title: Predictive testing of early CIN behaviour by molecular biomarkers.
abstract: Each year, 330,000 new Cervical Intraepithelial Neoplasias(CIN) occur in the European Union (EU) of which 120,000 are early CIN where grade (1, 2) indicates the progression-risk to CIN-3 and therefore determines the treatment choice. However, the Positive Predictive Value (PPV) of CIN grade to predict progression is low (10% and 20% for CIN-1 and -2 respectively, 16% on average) resulting in an enormous number of over-treatments indicating worrisome grade reproducibility.Certain molecular biomarkers such as Ki-67 have a higher PPV (30%, an improvement of 14%), which in Europe alone could improve treatment for many thousands of women per year with considerable cost reduction for the health care system. The quantitative Ki-67 prognostic model has been validated in independent retrospective and prospective studies from different laboratories. Moreover, the PPV of Ki-67 alone can be improved by additional molecular biomarkers (retinoblastoma protein = Rb, cytokeratins= CK-14/-13). Combined Ki67-Rb allows a 2-tiered progression-risk subgroup assignment as very low ( approximately 0% progression, 71% of all CIN-I/II patients)and high risk (48% progression risk, incidence 32%), leaving a small (7% of all) prognostically undetermined group (17% progression). Additional CK-14 and -13 analysis can sub-classify the high-risk in an intermediate and very high risk subgroup(with 40% and 100% progression risks respectively).Thus, molecular biomarkers are potentially important determinators of early CIN lesion behaviour. Important factors for widespread acceptance of molecular biomarkers are (1) market penetration by user-friendly equipment, (2) (inter)national keeping of GLP conditions (reproducibility, independent validation), requiring customer-driven industrial efforts,governmental measures, and additional PPV improvement to further reduce over-treatment.
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak
authors.forename: Arnold-Jan
authors.initials: AJ
authors.lastname: Kruse
authors.forename: Emiel
authors.initials: E
authors.lastname: Janssen
authors.forename: Bianca
authors.initials: B
authors.lastname: van Diermen
mesh_terms: D014408:Biomarkers, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen