0.81, Ptrend <0.001). Their protective effect was observed in cases diagnosed ≥5 years, 1-5 years and <1 year after blood collection (P<0.05). HLA-II expression was detected in 13 of 27 nasopharyngeal atypical dysplasia and its overexpression substantially promoted epithelial-cell-origin EBV infection.

Conclusion: Elevated EBV gp42-IgG titers can reduce NPC risk, indicating gp42 as a potential EBV prophylactic vaccine design target.

Trial registration: NCT00941538, NCT02501980, ChiCTR2000028776, ChiCTR2100041628.

Funding: Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program, Central Financial Transfer Payment Projects of the Chinese Government, Cancer Research Grant of Zhongshan City.