TY - JOUR
T1 - Natural history of high-grade cervical intraepithelial neoplasia: a review of prognostic biomarkers
AU - Koeneman, Margot M.
AU - Kruitwagen, Roy F. P. M.
AU - Nijman, Hans W.
AU - Slangen, Brigitte F. M.
AU - Van Gorp, Toon
AU - Kruse, Arnold-Jan
PY - 2015/4
Y1 - 2015/4
N2 - 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.
AB - 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.
KW - biological markers
KW - cervical intraepithelial neoplasia
KW - cervix
KW - human papillomavirus
KW - high-grade squamous intraepithelial lesions
KW - natural history
KW - regression
U2 - 10.1586/14737159.2015.1012068
DO - 10.1586/14737159.2015.1012068
M3 - Article
C2 - 25703310
SN - 1473-7159
VL - 15
SP - 527
EP - 546
JO - Expert Review of Molecular Diagnostics
JF - Expert Review of Molecular Diagnostics
IS - 4
ER -