Molecular events leading to HPV-induced high grade neoplasia

摘要

Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV) and develops via precursor stages, called cervical intraepithelial neoplasia (CIN). High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1) increase our understanding of cervical carcinogenesis, 2) yield biomarkers for early diagnosis, and 3) identify therapeutic targets for HPV-induced (pre) cancerous lesions.This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.