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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Web of Science)


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
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

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