title: Human Papillomavirus genotype testing combined with cytology as a 'test of cure' post treatment: the importance of a persistent viral infection.
abstract: BACKGROUND
  Human Papillomavirus (HPV) testing has been evaluated as a test of cure in patients following treatment of high-grade cervical intraepithelial neoplasia (CIN2+). Studies show that women who are HPV and cytology negative post treatment can be safely returned to routine recall. The management strategy for HPV positive women requires confirmation.
  
  
  OBJECTIVE
  To evaluate the clinical utility of the PapilloCheck(®) genotyping assay for predicting disease recurrence in a test of cure setting.
  
  
  METHODS
  Ninety-eight women (19-52 years) treated for CIN2+ by large loop excision of the transformation zone (LLETZ) were evaluated with samples taken before and 6 months after treatment for HPV testing. Cytology and histology were available from recruitment until 24 months post treatment.
  
  
  RESULTS
  Recurrent disease was evident in 4% of patients with 2 cases low-grade and 2 cases of high-grade disease. In women with no disease recurrence, 40% (95% CI 30.42-51.05%) were high risk (HR) HPV negative post LLETZ. Both cases with high-grade disease had persistent HPV16 infection. Genotyping before and after treatment revealed 83% (95% CI 75.74-88.78%) of total viral infections were cleared and 17% (95% CI 11.22-24.26) viral infections persisted. Post treatment, combined cytology and HPV test results predicted CIN2+ with 100% sensitivity, 91.7% specificity, 100% NPV and 20% PPV and measuring viral persistence marginally increased specificity and PPV.
  
  
  CONCLUSIONS
  Post treatment, cytology combined with a single HR HPV test has high sensitivity and specificity for predicting disease recurrence. HPV genotyping before and after LLETZ identifies persistent viral infections and could help refine patient management.
authors.affiliation: Department of Obstetrics & Gynaecology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom.
authors.forename: Joanne
authors.initials: J
authors.lastname: Jones
authors.forename: Azka
authors.initials: A
authors.lastname: Saleem
authors.forename: Nima
authors.initials: N
authors.lastname: Rai
authors.forename: T S
authors.initials: TS
authors.lastname: Shylasree
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ashman
authors.forename: Kate
authors.initials: K
authors.lastname: Gregory
authors.forename: Ned
authors.initials: N
authors.lastname: Powell
authors.forename: Amanda
authors.initials: A
authors.lastname: Tristram
authors.forename: Alison
authors.initials: A
authors.lastname: Fiander
authors.forename: Samantha
authors.initials: S
authors.lastname: Hibbitts
mesh_terms: D000328:Adult; D003584:Cytological Techniques; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000601:surgery / Q000821:virology; D012008:Recurrence; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000601:surgery / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000601:surgery / Q000821:virology