NO SIGNIFICANT association has been found between ever using oral contraceptives and liver cancer risk, although a slight increase in risk may exist with longer duration of use.
The potential link between oral contraceptive use and liver cancer has been debated for decades, with earlier evidence suggesting a possible increased risk. However, previous studies were often limited by small numbers of cases and retrospective designs. To provide more robust and contemporary evidence, researchers analysed data from two large UK prospective cohorts and conducted a comprehensive systematic review and meta-analysis of existing observational studies, aiming to clarify the relationship between oral contraceptive use and liver cancer risk.
This population-based study utilised data from the Million Women Study (MWS) and the UK Biobank, including women without a prior cancer diagnosis (except non-melanoma skin cancer) who had reported their oral contraceptive use. Incident liver cancer cases were identified via National Health Service cancer registries. The analysis compared women who had ever used oral contraceptives with those who had never used them, using multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In the MWS cohort, 2,765 of 1,305,024 women (0.21%) developed liver cancer over a median follow-up of 21.4 years, while in the UK Biobank, 191 of 253,408 women (0.08%) developed liver cancer over a median follow-up of 12.6 years. No significant association was observed in either cohort: HR 1.05 (95% CI 0.97–1.13; p=0.27) in MWS and HR 1.08 (0.76–1.55; p=0.66) in UK Biobank. The meta-analysis pooled 23 studies (5,422 liver cancer cases) and also found no association between ever use of oral contraceptives and liver cancer risk (RR 1.04, 0.98–1.11). However, for each additional five years of use, there was a small but statistically significant increase in risk (RR 1.06, 1.02–1.10), with similar findings for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
In summary, these findings provide reassurance that ever using oral contraceptives does not increase overall liver cancer risk. For clinical practice, the results support the continued use of oral contraceptives without heightened concern for liver cancer in the general population. However, clinicians should remain aware that longer durations of use may carry a slightly increased risk, although this may be influenced by other confounding factors. Future research should focus on clarifying the impact of very long-term use and exploring potential biological mechanisms underlying this modest association.
Reference
Watling CZ et al. Oral contraceptive use and risk of liver cancer: a population-based study, systematic review, and meta-analysis. The Lancet Oncology. 2025;DOI:10.1016/S1470-2045(25)00222-0.
