Hormonal contraceptive use, pregnancy and parity, and the risk of cervical intraepithelial neoplasia 3 among oncogenic HPV DNA-positive women with equivocal or mildly abnormal cytology

Oral contraceptive (OC) use, hormonal contraceptive use and multiparity are potential risk factors for cervical precancer, cervical intraepithelial neoplasia 3 (CIN3), but a limited number of studies have adequately accounted for possible confounding effect of oncogenic human papillomavirus (HPV) infection. To examine the relationships of these factors with CIN3, we conducted an analysis of women (n = 5,060) with minimally abnormal Pap smears who were enrolled in the ASCUS and LSIL Triage Study (ALTS), a clinical trial to evaluate management strategies. Cervical specimens collected at enrollment were tested for HPV DNA using 2 methods. Multivariate logistics regression models were used to assess associations (odds ratio [OR] with 95% confidence intervals [CI]) of the potential risk factors (e.g., OC use and parity) with testing oncogenic HPV positive among controls (<CIN2) (n = 4,114) and with rigorously reviewed cases of CIN3 identified throughout the study (n = 499) among women with oncogenic HPV (n = 3,126). Only former oral contraceptive use (OR = 1.3, 95% CI = 1.0-1.7) was associated marginally with having an oncogenic HPV infection among controls. Restricted to women with oncogenic HPV, current injectable hormonal contraceptive users were at an elevated risk of CIN3 (OR = 1.6, 95% CI = 1.2-2.1) compared to women who never used them. Similarly, restricted to women with HPV16 infection, current users of injectable contraceptives were at a marginally elevated risk of CIN3 (OR = 1.5, 95% CI = 1.0-2.3) compared to women who never used them. Oral contraceptive use, Norplant (implantable hormonal contraceptive) use, a history of pregnancy, age at first pregnancy, lifetime numbers of pregnancies and lifetime numbers of live births were not associated with CIN3. We conclude that only current injectable hormonal contraceptive use slightly elevated the risk (∼50%) of CIN3 in this young and low parity population of women with oncogenic HPV and minimally abnormal Pap smears but further confirmation of this relationship is needed.