Real-world multicenter study of immune checkpoint inhibitors in advanced cervical cancer across HPV-associated and HPV-independent subtypes

Background: Cervical cancer remains a major health problem, and HPV-independent subtypes such as gastric-type adenocarcinoma carry dismal outcomes. Although immune checkpoint inhibitors (ICIs) have improved survival in large trials, their real-world effectiveness including HPV-independent tumors is not well established. Methods: We conducted a retrospective multicenter study of two surrogate cohorts representing refractory cervical cancer: patients treated with bevacizumab (Bev-cohort, n=65) and those undergoing comprehensive genomic profiling (CGP-cohort, n=42). Early ICI administration was evaluated using landmark analysis (Bev: 180 days; CGP: 6 months), with differences in restricted mean survival time (ΔRMST) as the primary endpoint. Multivariable Cox models adjusting for stage, histology, and treatment interval were performed as secondary analyses. Exploratory analyses assessed HPV and molecular status for associations with ICI response. Results: In the Bev-cohort, 14 ICI-treated patients achieved significantly longer survival than 48 non-ICI patients (ΔRMST +19.4 days at 180 days; +56.2 days at 360 days). Multivariable Cox confirmed ICI as an independent predictor of survival (HR 0.15, 95%CI 0.01–0.69). In the CGP-cohort, 11 ICI-treated patients also experienced superior survival compared with 20 non-ICI patients (ΔRMST +1.05 months at 6 months; +2.33 months at 12 months). Among 36 ICI-treated cases overall, efficacy was not clearly associated with PD-L1 or tumor mutation burden status. Importantly, HPV-independent tumors, including gastric-type adenocarcinoma, demonstrated progression-free survival comparable to HPV-associated tumors. Conclusion: ICIs improved survival in advanced refractory cervical cancer across two real-world cohorts, with benefits observed irrespective of CPS/TMB status and extending to HPV-independent tumors.