Viral infections and the efficacy of PD-(L)1 inhibitors in virus-related cancers: Head and neck squamous cell carcinoma and hepatocellular carcinoma
Ting Liu, Qing Li, Zhen Lin, Peipei Wang, Yueyun Chen, Yang Fu, Zhenyu Ding
Abstract
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).