In a systematic review and meta-analysis reported in The Lancet Oncology, Arbyn et al found that the performance of a high-risk human papillomavirus (hrHPV) mRNA test in screening for cervical cancer was similar to that of validated hrHPV DNA tests in detection of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or 3 or worse (CIN3+).
Study Details
In the literature review, it was found that the only mRNA test with sufficient data to be included in the meta-analysis was the APTIMA HPV Test. The analysis population included 29,677 patients enrolled in eight studies assessing the cross-sectional accuracy of APTIMA vs hrHPV DNA assays in primary cervical cancer screening.
Key Findings
Compared with validated DNA assays, APTIMA exhibited similar sensitivity (relative sensitivity = 0.98, 95% confidence interval [CI] = 0.95–1.01) and slightly better specificity (relative specificity = 1.03, 95% CI = 1.02–1.04) for CIN2+. The relative sensitivity for CIN3+ was 0.98 (95% CI = 0.95–1.01).
Longitudinal performance was compared in four studies. Evaluation included the longitudinal sensitivity of mRNA tests and DNA tests for CIN3+ and the relative detection of CIN3+ among patients who screened negative for hrHPV mRNA or DNA (both used as measures of safety) at baseline, as well as pooled estimates by years of follow-up. Longitudinal relative sensitivity for CIN3+ with APTIMA vs DNA assays assessed over 4 to 7 years ranged between 0.91 and 1.05 at the study level and between 0.95 and 0.98, depending on time point, in the pooled analysis, with confidence intervals including or verging on unity. The detection rate ratios between 4 and 10 years after baseline negative mRNA vs negative DNA screening were imprecise and heterogeneous among studies, with summary ratios not differing from unity.
In one study with 10 years of follow-up, the cumulative rates of CIN3+ were 1.22% after an mRNA-negative test at baseline and 1.27% after a DNA-negative test at baseline, yielding a detection rate ratio of 0.96 (95% CI = 0.61–1.51).
Performance of APTIMA vs DNA tests with self-collected vs clinician-collected samples was assessed in five studies. APTIMA was less sensitive for CIN2+ (relative cross-sectional sensitivity = 0.84, 95% CI = 0.74–0.96) for self-collected samples and had similar specificity (relative specificity = 0.96, 95% CI = 0.91–1.01) for clinician-collected samples.
The investigators concluded, “HrHPV RNA testing with APTIMA had similar cross-sectional sensitivity for CIN2+ and CIN3+ and slightly higher specificity than DNA tests. Four studies with 4 to 7 years of follow-up showed heterogeneous safety outcomes. One study with up to 10 years of follow-up showed no differences in cumulative detection of CIN3+ after negative mRNA vs DNA screening. APTIMA could be accepted for primary cervical cancer screening on clinician-collected cervical samples at intervals of around 5 years. APTIMA is less sensitive on self-collected samples than clinician-collected samples.”
Marc Arbyn, PhD, of the Unit of Cancer Epidemiology, Belgian Cancer Centre, Brussels, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Horizon 2020 Framework Programme for Research and Innovation of the European Commission. For full disclosures of the study authors, visit thelancet.com.
