Association between parity, oral contraceptive use and cervical cancer.

Pooling of data by the International Agency for Research on Cancer from case-control studies of invasive cervical cancer (eight studies) and carcinoma in-situ (two studies) from four continents found that high parity and long-term use of hormonal contraception increased the risk of squamous-cell carcinoma of the cervix among women testing positive for human papillomavirus (HPV), consistent with previous studies. The decline in parity in most countries might therefore partly explain reductions in cervical cancer recently seen. High parity has long been suspected of being associated with an increased risk of cervical cancer, but previous analyses of this association did not take HPV into account. The odds ratio for seven full-term pregnancies or more was 3.8 compared with nulliparous women, and 2.3 compared with women who had had one or two full-term pregnancies. There was no significant association between risk of adenocarcinoma and adenosquamous carcinoma and number of full-term pregnancies. Hormonal contraceptive use for fewer than five years did not increase risk, but women reporting use of hormonal contraceptives for 5-9 years had 2.8 times the risk of women who had never used them. The relative-risk estimate was even higher (4.0) for those who had used hormonal contraceptives for 10 years or longer. Perhaps the chief importance of this new analysis is the demonstration that these associations are not due to any confounding effect of HPV infection, and adjustments for sexual behaviour provided only partial reassurance about confounding by HPV. Among the controls, multiparous women and those who had taken oral contraceptives were not more likely than others to be carriers of HPV DNA.

If these results are confirmed, there will be wider acceptance that high parity and long-term use of oral contraceptives can act as cofactors in the genesis of cervical cancer. The lack of association of these factors with the prevalence of HPV infection would suggest that each acts not by enhancing the acquisition or persistence of HPV infection, but rather by promoting progression to CIN and invasive cervical cancer. Although many case-control and cohort studies not restricted to women with HPV infection have shown an association between long-term oral contraception and risk of cervical cancer, the relative-risk estimates have generally been lower.

However, despite the importance of the IARC analysis, it could have overestimated the risk associated with long-term oral contraception for a number of reasons. Any causal relation between long-term oral contraception and cervical cancer would be most important in the developing world, where cervical cancer is common and few women have access to high-quality cytological screening. From a public health viewpoint, a key question is the extent to which effects persist after women stop taking oral contraceptives. There is now a need to bring together all the relevant data, to quantify any effects, and to assess how these might shift the balance of benefits and risk of oral contraception. The WHO has commissioned such work, to prepare the ground for a full assessment. For nearly two decades, concerns about oral contraceptives and cancer were focused mainly on breast cancer, with the eventual outcome of studies reassuring. Any relation with cervical cancer is also important to determine. (1-3)

(1.) Skegg DCG. Oral contraceptives, parity, and cervical cancer. Lancet 2002;359:1080-81.

(2.) Moreno V, Bosch FX, Munoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 2002;359:1085-95.

(3.) Munoz N, Franceschi S, Bosetti C, et al. Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet 2002; 359:1093-101.