Human Papillomavirus DNA and E6/E7 mRNA Testing as Triage in Liquid-Based Cytology Samples from Primary Screening

Sonia      Andersson; Miriam      Mints; Elisabete      Weiderpass; Bo      Johansson

doi:10.2174/1381612811319080018

Abstract

We estimated the frequency of detection of different human papillomavirus (HPV) types in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology in a population-based primary screening programme. 247 liquid-based cytology (LBC) samples with ASCUS/LSIL results were tested using the LINEAR ARRAY HPV Genotyping Test (LA; Roche Diagnostics), which detects 37 HPV types. 79.4% of samples were positive by LA, and 60.7% were positive for high-risk HPV types (ASCUS: 41.2%; LSIL: 71.0%). 34 of the 37 HPV types included in LA were detected in our samples. HPV16 was detected in 18.6% of samples, and 66.8% of samples contained more than one HPV type, with a maximum of nine types observed in one LSIL sample. A random subset of 47 samples from the 247 samples tested by LA, was also analysed using the AMPLICOR HPV Test (Amplicor, Roche Diagnostics). A separate set of 42 samples, which were positive by LA for the five high-risk HPV types included in the PreTect HPV-Proofer (Proofer, NorChip AS), was also analysed for E6/E7 mRNA expression using Proofer.

Concordance between LA and Amplicor was 91.5% (kappa=0.83). One false-negative and three false-positives were recorded for Amplicor, using LA as the “gold standard”. Concordance between LA and Proofer was 88.0%; 100% of Proofer samples that were HPV18- positive by LA, and 75.0% of HPV16-positive samples, expressed E6/E7 mRNA. In the present study using LBC samples in a triage situation, where negative predictive value is paramount, LA gave the most reliable results.

Keywords: HPV, genotyping, liquid-based cytology, secondary screening, E6/E7 mRNA, ASCUS, LSIL, LBC samples, triage, Proofer