Natural history of high-grade cervical intraepithelial neoplasia: a review of prognostic biomarkers

Koeneman, M. M., Kruitwagen, R. F. P. M., Nijman, H. W., Slangen, B. F. M., Van Gorp, T. & Kruse, A-J., Apr-2015, In : Expert review of molecular diagnostics. 15, 4, p. 527-546 20 p.

Research output: Contribution to journalReview articleAcademicpeer-review

  • Margot M. Koeneman
  • Roy F. P. M. Kruitwagen
  • Hans W. Nijman
  • Brigitte F. M. Slangen
  • Toon Van Gorp
  • Arnold-Jan Kruse

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.

Original languageEnglish
Pages (from-to)527-546
Number of pages20
JournalExpert review of molecular diagnostics
Issue number4
Publication statusPublished - Apr-2015


  • biological markers, cervical intraepithelial neoplasia, cervix, human papillomavirus, high-grade squamous intraepithelial lesions, natural history, regression, HUMAN-PAPILLOMAVIRUS TYPE-16, LOCAL IMMUNE-RESPONSE, REGULATORY T-CELLS, SPONTANEOUS REGRESSION, PROSPECTIVE-COHORT, INVASIVE CANCER, HPV INFECTION, EPITHELIAL BIOMARKERS, CLINICAL-SIGNIFICANCE, MICRORNA EXPRESSION

ID: 20593147