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HPVs

Friday 12 December 2003

Definition: Human papillomaviruses (HPVs) are nonenveloped DNA viruses that are members of the papovavirus family (which also includes polyomavirus, JC virus and SV-40).

Based on DNA sequence, papillomaviruses are classified into over 100 types.

Some HPVs cause papillomas (warts), benign tumors of squamous cells on the skin.

Other HPVs are associated with warts that can progress to malignancy, particularly squamous cell carcinoma of the cervix and the anogenital area.

Papillomaviruses are mainly transmitted by skin or genital contact. HPVs infect squamous epithelial cells, but their life cycle is not well understood since these viruses cannot be cultured in vitro. The expression of viral genes depends on the differentiation state of the epithelial cells.

Papilloma viruses initially infect basal cells in the epithelium, but there is limited expression of viral genes in these cells. As the epithelial cells differentiate, additional HPV genes are expressed. Mature virions are produced in the cells within the granular layer and shed from the stratum corneum.

In the upper spinous layers of the epithelium, HPV leads to a characteristic perinuclear vacuolization in the epithelial cells (koilocytosis).

HPV DNA is maintained as an episomal plasmid, and virus-encoded proteins promote cell growth and malignancy.

HPV E6 stimulates ubiquitination and degradation of p53, and HPV E7 binds to Rb, releasing the E2F transcription factor. Both these actions dysregulate the cell cycle and may promote cellular transformation and malignancy.

Cancer

Human papillomaviruses are the causative agent of cancers in stratified epithelial surfaces. They replicate in the upper parts of the epithelium, where cells would normally be dying to produce a cornified layer.

Infection with human papillomaviruses (HPVs) is a major public health burden worldwide and is associated with benign and malignant lesions of the skin and genital tract.

Therefore, they need to inhibit or delay differentiation and stimulate cell cycle progression to create an environment conducive for replication of the viral genome.

HPV causes cervical cancer, which represents the second most prevalent cancer in women worldwide. Functions of the viral oncogenes E6 and E7 are essential for carcinogenesis and for support of the viral life cycle.

The alterations both in differentiation and in the cell cycle are achieved by the viral proteins E6 and E7, which modulate cellular transcription mainly through their effects on p53 and the retinoblastoma family.

Subtypes

Genus Species Types properties
alpha-HPV 4 HPV-2, HPV-27, HPV-57 common skin warts, genital warts of children

Pathology

- cervical HPV infection

  • HPV-associated cervical squamous cell carcinoma

- HPV associated squamous cell carcinoma

  • HPV-associated cervical squamous cell carcinoma
  • HPV-associated tonsillar squamous cell carcinoma
  • HPV-associated laryngeal squamous cell carcinoma

Tumorigenesis

- HPV E6 and E7 oncoproteins are able to inactivate the tumor suppressor functions of p53 and Rb

  • HPV E6 protein
  • HPV E7 protein

Videos

- vulvar condyloma accuminata (by Washington Deceit)

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- Oncogenic effects on the cell cycle and apoptosis of human papillomavirus (Animated)

HPV detection

- HPV detection techniques (HPV assay)
- Third Wave’s HPV High-Risk Screening Test by Third Wave Technologies

Databases

- HPVdb

  • HPVdb: a data mining system for knowledge discovery in human papillomavirus with applications in T cell immunology and vaccinology.(24705205)

See also

- high-risk HPV

  • HPV-16
  • HPV-18

References

- Woodman CB, Collins SI, Young LS. The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer. 2007 Jan;7(1):11-22. PMID: 17186016

- Jones EE, Wells SI. Cervical cancer and human papillomaviruses: inactivation of retinoblastoma and other tumor suppressor pathways. Curr Mol Med. 2006 Nov;6(7):795-808. PMID: 17100604

- Roden R, Wu TC. How will HPV vaccines affect cervical cancer? Nat Rev Cancer. 2006 Oct;6(10):753-63. PMID: 16990853

- McCance DJ. Transcriptional regulation by human papillomaviruses. Curr Opin Genet Dev. 2005 Oct;15(5):515-9. PMID: 16099158

- Wentzensen N, Vinokurova S, von Knebel Doeberitz M. Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res. 2004 Jun 1;64(11):3878-84. PMID: 15172997

- Storey A. Papillomaviruses: death-defying acts in skin cancer. Trends Mol Med. 2002 Sep;8(9):417-21. PMID: 12223312