Role of Protein Biomarkers in the Detection of High-Grade Disease in Cervical Cancer Screening Programs

Figure 1

Cell cycle alterations induced by HPV E6 and E7 oncogenes in cervical neoplasia, adapted from Malinowski [11]. The presence of E7 disrupts G1-S phase regulation through the interference with E2F-Rb binding. P16INK40 is strongly expressed due to the loss of Rb/E2F repression and the strong activation by free E2F. The release of E2F results in the increased transcription of S-phase genes, including MCM2 and TOP2A. The interaction of E6 with p53 results in p53 ubiquitination and subsequent degradation, resulting in the abrogation of apoptosis. The proliferation marker Ki-67 is increased in the presence of cell cycle dysregulation caused by the E6 and E7 oncogenes.