title: Management of high-risk HPV-positive women for detection of cervical (pre)cancer.
abstract: Primary HPV-testing has been shown to provide a superior detection of women at risk of cervical (pre)cancer compared to cytology-based screening. However, as most high-risk HPV infections are harmless, additional triage testing of HPV-positive women is necessary to identify those with cervical (pre)cancer. In this paper, we compare the performance, advantages and limitations of clinically relevant available triage strategies for HPV-positive women.
  
  
  
  Many different colposcopy triage strategies, comprising both microscopy-based and molecular (virus/host-related) markers, have been suggested: Pap cytology, p16/Ki-67 dual-stained cytology, HPV16/18 genotyping, viral DNA methylation and host cell DNA methylation. Literature search was limited to triage strategies that have achieved at least phase 2 of the five-phase framework for biomarker development and studies including large cohorts (≥100 hrHPV-positive women). Triage markers were stratified by sample type (cervical scrape, self-collected sample) and by study population (screening, non-attendee, referral). Expert commentary: At present, repeat Pap cytology and Pap cytology combined with HPV16/18 genotyping are the only triage strategies that have been robustly shown to be ready for implementation. Other strategies such as p16/Ki-67 dual-stained cytology and host cell DNA methylation analysis, with or without additional HPV16/18 genotyping, are attractive options for the near future.
authors.affiliation: a Department of Pathology , VU University Medical Center , Amsterdam , the Netherlands.|b Department of Obstetrics & Gynecology , Diakonessenhuis , Utrecht , the Netherlands.
authors.forename: Roosmarijn
authors.initials: R
authors.lastname: Luttmer
authors.affiliation: a Department of Pathology , VU University Medical Center , Amsterdam , the Netherlands.
authors.forename: Lise M A
authors.initials: LM
authors.lastname: De Strooper
authors.affiliation: a Department of Pathology , VU University Medical Center , Amsterdam , the Netherlands.
authors.forename: Renske D M
authors.initials: RD
authors.lastname: Steenbergen
authors.affiliation: c Department of Epidemiology & Biostatistics , VU University Medical Center , Amsterdam , the Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Berkhof
authors.affiliation: a Department of Pathology , VU University Medical Center , Amsterdam , the Netherlands.
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.affiliation: a Department of Pathology , VU University Medical Center , Amsterdam , the Netherlands.
authors.forename: Daniëlle A M
authors.initials: DA
authors.lastname: Heideman
authors.affiliation: a Department of Pathology , VU University Medical Center , Amsterdam , the Netherlands.
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D005260:Female; D060005:Genotyping Techniques / Q000379:methods; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism; D052161:Human papillomavirus 18 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D065006:Papanicolaou Test / Q000379:methods; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D011230:Precancerous Conditions / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000821:virology; D014218:Triage / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000821:virology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D019394:Ki-67 Antigen
keywords: DNA methylation; Human papillomavirus; biomarker; cervical cancer; cervical intraepithelial neoplasia (CIN); cytology; genotyping; p16/Ki-67 dual-stained cytology; screening; triage