title: Human papillomavirus in false negative archival cervical smears: implications for screening for cervical cancer.
abstract: OBJECTIVE
  To assess the value of detecting human papillomavirus (HPV) DNA in false negative archival cervical smears in population based screening programmes for cervical cancer.
  
  
  METHODS
  Cytomorphologically classified false negative archival Pap smears (n = 27) taken from 18 women up to six years before cervical cancer was diagnosed were blindly mixed with 89 smears from hospital patients with a variety of gynaecological complaints and tested for HPV by the polymerase chain reaction (PCR). Corresponding cervical cancer biopsy specimens were also available for HPV analysis. Neither the examining cytopathologist nor the molecular biologist was aware of the study design.
  
  
  RESULTS
  HPV DNA was detected in the smears of 16 patients with cervical cancer missed previously by cytology. HPV 16 and 18 were found predominantly in those smears taken up to six years before the diagnosis of cervical cancer. The smears of the two remaining patients were reclassified as inadequate for cytology or contained no suitable DNA for PCR. In 15 patients the same HPV type could be found in the smears and the cervical cancer biopsy specimens.
  
  
  CONCLUSIONS
  The results indicate that high risk HPV types can be detected in archival smears classified as false negative on cytology and that cytological screening errors may be reduced if combined with PCR testing for HPV.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Walboomers
authors.forename: A M
authors.initials: AM
authors.lastname: de Roda Husman
authors.forename: P J
authors.initials: PJ
authors.lastname: Snijders
authors.forename: H V
authors.initials: HV
authors.lastname: Stel
authors.forename: E K
authors.initials: EK
authors.lastname: Risse
authors.forename: T J
authors.initials: TJ
authors.lastname: Helmerhorst
authors.forename: F J
authors.initials: FJ
authors.lastname: Voorhorst
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D004279:DNA, Viral / Q000302:isolation & purification; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D008403:Mass Screening; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control / Q000821:virology*; D014626:Vaginal Smears
chemical_list: D004279:DNA, Viral