Human papillomaviruses: Genetic basis of carcinogenicity

Robert D. Burk, Zigui Chen, Koenraad Van Doorslaer

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Persistent infection by specific oncogenic human papillomaviruses (HPVs) is established as the necessary cause of cervix cancer. DNA sequence differences between HPV genomes determine whether an HPV has the potential to cause cancer. Of the more than 100 HPV genotypes characterized at the genetic level, at least 15 are associated, to varying degrees, with cervical cancer. Classification based on nucleotide similarity places nearly all HPVs that infect the cervicovaginal area within the α-PV genus. Within this genus, phylogenetic trees inferred from the entire viral genome cluster all cancer-causing types together, suggesting the existence of a common ancestor for the oncogenic HPVs. However, in separate trees built from the early open reading frames (ORFs; i.e. E1, E2, E6, E7) or the late ORFs (i.e. L1, L2), the carcinogenic potential sorts with the early region of the genome, but not the late region. Thus, genetic differences within the early region specify the pathogenic potential of α-HPV infections. Since the HPV genomes are monophyletic and sites are highly correlated across the genome, diagnosis of oncogenic types and non-oncogenic types can be accomplished using any region across the genome. Here we review our current understanding of the evolutionary history of the oncogenic HPVs, in particular, we focus on the importance of viral genome heterogeneity and discuss the genetic basis for the oncogenic phenotype in some but not all α-PVs.

Original languageEnglish (US)
Pages (from-to)281-290
Number of pages10
JournalPublic Health Genomics
Volume12
Issue number5-6
DOIs
StatePublished - Aug 2009

Fingerprint

Medical Genetics
Open Reading Frames
Viral Genome
Genome
Human Genome
Uterine Cervical Neoplasms
Papillomavirus Infections
Genetic Heterogeneity
Neoplasms
Nucleotides
History
Genotype
Phenotype
Infection

Keywords

  • Cervix cancer
  • Evolution
  • Human papillomavirus
  • Phylogeny

ASJC Scopus subject areas

  • Genetics(clinical)
  • Public Health, Environmental and Occupational Health

Cite this

Human papillomaviruses : Genetic basis of carcinogenicity. / Burk, Robert D.; Chen, Zigui; Van Doorslaer, Koenraad.

In: Public Health Genomics, Vol. 12, No. 5-6, 08.2009, p. 281-290.

Research output: Contribution to journalArticle

Burk, Robert D. ; Chen, Zigui ; Van Doorslaer, Koenraad. / Human papillomaviruses : Genetic basis of carcinogenicity. In: Public Health Genomics. 2009 ; Vol. 12, No. 5-6. pp. 281-290.
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