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

doi:10.1016/j.intimp.2021.108128

Viral infections and the efficacy of PD-(L)1 inhibitors in virus-related cancers: Head and neck squamous cell carcinoma and hepatocellular carcinoma

Int Immunopharmacol. 2021 Nov:100:108128. doi: 10.1016/j.intimp.2021.108128. Epub 2021 Sep 17.

Authors

Ting Liu¹, Qing Li¹, Zhen Lin¹, Peipei Wang¹, Yueyun Chen¹, Yang Fu¹, Zhenyu Ding²

Affiliations

¹ Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: dingzhenyu@scu.edu.cn.

PMID: 34537483
DOI: 10.1016/j.intimp.2021.108128

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).

Keywords: Cancer patients; Immune checkpoint inhibitors; Meta-analysis; Systematic review; Viral infection status.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

B7-H1 Antigen
Carcinoma, Hepatocellular / drug therapy*
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic
Head and Neck Neoplasms / drug therapy
Humans
Immune Checkpoint Inhibitors / pharmacology*
Immunotherapy
Randomized Controlled Trials as Topic
Squamous Cell Carcinoma of Head and Neck / drug therapy*
Virus Diseases / drug therapy*

Substances

B7-H1 Antigen
Immune Checkpoint Inhibitors