Primary human papillomavirus (HPV)-based cervical screening will be introduced in the Netherlands in 2016. We assessed the 5-year cervical (pre)cancer risk of women with different combinations of HPV and cytology test results. Special attention was paid to risks for cervical intraepithelial neoplasia grade 3 and 2 or more (CIN3þ/2þ) of HPV-positive women with a negative triage test, because this determines the safety of a 5-year screening interval for HPV-positive, triage test-negative women. In addition, agerelated effects were studied. A total of 25,553 women were screened by HPV testing and cytology in a screening setting. Women were managed on the presence of HPV and/or abnormal cytology. Five-year cumulative incidences for CIN3þ/2þ were calculated. Five-year CIN3þ(2þ) risk was 10.0% (17.7%) among HPV-positive women. When stratified by cytology, the CIN3þ (CIN2þ) risk was 7.9% (12.9%) for women with normal cytology and 22.2% (45.3%) for women with equivocal or mildly abnormal (i.e., BMD) cytology. For HPV-negative women, the 5-year CIN3þ(2þ) risk was 0.09% (0.21%). Additional triage of HPVpositive women with normal cytology by repeat cytology at 12 months showed a 5-year CIN3þ(2þ) risk of 4.1% (7.0%). HPVnon 16/18-positive women with normal cytology at baseline had comparable risks of 3.5% (7.9%). HPV-non 16/18-positive women with normal baseline cytology and normal repeat cytology had a 5-year CIN3þ risk of 0.42%. No age-related effects were detected. In conclusion, HPV-positive women with normal cytology and a negative triage test, either repeat cytology after 12 months or baseline HPV 16/18 genotyping, develop a nonnegligible CIN3þ risk over 5 years. Therefore, extension of the screening interval over 5 years only seems possible for HPV screen-negative women. Cancer Prev Res; 8(6); 502-8. Ó2015 AACR.