Gynecological malignancy signal triage: A two-dimensional framework integrating US-derived FAERS data with comparative US–China GBD trajectories

BACKGROUND: Cancer-related adverse-event reports are difficult to interpret because statistical disproportionality, stimulated reporting, and background disease burden are distinct phenomena. To address this, we formalized a two-dimensional prioritization framework that combines FAERS signal credibility with independent GBD burden context. Because the FAERS dataset is overwhelmingly of US origin, we utilized China exclusively as a prespecified macro-epidemiological GBD comparator, strictly avoiding cross-national pharmacovigilance extrapolations. METHODS: We analyzed FAERS reports (2004-2023) and female GBD 2023 estimates for China and the United States. Four disproportionality algorithms (ROR, PRR, IC, and EBGM) were evaluated for 150 high-frequency primary-suspect drug-event pairs (50 per cancer group). We report any-algorithm positivity and four-algorithm concordance alongside case-definition sensitivity analyses. GBD trends, age-period-cohort models, and exploratory projections to 2053 were integrated to provide population-level context, explicitly not as exposure denominators or for causal validation. RESULTS: FAERS cohorts yielded 19,717 cancer-associated report records. Among 150 high-frequency candidate pairs, 42 met all four algorithmic thresholds. The top-50 candidate screen captured approximately 72.8%-75.8% of primary-suspect records, serving as a variance-reduction step rather than a complete all-drug screen. Drugs like ranitidine and talc demonstrated marked disproportionality but also exhibited reporter and temporal features heavily compatible with stimulated reporting. Time-to-onset distributions reflected recorded administrative reporting intervals rather than biological carcinogenesis. GBD estimates revealed divergent China-US trajectories, notably a rising baseline for US uterine cancer. CONCLUSIONS: The formalized F × G framework operates as a transparent triage tool, not a causal classifier. FAERS disproportionality generates hypotheses; GBD trajectories indicate potential public-health priority. All prioritized signals-particularly those involving consumer products or immunosuppressants-require formal causal evaluation in longitudinal exposure-denominator datasets.