Hepatocellular carcinoma (HCC) is an aggressive malignancy with its global incidence and mortality rate continuing to rise, although early detection and surveillance are suboptimal. We performed serological profiling of the viral infection history in 899 individuals from an NCI-UMD case-control study using a synthetic human virome, VirScan. We developed a viral exposure signature and validated the results in a longitudinal cohort with 173 at-risk patients who had long-term follow-up for HCC development. Our viral exposure signature significantly associated with HCC status among at-risk individuals in the validation cohort (area under the curve: 0.91 [95% CI 0.87–0.96] at baseline and 0.98 [95% CI 0.97–1] at diagnosis). The signature identified cancer patients prior to a clinical diagnosis and was superior to alpha-fetoprotein. In summary, we established a viral exposure signature that can predict HCC among at-risk patients prior to a clinical diagnosis, which may be useful in HCC surveillance.

肝细胞癌（HCC）是一种侵袭性恶性肿瘤，尽管早期发现和监测效果不佳，但其全球发病率和死亡率持续上升。我们使用合成的人类病毒组 VirScan 对来自 NCI-UMD 病例对照研究的 899 名个体的病毒感染史进行了血清学分析。我们开发了病毒暴露特征，并在 173 名高危患者的纵向队列中验证了结果，这些患者对 HCC 的发展进行了长期随访。我们的病毒暴露特征与验证队列中高危个体的 HCC 状态显着相关（曲线下面积：基线时为 0.91 [95% CI 0.87–0.96]，诊断时为 0.98 [95% CI 0.97–1]）。该特征可以在临床诊断之前识别出癌症患者，并且优于甲胎蛋白。总之，我们建立了一种病毒暴露特征，可以在临床诊断之前预测高危患者中的 HCC，这可能有助于 HCC 监测。