The aim of our study was to assess the cumulative 5-year diagnoses of CIN2, CIN3 or invasive cervical cancer (CIN2+) after concurrent screening by high-risk HPV test and Pap smear in a primary screening setting. Four thousand thirty-four women from Eastern Thuringia/Germany were recruited from 1996 to 1998 for baseline screening that included routine cytology, high-risk HPV testing by consensus primer PCR GP5+/6+ and routine colposcopy. After a median of 59 months 3,153 women participated in final screening using identical methods. Women with abnormal cytology or colposcopy or a positive high-risk HPV test at any time during the study period were recalled for expert colposcopy and histologic verification. CIN2+ was detected in 160 women resulting in a cumulative 5-year proportion of 4.4% (95% CI: 3.7–5.0%). Of 3,702 women who were high-risk HPV negative at baseline, 34 (1.1–95% CI: 0.7–1.4%) had either prevalent CIN2+ or developed CIN2+ within the observation period. HPV/cytology double negatives at baseline were at lowest risk for CIN2+ (1.0–95% CI: 0.7–1.4%) compared to screening positives (16.8–100% depending on combined test results). The 5-year negative predictive value in HPV−/Cyto− women was 99.0% (95% CI: 98.6–99.3%). This suggests that a prolongation of the screening intervals in this group is feasible. However, it should be noted that 1 woman developed a microinvasive carcinoma within the observation period. Moreover, 2 women with prevalent cancer were missed by both tests. The prognostic relevance of concurrent high-risk HPV/cytology screening needs to be verified further by randomized trials. © 2005 Wiley-Liss, Inc.