Global Research Sources—Asking Questions Ignored by FDA
An analysis of case-control studies has found that use of oral contraceptives for ≥ 5 years in women with human papillomavirus (HPV) infection is associated with an increased risk of cervical cancer. This confirms existing knowledge and emphasises the need for regular cervical screening of all women aged 20-69 years who have ever been sexually active.
Not all HPV infection is persistent or leads to cancer
The presence of human papillomavirus (HPV) infection is known to play the major causative role in cervical cancer. However, the development of such cancer is multi-factorial and HPV infection alone is not thought to be sufficient.[1,2] More than 30 HPV types infect the genital tract, and these have been classified as either low or high risk types according to the potential of infected cells to progress to carcinoma. Many sexually active women have HPV present at some time in their lives, and in most cases it disappears after a time with no resultant problems. It is the persistence of HPV, in particular a high risk type, that contributes to the development of cervical intraepithelial neoplasia and invasive cancer. Women with persistent HPV on smear tests are usually referred for colposcopy.
Increase in cervical cancer with OC use for ≥ 5 years in HPV-positive women
A pooled analysis of eight case-control studies looking at the effect of oral contraceptives (OCs) on the risk of cervical cancer was published in March 2002 in the Lancet. The International Agency for Research on Cancer (IARC) conducted the original studies in Spain, South America, Asia and Africa, between 1985 and 1997. The IARC analysis looked only at women who were HPV-positive.
The results showed that women with HPV, who used oral contraceptives for less than five years, had no increase in risk of squamous-cell cervical cancer, compared to women with HPV who had never used OCs. In contrast, a duration of OC use of 5-9 years was associated with an almost three-fold increase in risk, compared with never-users, and a four-fold increase for usage of 10 years or longer. These estimates of risk were higher than those reported in most other studies. Further research is needed to determine how long these risks persist after stopping OC use. The questionnaire used in the studies did not specifically ask about type of hormonal contraceptive but from independent surveys and country usage data it is likely that the majority were taking a combined OC.
Analysis of only HPV-positive women reduces confounding
The IARC paper eliminates a potential source of confounding present in earlier studies by analysing the effect of combined OC use in HPV-positive women. It was previously difficult to assess the influence of OC use on cervical cancer risk due to possible confounding by differences in sexual behaviour and HPV infection rates that may have been associated with use of OCs.
No association was found between presence of HPV and use of OCs among the controls. This suggests that the increase in risk of cervical cancer from OCs is due to an effect on progression (from HPV infection to cancer), rather than affecting susceptibility or persistence of HPV infection.
Regular cervical screening likely to offset increase in cancer risk
It is important to note that these case-control studies were mostly in countries without a cervical screening programme. The Medicines Adverse Reactions Committee (MARC) has reviewed the IARC paper and believes that the increase in cervical cancer risk in long-term users of OCs found in this study would be greatly reduced by the cervical screening programme in place in New Zealand. The MARC did not recommend that women with abnormal smears should stop taking OCs. The findings must be considered in light of the benefits of combined OCs (such as control of fertility and reduction in risk of uterine and ovarian cancer), and add further to our knowledge about the risks and benefits of hormonal contraception. The IARC paper emphasises the importance of regular cervical screening in all women with a history of sexual activity, whether on OCs or not.
Chief Researcher: Dr Natasha Rafter, Public Health Registrar, Auckland University
Correspondence to Dr Natasha Rafter, Division of Community Health, Auckland University, Private Bag 92019, Auckland. E-mail: email@example.com
[1.] Moreno V, Bosch FX, Muñoz N, et al, for the International Agency for Research on Cancer (IARC) Multicentric Cervical Cancer Study Group. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 2002;359:1085-1092.
[2.] Skegg DCG. Oral contraceptives, parity, and cervical cancer [Commentary]. Lancet 2002;359:1080-1081.
[3.] Galloway DA. Biology of genital human papillomaviruses. In Holmes KK, Mårdh P-A, Sparling PF et al (Eds). Sexually Transmitted Diseases 3rd Edn. 1999:McGraw Hill, USA, p335-348.
[4.] National Cervical Screening Programme. http://www.healthywomen.org.nz/ncsp/default.asp
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