Cancer risk and screening-preventable malignancies in transgender populations: A systematic review and meta-analysis.

e22522 Background: Transgender people experience health vulnerabilities shaped by structural barriers to care and differential exposure to cancer risk factors. However, epidemiologic evidence on cancer risk and screening-relevant malignancies in TGD populations remains scarce and fragmented. Methods: We conducted a PRISMA-guided systematic review and meta-analysis to synthesize relative risks of malignancies amenable to screening in TGD populations compared with cisgender reference groups. We searched MEDLINE/PubMed, Embase, and LILACS through December 2025 (last search January 2026), with no language restrictions. Observational studies reporting standardized risk measures (SIR, PIR, HR, or equivalent) were included. Random-effects meta-analyses were performed when clinically and statistically appropriate, and study quality was assessed using the Newcastle–Ottawa Scale. Results: Twelve studies met inclusion criteria. Among transgender women, prostate cancer risk was significantly reduced compared with cisgender men (pooled RR 0.35; 95% CI 0.28–0.42). Anal canal cancer risk was markedly increased in transgender populations compared with cisgender men (RR 13.6; 95% CI 7.6–24.4), with consistent findings across sensitivity analyses. Breast cancer risk in transgender women was substantially higher than in cisgender men (RR 32.3; 95% CI 17.7–58.8) but lower than in cisgender women (RR 0.28; 95% CI 0.21–0.38). Transgender men showed increased breast cancer risk compared with cisgender men, while comparisons with cisgender women were inconclusive. For lung cancer, transgender populations had higher risk compared with cisgender women (RR 1.55; 95% CI 1.31–1.84) and no significant difference compared with cisgender men. Evidence for colorectal and cervical cancers was insufficient for meta-analysis. Conclusions: Cancer risk in TGD populations varies by tumor site and likely reflects biological, behavioral, and structural factors, including differential screening and data limitations. These findings support organ-based, gender-affirming approaches to prevention and early detection and highlight the need for improved gender identity data capture in health systems.