title: Human Papillomavirus negative but dyskaryotic cervical cytology: re-analysis of molecular testing.
abstract: BACKGROUND
  Evaluation of molecular Human Papillomavirus (HPV) testing into UK Cervical Screening Programmes is underway. In South Wales the current HPV prevalence in women attending routine screening is 13.5% with 76.3% HR HPV positive in cases with reported dyskaryotic cervical cytology [Hibbitts S, Jones J, Powell N, Dallimore N, McRea J, Beer H, et al. Human papillomavirus prevalence in women attending routine cervical screening in South Wales, UK: a cross-sectional study. Br J Cancer 2008;99(December (11)):1929-33].
  
  
  OBJECTIVE
  The aim of this study was to re-analyse the 23.7% cases with reported dyskaryotic cytology that were HR HPV negative (n=52 out of 219 in a population of 10,000).
  
  
  METHODS
  Three procedures were performed: (i) GP5+/GP6+ PCR-EIA repeat on original DNA extracts; (ii) DNA extraction and GP5+/GP6+ HPV PCR-EIA; (iii) DNA extraction and HPV typing using Greiner Bio-One PapilloCheck DNA microarray.
  
  
  RESULTS
  51 out of 52 samples were re-analysed. Direct repeat HPV PCR-EIA identified 24% (n=12/51) of samples positive for HR HPV. Re-extracted DNA and PCR-EIA increased detection to 41.2% (n=21/51) and PapilloCheck detected 78.4% (n=40/51). HR HPV detection by PapilloCheck was significantly higher compared with the other methods of re-analysis. Eleven samples were persistently HR HPV negative but 4 tested positive for low risk HPV.
  
  
  CONCLUSIONS
  This study identifies that up to 78% of samples with dyskaryotic cervical cytology that test negative for HPV can be found to be HPV positive on re-analysis. The reliance on a single negative HPV test result could lead to missed HPV related disease in a subset of patients, the number dependant on which HPV test is performed. The clinical significance of a false negative HPV result depends on the screening interval and how HPV testing is incorporated into screening.
authors.affiliation: HPV Research Group, Department of Obstetrics and Gynaecology, School of Medicine, Heath Park, Cardiff University, Cardiff, UK. peevorrj@cardiff.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Peevor
authors.forename: S
authors.initials: S
authors.lastname: Bowden
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: A N
authors.initials: AN
authors.lastname: Fiander
authors.forename: S
authors.initials: S
authors.lastname: Hibbitts
mesh_terms: D002467:Cell Nucleus / Q000473:pathology*; D002584:Cervix Uteri / Q000473:pathology* / Q000821:virology*; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D027383:Papillomaviridae / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D006113:United Kingdom; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D014852:Wales