Abstract
This study aimed to systematically investigate the epidemiological distribution characteristics and disease burden of cervical cancer (CC) in Asian populations, and to assess the causal relationship between smoking, a key modifiable risk factor, and the incidence of CC based on genetic evidence, thereby providing a scientific basis for targeted prevention and control strategies in Asia. This study first used the GBD 2021 database to analyze trends in CC incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021 across global, Asian, and East Asian regions, along with age distribution and attributable risk factors. It then applied 2-sample Mendelian randomization (MR) using genome-wide association study (GWAS) data from East Asian populations, with multiple smoking-related behaviors (e.g., current smoking, cigarettes per day, household smoking exposure) as exposures and CC as the outcome. GBD analysis revealed that in 2021, Asia accounted for over half of the global CC disease burden. Although point estimates suggested a potential upward trend in CC burden across Asia from 1990 to 2021, statistical significance was not reached for the overall Asian population. Despite a general decline in the global incidence rate, the incidence in Japan exhibited a statistically supported upward trend, while point estimates in several other East Asian countries also suggested an increase. The peak disease burden was concentrated among women aged 55 to 59 years. Risk attribution analysis indicated that unsafe sexual behavior was the primary attributable factor for CC-related DALYs, while the attributable burden of smoking was significantly higher in Japan than in other regions. However, MR analysis did not identify statistically significant causal associations between any smoking-related exposure factors and CC risk (
P
-FDR ≥ .05 after false discovery rate correction). Sensitivity analyses revealed no substantial heterogeneity or pleiotropy bias. Asia, particularly East Asia, faces a substantial and potentially growing burden of CC. Causal inference based on genetic data from East Asian populations did not confirm a direct causal relationship between smoking and the incidence of cervical cancer. Future studies with larger genetic samples are needed to further elucidate the precise role of smoking.