title: Alterations in human papillomavirus-related biomarkers after treatment of cervical intraepithelial neoplasia.
abstract: OBJECTIVE
  This study aims to assess the alterations in various HPV-related biomarkers 6 months post-treatment and how these relate to various risk factors and individual characteristics; their role for the prediction of treatment failure was also evaluated.
  
  
  METHODS
  
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  Women planning to undergo treatment for cervical intraepithelial neoplasia.
  
  
  METHODS
  A liquid-based cytology sample was taken pre-operatively. This was tested for HPV genotyping, Nucleic Acid Sequence Based Amplification, flow cytometric evaluation and p16 immunostaining. A repeat LBC sample was obtained 6 months post-treatment and was tested for the same biomarkers.
  
  
  RESULTS
  The alterations of the biomarkers 6 months post-treatment were recorded. Their relation to individual characteristics and risk factors (age, smoking, sexual history, use of condom, CIN grade, excision margin status, crypt involvement) as well as their role for the prediction of residual/recurrent disease were assessed.
  
  
  METHODS
  The accuracy parameters (sensitivity, specificity, positive and negative predictive value and the likelihood ratios) of each biomarker for the prediction of recurrent/residual CIN were calculated.
  
  
  RESULTS
  A total of 190 women were recruited. All biomarkers had significantly higher negativity rates post-treatment compared to pre-treatment ones. Multivariate analysis demonstrated that consistent condom use post-treatment significantly reduces the high-risk HPV positivity rates in comparison to no use (OR=0.18; 95% CI: 0.09-0.38). Sensitivity and specificity for all high risk HPV DNA testing were 0.5/0.62, respectively; the relevant values for only type 16 or 18 DNA typing were 0.5/0.92, for NASBA 0.5/0.94, for flow 0.5/0.85 and for p16 0.25/0.93.
  
  
  CONCLUSIONS
  CIN treatment reduces positivity for all HPV-related biomarkers. Consistent condom use significantly reduces high-risk HPV positivity rates. More cases of treatment failures are required in order to specify whether different combinations of HPV-related biomarkers could enhance the accuracy of follow up, possibly in the form of a Scoring System that could allow tailored post-treatment surveillance.
authors.affiliation: University Hospital of Ioannina, Ioannina, Greece. gvalasoulis@gmail.com
authors.forename: G
authors.initials: G
authors.lastname: Valasoulis
authors.forename: G
authors.initials: G
authors.lastname: Koliopoulos
authors.forename: C
authors.initials: C
authors.lastname: Founta
authors.forename: M
authors.initials: M
authors.lastname: Kyrgiou
authors.forename: I
authors.initials: I
authors.lastname: Tsoumpou
authors.forename: O
authors.initials: O
authors.lastname: Valari
authors.forename: P
authors.initials: P
authors.lastname: Martin-Hirsch
authors.forename: A
authors.initials: A
authors.lastname: Daponte
authors.forename: P
authors.initials: P
authors.lastname: Karakitsos
authors.forename: E
authors.initials: E
authors.lastname: Paraskevaidis
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004598:Electrosurgery; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D011237:Predictive Value of Tests; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery* / Q000821:virology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology / Q000601:surgery* / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor