Risk of venous thromboembolism following human papillomavirus vaccination: a systematic review and meta-analysis

• Past reports suggested that risk of venous thromboembolism (VTE) was increased after human papillomavirus (HPV) vaccination. • We conducted a systematic review and meta -analysis of eight observational studies involving millions of participants. • Current evidence indicates that HPV vaccination is not associated with an increased risk of VTE. Sporadic reports linking human papillomavirus (HPV) vaccination to venous thromboembolism (VTE) have raised safety concerns. We intended to provide an updated and comprehensive evaluation of this potential association using recent large-scale data. We conducted a systematic review and meta -analysis of observational studies evaluating HPV vaccination and the risk of VTE. Major databases were searched from their inception through December 10, 2025. We pooled risk estimates using a random-effects model and assessed risk of bias using the ROBINS-I tool. Eight observational studies involving millions of participants were included. The pooled analysis showed no statistically significant association between HPV vaccination and VTE risk (Risk Ratio = 0.87; 95%CI: 0.71–1.07; P = 0.183). Consistency was observed across all subgroups, including age (<18 vs. ≥18 years), sex (female vs. male), and vaccine valency (including 9-valent). Current evidence indicates that HPV vaccination is not associated with an increased risk of VTE. These findings reinforce the favorable safety profile of HPV vaccines across diverse populations and support continued vaccination programs.