HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway

In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005-2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3-6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups <34 years, 34-50 years, and >50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alone.