The diagnostic accuracy of two methods for E6&7 mRNA detection in women with minor cytological abnormalities

Abstract

Objective. To examine the diagnostic accuracy of nucleic acid sequence based amplification (NASBA) and flow cytometry for E6&7 human papillomavirus (HPV) mRNA detection in the triage of minor cytological abnormalities. Design. Prospective diagnostic accuracy study. Setting. Gynecology outpatient clinics of a university hospital. Population. 472 women with low-grade squamous intraepithelial lesion (LSIL) or atypical squamous cells of undetermined significance (ASCUS).Methods. Residual material of the liquid-based smears was tested by NASBA and by flow cytometry for E6&E7 mRNA expression. Histological diagnosis was used as reference standard. Main outcome measures. Accuracy indices of the two techniques and of type 16-specific NASBA for the detection of cervical intraepithelial neoplasia (CIN) 2+and CIN3+, accuracy indices at age>35 years, correlation between NASBA and flow, comparison between integrated and episomal high-risk HPV infection for risk of CIN2+. Results. Both tests showed increased positivity rates with increasing severity of the lesion (p <0.05, chi-squared test for trend). There was a positive correlation betweenNASBA and flowresults (phi coefficient=0.325).NASBA-positive cases were more likely to have CIN2+ than were NASBA-negative/DNA-positive for types 16, 18, 31, 33, 45 (25/73 vs. 4/52, p = 0.0004; Fisher's exact test). In the LSIL group theNASBAaccuracy indices forCIN3+were: sensitivity75%, specificity 78.7% and positivity rate 20.8%, and for flow77.8%, 64.5% and 35.9%, respectively. Conclusions. NASBA has favorable specificity and positivity rates for triaging LSIL prior to colposcopy. A relatively low sensitivity warrants cytological surveillance of the NASBA-negative LSILs. Flow cytometry does not perform as well overall. © 2012 The Authors. © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.