March 2002

From Lancet

Long-term use of oral contraceptives could increase risk of cervical cancer for women with HPV

Web publication: Wednesday 27 March 2002

Women who are positive for the sexually transmitted human papillomavirus (HPV) could be at a three times greater risk of cervical cancer if they have used oral contraceptives for five years or longer, suggest authors of a study in this week's issue of THE LANCET. However, there is no evidence that long-term oral-contraceptive use increases the risk of cervical cancer in the absence of HPV.

The absolute risk of cervical cancer ranges from around 1% in developed countries to 5% in less-developed settings. The effect of HPV-the main cause of cervical cancer-has not usually been taken into account in previous studies investigating a possible link between oral-contraceptive use and cervical cancer. Victor Moreno and colleagues from the International Agency for Research on Cancer (IARC) aimed to assess how use of oral contraceptives affected risk of cervical cancer in women who tested positive for HPV DNA.

The investigators pooled data from eight case-control studies of patients with histologically confirmed invasive cervical carcinoma (ICC) and from two studies of patients with carcinoma in situ (ISC [a precursor of ICC]). Information about use of oral contraceptives was obtained from personal interviews. Data were available for around 1900 women from Thailand, the Philippines, Morocco, Brazil, Peru, Paraguay, Colombia, and Spain.

94% of women with ICC, 72% with ISC, and 13% of women without cervical cancer were positive for HPV DNA. Compared with women who had never used oral contraceptives, those who had used oral contraceptives for fewer than 5 years did not have an increased risk of cervical cancer. Women who used oral contraceptives for between five and nine years were around three times more likely to have cervical cancer; there was a four-fold increased risk for oral contraceptive use of 10 years or more.

Silvia Franceschi comments: "We think that our results lend support to the existence of an association between oral contraceptives and HPV. They could help women who have persistent HPV infection to balance the benefits (prevention of pregnancy and cancers of the ovary and uterus) and harms of long-term oral contraceptive use, and suggest that long-term users of oral contraceptives should be included in cervical screening programmes."

In an accompanying Commentary (p 1080), David Skegg from the University of Otago, New Zealand, concludes: "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 risks 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 neoplasia were focused mainly on breast cancer-with the eventual outcome being reassuring. Ironically the relation with cervical cancer may turn out to be more important."

A second study by the IARC investigators (p 1093) assessed the effect of parity (number of livebirths) on risk of cervical cancer for women positive for HPV. Women who had seven or more livebirths were nearly four times more likely to have cervical cancer than childless women, and more than twice as likely to have cervical cancer compared with women who had one or two full-term pregnancies. The investigators comment that the general decline in parity might partly explain the reduction in cervical cancer recently seen in most countries.

Contact: Dr Nubia Munoz T) +33 4 72 73 80 52: E) munoz@iarc.fr
Dr Silvia Franceschi T) +33 4 72 73 84 02; E) franceschi@iarc.fr; or
Dr Jennifer Smith T) +33 4 72 73 84 21; E) smith@iarc.fr;
Field and Intervention Studies Unit, International Agency for Research on
Cancer, 150, Cours Albert Thomas, F-69372 Lyon Cedex 08, France.

Professor David C G Skegg,
Dept of Preventive and Social Medicine,
Otago Medical School, University of Otago,
PO Box 913, Dunedin, New Zealand;
T) +64 3 479 7201; F) +64 3 479 7298; E) jennifer.robinson@stonebow.otago.ac.nz











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