HPV is acquired via sexual intercourse (“incidence”), but the majority of HPV is “cleared” within 2 years in most women. Approximately 60% of women with HPV DNA detected will develop serum antibodies against HPV (HPV seropositive), and if cellular samples are collected during peak viral production, mild cytologic abnormalities may be detected on Pap smears. A minority of HPV infections persist, and individuals with persistent high-risk HPV are at a substantial risk of developing cervical precancer, or CIN3. The CIN3 lesions are the targets of screening, because more than one-third of these will progress to invasive cervical cancer within 10–20 years. The dashed lines reflect the uncertainty in the natural history of HPV. Namely, it is unclear whether anti-HPV antibody developed following natural HPV infection protects against reinfection, and whether loss of HPV detection reflects virologic clearance or establishment of viral latency.