What is this about?
It has long been noted that women who use combined oral contraceptives (COCs) have a small increased risk of cervical cancer. Since cervical cancer is usually caused by human papillomavirus (HPV), a sexually transmitted infection, it was previously unclear whether this association is due directly to the effect of COCs or whether it is at least partly a result of other confounding factors such as number of sexual partners and age at first intercourse, smoking, etc.
What do these new data suggest?
This analysis of more than 16,500 women with cervical cancer and more than 35,500 controls found that, compared with never-users, current use of COCs for more than five years is associated with a 90% increased risk of cervical cancer: (relative risk 1·90, 95% confidence intervals [95%CI] 1·69–2·13]). Although this might sound alarming, it is essential that one bears in mind the relatively low baseline risk of cervical cancer. (For example, increasing my chance of winning the national lottery by 100% by buying 2 tickets instead of 1 does not make much difference in absolute terms because the baseline probability of winning is low: the chance is now 2 in several million instead of 1 in several million). The baseline risk of cervical cancer increases with age, and the number of extra cases in COC users increases with age. The new report estimates that:
Women who use COCs for 5 years from age 20 years have increased cumulative incidence of cervical cancer at age 50 years from 38 cases per 10,000 (in never-users) to 40 cases per 10,000 (ie an extra 2 cases per 10,000).
Women who use COCs for 10 years from age 20 years have increased cumulative incidence of cervical cancer at age 50 years from 38 cases per 10,000 (in never-users) to 45 cases per 10,000 (ie, an extra 7 cases per 10,000).
Risk falls when COCs are stopped; after about 10 years, risk reaches the same level as that for never-users of COCs.
The risk of cervical cancer in users of progestogen-only injectable contraceptives may be similar to that for COC users. No epidemiological data are available for the risk of cervical cancer in users of Evra▼ patches, NuvaRing, (a combined hormonal intravaginal contraceptive), progestogen-only pills, Implanon (a progestogen-only implant), or Mirena (a progestogen-only intrauterine device).
What about the risk of ovarian cancer?
The same issue of Drug Safety Update highlights another paper in The Lancet. This study of more than 23,200 women with ovarian cancer has confirmed that use of COCs reduces the risk of ovarian cancer. This effect increases with longer duration of use and persists for many years after stopping. The researchers estimate that about two cases of ovarian cancer and one death from the disease before age 75 years are prevented for every 5,000 women-years of use of COCs
Women considering using COCs should consider the effects on cancer risk when making their decision, and weigh these up against other considerations (eg the relative ease of use, reliability and possible side effects of the different forms of contraception she might use). These are explored more fully in a MeReC bulletin and on the contraception section of NPC. A question and answer document and information for women taking COCs, which both talk about the cervical cancer risk, are available from the MHRA.
Women should also take note of the national cervical cancer screening programme. Routine vaccination against HPV infection will be introduced in autumn 2008 for girls aged 12–13 years. A two-year catch-up programme will start from September 2009 for girls aged up to 18 years. Nevertheless, women should note that the vaccine does not protect against all HPV subtypes that may cause cervical cancer and regular cervical screening is still recommended when they reach the appropriate age.