Evidence map›Paper›PMID 40617239›Full record

SynthesisThe Lancet. Oncology2025

Oral contraceptive use and risk of liver cancer: a population-based study, systematic review, and meta-analysis.

Cody Z Watling, Siân Sweetland, Aika Wojt, Gisela Butera, Barry I Graubard, Sarah Floud, Charles E Matthews, Gillian K Reeves, Katherine A McGlynn

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in The Lancet. Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Cody Z WatlingMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rochville, MD, USA.
Siân SweetlandCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Aika WojtMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rochville, MD, USA.
Gisela ButeraOffice of Research Services, Division of Library Services, National Institutes of Health Library, Bethesda, MD, USA.
Barry I GraubardBiostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rochville, MD, USA.
Sarah FloudCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Charles E MatthewsMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rochville, MD, USA.
Gillian K ReevesCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Katherine A McGlynnMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rochville, MD, USA. Electronic address: mcglynnk@nih.gov.

Funding

Cancer Research UK A29186
6 · The paper itself

Abstract

backgroundOral contraceptive use has been suggested to increase the risk of liver cancer. Although the International Agency for Research on Cancer concluded in 1999 that there was sufficient evidence of an association, this was based on case-control studies with few liver cancer cases. We aimed to provide more robust epidemiological evidence on this association by analysing data from two large prospective UK cohorts and additionally conducting a systematic review and meta-analysis of previous observational studies.

methodsIn our population-based study, the relationship between oral contraceptive use and liver cancer risk was examined using data from the Million Women Study (MWS) and the UK Biobank. We included women from both cohorts who did not have a prevalent cancer at baseline (except non-melanoma skin cancer) and had provided data on oral contraceptive use; incident liver cancer diagnoses were determined using linkage to National Health Service cancer registries. We compared risk in women who had ever used oral contraceptives with women who had never used oral contraceptives. Multivariable Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CIs. For the systematic review and meta-analysis, we searched PubMed, Embase, CINAHL Plus, Web of Science, and Scopus from database inception to June 28, 2024, for existing observational studies. Study-specific log odds ratios (ORs) or log HRs were pooled and we determined the relative risk (RR) between oral contraceptive use and liver cancer across all studies using a fixed-effects model (PROSPERO number CRD42024552518).

findingsA total of 2765 (0·21%) of 1 305 024 participants developed liver cancer in the MWS cohort (median follow-up 21·4 years; IQR 18·4-22·4) and 191 (0·08%) of 253 408 participants developed liver cancer in the UK Biobank (median follow-up 12·6 years; IQR 11·8-13·4). No association was observed between ever versus never use of oral contraceptives and liver cancer risk in either the MWS (HR 1·05, 95% CI 0·97-1·13; p=0·27) or the UK Biobank (1·08, 0·76-1·55; p=0·66). The meta-analysis of 23 observational studies, which included 5422 individuals with liver cancer, found no evidence of an association between ever versus never oral contraceptive use and liver cancer (RR 1·04, 0·98-1·11; I

interpretationThe totality of observational studies suggests there is no association between ever versus 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.

fundingCanadian Institutes of Health Research, National Institutes of Health Intramural Program, and Cancer Research UK.

Indexed as

Contraceptives, OralLiver NeoplasmsAdultFemaleHumansMiddle AgedProspective StudiesRisk AssessmentRisk FactorsUnited KingdomContraceptives, Oral

Identifiers

PMID40617239
PMCPMC12303860

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.