ObjectiveTo evaluate the association between potential risk factors for high-risk human papillomavirus (HR-HPV) infection and cofactors for cervical intraepithelial lesions grade 2 or worse (CIN2+) in women attending cervical screening in Amazonian Peru.Materials and MethodsParticipants completed a risk factor questionnaire before screening. High-risk human papillomavirus infection was determined by Hybrid Capture II. Logistic regression was used to evaluate associations between potential risk factors for HR-HPV infection and between cofactors and risk of CIN2+ among women with HR-HPV infection.ResultsScreening and questionnaires were completed by 5435 women aged 25 to 49 years. The prevalence of HR-HPV was 12.6% (95% confidence interval [CI], 11.8%–13.6%) and decreased by age. Early age at first sexual intercourse and several lifetime sexual partners increased the risk of having HR-HPV (age-adjusted odds ratio [AOR] of age at first sexual intercourse <18 vs ≥20, 1.5; 95% CI, 1.2–2.0; AOR of ≥5 lifetime sexual partners vs 1, 2.1; 95% CI, 1.4–3.2). Among women with HR-HPV infection, those with no schooling (AOR relative to 1–5 years of schooling, 3.2; 95% CI, 1.3–8.3) and those with parity ≥3 (AOR relative to parity <3, 2.6; 95% CI, 1.4–4.9) were at increased risk of CIN2+. The effect of parity was stronger for cancer (AOR of parity ≥3 vs <3, 8.3; 95% CI, 1.0–65.6). Further analysis showed that the association between parity and CIN2+ was restricted to women younger than 40. Most women (83%) had previously been screened. Sixty-four percent of CIN2+ cases detected in this study occurred in women who reported having had a Papanicolaou test in the previous 3 years. Only 4 of 20 cancers were detected in women never screened before. Having had a previous abnormal Papanicolaou test increased the risk of CIN2+ (OR, 16.1; 95% CI, 6.2–41.9).ConclusionAmong women with HR-HPV, high parity (in young women), no schooling, lack of good-quality screening and of adequate follow-up care are the main risk factors for high-grade cervical disease in Peru.