Comparison of the clinical performance of an HPV mRNA test and an HPV DNA test in triage of atypical squamous cells of undetermined significance (ASC‐US)

M. Waldstrom and D. Ornskov
Comparison of the clinical performance of an HPV mRNA test and an HPV DNA test in triage of atypical squamous cells of undetermined significance (ASC‐US) Objective: The effect of triaging women with atypical squamous cells of undetermined significance (ASC‐US) with human papillomavirus (HPV) DNA testing has been well documented. New tests detecting HPV E6/E7 mRNA are emerging, claiming to be more specific for detecting high‐grade disease. We evaluated the clinical performance of two HPV tests: the Linear Array HPV genotyping test (LA) detecting HPV DNA from 37 oncogenic and non‐oncogenic HPV types and the Aptima HPV assay detecting E6/E7 mRNA from 14 oncogenic HPV types. Methods: We identified 369 consecutive PreservCyt samples diagnosed with ASC‐US tested for HPV DNA using the LA test. The Aptima HPV test was performed on residual material in the same vial. Follow‐up of 325 women was available. The gold standard used was histologically confirmed cervical intraepithelial neoplasia (CIN) grade 2+ or 3+. Results: LA and Aptima HPV assays were positive in 44.3% and 31.7% of the cases, respectively. The concordance was 81.2%. The two tests had identical sensitivity for detecting CIN3+ 92.6% (95% CI, 75.7–99.1)] but the Aptima HPV assay showed a significantly better specificity of 73.8% (95% CI, 68.5–78.7) versus 60.1% (95% CI, 54.3–65.7) for LA for detecting CIN3+. When using CIN2+ as the gold standard the sensitivity for LA was higher than for the Aptima HPV assay 93.8% (95% CI, 82.8–98.7) versus 87.5% (95% CI, 74.8–95.3)], but the specificity was higher for the Aptima HPV assay: 78.0% (95% CI, 72.6–82.7) versus 64.3% (95% CI, 58.3–69.9). Conclusions: Both tests showed good and equal clinical sensitivities for detecting CIN3+, but the Aptima HPV assay had significantly higher specificity for detecting CIN2+ and CIN3+ in women aged 30 years or older with ASC‐US.