OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test.

METHODS: In this prospective cohort study, consecutive liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up to 10.5 years for development of CIN 3 or worse.

RESULTS: The 8-year absolute risk of CIN 3 or worse was 1.1% (95% confidence interval [CI] 1.0-1.3%) for HPV-negative women; 1.7% (0.8-2.6%) for low-risk HPV-positive women without concurrent high-risk HPV; 17.4% (16.4-18.5%) for high-risk HPV-positive women without concurrent low-risk HPV; and 15.9% (13.5-18.3%) for women with concurrent high-risk and low-risk HPV. The 8-year absolute risk of CIN 3 or worse after a negative high-risk HPV test (irrespective of low-risk HPV status) was lower than after a normal cytology result among women aged younger than 30 years (3.5% [95% CI, 2.9-4.0%] compared with 6.9% [6.2-7.5%], P<.001) and women aged 30 years or older (0.7% [95% CI, 0.6-0.9%] compared with 1.8% [95% CI, 1.6-2.0%], P<.001).

CONCLUSION: A negative high-risk HPV test provides greater long-term reassurance against CIN 3 or worse than normal cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types.

LEVEL OF EVIDENCE: II.