ArticlesCervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16 573 women with cervical cancer and 35 509 women without cervical cancer from 24 epidemiological studies
Introduction
The International Agency for Research on Cancer (IARC) has classified combined oral contraceptives as carcinogenic to humans; this assessment was made partly on the basis of increased risk for cancer of the cervix.1 The incidence of cervical cancer increases with age and so the contribution of hormonal contraceptives to the lifetime incidence of cervical cancer will depend largely on the effects at older ages, when most women are past users.2 The Collaborative Group on Epidemiological Studies of Cervical Cancer has brought together and reanalysed individual participant data from relevant epidemiological studies worldwide, to examine the relation between cervical cancer and the pattern of use of hormonal contraceptives.3, 4, 5
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Identification of studies and data collection
Epidemiological studies with an outcome of invasive cervical cancer, or cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ, with information on duration of use of hormonal contraceptives, were eligible for inclusion. Cases were defined as women with invasive cancer or CIN3/carcinoma in situ, and controls defined as women without cervical cancer. Case-control studies with at least 100 cases of invasive cancer or at least 200 cases of CIN3/carcinoma in situ, and cohort
Results
In all, 35 eligible studies were identified: data from 24 studies,7, 8, 10, 12, 13, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55 were available for this analysis, including three international multicentre studies (IARC,7, 8, 27, 39, 40, 41, 42, 43, 44, 45, 46 Brinton Latin America,37, 38 and WHO50, 51, 52, 53, 54, 55). Data could not be retrieved for ten studies,56, 57, 58, 59, 60,
Discussion
This collaborative reanalysis confirms that current and recent use of combined oral contraceptives is associated with an increase in the risk of invasive cancer of the uterine cervix.1 The relative risk in current users increases with increasing duration of oral contraceptive use: use for 5 or more years (mean 11·1 years) is associated with about a doubling in risk. The increased risk of cervical cancer associated with use of combined oral contraceptives diminishes with time since last use
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Collaborators listed at end of article