title: Molecular biomarkers in cervical cancer diagnosis: a critical appraisal.
abstract: BACKGROUND
  It is expected that in the near future high-risk human papillomavirus (hr-HPV) testing will be implemented as the primary cervical cancer screening method in some countries. However, only a fraction of hr-HPV positive women will have a clinically relevant lesion. As a result, there is an urgent need for additional biomarkers that can detect these lesions and that can at the same time be applied to cytological specimens. This overview evaluates the most promising cytological biomarkers.
  
  
  METHODS
  Cytological biomarkers that can be used are being discussed in view of their molecular background. The most promising biomarkers are p16(INK4a)/Ki-67 dual immunostaining; methylation of the promoter region of the cell adhesion molecule 1 (CADM1) gene and the T-lymphocyte maturation associated protein (MAL) gene and viral integration. Their sensitivity, specificity and limitations are discussed in detail and their diagnostic accuracy is evaluated.
  
  
  CONCLUSIONS
  The most promising cytological biomarkers for cervical cancer screening are p16(INK4a)/Ki-67 dual immunostaining, methylation of CADM1 and MAL and viral integration. Although some of the biomarkers are very promising for this purpose, no studies have evaluated how accurately these biomarkers classify or predict the outcome. Additional clinical trials are needed to determine the true clinical value of these promising cytological biomarkers.
authors.affiliation: Maastricht University Medical Centre, GROW-School for Oncology and Developmental Biology, Department of Obstetrics and Gynaecology, PO Box 616, 6200MD Maastricht, The Netherlands. r.litjens@maastrichtuniversity.nl
authors.forename: Rogier J N T M
authors.initials: RJ
authors.lastname: Litjens
authors.forename: Anton H N
authors.initials: AH
authors.lastname: Hopman
authors.forename: Koen K
authors.initials: KK
authors.lastname: van de Vijver
authors.forename: Frans C S
authors.initials: FC
authors.lastname: Ramaekers
authors.forename: Roy F P M
authors.initials: RF
authors.lastname: Kruitwagen
authors.forename: Arnold-Jan
authors.initials: AJ
authors.lastname: Kruse
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor