In a UK population-based study reported in The Lancet Oncology, Watling et al examined the relationship between ever use vs never use of oral contraceptives and the risk of liver cancer. Some findings suggested the possibility of slightly increased risk with longer-term use.
As noted by the investigators, earlier case-control analyses suggested a potential association, although findings were based on a small number of observed liver cancer cases.
Study Details
The analysis used data from two large prospective UK cohorts—the Million Women Study (MWS) and UK Biobank—on women who had no cancer at baseline and had data on oral contraceptive use. A systematic review and meta-analysis of previous additional observational studies was also performed.
Key Findings
Numbers of ever-users vs never-users were 774,050 vs 530,974 in the MWS cohort and 206,118 vs 47,290 in the UK Biobank cohort.
In the MWS cohort, 2,765 (0.21%) of 1,305,024 participants developed liver cancer at a median follow-up of 21.4 years (interquartile range [IQR] = 18.4–22.4 years). There were 1,501 cases in ever-users vs 1,264 in never-users (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.97–1.13, P = .27).
In the UK Biobank cohort, 191 (0.08%) of 253,408 participants developed liver cancer at a median follow-up of 12.6 years (IQR = 11.8–13.4 years). There were 148 cases in ever-users vs 43 in never-users (HR = 1.08, 95% CI = 0.76–1.55, P = .66).
In meta-analyses involving 23 observational studies (including the MWS and UK Biobank) with a total of 5,422 participants who developed liver cancer, there was no significant association between ever use vs never use and risk of liver cancer (relative risk [RR] = 1.04, 95% CI = 0.98–1.11, P = .0080). An increased risk of liver cancer per 5 years of use vs never use was observed (RR = 1.06, 95% CI = 1.02–1.10, P < .0001); in this analysis, risk ratios were 1.07 (95% CI = 1.00–1.14) for hepatocellular carcinoma and 1.06 (95% CI = 1.01–1.11) for intrahepatic cholangiocarcinoma (P for heterogeneity = .82).
The investigators concluded: “The totality of observational studies suggests there is no association between ever vs never use of oral contraceptive and liver cancer risk. When looking at associations by duration of oral contraceptive use, there was little or no association with all liver cancer or its two main subtypes. There might be a small increased risk of liver cancer with longer duration of use, but residual confounding cannot be ruled out.”
Katherine McGlynn, PhD, of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Canadian Institutes of Health Research, National Institutes of Health Intramural Program, and Cancer Research UK. For full disclosures of all study authors, visit The Lancet Oncology.
