title: Primary hrHPV DNA testing in cervical cancer screening: how to manage screen-positive women? A POBASCAM trial substudy.
abstract: BACKGROUND
  High-risk human papillomavirus (hrHPV) testing has higher sensitivity but lower specificity than cytology for cervical (pre)-cancerous lesions. Therefore, triage of hrHPV-positive women is needed in cervical cancer screening.
  
  
  METHODS
  A cohort of 1,100 hrHPV-positive women, from a population-based screening trial (POBASCAM: n = 44,938; 29-61 years), was used to evaluate 10 triage strategies, involving testing at baseline and six months with combinations of cytology, HPV16/18 genotyping, and/or repeat hrHPV testing. Clinical endpoint was cervical intraepithelial neoplasia grade 3 or worse (CIN3(+)) detected within four years; results were adjusted for women not attending repeat testing. A triage strategy was considered acceptable, when the probability of no CIN3(+) after negative triage (negative predictive value, NPV) was at least 98%, and the CIN3(+) risk after positive triage (positive predictive value, PPV) was at least 20%.
  
  
  RESULTS
  Triage at baseline with cytology only yielded an NPV of 94.3% [95% confidence interval (CI), 92.0-96.0] and a PPV of 39.7% (95% CI, 34.0-45.6). An increase in NPV, against a modest decrease in PPV, was obtained by triaging women with negative baseline cytology by repeat cytology (NPV 98.5% and PPV 34.0%) or by baseline HPV16/18 genotyping (NPV 98.8% and PPV 28.5%). The inclusion of both HPV16/18 genotyping at baseline and repeat cytology testing provided a high NPV (99.6%) and a moderately high PPV (25.6%).
  
  
  CONCLUSIONS
  Triaging hrHPV-positive women by cytology at baseline and after 6 to 12 months, possibly in combination with baseline HPV16/18 genotyping, seems acceptable for cervical cancer screening.
  
  
  CONCLUSIONS
  Implementable triage strategies are provided for primary hrHPV screening in an organized setting.
authors.affiliation: Authors' Affiliations: Departments of Pathology and Epidemiology and Biostatistics, VU University Medical Center; Department of Obstetrics and Gynaecology, St. Lukas Andreas Ziekenhuis, Amsterdam; Department of Pathology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; and Department of Pathology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Maaike G
authors.initials: MG
authors.lastname: Dijkstra
authors.forename: Dirk
authors.initials: D
authors.lastname: van Niekerk
authors.forename: Dorien C
authors.initials: DC
authors.lastname: Rijkaart
authors.forename: Folkert J
authors.initials: FJ
authors.lastname: van Kemenade
authors.forename: Daniëlle A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Johannes
authors.initials: J
authors.lastname: Berkhof
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003127:Colposcopy / Q000379:methods; D003584:Cytological Techniques / Q000379:methods; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology*; D014218:Triage / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*
chemical_list: D004279:DNA, Viral