Establishment and validation of a two‐step screening scheme for improved performance of serological screening of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC), which is closely associated with Epstein–Barr virus (EBV), is one of the most prevalent cancers in southeast China. Most NPC patients are diagnosed at late stage due to inconspicuous symptoms at the early stage, and the prognosis of these patients is poor. The early diagnosis rate of NPC could be significantly increased by serological screening, but the positive predictive value (PPV) is relatively low. A simple two‐step serological screening scheme was established to improve the PPV of the screening strategy and was validated by a prospective cohort. Serum antibodies specific for EBNA1, Zta, Thymidine Kinase (TK), EAD, EAR, and VCA were detected by enzyme‐linked immunosorbent assay. The combination of EBNA1/IgA and VCA/IgA was used in the first step of screening, and anti‐early antigens (EAs) were used in the second step of screening. EAD/IgA was the most prominent marker in the second step of screening, and other anti‐EAs were complementary to EAD/IgA. As validated by a prospective cohort including 4200 participants, using the combination of EAD/IgA and TK/IgA in the second step decreased the number of high‐risk participants from 128 to 27, and increased the PPV from 4.69% to 18.52%, with only one very early‐stage case missed. The two‐step screening scheme provides a standardized approach for NPC screening with an improved PPV and may be used in future field studies. With this two‐step serological screening method, more people benefit from the screening program without increasing the need for fiberoptic endoscopy.