Progression of Ano-Genital Intraepithelial Neoplasia and Tumors in Relation to Biomarkers

Dear Colleagues,

Oncological biomarkers are used in clinical practice to predict the progression of invasive cancer and choose the best targeted treatment available. The same has also been recently proposed for intraepithelial neoplasia to avoid unnecessary treatments and to preserve the full function of organs. This is especially true for genital organs to avoid impairing sexual function and fertility. The problem for anal precancerous disease is that it is more difficult to screen and diagnose early enough, because of the extension of the anal mucosa and its visualization.

Cytology and high-risk HPV evidence are insufficient in predicting progression since 70–90% of high-risk HPV become clear without medical intervention before 2 years after infection. The goal of improved screening programs should be to identify the remaining 10–30% of women with high-risk HPV persistency prone to progressive oncological disease. The biomarkers that can be used to address this challenge are markers for persistency like E6 and E7 oncoproteins, the numbers of p16/Ki-67-positive cells in cytological screening tests, the p16/Ki-67 immunoscore in histopathology, and, finally, very promising epigenetic tests. Such epigenetic tests also have the potential to identify progression in diseases not related to HPV infections, based either a) on the methylation of the host cell gene and, as a consequence, the impaired function of tumor suppressor genes of genital epithelial cells; or b) on the promoter methylation of specific regions of the HPV genome itself, such as oncogenes E6 and E7, giving information about its oncogenic activity.

Dr. Attila Louis Major
Guest Editor

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