title: Predicting CIN2+ when detecting HPV mRNA and DNA by PreTect HPV-proofer and consensus PCR: A 2-year follow-up of women with ASCUS or LSIL Pap smear.
abstract: It has been suggested that human papillomavirus (HPV) testing improves follow-up of atypical cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) in cervical cancer screening programs. To evaluate the prognostic value of including HPV testing as an adjunct to cytology, we carried out a 2-year follow-up study of 77 women with ASCUS or LSIL Papanicolaou (Pap) smear in the Norwegian Cervical Cancer Screening Program (NCCSP) for detection of histological cervical intraepithelial neoplasia (CIN) 2+. The study includes a comparison between viral mRNA and DNA detection. PreTect HPV-Proofer was used for HPV E6/E7 mRNA detection from the 5 high-risk types 16, 18, 31, 33 and 45, and Gp5+/6+ consensus PCR was used for HPV DNA detection. Twice as many women were positive for HPV DNA (54.6%) than for HPV mRNA (23.4%). PreTect HPV-Proofer and consensus PCR had a sensitivity of 85.7% (95% confidence interval [CI] = 42.1-99.6) for detecting CIN2+ during follow-up. The specificity was significantly higher for PreTect HPV-Proofer, 84.9% (95% CI = 73.9-92.5), than for consensus PCR, 50.0% (95% CI = 37.4-62.6). PreTect HPV-Proofer positive women were 69.8 times (95% CI = 4.3-1137.3) more likely to be diagnosed with CIN2+ within 2 years than PreTect HPV-Proofer negative women. Consensus PCR-positive women were 5.7 times (95% CI = 0.6-52.0) more likely to be diagnosed with CIN2+ within 2 years than PCR-negative women. With equal sensitivity and higher specificity than consensus PCR, the PreTect HPV-Proofer might offer an improvement for the triage of women with ASCUS or LSIL Pap smear.
authors.affiliation: Institute of Pathology, The National University Hospital, 0027 Oslo, Norway. t.e.f.molden@labmed.uio.no
authors.forename: Tor
authors.initials: T
authors.lastname: Molden
authors.forename: Jan F
authors.initials: JF
authors.lastname: Nygård
authors.forename: Irene
authors.initials: I
authors.lastname: Kraus
authors.forename: Frank
authors.initials: F
authors.lastname: Karlsen
authors.forename: Mari
authors.initials: M
authors.lastname: Nygård
authors.forename: Gry Baadstrand
authors.initials: GB
authors.lastname: Skare
authors.forename: Hanne
authors.initials: H
authors.lastname: Skomedal
authors.forename: Steinar O
authors.initials: SO
authors.lastname: Thoresen
authors.forename: Bjørn
authors.initials: B
authors.lastname: Hagmar
mesh_terms: D000328:Adult; D002584:Cervix Uteri / Q000166:cytology* / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008403:Mass Screening; D008875:Middle Aged; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics* / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology*
chemical_list: D004279:DNA, Viral; D012333:RNA, Messenger