N° 138
26 March 2002 

Long-term use of oral contraceptives and a high number of children
increase the risk of cervical cancer in women with HPV infection

Cancer of the cervix uteri is the third most frequent cancer in women worldwide, and the most common one in large parts of Africa, Latin America and Asia. Out of approximately 200,000 yearly deaths from this cancer, 80% occur in developing countries.

A virus, the human papillomavirus (HPV), has been found in virtually all cervical cancers and is now considered to be a necessary cause of this disease. In the majority of women, however, HPV infections are harmless. Some co-factors should, therefore, exist which increase the chance of persistence and/or of progression of HPV infection into cancer.

The identification of such co-factors requires an adequate control for the strong effect of HPV and a large study population. These two prerequisites were fulfilled in a multi-centric study carried out between 1985 and 1993 by the International Agency for Research on Cancer (IARC) in 10 countries. This study included nearly 2000 women with cervical cancer and a similar number of healthy control women recruited from high-risk areas for cervical cancer in Colombia, Brazil, Peru, Paraguay, and Morocco, from intermediate-risk areas in Thailand and the Philippines, and from Spain, a low-risk country. To take into account the strong causative effect of HPV, the main analyses were restricted to women who were infected by the virus.

Two reports from the IARC study are published on 30 March in The Lancet. One concerns the use of oral contraceptives (Victor Moreno, from the Catalan Institute of Oncology, Barcelona, Spain, and colleagues), while the other analyzes the effects of reproductive factors, especially the number of children (Nubia Muñoz, from IARC, and colleagues).

They showed that women who had an HPV infection and who have used oral contraceptives for over five years have a three-fold increase in the risk of cervical cancer compared to never users. Women who had five children or more had also a three-fold increase in risk compared to women with no children. The researchers concluded that both long-term use of oral contraceptives and a high number of children are co-factors that, in conjunction with HPV infection, increase the risk of developing cervical cancer.

Cervical cancer has been declining in most countries in the last two or three decades. The decrease in the number of children per woman may have contributed to this favourable trend. Concerning oral contraceptives, more research is needed, the key question being the extent to which any adverse effect of oral contraceptives persists after women stop taking them. Differences between various types of hormonal contraceptives (e.g. progestogen-only contraceptives, oral contraceptives with different oestrogen dosages) should also be explored further.

It is important to bear in mind that cervical cancer is largely preventable by means of screening. The IARC study, therefore, indicates that long-term users of oral contraceptives deserve a special effort not to be missed by cervical cancer screening programs.

For further information please contact Dr Silvia Franceschi, Chief, Unit of Field and Intervention Studies ( ) or Dr Jennifer Smith () or Dr Nubia Muñoz ()

World Health Organization
International Agency for Research on Cancer

Organisation mondiale de la Santé
Centre international de Recherche sur le Cancer

150, cours Albert-Thomas 69372 Lyon Cedex 08 (France)
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