**2. Population screening of NPC**

As literature reported, before the clinical onset of NPC, the serological EBV antibody level has already been sustained elevated within a window of 37 months, which serves as an efficient screening biomarker [22]. At present, serological detection of EBV, testing the titers of viral capsid antigen (VCA)-IgA, early antigen (EA)-IgA, and EBV nuclear antigen 1 (EBNA1)-IgA antibodies of EBV is widely used in the mass screening of NPC in an endemic region, which is helpful for early diagnosis [23–25]. No matter using the traditional immunofluorescent/ Immunoenzymatic assays or enzyme-linked immunosorbent assays (ELISA) assay, once the elevated EBV-IgA were detected in screening participants, they were defined as "high-risk" objects of NPC. Next, an indirect mirror examination in the nasopharynx and/or lymphatic palpation should be carried out. If abnormal enlargement of the lymph node in the upper neck and elevate, rough nasopharyngeal surface were observed, the objects will be concluded as suspicious NPC patients. Further fiberoptic endoscopy and biopsy are necessary for diagnosis [25]. The benefit of screening was illustrated by finding early NPC cases.

Scientists are devoted to improving the methods of detecting EBV to enhance the effectiveness of screening. For instance, collecting nasopharyngeal swabs for additional nasopharyngeal EBV DNA load analysis could effectively reduce the "high risk" population who needed follow-up examination [26]. Recently, utilizing circulating cell-free EBV DNA has been proposed for early NPC screening, with sensitivity and specificity as 97.1% and 98.6%, respectively [27].
