Comparative performance of human papillomavirus messenger RNA versus DNA screening tests at baseline and 48 months in the HPV FOCAL trial

Background: HPV FOCAL is a randomized trial comparing high-risk HPV [Hybrid Capture 2 (HC2)] vs. liquid-based cytology (LBC) for primary cervical screening. Objective: The present study objective was to compare Aptima HPV (AHPV) and HC2 assay performance at the intervention arm baseline and 48 mo. screens in relation to the rates of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). Study design: Women enrolled after December 2010 (n = 3475) were screened at baseline with both AHPV and HC2 (AHPV was blinded). Women with CIN2+ exited the trial; HC2 negative (-) women and those HC2 positive (+) with < CIN2 returned for 48 mo. screening with AHPV, HC2, and LBC. Results: At baseline, 7.2% were AHPV + vs. 8.4% for HC2 (p = 0.06). Round 1 AHPV CIN2+ sensitivity (relative to HC2) was 96.0% (95% CI: 86.5-99.0; p = 0.15) and 100% (95% CI: 82.4-100) for CIN3+. AHPV and HC2 specificities (< CIN2) were 94.1% vs. 93.0% respectively (p = 0.05). At 48 mo., 4.8% and 5.2% were AHPV + and HC2+ respectively (p = 0.41), and both tests had the same CIN2+ and CIN3+ sensitivities (87.5% and 85.0% respectively). AHPV specificity (95.8%) was higher, but not significantly, than HC2 (95.3%; p = 0.38). Of 3226 baseline AHPV - women, 12/2,858 (0.4%) had CIN2+ vs. 13/2821 (0.5%) for the 3184 baseline HC2-women. Conclusions: There was no significant difference in CIN2+ detection for AHPV vs. HC2 at baseline or at 48 mo. Baseline AHPV - and HC2 - women had similar CIN2+ rates at 48 mo., demonstrating the safety of a four year screening interval for AHPV-women.