ArticlesCervical cancer and use of hormonal contraceptives: a systematic review
Introduction
Cancer of the uterine cervix is the second most common cancer among women in less-developed countries.1 Persistent infection of cervical epithelial cells with certain high-risk types of the human papillomavirus (HPV) is believed to be the most important cause of cervical cancer.2, 3 The types of HPV associated with cervical cancer are transmitted sexually and it seems that a high proportion of sexually active women are infected by one or more of these viruses at some time during their lives.2 Whether women who have been infected by HPV develop a persistent infection or cervical cancer may be affected by other factors, including the use of hormonal contraceptives. Recent studies have suggested that there is an increased risk of cervical cancer in HPV-DNA positive women if they use oral contraceptives for longer than 5 years.4 Due to the potential public health importance of any effects of oral contraceptives on cervical cancer WHO commissioned a systematic review of published evidence.5 Here, we present the results of this review with particular attention to the role of HPV infection, and to the pattern of risk according to duration of use and time since last use of hormonal contraceptives.
Section snippets
Definitions and identification of eligible studies
Epidemiological studies were identified through a Medline search (January, 1966, to July, 2002) and from references cited in identified papers. Key search words included the terms: cervical intraepithelial neoplasia, cervix dysplasia, cervix neoplasms, risk factors, contraceptive agents, papillomavirus human, and (pre-1994) papillomavirus. The search was limited to human studies and restricted to peer-reviewed articles. No language or date limitations were imposed. Studies were potentially
Results
Overall 28 studies were eligible for this systematic review; these studies are described in the table.4, 7, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 The details of the eight studies32, 33, 34, 35, 36, 37, 38, 39, 40, 41 included in the pooled analysis of squamous cell carcinoma by Moreno and colleagues are combined in the table, since not all of the eight contributing studies have published relevant data separately. Results from the WHO
Taking HPV status into account
One approach to taking HPV status into account when looking at the effect of hormonal contraceptives on cervical cancer is to restrict analyses to women who tested positive for HPV. Figure 5 summarises the results from the 12 studies that included 3000 cases (24% of the total) that have done so: the relative risks for short, medium, and long duration use of oral contraceptives of approximately less than 5 years, 5–9 years, and 10 years or longer, were, respectively, 0·9 (0·7–1·2), 1·3
Potential confounding by other factors and subgroup analyses
The studies listed in table 1 had adjusted their main results on the relative risk of cervical cancer in relation to use of oral contraceptives by various potential confounding factors, although the precise adjustment factors varied from study to study. To assess whether adjustment for number of sexual partners, previous cervical screening, smoking, or use of barrier methods of contraceptives might have affected the results with respect to the use of oral contraceptives, published results were
Discussion
The results of this systematic review of published data show that the relative risk of cervical cancer increases with increasing duration of oral contraceptive use, in virtually every way that data were examined. When the results from all studies are combined, the findings are broadly similar for all women, for HPV positive women, for studies that adjusted for HPV status, sexual partners, previous cervical smears, smoking, and use of barrier methods of contraception, and for invasive, in-situ,
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