Human papillomavirus pathophysiology: Difference between revisions
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{{Human papillomavirus}} | {{Human papillomavirus}} | ||
{{CMG}} | {{CMG}}{{AE}}{{AA}} | ||
== HPV Life-cycle == | == HPV Life-cycle == | ||
Revision as of 19:02, 13 October 2016
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Human papillomavirus Microchapters |
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Human papillomavirus pathophysiology On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]
HPV Life-cycle
The HPV life-cycle strictly follows the differentiation program of the host keratinocyte. It is thought that the HPV virion infects epithelial tissues through micro-abrasions, whereby, the virion associates with putative receptors such as alpha integrins and laminins, leading to entry of the virions into basal epithelial cells through clathrin-mediated endocytosis and/or caveolin-mediated endocytosis depending on the type of HPV. At this point, the viral genome is transported to the nucleus by unknown mechanisms and establishes itself at a copy number between 10-200 viral genomes per cell. A sophisticated transcriptional cascade then occurs as the host keratinocyte begins to divide and become increasingly differentiated in the upper layers of the epithelium. The viral oncogenes, E6 and E7, are thought to modify the cell cycle so as to retain the differentiating host keratinocyte in a state that is amiable to the amplification of viral genome replication and consequent late gene expression. In the upper layers of the host epithelium, the late genes L1 and L2 are transcribed/translated and serve as structural proteins which encapsidate the amplified viral genomes. Virions can then be sloughed off in the dead squames of the host epithelium and the viral life-cycle continues.
HPV-Induced Diseases
| Disease | HPV type |
|---|---|
| Common warts | 2, 7 |
| Plantar warts | 1, 2, 4 |
| Flat cutaneous warts | 3, 10 |
| Anogenital warts | 6, 11, 42, 43, 44, 55 and others |
| Genital malignancies | 16, 18, 31, 33, 35, 39, 45, 51 |
| Epidermodysplasia verruciformis | more than 15 types |
| Focal epithelial hyperplasia (oral) | 13, 32 |
| Oral papillomas | 6, 7, 11, 16, 32 |
Skin Warts
- Common warts: Some "cutaneous" HPV types, such as HPV-1 and HPV-2, cause common skin warts. Common warts are often found on the hands and feet, but can also occur in other areas, such as the elbows or knees. Common warts have a characteristic cauliflower-like surface and are typically slightly raised above the surrounding skin. Cutaneous HPV types do not usually cause genital warts and are not associated with the development of cancer.
- Plantar warts are found on the soles of the feet. Plantar warts grow inward, generally causing pain when walking.
- Subungual or periungual warts form under the fingernail (subungual), around the fingernail or on the cuticle (periungual). They may be more difficult to treat than warts in other locations.
- Flat warts: Flat warts are most commonly found on the arms, face or forehead. Like common warts, flat warts occur most frequently in children and teens. In people with normal immune function, flat warts are not associated with the development of cancer.
Genital Warts
Genital or anal warts (condylomata acuminata or venereal warts) are the most easily recognized sign of genital HPV infection. Although a wide variety of HPV types can cause genital warts, types 6 and 11 account for about 90% of all cases.[2][3]
Most people who acquire genital wart-associated HPV types clear the infection rapidly without ever developing warts or any other symptoms. People may transmit the virus to others even if they don't display overt symptoms of infection. However, in the vast majority of cases, this is not a cause for concern if proper tests are routinely administered.
HPV types that tend to cause genital warts are not the same ones that cause cervical cancer. However, since an individual can be infected with multiple types of HPV, the presence of warts does not rule out the possibility of high risk types of the virus also being present.
Condyloma accumulata is another form of genital warts.
Cancer
About a dozen HPV types (including types 16, 18, 31 and 45) are called "high-risk" types because they can lead to cervical cancer, as well as anal cancer, vulvar cancer, and penile cancer.[4] Several types of HPV, particularly type 16, have been found to be associated with oropharyngeal squamous-cell carcinoma, a form of head and neck cancer.[5] HPV-induced cancers often have viral sequences integrated into the cellular DNA. Some of the HPV "early" genes, such as E6 and E7, are known to act as oncogenes that promote tumor growth and malignant transformation.
The p53 protein prevents cell growth in the presence of DNA damage primarily through the BAX domain, which blocks the anti-apoptotic effects of the mitochondrial BCL-2 receptor. In addition, p53 also upregulates the p21 protein, which blocks the formation of the Cyclin D/Cdk4 complex, thereby preventing the phosphorylation of RB and, in turn, halting cell cycle progression by preventing the activation of E2F. In short, p53 is a tumor suppressor gene that arrests the cell cycle when there is DNA damage. The E6 and E7 proteins work by inhibiting tumor suppression genes involved in that pathway: E6 inhibits p53, while E7 inhibits p53, p21, and RB.
A history of infection with one or more high-risk HPV types is believed to be a prerequisite for the development of cervical cancer (the vast majority of HPV infections are not high risk); according to the American Cancer Society, women with no history of the virus do not develop this type of cancer. However, most HPV infections are cleared rapidly by the immune system and do not progress to cervical cancer. Because the process of transforming normal cervical cells into cancerous ones is slow, cancer occurs in people who have been infected with HPV for a long time, usually over a decade or more.[6][7]
Sexually transmitted HPVs also cause a major fraction of anal cancers and approximately 25% of cancers of the mouth and upper throat (known as the oropharynx) (see figure). The latter commonly present in the tonsil area and HPV is linked to the increase in oral cancers in non-smokers.[8][9] Engaging in anal sex or oral sex with an HPV-infected partner may increase the risk of developing these types of cancers.[5]
Respiratory Papillomatosis
HPV types 6 and 11 can cause a rare condition known as recurrent respiratory papillomatosis, in which warts form on the larynx or other areas of the respiratory tract.[10][7]
These warts can recur frequently, may require repetitive surgery, may interfere with breathing, and in extremely rare cases can progress to cancer.[11][7]
References
- ↑ http://picasaweb.google.com/mcmumbi/USMLEIIImages/photo#5089143144241737026
- ↑ Greer CE, Wheeler CM, Ladner MB; et al. (1995). "Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts". J. Clin. Microbiol. 33 (8): 2058–63. PMID 7559948.
- ↑ Gearheart PA, Randall TC, Buckley RM Jr (2004). "Human Papillomavirus". eMedicine.
- ↑ Parkin DM (2006). "The global health burden of infection-associated cancers in the year 2002". Int. J. Cancer. 118 (12): 3030–44. doi:10.1002/ijc.21731. PMID 16404738.
- ↑ 5.0 5.1 D'Souza G, Kreimer AR, Viscidi R; et al. (2007). "Case-control study of human papillomavirus and oropharyngeal cancer". N. Engl. J. Med. 356 (19): 1944–56. doi:10.1056/NEJMoa065497. PMID 17494927.
- ↑ Greenblatt R.J. 2005. Human papillomaviruses: Diseases, diagnosis, and a possible vaccine. Clinical Microbiology Newsletter, 27(18), 139-145. Abstract available.
- ↑ 7.0 7.1 7.2 Sinal SH, Woods CR (2005). "Human papillomavirus infections of the genital and respiratory tracts in young children". Seminars in pediatric infectious diseases. 16 (4): 306–16. doi:10.1053/j.spid.2005.06.010. PMID 16210110.
- ↑ Gillison ML, Koch WM, Capone RB; et al. (2000). "Evidence for a causal association between human papillomavirus and a subset of head and neck cancers". J. Natl. Cancer Inst. 92 (9): 709–20. PMID 10793107.
- ↑ Gillison ML (2006). "Human papillomavirus and prognosis of oropharyngeal squamous cell carcinoma: implications for clinical research in head and neck cancers". J. Clin. Oncol. 24 (36): 5623–5. doi:10.1200/JCO.2006.07.1829. PMID 17179099.
- ↑ Wu R, Sun S, Steinberg BM (2003). "Requirement of STAT3 activation for differentiation of mucosal stratified squamous epithelium". Mol. Med. 9 (3–4): 77–84. PMID 12865943.
- ↑ Moore CE, Wiatrak BJ, McClatchey KD; et al. (1999). "High-risk human papillomavirus types and squamous cell carcinoma in patients with respiratory papillomas". Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 120 (5): 698–705. doi:10.1053/hn.1999.v120.a91773. PMID 10229596.