The rates of acquisition and the times of incident high-risk (HR) human papillomavirus (HPV) infectionsand Pap smear abnormalities and their predictive factors were analyzed in women participating in a multicenter screening study in three countries of the New Independent States of the former Soviet Union. The 423 patients were prospectively monitored for a mean of 21.6 months. At the baseline, 118 women were HR HPV DNA negative (Hybrid Capture II assay) and Pap smear negative (group 1), 184 were HPV DNA positive and Pap smear negative (group 2), and 121 were HPV DNA negative and Pap smear positive (group 3). The time to the acquisition of an incident abnormal Pap smear (19.4 months) was significantly longer in group 1 than in group 2 (9.2 months) (P ؍ 0.0001). The times of acquisition of incident HR HPV infection were 16.6 and 11.0 months in group 1 and group 3, respectively (P ؍ 0.006). The monthly rates of acquisition of incident HR HPV infections were very similar in group 1 (1.0%) and group 3 (0.8%), whereas the rate of acquisition of an abnormal Pap smear was significantly higher in group 2 (3.1%) than in group 1 (1.5%) (P ؍ 0.0001). The acquisition of HR HPV infection (but not a positive Pap smear result) was significantly (P ؍ 0.0001) age dependent. The only significant independent (P ؍ 0.001) predictor of the incidence of an abnormal Pap smear result was a high HR HPV load of >20 relative light units/control value (CO) (rate ratio, 2.050; 95% confidence interval, 1.343 to 3.129). Independent predictors of incident HR HPV infection were patient category (a sexually transmitted disease) and ever having been pregnant. The time of acquisition of HR HPV infection was 3 months shorter than that of an abnormal Pap smear. At the baseline the high load of a particular HR HPV type is the single most important predictor of an incident Pap smear abnormality, whereas young age and having a sexually transmitted disease predict incident HR HPV infections.The accumulated data from prospective follow-up studies suggest that the natural history of clinical human papillomavirus (HPV) infections of the uterine cervix is basically identical to that of cervical intraepithelial neoplasia (CIN) lesions, with (i) progression, (ii) persistence, and (iii) regression as the main outcome measures (7,13,23). However, special features of the natural history of HPV infections seem to be intimately linked to different risks of the development of cervical cancer (7,22,30,31). These include the presence of latent and subclinical HPV infections and the propensity of the virus to remain persistent (latent) for prolonged periods or to become reactivated or for the infection to undergo spontaneous resolution (3,7,22,30,31).This HPV involvement forms the biological basis of additional patterns recently described in studies of the natural history of CIN lesions, called early regression, fluctuation, and late regression (3,20,21,23,24). It seems obvious that the HPV type, viral load, the acquisition of new (incident) infections, as wel...