Human papillomavirus brief overview

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Human Papillomavirus lineage

Viruses - dsDNA viruses, no RNA stage - Papillomaviridae - Human papillomavirus types

General information

• Papillomaviruses (PVs) (Papillomaviridae) are small, non-enveloped DNA viruses infecting birds and most mammals including humans.
• Papillomaviruses are causative agents of usually benign tumors (warts, papillomas), however, several human papillomavirus types (including types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66) have been classified as group 1 carcinogens by the International Agency for Research in Cancer (IARC). Among them HPV16 accounts for almost 60% occurrences of cervical cancer, the second largest cause of cancer-related death in women worldwide. Second most important cancer-associated PV is HPV type 18.
• Papillomaviruses are absolutely species-specific and extremely tissue-specific. The individual viruses show tropism for either cutaneous or mucosal surfaces usually at specific sites of the body, and, within these groups, they can be separated into high, moderate or low risk types, depending on their oncogenic potential.
• Most people in the world are probably infected with at least one if not several types of HPV during their life.

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Place among other viruses

• In the past PVs and Polyomaviruses were placed in a common family, Papoviridae. In 1980's PVs were separated into their own family Papillomaviridae.

Read more about place of HPV among other viruses

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Principles of classification based on genotype

• Genera
• Species
• Types
• Subtypes
• Variants

Read more about HPV classification principles

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Genome structure of HPV

All PVs contain a double-stranded, circular DNA genome approximately 8 kb in size that can be divided into 3 major regions. These regions are separated by two polyadenylation (pA) sites: early pA and late pA.

• Long Control Region (LCR)
• Early region
• Early pA
• Late region
• Late pA

Read more about HPV genome structure

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Human Papillomavirus proteins

• Nonstructural proteins
  • Regulatory proteins
    • E1 protein
    • E2 protein
    • E4 protein
  • Oncogenes
    • E5 protein
    • E6 protein
    • E7 protein
• Structural capsid proteins
  • L1 protein
  • L2 protein

Read more about HPV proteins

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Human Papillomavirus life cycle

• Infection
• Viral replication
  • Replication initiation
  • Maintenance replication
  • Vegetative replication

Read more about HPV life cycle

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Mechanism of cancer induction

The highest risk of cancer development occurs after prolonged persistent infection. The virus establishes the persistent infection at maintenance replication stage by obviating host's immune responses and, ultimately, integrating its DNA into the host's genome.

More about how Human Papillomavirus causes cancer

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Development of cervical cancer caused by HPV16

• Initial infection
• Viral persistence
• Cervical intraepithelial neoplasia (CIN)
  • Cervical intraepithelial neoplasia grade 1 (CIN1)
  • Precancer
    • Cervical intraepithelial neoplasia grade 2 (CIN2)
    • Cervical intraepithelial neoplasia grade 3 (CIN3)
• Invasive cancer

Read more about cervical cancer development

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Vaccination

• Gardasil ™ (Merk) quadrivalent vaccine. This vaccine also targets HPV6 and HPV11.
• Cervarix ™ (GlaxoSmithKline) bivalent vaccine. This vaccine uses a new proprietary adjuvant to boost immunogenicity (ability to induce both humoral as well as cell-mediated immunity). Furthermore, Cervarix ™, has shown evidence of protection against infections by related carcinogenic viruses, such as HPV45 and HPV31.

Read more about vaccination against HPV

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Detailed taxonomy of Human Papillomavirus

• Alphapapillomavirus
  
  • Human papillomavirus - 10
  • Human papillomavirus - 16
  • Human papillomavirus - 18
  • Human papillomavirus - 2
  • Human papillomavirus - 26
  • Human papillomavirus - 26
  • Human papillomavirus - 34
  • Human papillomavirus - 53
  • Human papillomavirus - 6
  • Human papillomavirus - 61
  • Human papillomavirus - 7
• Betapapillomavirus
  
  • Human papillomavirus - 49
  • Human papillomavirus - 5
  • Human papillomavirus - 9
• Deltapapillomavirus
  
  • Bovine papillomavirus - 1
• Gammapapillomavirus
  
  • Human papillomavirus - 4
  • Human papillomavirus - 48
  • Human papillomavirus - 50
  • Human papillomavirus - 60
  • Human papillomavirus - 88
• Mupapillomavirus
  
  • Human papillomavirus - 1
  • Human papillomavirus - 63
• Nupapillomavirus
  
  • Human papillomavirus - 41

Read more: HPV detailed taxonomic tree with references

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Bibliography

PubMed articles

• Zheng ZM, Baker CC. Front Biosci. 2006 Sep 1;11:2286-302.
• de Villiers EM et al. Virology. 2004 Jun 20;324(1):17-27.
• Bernard HU. J Clin Virol. 2005 Mar;32 Suppl 1:S1-6.
• Stanley MA, Pett MR, Coleman N. Biochem Soc Trans. 2007 Dec;35(Pt 6):1456-60.
• Schiffman M et al. Lancet. 2007 Sep 8;370(9590):890-907.
• McBride AA. Adv Virus Res. 2008;72:155-205.
• Stanley M et al. Vaccine. 2008 Aug 19;26 Suppl 10:K62-7.
• Jenkins D. Gynecol Oncol. 2008 Sep;110(3 Suppl 1):S18-25.
• Schwarz TF. Expert Rev Vaccines. 2008 Dec;7(10):1465-73.
• Hakim AA et al. Curr Treat Options Oncol. 2007 Dec;8(6):393-401.

Human Papillomavirus references with links at MetaPathogen

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