Performance of the HPV E6/E7 mRNA Aptima HPV assay combined with partial genotyping compared with the HPV DNA Cobas 4800 HPV test for use in primary screening: Results from the CERVIVA HPV primary screening study in Ireland

There are currently several validated HPV tests. However, longitudinal data which spans appropriate age ranges, as well as evaluation of potential screening algorithms are necessary for screening programmes choice of test. The objective of our study was to evaluate the performance of HPV mRNA and HPV DNA testing, including partial genotyping, in routine cervical screening. As part of the CERVIVA HPV Primary Screening Study, ThinPrep samples from 10 150 women were tested for HPV mRNA using the Aptima HPV assay and HPV DNA using the Cobas 4800 HPV test. HPV mRNA-positive women were further assessed with the Aptima genotyping assay for HPV 16/18/45. Baseline cytology and prospective follow-up data were collected. The performance of the two tests was examined over 42 months (to date). HPV mRNA demonstrated equivalent sensitivity to HPV DNA testing for detection of CIN2+ (93.2% [92.4-93.9] vs 92.8% [92.0-93.6], respectively) and CIN3+ (94.6% [93.8-95.3] vs 94.6% [93.8-95.3]). HPV mRNA testing had significantly higher specificity compared to HPV DNA for detection of CIN2+ (84.0% [83.5-84.5] vs 80.8% [80.2-81.4], respectively) and CIN3+ (88.44% [88.2-88.6] vs 85.62 [85.4-85.9]). The proportion of CIN2+ and CIN3+, over 3 years (42 months), in HPV-negative women was comparable for both RNA (0.20% and 0.10%) and DNA (0.22% and 0.11%). Genotyping data was comparable across both assay platforms. In the context of HPV primary screening HPV mRNA testing has potential to reduce triage tests and follow-up tests at 12 months compared to DNA testing, with no significant difference in detection of CIN2+ and CIN3+.