Stepwise algorithm combining HPV high-risk DNA-based assays and RNA-based assay for high grade CIN in women with abnormal smears referred to colposcopy.

Background: The detection of high-risk human papillomavirus (HPV) DNA provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN).

Objective: The aim of this study was to combine DNA- and RNA-based assays in order to improve the detection of advanced disease (CIN2+).

Methods: 107 ASCUS+ women were included in Marseilles (France) between March 2007 and June 2008. Up to five tests were carried out on a liquid PreservCyt sample: Hybrid Capture 2 (HCII) (Digene), Papillocheck (Greiner), Abbott RealTime HR HPV (RT HR HPV) (Abbott), Linear Array (Roche), and EasyQ HPV (Biomérieux).

Results: 36 (34%) women had CIN2+ histology; among them 6 (6%) had CIN3+ histology. For CIN2+ detection, all tests had comparable sensitivities except EasyQ HPV test: HCII 94%, Papillocheck and LA 92%, RT HR HPV 89%, and NucliSENS EasyQ HPV 75% (P not significant). On the other hand, EasyQ HPV had a higher specificity than the other assays (except RT HR HPV assay). Combining DNA-based and RNA-based assay would allow to reduce the need of colposcopies to be performed among patients HPV positive with DNA-based assay: 32% (7/22) colposcopies not needed in < 30 years old patients, and 29% (14/49) colposcopies not needed in ≥ 30 years patients.

Conclusions: All tests had comparable diagnostic values for CIN2+ detection, but DNA-based tests seemed to be more sensitive and RNA-based assay more specific. The combined use of DNA- and RNA-based assays considerably reduces the number of colposcopies to be performed, and provides better diagnostic accuracy for CIN2+ disease.