title: The impact of HPV cervical screening on negative large loop excision of the transformation zone (LLETZ): A comparative cohort study.
abstract: OBJECTIVE
  To determine the incidence and predictors of negative large loop excision of the transformation zone (LLETZ) following the introduction of Human Papillomavirus (HPV) cervical screening.
  
  
  METHODS
  A retrospective cohort study. Two independent cohorts, who attended for a LLETZ procedure, before and after the introduction of HPV cervical screening were compared. For each cohort, 401 individuals were randomly selected from a colposcopy database. Clinical and colposcopic variables were extracted. The incidence of negative LLETZ was estimated in each cohort. Regression analysis was used to adjust for potential confounders and explore predictors of negative LLETZ.
  
  
  RESULTS
  Eighty women (19.9%) from the pre-HPV testing cohort and 54 women (13.4%) from the post-HPV cohort were negative for cervical intraepithelial neoplasia (RR 0.75, CI: 0.55 to 0.93). In the post-HPV testing cohort, independent predictors of negative LLETZ were low grade cytology (RR 3.60, CI: 2.18-5.97) and a type 3 transformation zone (TZ) (RR 2.88, CI: 1.76-4.72). Women with both low grade cytology and a TZ type 3 were 10.4 times more likely to have a negative LLETZ (absolute risk 40%, 95% CI: 27-54%).
  
  
  CONCLUSIONS
  Despite a 25% reduction in negative LLETZ following the introduction of HPV cervical screening, the incidence is still high. These results highlight the importance of continuing to improve the specificity of cervical intraepithelial neoplasia screening; this should include the use of biomarkers that detect HPV-transforming infections and techniques that sample an entirely endocervical transformation zone.
authors.affiliation: Department of Gynaecological Oncology, University Hospitals Bristol NHS Foundation Trust, St. Michael's Hospital, Southwell Street, Bristol, BS2 8EG, UK; University of Bristol, School of Clinical Sciences, St. Michael's Hospital, Bristol, BS2 8EG, UK. Electronic address: Kristyn.Manley@UHBristol.nhs.uk.
authors.forename: K M
authors.initials: KM
authors.lastname: Manley
authors.affiliation: University of Bristol, Applied Statistics and Epidemiology, Biomedical Research Unit, Level 3, UBHT Education Centre, BS2 8AE, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Wills
authors.affiliation: Department of Gynaecological Oncology, University Hospitals Bristol NHS Foundation Trust, St. Michael's Hospital, Southwell Street, Bristol, BS2 8EG, UK.
authors.forename: G C
authors.initials: GC
authors.lastname: Morris
authors.affiliation: Department of Gynaecological Oncology, University Hospitals Bristol NHS Foundation Trust, St. Michael's Hospital, Southwell Street, Bristol, BS2 8EG, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Hogg
authors.affiliation: University of Bristol, School of Clinical Sciences, St. Michael's Hospital, Bristol, BS2 8EG, UK.
authors.forename: A
authors.initials: A
authors.lastname: López Bernal
authors.affiliation: Department of Gynaecological Oncology, University Hospitals Bristol NHS Foundation Trust, St. Michael's Hospital, Southwell Street, Bristol, BS2 8EG, UK.
authors.forename: J B
authors.initials: JB
authors.lastname: Murdoch
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003127:Colposcopy / Q000379:methods; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D008403:Mass Screening; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D012044:Regression Analysis; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000601:surgery* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000601:surgery* / Q000821:virology*
chemical_list: D004279:DNA, Viral
keywords: HPV testing; Negative LLETZ; Unsatisfactory colposcopy