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.

Prognostic factors for spontaneous regression of high-risk human papillomavirus-positive cervical intra-epithelial neoplasia grade 2

“…Previous studies that assessed prognostic markers in cervical intra-epithelial neoplasia grade 2 also included hrHPV-negative lesions or lesions with unknown HPV status 4 14–16. We hypothesized that the effect of potential predictors may be different in a population of exclusively high-grade HPV-positive cervical intra-epithelial neoplasia grade 2, due to a prognostic effect of hrHPV itself 13. Indeed, our study results differ from previous studies.…”

Clinical value of fully automated p16/Ki‐67 dual staining in the triage of HPV‐positive women in the Norwegian Cervical Cancer Screening Program

“…The development of a cervical lesion is determined by interactions between an individual's immune response, viral factors, and cellular mechanisms. Unfortunately, at present, we do not have biomarkers that take all these factors into consideration …”

<b><i>c-myc</i></b> Gene Copy Number Variation in Cervical Exfoliated Cells Detected on Fluorescence in situ Hybridization for Cervical Cancer Screening

“…Not all CIN lesions progress to high-grade disease; 90% of CIN1 resolve without treatment [24]. Thus, the natural progression of CIN is largely unpredictable, and histopathological examination cannot differentiate between lesions that will regress and those that will not [25]. In general, the clinical treatment of low- and high-grade disease is distinct: it is recommended that CIN1 be monitored, while CIN2/3 lesions should be treated aggressively (except in cases of pregnancy).…”