title: Implementing specificity of HPV-DNA primary screening in a successful organised cervical cancer prevention programme.
abstract: OBJECTIVE
  This two-arm longitudinal study was performed within a regional organized cervical-cancer-prevention program in which HPV-DNA test is used in primary screening. The aim was to analyze the diagnostic performances of p16INK4a/Ki-67 dual-test and E6/E7-mRNA test in identifying CIN2+ lesion among HPV-DNA positive (HPV-DNAve) women triaged for LSIL-or-worse liquid based cytology (LBC).
  
  
  METHODS
  Thirty-six thousand thirty-one women participated to HPV-DNA screening program pilot study. Three thousand six hundred forty-one resulted HPV-DNAve; among these, 43% were LSIL-or-worse (LSIL+). HPV-DNAve/LSIL+ patients were submitted to colposcopy and histological assessment of any visible lesions. Dual-test was performed on 794 residual LBC specimens. In 405 cases, dual-test result was related to histology, considering CIN2+ as endpoint. mRNA test has been carried out retrospectively, on a subset of 173 residual LBC specimens.
  
  
  RESULTS
  Agreement between dual-test and histological diagnosis was 59%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytology-plus-dual-test approach were 62.3%, 76.8%, 63.1% and 84.2%, respectively. Dual-test improved specificity, PPV and NPV of cytological triage Agreement between mRNA testing and histology was 65%. Cytology-plus mRNA testing showing sensitivity, specificity, PPV and NPV reaching 32.1%, 94.9%, 75% and 50%, respectively; implemented specificity and PPV of cytology alone in triaging DNA-ve/LSIL+ patients (p<0.01).
  
  
  CONCLUSIONS
  We provided promising data indicating the important role that p16(INK4)/Ki-67 dual-test, and mostly E6/E7 mRNA test, might have in triaging HPV-DNAve. These approaches would exclude the occurrence of cervical cancer and would avoid overtreatment, at the same time. Further longitudinal analysis has to be considered.
authors.affiliation: Cytopathology Unit, Clinical and Experimental Sciences Department, G. d'Annunzio University of Chieti-Pescara, Via dei Vestini, 66100, Chieti, Italy. zappacosta2@hotmail.com
authors.forename: Roberta
authors.initials: R
authors.lastname: Zappacosta
authors.forename: Donatella
authors.initials: D
authors.lastname: Caraceni
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccocioppo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rotondo
authors.forename: Serena
authors.initials: S
authors.lastname: Capanna
authors.forename: Daniela Maria Pia
authors.initials: DM
authors.lastname: Gatta
authors.forename: Chiara
authors.initials: C
authors.lastname: D'Angelo
authors.forename: Sandra
authors.initials: S
authors.lastname: Rosini
mesh_terms: D000328:Adult; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009363:Neoplasm Proteins; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012189:Retrospective Studies; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology*; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014759:Viral Envelope Proteins