title: High-risk human papillomavirus DNA test and p16(INK4a) in the triage of LSIL: a prospective diagnostic study.
abstract: OBJECTIVE
  The detection of high-grade cervical intraepithelial neoplasia (CIN) amongst patients with low-grade cytology (LSIL) is challenging. This study evaluated the role of high-risk HPV (HR-HPV) DNA test and p16(INK4a) immunostaining in identifying women with LSIL cytology at risk of harboring CIN2 or worse (CIN2+) and the role of p16(INK4a) in the triage of a population of HR-HPV positive LSIL.
  
  
  METHODS
  We conducted a prospective study including women with LSIL cytology. Detection of HR-HPV was carried out by means of a polymerase chain reaction based assay. p16(INK4a) immunostaining was performed using the Dako CINtec cytology kit. All patients had colposcopically directed punch biopsies or large loop excision of the transformation zone of the cervix. The endpoint was detection of a biopsy-confirmed CIN2+.
  
  
  RESULTS
  A series of 126 women with LSIL cytology were included. HR-HPV test had sensitivity 75% and specificity 64% for an endpoint of CIN2+. p16(INK4a) had significantly higher specificity of 89% (p=0.0000) but low sensitivity of 42%. The role of p16(INK4a) immunostaining in the triage of LSIL positive for HR-HPV was also evaluated. p16(INK4a) triage had 70% positive predictive value (PPV); however, this was not significantly higher than the PPV (56%) of HR-HPV test alone (p=0.4).
  
  
  CONCLUSIONS
  The results indicate that HR-HPV or p16(INK4a) cannot be used as solitary markers for the assessment of LSIL. The addition of p16(INK4a) immunostaining led to an increase in HR-HPV specificity; however, the biomarker needs to be assessed further to establish its role as an adjunct test in the triage of LSIL.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospitals of South Manchester, Manchester, UK. ioantsoumpou@hotmail.com
authors.forename: I
authors.initials: I
authors.lastname: Tsoumpou
authors.forename: G
authors.initials: G
authors.lastname: Valasoulis
authors.forename: C
authors.initials: C
authors.lastname: Founta
authors.forename: M
authors.initials: M
authors.lastname: Kyrgiou
authors.forename: M
authors.initials: M
authors.lastname: Nasioutziki
authors.forename: A
authors.initials: A
authors.lastname: Daponte
authors.forename: G
authors.initials: G
authors.lastname: Koliopoulos
authors.forename: V
authors.initials: V
authors.lastname: Malamou-Mitsi
authors.forename: P
authors.initials: P
authors.lastname: Karakitsos
authors.forename: E
authors.initials: E
authors.lastname: Paraskevaidis
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D003127:Colposcopy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000821:virology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral