A review of the natural history of cervical intraepithelial neoplasia.

Cervical Intraepithelial Neoplasia (CIN) is a premalignant lesion of cervical squamous cell carcinoma which over time may persist unchanged, regress to normal or a lesser grade of CIN, or progress to a higher grade of CIN or invasive carcinoma. Rates of progression correlate directly with the CIN grade. Human Papilloma Virus (HPV) detection is a significant determinant of CIN regardless of grade. Studies of risk factor profiles, cytogenetic abnormalities, cell proliferation indices, cell cycle and senescence control, oncogene and tumor suppressor gene expression, protein expression, and HPV status have been conducted to identify determinants of CIN I and CIN II/III and predictors of CIN 1 progression. Differences in these attributes suggest that CIN I is a sexually transmitted, productive HPV infection, whereas CIN II/III is a dysplastic lesion resulting from repeated exposure to a sexually transmitted HPV and possibly an additional agent. HPV16 positivity and increased viral load in some earlier studies were predictive of prevalent CIN II/III. More recent studies with more sensitive HPV assays did not corroborate these findings. The role of cigarette smoking is controversial and requires additional study. Accumulating evidence suggests that high risk HPV DNA detection and persistence are predictive of CIN I progressing to CIN II/III. Other possibilities are persistence of a high risk HPV variant, altered cell immunity, and cigarette and oral contraceptive use. Possible biomarkers include aneuploidy, aneusomy of chromosomes 1 and 3, Ras and bcl-2 oncogene over expression, and cytokeratin 13 protein under-expression.