[Human papillomaviruses : origin, oncogenic factors and markers for cervical cancer screening].

Abstract

The Human papillomaviruses (HPV) have existed in the human population since the archaic hominids. Over the course of human migration and evolution, HPVs have co-evolved with humans on all continents to become today the leading cause of cervical cancer. HPVs are classified by genera, species, genotype, lineage, sub-lineage and variants. Among more than 200 HPV genotypes, HPV16 is the most common and the most oncogenic at high-risk (HPV-HR). If viral oncogenesis is governed by numerous factors and mechanisms involving the virus and its host, the E6/E7 oncogenic proteins of HR-HPV play a central role and are always expressed in cervical cancers. Those of HPV16 have the greatest affinity for cellular proteins involved in cellular control, p53/E6 and pRb/E7. Some E6/E7 HPV16 mutants are associated with persistent infection, correlating with viral lineages and their ethnic and geographical origin. If the splicing of viral mRNAs encoding E6/E7 allows the overexpression of the E7 protein, which is an essential condition for the establishment of HR-HPV oncogenesis, other mechanisms contribute to strengthening it. On the one hand, the accidental integration of the viral genome, in particular the E1/E2 coding region, participates in the transformation of the infected cell. On the other hand, hypermethylation of the viral L1/L2 genomic regions is observed in the advanced stages of infection. Different methods for analyzing mutations, splice sites, integrations and methylations of the viral genome have been described. These virological markers could complete the detection of HR-HPV in the context of cervical cancer screening, currently recommended in France.