title: High-risk HPV platforms and test of cure: should specific HPV platforms more suited to screening in a 'test of cure' scenario be recommended?
abstract: OBJECTIVE
  When the Sheffield screening laboratory changed the high-risk human papillomavirus (hrHPV) platforms from hybrid capture 2(®) (HC2; Digene Ltd) and to cobas 4800(®) (Roche) an unexpected and substantial increase in the number of cytology-negative/hrHPV-positive test-of-cure (ToC) samples after large loop excision of the transformation zone (LLETZ) was noted. We explore the potential reasons for these increased rates and discuss the implications this may have on the English NHS cervical screening programme (CSP).
  
  
  METHODS
  A retrospective cohort study with interval analysis between June 2007 and June 2012.
  
  
  RESULTS
  ToC was performed on 1530 women with HC2 and 396 with cobas 4800: 95.1% and 92.4% of women had negative cytology at ToC in the HC2 and cobas4800 testing period, respectively. Of these 13.9% and 27.8% tested positive for hrHPV in the HC2 and cobas 4800 group, respectively (P = <0.0001). No clinically significant increase in the number of cases of cervical intraepithelial neolpasia (CIN) was detected by the cobas4800 test in spite of doubling the number of cytology-negative/hrHPV-positive ToC samples.
  
  
  CONCLUSIONS
  As far as we are aware, this is the first study reporting potential differences between different HPV platforms currently available in the English programme. The immediate impact of this increase in rates of hrHPV detection with cobas4800 is an increased number of colposcopy referrals to our service. The NHSCSP needs to assess whether this increase is acceptable and, if not, whether specific HPV platforms more suited to screening in a ToC scenario should be recommended.
authors.affiliation: Department of Gynaecological Oncology/Jessop Wing Colposcopy Unit, Sheffield Hospitals NHS Trust, Sheffield, UK.
authors.forename: A
authors.initials: A
authors.lastname: Innamaa
authors.affiliation: Department of Cytology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors.forename: N
authors.initials: N
authors.lastname: Dudding
authors.affiliation: Department of Cytology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors.forename: K
authors.initials: K
authors.lastname: Ellis
authors.affiliation: Department of Cytology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors.forename: J
authors.initials: J
authors.lastname: Crossley
authors.affiliation: East Pennine Cytology Training Centre, Department of Histopathology & Cytology, Sheffield Hospitals NHS Trust, Sheffield, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Smith
authors.affiliation: Department of Gynaecological Oncology/Jessop Wing Colposcopy Unit, Sheffield Hospitals NHS Trust, Sheffield, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Tidy
authors.affiliation: Department of Gynaecological Oncology/Jessop Wing Colposcopy Unit, Sheffield Hospitals NHS Trust, Sheffield, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Palmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002584:Cervix Uteri / Q000473:pathology* / Q000601:surgery; D015331:Cohort Studies; D003127:Colposcopy; D004279:DNA, Viral / Q000302:isolation & purification*; D055088:Early Detection of Cancer; D004598:Electrosurgery; D004739:England; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000473:pathology*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000473:pathology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000473:pathology*
chemical_list: D004279:DNA, Viral
keywords: Cobas® 4800; Hybrid Capture® 2; cervical intraepithelial neoplasia; high-risk human papillomavirus; large loop excision of the transformation zone; test of cure