RNA Extended Interventional Nucleic Acid (REINA) Longitudinal Study: Decreased Risk of CIN2+/CIN3+ With Low-Grade Cytology After A Previous Negative HPV Test.

OBJECTIVE

To analyse the impact of a previous negative mRNA HPV test in the immediate and 6 year risk of developing CIN2+/CIN3+ lesions in women with low-grade (LG, including ASC-US and LSIL) cytology in the second round of cotest screening.

METHODS

A prospective longitudinal study with LBC (ThinPrep, Hologic) and mRNA Aptima HPV test. Cotest was performed to 5053 asymptomatic women aged 25-65 years within an opportunistic screening programme in Madrid. Women with LG cytology, regardless of the mRNA HPV test result, were followed up (FU) to 10 years. The interventional arm 'RNA-based Extended Interventional Nucleic Acid (REINA)' recruited 2000 women with negative results in the first round for a second cotest 4 years later, and were FU to 6 more years. The risk of a CIN2+/CIN3+ at 6 years after a first LG cytology was calculated.

RESULTS

With an unknown HPV history, 18.7% of mRNA HPV-positive women at first cotest had LG cytology. Their immediate CIN2+ and CIN3+ risks were 24.7% and 12.8%, respectively, increasing to 31.8% and 17.0% after a 6-year FU. The long-term incidence of CIN2+ was strongly associated with mRNA HPV infection (p = 0.00001). From REINA, 20% of women with a new positive mRNA HPV result at second cotest had LG cytology, carrying much lower immediate and 6-year cumulative CIN2/CIN3 risks (5.0% and 10.0% respectively).

CONCLUSIONS

A previous negative Aptima mRNA HPV test confers a protective effect for CIN2+/CIN3+ in mRNA HPV-positive women with minor cytological changes. The adjusted risks impact patient management, decreasing colposcopy referrals.