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  • Title: Oral contraceptives and cancer of the cervix uteri. A meta-analysis.
    Author: Delgado-Rodriguez M, Sillero-Arenas M, Martin-Moreno JM, Galvez-Vargas R.
    Journal: Acta Obstet Gynecol Scand; 1992 Jul; 71(5):368-76. PubMed ID: 1326213.
    Abstract:
    AIM AND OBJECTIVE: Because the findings of epidemiologic studies of the relationship between oral contraceptive use and cervical cancer have not been consistent, we reanalyzed the relationship. DESIGN: Meta-analysis of studies published to date. SETTING AND SUBJECTS: Papers were located by searching the MEDLINE data base, supplemented by a hand search of all the references in the articles recovered. MEASUREMENTS: Studies were graded as to quality. Two meta-analyses were performed: one including all the studies gathered and one including methodologically acceptable studies only. The method of Woolf was used to combine relative risks. Heterogeneity of the effect was assessed. MAIN RESULTS: Fifty-one published studies were collected: 21 case-control, 18 cross-sectional, and 12 cohort designs. Twenty-one of these were considered as methodologically acceptable, but only 18 could be pooled. The main results observed were: relative risks was 1.52 (1.3-1.8) for dysplasia, 1.52 (1.3-1.8) for carcinoma in situ, and 1.21 (1.1-1.4) for invasive cancer. A significant linear dose-response effect was observed in dysplasia, carcinoma in situ, and invasive cervical cancer. Heterogeneity of the effect was present in some of the former estimates. CONCLUSIONS: Oral contraceptive use may be a risk factor for all stages of the natural history of cervical cancer, which may imply an initiator effect. Limitations to this research are discussed. Researchers in Spain conducted a literature search of the medical database called MEDLINE, of the Spanish Medical Index, and of all references in recovered pertinent articles to conduct a metaanalysis of epidemiologic studies that dealt with the association between oral contraceptive (OC) use and cervical cancer. They analyzed data from 51 studies (18 cross-sectional studies, 22 case-control studies, and 12 cohort analyses) in 58 publications. They considered 30 studies to be likely biased. These 30 studies were included in the large metaanalysis (metaanalysis I), but excluded from metaanalysis II. They discarded 3 studies because they were unable to derive a summary relative risk (RR) from 1 study, unable to compute the variance of the RR from another. Participants in the 3rd study already had cervical dysplasia. RR estimates of metaanalysis I were lower than those of metaanalysis II. The researchers confined their comments to metaanalysis II. Overall findings included an RR for dysplasia of 1.52, for carcinoma in situ of 1.52, and for invasive cancer of 1.21. This risk increased with duration of OC use. A significant linear dose-response effect occurred for dysplasia (p.01 for cohort studies only), carcinoma in situ (p.01 overall), and invasive cervical cancer (p.01 overall). Since the risk increased at all stages of cervical cancer, it suggested that OCs may be tumor initiators. When the researchers pooled risk estimates of all stages of cervical cancer study, they found a very significant heterogeneity which decreased with stratification by stage and design. This indicated that OCs' effect on cervical cancer risk may depend on the stage of its natural history. Since hormone dose has decreased over time, the researchers did not know whether the RR for currently marketed OCs remains. Nevertheless they recommended all women who had every sued OCs to visit a health practitioner periodically for early detection of cervical cancer.
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