RESUMEN
HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of proto-oncogenes and the silencing of tumor suppressor genes; some of these are proteins with PDZ domains involved in homeostasis and cell polarity. Through a bioinformatics approach based on interaction networks, a group of proteins associated with HPV 16 infection, PDZ domains, and direct physical interaction with E6 and related to different hallmarks of cancer were identified. MAGI-1 was selected to evaluate the expression profile and subcellular localization changes in premalignant lesions and ISCC with HPV 16 in an integrated state in cervical cytology; the profile expression of MAGI-1 diminished according to lesion grade. Surprisingly, in cell lines CaSki and SiHa, the protein localization was cytoplasmic and nuclear. In contrast, in histological samples, a change in subcellular localization from the cytoplasm in low-grade squamous intraepithelial lesions (LSIL) to the nucleus in the high-grade squamous intraepithelial lesion (HSIL) was observed; in in situ carcinomas and ISCC, MAGI-1 expression was absent. In conclusion, MAGI-1 expression could be a potential biomarker for distinguishing those cells with normal morphology but with HPV 16 integrated from those showing morphology-related uterine cervical lesions associated with tumor progression.
RESUMEN
Cervical cancer is one of the main causes of female cancer death worldwide, and human papilloma virus (HPV) its causal agent. To investigate viral oncogenesis several studies have focused on the effects of HPV oncoproteins E6 and E7 and the mechanisms by which these proteins stimulate the cellular transformation process. However, phenomena such as the physical state of the viral genome (episomal or integrated) and the effects of this integration on cell proliferation contribute new clues to understand how HPV infection causes carcinogenesis. New molecular technologies are currently facilitating these discoveries. This paper reviews the tumor development process initiated by HPV, recent findings on the process of viral integration into the host genome, new methods to detect HPV integration, and derived associated effects.