Abstract 1194: Oral contraceptive use and risk of liver cancer: A prospective analysis in over 1.5 million women and systematic review and meta-analysis of observational studies

Abstract Background: Oral contraceptive use has been suggested to increase the risk of liver cancer. While the International Agency for Research on Cancer concluded in 1999 that there was sufficient evidence of an association, this conclusion was based on case-control studies with few liver cancer cases. Current evidence of an association with all liver cancer or with its two major histologic types, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) remains unclear. Methods: The relationship between oral contraceptive use and liver cancer risk was examined using data from the Million Women Study (MWS) and the UK Biobank. Multivariable Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). In addition, we conducted a systematic review and a meta-analysis of existing observational studies of oral contraceptive use and liver cancer. Results: A total of 2, 765 (median follow-up=21.4 years) and 191 (median follow-up=12.6 years) cases of liver cancer were observed in MWS and UK Biobank, respectively. No association was observed between ever- versus never-users of oral contraceptives and liver cancer risk in either the MWS or the UK Biobank (HR: 1.05, 95% CI: 0.97-1.13 and 1.08, 0.76-1.55, respectively). The meta-analysis of 23 observational studies, which included 5, 424 cases of liver cancer, found no evidence of an association between ever versus never oral contraceptive use and liver cancer; relative risk (RR):1.04, 0.98-1.11. In the meta-analysis of longer duration of use, women who used oral contraceptives for 4+ years had a slightly higher risk of total liver cancer (RR:1.10, 1.03-1.18) that was due to a small positive association with ICC (RR:1.11, 1.01-1.21). In contrast, there was no significant association between oral contraceptive use of 4+ years and HCC (RR: 1.07, 0.95-1.21). Conclusions: The totality of observational studies, including those that assessed associations by duration of use, suggests there is little or no association between oral contraceptive use and all liver cancer or HCC. There may be a small increased risk for ICC with longer duration of use, but confounding cannot be ruled out. Citation Format: Cody Z. Watling, Siân Sweetland, Aika Wojt, Gisela Butera, Barry I. Graubard, Sarah Floud, Charles E. Matthews, Gillian Reeves, Katherine A. McGlynn. Oral contraceptive use and risk of liver cancer: A prospective analysis in over 1.5 million women and systematic review and meta-analysis of observational studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1194.