Human papillomavirus (HPV) persistence is essential for cervical cancer development. We accrued nested-cohort subjects from a population-based study to investigate the host and viral factors related to outcome of HPV infection. Women (age > or = 30 years old) with HPV-positive but normal cytology and negative colposcopy were invited to participate. After signing informed consent, every participant completed a structured questionnaire and had 6-monthly follow-ups of Pap smear, HPV testing and colposcopy. Total and type-specific HPV clearance rates as well as host and viral factors associated with clearance in 3-year longitudinal follow-up were analyzed. Adjusted hazard ratios (HRs) of progression to > or = cervical intraepithelial neoplasia (CIN) 2 according to baseline HPV of the women with normal cytology were calculated from national registry database. Among the 626 eligible women, 526 (median age 47, 29-75) were enrolled and 412 returned for follow-up at least once. The median follow-up of enrolled subjects was 23 months (range 6.8-39). The 3-year cumulative total HPV clearance rate was 49.0% (95% confidence interval [CI]: 43.3-54.7%). The median 3-year cumulative type-specific HPV clearance rate was 50.0% (range 0-100.0%) with a median time to clearance of 12.4 months (6.4-24.5). Older age was associated with significantly decreased total HPV clearance and decreased type-specific clearance in HPV-18 and -53, while high viral load was associated with decreased total and type-specific clearance. After adjusting confounding variables, the HR of developing > or =CIN2 in baseline HPV-positive women was 34.0-fold (95% CI: 15.5-74.7) as compared to HPV-negative women.