RNA extended interventional nucleic acid longitudinal study: Clinical performance of Aptima messenger RNA HPV testing in cervical cancer screening with a 9‐year follow‐up

Background There is a need for additional longitudinal studies with the Aptima messenger RNA human papillomavirus test (AHPV) to support the safety of extended screening intervals. RNA‐based extended interventional nucleic acid (REINA) provides relevant information on the clinical performance of AHPV. Methods This is a longitudinal prospective analysis of 1538 participants after AHPV and liquid‐based cytology (LBC) co‐test complemented with REINA interventional protocol with a second co‐test 4 years after negative screening on 2000 women. Diagnostic accuracy and cumulative risks for CIN2+ up to 9 years were calculated for all test combinations. Results Sensitivity and specificity for CIN2+ were 96.9% and 88.0% for AHPV and 72.3% and 92.0% for LBC. Negative predictive value (NPV) and positive predictive value (PPV) of AHPV were 99.9% and 23.6%. The 5‐ and 9‐year risks of AHPV‐negative women were 0.4% and 1.0% (CIN2+) and 0.3% and 0.7% (CIN3+), a 73% and 64% lower risk than with negative LBC (p ≤ .002). REINA participants with an AHPV‐positive result at second co‐test after a negative AHPV in first round had a significantly lower 5‐year risk of CIN2+ (11.1%) than AHPV‐positive women with unknown HPV history (29.5%). Conclusions Currently, this constitutes the longest European longitudinal study with AHPV testing in screening population. It reveals 99.9% NPV and a significant protective effect of a previous negative test 5 years after a new HPV infection. These findings support the safety of Aptima for screening intervals beyond 5 years. The risk of disease is lower 9 years after a negative AHPV test than 3 years after a negative LBC. High specificity and PPV of Aptima may benefit controlling overtreatment and colposcopy referrals. This is the first European study to show a safe screening interval of 9 years with messenger RNA (mRNA) human papillomavirus (HPV) Aptima testing with a 99.9% negative predictive value. REINA study demonstrated the protective role of a previous negative Aptima mRNA HPV test with a low 5‐year cumulative risk of CIN2+ following a new HPV infection.