Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study

Abstract

Background: Use of oral contraceptives could increase risk of cervical cancer; however the effect of human papillomavirus (HPV), the main cause of cervical cancer, is not usually taken into account. We aimed to assess how use of oral contraceptives affected risk of cervical cancer in women who tested positive for HPV DNA.

Methods: We 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). Information about use of oral contraceptives was obtained from personal interviews. Effects were estimated as odds ratios, with logistic-regression models adjusted for possible confounders.

Findings: 1465 of 1561 (94%) patients with ICC, 211 of 292 (72%) with ISC, and 255 of 1916 (13%) controls were positive for HPV DNA. Compared with never-users, patients who had used oral contraceptives for fewer than 5 years did not have increased risk of cervical cancer (odds ratio 0.73; 95% CI 0.52-1.03). The odds ratio for use of oral contraceptives was 2.82 (95% CI 1.46-5.42) for 5-9 years, and 4.03 (2.09-8.02) for use for 10 years or longer, and these risks did not vary by time since first or last use.

Interpretation: Long-term use of oral contraceptives could be a cofactor that increases risk of cervical carcinoma by up to four-fold in women who are positive for cervical HPV DNA. In the absence of worldwide information about HPV status, extra effort should be made to include long-term users of oral contraceptives in cervical screening programmes.