Purpose

This study aimed to test the interaction between viral infections and immune checkpoint inhibitor (ICI) efficacy for two virus-associated tumors, head and neck squamous carcinoma (HNSCC) and hepatocellular carcinoma (HCC), by conducting a systematic review and meta-analysis.

Methods

We searched databases from inception until December 30, 2020 to identify phase 2 or 3 randomized clinical trials involving ICI treatments with data on hazard ratios (HRs) for survival according to viral infection status. We evaluated the heterogeneity between patients with and without viral infections using an interaction test. Subgroup analyses were conducted to explore variations in the efficacy of immunotherapy according to viral infection status.

Results

Six phase 3 trials with 3672 patients (1382 with viral infections [38%] and 2115 without viral infections [57%]) were included. Among these patients, the pooled HR for survival was 0.69 (95% confidence interval [CI], 0.60–0.79) for those with viral infections and 0.84 (95% CI, 0.77–0.91) for those without infections after ICI treatment. Patients with viral infections achieved a better prognosis after ICI therapy than those without infections (P = 0.018). This was evident in patients with hepatitis B virus-associated HCC (P = 0.016), but not in patients with hepatitis C virus-associated HCC (P = 0.081) or in patients with human papillomavirus-positive HNSCC (P = 0.67).

Conclusion

Patients with advanced HNSCC and HCC, regardless of viral infection status, could benefit from ICI treatment. Patients with hepatitis B virus-associated HCC were more likely to benefit from ICI treatment than patients without viral infections.

Registration

Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews on March 27, 2020 (registration number CRD42020155326).

中文翻译：

---

病毒感染和 PD-(L)1 抑制剂在病毒相关癌症中的疗效：头颈部鳞状细胞癌和肝细胞癌

目的

本研究旨在通过系统评价和荟萃分析，测试病毒感染与免疫检查点抑制剂 (ICI) 对两种病毒相关肿瘤（头颈部鳞状细胞癌 (HNSCC) 和肝细胞癌 (HCC) 的疗效）之间的相互作用。

方法

我们搜索了从开始到 2020 年 12 月 30 日的数据库，以确定涉及 ICI 治疗的 2 期或 3 期随机临床试验，其中包含根据病毒感染状态生存的风险比 (HR) 数据。我们使用交互测试评估了有和没有病毒感染的患者之间的异质性。进行亚组分析以探索根据病毒感染状态的免疫治疗效果的变化。

结果

包括 6 项 3672 名患者（1382 名病毒感染 [38%] 和 2115 名无病毒感染 [57%]）的 3 期试验。在这些患者中，病毒感染患者的合并生存 HR 为 0.69（95% 置信区间 [CI]，0.60-0.79），ICI 治疗后未感染的患者为 0.84（95% CI，0.77-0.91）。ICI 治疗后病毒感染患者的预后优于未感染患者（P  = 0.018）。这在乙型肝炎病毒相关 HCC 患者 ( P  = 0.016) 中很明显，但在丙型肝炎病毒相关 HCC 患者 ( P  = 0.081) 或人乳头瘤病毒阳性 HNSCC 患者中 ( P  = 0.67) 不明显。

结论

无论病毒感染状态如何，晚期 HNSCC 和 HCC 患者都可以从 ICI 治疗中受益。与没有病毒感染的患者相比，乙型肝炎病毒相关 HCC 患者更有可能从 ICI 治疗中受益。

登记

我们的系统评价方案已于 2020 年 3 月 27 日在国际系统评价前瞻性注册中心注册（注册号 CRD42020155326）。