Cervical human papillomavirus (HPV) infections are at high risk of neoplastic progression if they persist. Persistence can be measured by repeated HPV DNA tests or by cytologic testing. Thus, it is useful to understand the relationship between these 2 measurements. To explore the relative timing of HPV DNA clearance versus cytologic regression, data were analyzed from 840 study participants who were followed-up by repeat thin-layer cytology and HPV testing by a hybrid capture test at 6-month intervals for 2 years. On average, HPV DNA detection persisted longer than related cytologic abnormalities (P<.001). HPV type-specific data from a subset of 448 women with complete polymerase chain reaction test data confirmed that HPV DNA persisted longer than cytologic abnormalities (P<.001). It appears that the natural history of HPV typically includes periods before and after cytologic abnormality, in which HPV DNA is the more sensitive indicator of infection.