title: Natural history of high-grade cervical intraepithelial neoplasia: a review of prognostic biomarkers.
abstract: The natural history of high-grade cervical intraepithelial neoplasia (CIN) is largely unpredictable and current histopathological examination is unable to differentiate between lesions that will regress and those that will not. Therefore, most high-grade lesions are currently treated by surgical excision, leading to overtreatment and unnecessary complications. Prognostic biomarkers may differentiate between lesions that will regress and those that will not, making individualized treatment of high-grade CIN possible. This review identifies several promising prognostic biomarkers. These biomarkers include viral genotype and viral DNA methylation (viral factors), human leukocyte antigen-subtypes, markers of lymphoproliferative response, telomerase amplification and human papillomavirus-induced epigenetic effects (host factors) and Ki-67, p53 and pRb (cellular factors). All identified biomarkers were evaluated according to their role in the natural history of high-grade CIN and according to established criteria for evaluation of biomarkers (prospective-specimen-collection, retrospective-blinded-evaluation [PROBE] criteria). None of the biomarkers meets the PROBE criteria for clinical applicability and more research on prognostic biomarkers in high-grade CIN is necessary.
authors.affiliation: GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Margot M
authors.initials: MM
authors.lastname: Koeneman
authors.forename: Roy F P M
authors.initials: RF
authors.lastname: Kruitwagen
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
authors.forename: Brigitte F M
authors.initials: BF
authors.lastname: Slangen
authors.forename: Toon
authors.initials: T
authors.lastname: Van Gorp
authors.forename: Arnold-Jan
authors.initials: AJ
authors.lastname: Kruse
mesh_terms: D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002472:Cell Transformation, Viral; D005260:Female; D006801:Humans; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology; D030361:Papillomavirus Infections / Q000150:complications; D011379:Prognosis; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor
keywords: biological markers; cervical intraepithelial neoplasia; cervix; high-grade squamous intraepithelial lesions; human papillomavirus; natural history; regression