REVIEW

Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers

J P A Baak¹, A-J Kruse², S J Robboy⁴, E A M Janssen², B van Diermen² and I Skaland²

¹ Stovagen University Hospital and the Gade Institute, University of Bergen, Bergen, Norway; Free University, Amsterdam, The Netherlands
² Department of Pathology, Stavanger University Hospital, Stavanger, Norway
³ Department of Gynecology, Academic Medical Center Maastricht, Maastricht, The Netherlands
⁴ Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA; Department of Obstetrics and Gynecology, Duke University Medical Center

Correspondence to:
Correspondence to:
J P A Baak
Department of Pathology, Stavanger University Hospital, Armauer Hansen Road 20, N-4068 Stavanger, Norway; baja{at}sos.no

The microscopic phenotype of cervical intraepithelial neoplasia (CIN) reflects a fine balance between factors that promote or reduce CIN development. A shortcoming of the current grading system is its reliance on static morphology and microscopic haematoxylin–eosin features of the epithelium alone. In reality, CIN is a dynamic process, and the epithelium may exhibit differing results over time. Functional biomarkers p16, Ki-67, p53, retinoblastoma protein cytokeratin (CK)14 and CK13, help in the assessment of an individual CIN’s lesion’s potential for progression and regression. The aggregate information provided by these biomarkers exceeds the value of the classic grading system. Consequently, many more CINs that will either regress or progress can be accurately identified. These findings agree with known molecular interactions between HPV and the host. For accurate interpretation of a CIN, it is essential that these biomarkers be determined quantitatively and separately in the superficial, middle and deep layers of the epithelium. Such geography-specific epithelial evaluations of quantitative biomarkers emphasise the dynamic nature of a particular CIN lesion, thereby changing the art of static morphology grading into dynamic interpretation of the diseased tissue, with a strong prognostic effect.

Abbreviations: CIN, cervical intraepithelial neoplasia; CK, cytokeratin; HLA, human leucocyte antigen; HPV, human papillomavirus; hrHPV, high-risk human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; pRb, retinoblastoma protein; SI, Stratification Index; SIL, squamous intraepithelial lesion

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