Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.

Current Chinese national guidelines recommend routine screening for liver cancer in patients positive for HBsAg, irrespective of fibrosis status, age, or family history of liver cancer. We aim to evaluate whether the recommended screening strategy could reduce liver-cancer-specific mortality. We conducted a liver cancer mass screening trial in Xiaolan Town, Zhongshan City, China, among residents aged 35–64 years in 2012. All volunteers were offered serological testing for hepatitis B virus surface antigen (HBsAg). We proposed biannual screening using serum alpha-fetoprotein (AFP) and ultrasonography examination for subjects positive for HBsAg. Among 17,966 participants (26.2% of 68,510 eligible residents) who were free of liver cancer at baseline in 2012, we identified 57 incident cases of liver cancer within the first 4 years of follow-up (i.e., 43 among 2,848 HBsAg-positive participants and 14 among 15,118 HBsAg-negative participants), compared with 104 cases identified in non-participants (N = 50,544). A total of 207 participants had the recommended number of ultrasonography examinations (every 6 months) during the screening period. Compared with cases identified from non-participants, the cases arising among participants were more likely to be at early stage and had better survival than those among non-participants. However, we did not observe a reduction in liver cancer-specific mortality rate among participants (relative risk = 1.04, 95% confidence interval = 0.68, 1.58, P = 0.856). Our demonstration screening study does not show a reduction in liver cancer mortality within the first 4 years of follow-up according to current guidance in China, although long-term efficacy remains to be evaluated. Targeted surveillance among high-risk individuals as recommended by international guidelines, along with measures to improve compliance, should be evaluated in the Chinese population.

Background: Nasopharyngeal carcinoma (NPC) remains as a major public health burden in Southern China. Over the last decade, Epstein-Barr virus (EBV) serological detection has been the most promising tool used for NPC screening. The present study aims to evaluate the long-term diagnostic performance of a new NPC screening scheme (probability of NPC units [logit P], PROB≥0.65), and compare this with other EBV seromarkers used within 2009-2015.Methods: Enzyme-linked immunosorbent assay (ELISA) for EBV capsid antigen (VCA/IgA) and nuclear antigen-1 (EBNA1/IgA) was performed in 16,712 subjects, who were within 30-59 years old.All subjects were followed up for six years. The area under the receiver operating characteristic curve (AUC) and correlation analyses were preformed to evaluate the diagnostic value of different measures. Furthermore, the rates of early diagnosis in NPC patients were statistically analyzed.Results: The new NPC screening scheme (PROB≥0.65) and the four strategies (VCA/IgA, EBNA1/IgA, VCA/IgA and EBNA1/IgA, and VCA/IgA or EBNA1/IgA) had comparable rates of early diagnosis for NPC (no significant difference was found), but the sensitivity of the new scheme (95.7%) was higher than that of the others. The top three seromarkers with the largest AUC were PROB≥0.65 (AUC:0.926, 95% CI: 0.885-0.966), VCA/IgA or EBNA1/IgA (AUC:0.883, 95% CI:0.824-0.942), and EBNA1/IgA (AUC: 0.866, 95% CI: 0.794-0.938).Conclusion: The new NPC screening scheme (PROB≥0.65) based on VCA/IgA and EBNA1/IgA outperforms the other seromarkers, and making it the preferred serodiagnostic strategy for long-term NPC screening in high-incidence areas.