Molecular Markers for Early Detection of Cervical Neoplasia

In the United States, cervical cancer screening programs based on exfoliated cervical cytology (Pap smears) have significantly reduced the incidence of invasive cervical cancer. As a result of this success, current cervical cancer screening programs in the US are not directed at invasive disease, but at detection of the precursors of carcinoma, referred to as dysplasias, squamous intraepithelial lesions (SIL) or cervical intraepithelial neoplasias (CIN). The progressive histologic and cytologic changes that occur during the multistep process of cervical carcinogenesis can be divided into multiple stages, early lesions known as CIN 1 or LSIL and high grade lesions known as CIN 2, 3 or HSIL. The natural history of these cervical cancer precursor lesions is difficult to study because they are usually biopsied or otherwise treated as soon as detected. However, it is clear that CIN 1 and 2 lesions are more likely to regress than to progress to invasive disease [37, 69]. While the risk of progression is greatest for CIN 3 lesions, not all of these lesions progress and regression is recognized to occur in a significant but variable number of cases [69]. Because of the slow rate of disease progression, targeting early detection at CIN 3 lesions is an effective strategy to avoid invasive cancer and at