Paper Title
3-Type HPV MRNA Test in Detection of cin2+ in young women with Normal Cytology

Abstract
Despite a well-established cervical cancer (CC) screening program in Norway, the incidence of CC in young women is increasing, peaking at 35 years. Twenty-five percent of all women diagnosed with CC had normal cytology within 3 years of cancer diagnosis, addressing the need of improvement of screening program to further reduce cancer incidences missed by cytology. We wanted to investigate the detection rate of CIN2+ in young women with normal cytology by using a 3-type HPV mRNA test. In 2014-2017, 2,382 women <40 years with normal cytology at Nordlandssykehuset-Bodo, Norway, were HPV-tested using a 3-type HPV E6/E7 mRNA test (PreTect SEE; direct genotyping 16, 18 and 45). Index cytology from women with a positive HPV mRNA test were rescreened. Women with revised cytological diagnoses were followed-up according national guidelines until August 2018. We used histologically confirmed CIN2+ as study endpoint. Overall, 2.1% (50/2,382) had positive HPV mRNA test. The cytology was revised in 52.0% (26/50); 11 ASC-US, 6 LSIL, 1 AGUS, 6 ASC-H and 2 HSIL. During follow-up, biopsy was taken from 30 women. CIN2+ was detected in 56.6 % (17/30) from women that tested HPV mRNA positive (8 CIN2 and 9 CIN3), giving a total prevalence of CIN2+ of 0.7% (17/2,382) in presumed cytology normal women. By testing women <40 years with normal cytology with a specific 3-type HPV mRNA test, an increase in screening program sensitivity can be achieved without an excessive workload. The volume of rescreened smears is low (2.1%). The PPV for CIN2+ is high (56.6%). When more women with CIN2+ are detected and treated in the first screening round, less women will develop cervical cancer before next screening round. Keywords - HPV, mRNA, Cervix, Cytology, Screening