HPV DNAtesting improvesCIN2+ risk stratification and detection ofCIN2+ in delayed triage ofASCUSandLSIL. A population‐based follow‐up study fromWesternNorway

Abstract

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.

Human papillomavirus type specific risk of progression and remission during long‐term follow‐up of equivocal and low‐grade HPV‐positive cervical smears

“…Based on these criteria 1,262 women were selected from of 201,104 evaluated cytological smears. It should be noted that the outcome of HPV positivity and negativity in the first control after ASCUS/LSIL has been reported on previously in a partly overlapping cohort (2005–2007) of our study . For the 2006–2007 cohort, covering about half of the women in our study, 410 women (45.9%) tested positive and 484 (54.1%) tested negative at their first follow‐up of ASCUS/LSIL at baseline.…”

“…In all these analyses the Pearson's χ 2 test was used to evaluate associations between categorical variables. Also, the progression risk of hr HPV‐negative women in a similar screening population cohort, were included for comparison. For some parameters mean ± standard error of the mean (SEM), median and progression risk with ±95% confidence intervals (CIs) were determined.…”

HPV infection and p16 promoter methylation as predictors of ASC‐US/LSIL progression

“…The ability to predict the risk of disease progression to HSIL would result in the improved management of ASC‐US/LSIL, with fewer patients being exposed to unnecessary colposcopic examinations or tissue biopsies. Recent studies have shown that human papillomavirus (HPV) infection is helpful in the risk stratification of lesions of CIN2 or higher . Likewise, the use of biomarkers to predict the progression of ASC‐US/LSIL could assist with triage care.…”

Cumulative High-Grade Squamous Intraepithelial Lesion Rate and Need for Surgical Intervention of Atypical Squamous Cells of Undetermined Significance Cytology-Diagnosed Patients: A Prospective Study

“…More specified classification of ASCUS cytology, such as ASCUS-reactive, ASCUS-LGSIL etc., might permit the optimal diagnostic and therapeutic management [1] . Furthermore, implementation of HPV-DNA testing in the follow-up of ASCUS cytology may contribute to the earlier diagnosis of HGSIL cases [20] .…”