Oral contraception and the risk of hepatocellular carcinoma☆

Backgrounds/Aims

We performed a meta-analysis of observational epidemiological studies to examine the association between oral contraceptives (OC) and hepatocellular carcinoma (HCC).

Methods

Two independent researchers conducted PubMed searches followed by systematic abstraction of studies that compared OC use between patients with HCC and a group of controls. Pooling of ORs was conducted using a random effects model. Heterogeneity and publication bias among studies were examined.

Results

Twelve case-control studies that included 739 cases and 5223 controls met the inclusion and exclusion criteria. The pooled estimate of ORs (age- and sex-matched only) from all 12 studies was 1.57 (95% CI=0.96–2.54, p=0.07) with a heterogeneity of I²=39.9. Exclusion of one large multi-national European study decreased the heterogeneity to I²=16.9 and increased the pooled OR to 1.70 (95% CI=1.12–2.59, p=0.01). Eight studies reported adjusted ORs (in addition to age and sex); the pooled estimate was 1.45 (95% CI=0.93–2.27, p=0.11) with a heterogeneity of I²=20.4. Only few studies identified or adjusted for other HCC risk factors. Six studies showed a significant 2- to 20-fold increase in HCC risk with longer durations of OC use; however, the reporting was too inconsistent to allow meta-analysis.

Conclusions

The evidence is inconclusive to establish a relation between oral contraceptives and the risk of hepatocellular carcinoma. Future studies should focus on the duration, intermittency, and recency of OC use.

Keywords: Epidemiology, Risk factors, Meta-analysis, Hormones, Liver cancer