Main molecular mechanisms of carcinogenesis induced by human papillomavirus

The most widespread infectious factors causing malignant neoplasms are human papillomaviruses (HPV). HPV genotype 16 is often involved in the carcinogenesis of oropharyngeal squamous cell carcinoma, which occurs in 80 % of cases. The viral proteins E5, E6, and E7 are the main drivers responsible for the initiation and progression of cancer through the stimulation of cell proliferation, cell survival, inhibition of cell apoptosis and modulation of keratinocyte differentiation. The early promoter is initiated upstream of E6 independently of cell differentiation and synthesizes transcripts that are translated early in the viral life cycle. The launch of the late promoter depends on cell differentiation and activated for production transcripts that induce translation of the L1 and L2 proteins. During the entry of the virus into the cell, the L1 protein attaches to heparan sulfate proteoglycans (HSPG) on the extracellular matrix, after which the virus enters the cell by micropinocytosis. The interaction with HSPG is considered the initial contact that promotes conformational changes in the capsid, allowing the transfer of the virion to the secondary entry receptor. Cell division plays an important role in the delivery of the viral genome to the nucleus. HPV moves through the cytoplasm in the lumen of transport vesicles, which originate from the Golgi complex, line up along microtubules and are transmitted to condensed chromosomes. It is believed that the integration of the HPV genome increases the expression of HPV oncogenes in the cell, which contributes to uncontrolled cell proliferation and significant DNA damage. Integrated transcripts may be more stable and oncogenic than episomal-derived HPV transcripts