Comparative effectiveness of immune checkpoint inhibitors in squamous vs. non-aquamous cervical carcinoma: a meta-analysis of randomized controlled trials

Abstract Objective The differential efficacy of immune checkpoint inhibitor (ICI) treatment between cervical squamous cell carcinoma (SCC) and non-squamous cell carcinoma(non-SCC) patients was unclear. This study aimed to evaluate the efficacy of ICI therapy in metastatic cervical SCC versus non-SCC. Methods A literature search was conducted across PubMed/Embase/the Cochrane Library to identify randomized controlled trials (RCTs) assessing the efficacy of ICI treatment in metastatic cervical cancer. Primary endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results Four RCTs were included in the meta-analysis. ICI treatment demonstrated significant improvements in PFS and OS compared to control treatment in both SCC and non-SCC patients. Anti-PD-1 therapy significantly enhanced ORR in SCC patients (P = 0.0001) but not in non-SCC patients (P = 0.23). Subgroup analysis revealed anti-PD-1 and anti-PD-1/CTLA4 therapies prolonged PFS in SCC patients (both P < 0.0001) but not in non-SCC patients (P = 0.13 and P = 0.83, respectively). Conversely, anti-PD-L1 therapy did not improve PFS in SCC patients (P = 0.22) but significantly enhanced PFS in non-SCC patients (P < 0.0001). OS subgroup analysis indicated prolonged OS in SCC patients treated with anti-PD-1, anti-PD-L1, or anti-PD-1/CTLA4. In non-SCC patients, only the anti-PD-1 subgroup exhibited OS benefit (P = 0.006), while no significant differences were observed in the anti-PD-L1 and anti-PD-1/CTLA4 subgroups (P = 0.08 and P = 0.83, respectively). Conclusions ICI treatment improves outcomes in metastatic cervical cancer; however, the efficacy varies significantly between SCC and non-SCC patients. These findings deserve high clinical attention.