Results
Description of the studies
In total, 1540 articles were initially identified and five were finally selected according to the exclusion criteria, with a total of 2005 patients The specific screening process is shown in Figure 1. The five articles included four phase III RCT clinical trials and one phase II RCT clinical trial. Treatment with PD-1/PD-L1 inhibitors was one of the intervention programmes, and this was compared with other treatment methods. Overall response rate (ORR), overall survival (OS), and progression-free survival (PFS) were the end points in each study. The median follow-up time ranged from 5.2 to 17 months. Specific information on each study is shown in Table 1 and the results of methodological quality evaluation for each study are shown in Table 2.
[Figure 1 near here]
Outcome results of meta-analysis
Overall response rate (ORR): All five of the articles reported the ORR of the patients in each group. Through software analysis (Figure 2), there was heterogeneity between the studies (I2 = 87%), so using the random effects model, the results showed that there was no statistically significant difference between the group treated with PD-1/PD-L1 and the group with other treatments (P = 0.35).
[Figure 2 near here]
Overall survival (OS): Four of the five articles reported the OS in each experimental group. Through software analysis (Fig. 3), there was no heterogeneity (I2 = 0%), so the fixed effects model was used. The results showed that treatment with PD-1/PD-L1 inhibitors alone could reduce the risk of death in patients with recurrent/metastatic HNSCC, and the difference between patients treated with PD-1/PD-L1 and the group with other treatments was statistically significant (P = 0.004).
[Figure 3 near here]
Progression-free survival (PFS): Four of the five articles reported the PFS of patients in each group. Through software analysis (Figure 4), there was no heterogeneity (I2 = 0%), so the fixed effects model was used. The results showed that there was no statistically significant difference in PFS between the group treated with PD-1/PD-L1 and the group with other treatments (P = 0.47).
[Figure 4 near here]
Adverse events
The five articles included in the study reported the adverse events of diarrhoea, asthenia, rash, fatigue, anaemia and nausea after treatment. Meta-analysis showed that there was no significant difference in diarrhoea, asthenia, rash or fatigue between the PD-1/PD-L1 inhibitor treatment group and the other treatment group, but PD-1/PD-L1 inhibitor treatment significantly reduced the risk of anaemia (P < 0.0001) and nausea (P < 0.0001), as shown in Table 3.
Publication bias analysis
A funnel chart test was carried out for OS, PFS, ORR and adverse reaction results to judge the effect of possible publication bias. However, due to the inclusion of less than 10 documents, it was impossible to use a forest map to judge publication bias. In order to reduce the effects of publication bias, we searched the unpublished clinical trial registry data. We use search terms Head and Neck Squamous Cell Carcinoma, and also searched for Squamous cell carcinoma of head and neck, Squamous cell carcinoma of the head and neck, head and neck cancer, head and neck neoplasms or HNSCC and PD-1/PD-L1 inhibitors or Pembrolizumab or Keytruda or Nivolumab or Opdivo or Durvalumab or MEDI4736 or Atezolizumab or checkpoint inhibitors. We found 217 studies but after removal of duplicates and consideration of inclusion criteria, we had to remove them all.