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

Elisabeth B Budal,Bjørn O Mæhle,Hans K Haugland,Tone Bjørge,Robert Skar,Olav K Vintermyr

doi:10.1002/cam4.171

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.

Highlights

Uterine cervical cancer is the second most common cancer among women worldwide [1]
We report on women with an index sample of atypical squamous cells of uncertain significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) and monitoring with cytology and human papillomavirus (HPV) testing in delayed triage
The HPV test was positive in 37% of women with index ASCUS and in 70% of women with index LSIL, respectively (Table 1)

Summary

Introduction

Squamous cell carcinomas account for about 75–80% of the new cancer cases [2]. They develop through a multistep sequence of events from low- through high-grade cellular lesions and into cancer [3, 4]. Most developed countries have established nationwide screening programs to detect and treat highgrade cellular lesions and to monitor atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL). These programs are mainly based on cytology as the primary screening method. The approach has proven useful in the sense that the incidence rates of cervical cancer have decreased [11,12,13] despite an increasing prevalence of genital hrHPV infections in Western countries [14]

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