Hpv - Human Papillomavirus Infection

What is human papillomavirus (HPV)?

The human papillomavirus, also known as HPV, is a genus of the family Papillomaviridae. Papilloma Viruses can cause asing cell growth of skin and mucous membranes and are the cause of warts. Human papillomavirus infection can also increase the risk of developing some forms of cancer, such as cervical cancer. Some types can, if not in time to be destroyed by the body, causing a sexually transmitted disease (STD). They were discovered by German physician and virologist Harald zur Hausen.

There are over a hundred different types of human papilloma virus known, most rare and harmless. Some are responsible for warts on hands and feet. About thirty types are seen as a STI, the types 6 and 11 cause genital warts and on the vocal cords warts, types 16 and 18 are responsible for many cases of cervical intra-epithelial neoplasia or other genital tumors. Papillomaviruses are species specific, there also exist, for example, bovine papilloma viruses, and can only infect epithelial cells. The virus settles in the basal cell layer.

 is a genus of the family Papillomaviridae HPV - Human Papillomavirus Infection

Human papillomavirus is the most common cause of STI: approximately 80% of all people infected or has ever been infected with human papillomavirus. Most have no experience and makes it either, but still infect other people. The HPVs are generally classified into two types: the low- and the high-risk group. The high-risk group is responsible for several types of cancer. Die every year worldwide a quarter of a million women from cervical cancer.

Although human papillomavirus occurs in both sexes are equally, women have a much better chance if they are infected by high-risk HPV, develop cancer. It is in 75% of cases of cervical cancer caused by certain types of human papillomavirus. This does not exclude that men can get cancer by infection with human papillomavirus from the high-risk group.

HPV (Human papillomavirus)

HPV is an icosahedron by 78 capsomeren and about 55 nm in diameter. It has circular double strand DNA of approximately 7900 base pairs. The genome encodes 9 proteins. These proteins are divided into two groups: seven Early (E) and two Late (L). The Early-proteins are formed and the basal cells in the infected Late only when these cells are differentiated.

The E5, E6 and E7 proteins-the first to be expressed. This destabilized the cell and induce replication. When a cell migrates differentiates it up. This induces the expression of the E1, E2 and E4 genes. The E1 and E2 proteins produce more copies of the viral genome and E4 destabilizes the cytoskeleton. The cell migrates still further upwards. Only in the upper layers of the epidermis, the two late proteins for expression. L1-proteins form the capsid. This is done by means of car Assembly, that is, than the no enzymatic needs help. The L2 protein will then for that viral DNA comes in the capsid. And then you have complete virions, virus particles that can very easily through direct contact "Skip".

Human papillomavirus infections can be distinguished into three types:

Residential means that the virus is present in the cells of the basal layer but it doesn't do anything. It sits there in the core, separate from the human DNA, and can sit there years before it becomes active. And then it doesn't matter if it's a high risk or low risk variant is, they can do both.
Human papillomavirus DNA at a episomale infection is active and it is engaged in producing of its proteins. This is macroscopically visible as a wart and microscopically as koilocytosis. This enables both the HR as the LR variants.
The most dangerous variant. It has a basal cell infected with human papillomavirus viral DNA in his own genome built. There is no control mechanism on where this happens, so this may happen on each chromosome. However, this is also detrimental to the virus, because human papilloma virus DNA in the genome of the because the cell is, the cell can no longer produce virus particles. The circular DNA of the virus is usually the cut making it virus activity of E2 loses, the protein that suppresses the expression of E6 and E7. This can now easily further develop into a tumor.


Integration of the high risk human papillomavirus, the loss of the E2 activity and continuous expression of E6 and E7 will lead to dysplasia (cervical intraepithelial neoplasia (CIN)), but not directly into a tumor. Most infections will disappear even without treatment after a few years. Thus, there are additional mutations needed before any invasive cells are formed. And this will take years.

Cells have six strategies to prevent the emergence of a carcinoma. Normal cells must therefore itself to obtain these mutations to form a malignant tumor. E6 and E7 allow circumvention four of the six mechanisms. They prevent apoptosis by checkpoint controls in the cell cycle to remove, to add self-growth signals, and render the cell insensitive to anti-growth signals. In addition, E6 seems to increase telomerase activity and the DNA so as to make the cell "immortal". As can be seen in the picture is missing the cell than two more features to be carcinogenic. These two, angiogenesis and metastasis, the cell through mutations should gain.


There are, however, new possibilities to prevent human papillomavirus infection, preventive vaccines and therapeutic vaccines. There are since 2008 in Europe two vaccines on the market: Gardasil and Cervarix. (In the Netherlands, both equally expensive). These vaccines reduce the chance of a cervical carcinoma by an estimated 73% and the risk of pre-cancerous lesions of the cervix and vulva by an estimated 50-60%. However, this has never been shown since it takes years for cervical cancer develops. In February 2014 a study was published which describes that in vaccinated Danish women are less likely than unvaccinated women endo-cervical atypia was seen.

Merck & Co. produces Gardasil directed against HPV 16 and 18 (HPV related together cause 70% of all CIN nvt. other 30% by among other HPV 31, 33, 35, 39, 45, 51, 66) and at 6 and 11, all responsible for 90% of genital warts. GlaxoSmithKline makes Cervarix aimed against HPV 16 and 18. Both use so-called Virus Like Particles (VLPs). These are formed by the L1 capsid proteins. As mentioned before, these autoassemblerend. How these are procured both manufacturers is different.

Merck uses yeast. The yeast got a plasmid (pGal110-11) with the L1-gene offered. This was expressed.

GlaxoSmithKline makes use of the so-called BEVS instead of yeast. Baculovirus Expression Vector System stands for BEVS. Advantage of this is that the mother cell much posttranslationale can perform modifications, such as phosphorylation, glycosylation and formation of disulfide bridges.

The national immunization programme
In Health Council of the Netherlands advised the on april 1, 2008 to Minister Ab Klink of health, girls of twelve years now within the national vaccination programme to vaccinate against cervical cancer. The cost of such vaccination are high but on several hundred cases of cervical cancer each year term can be avoided and more than a hundred deaths, the Council. It is still not a foregone conclusion among epidemiologists or this vaccination in Netherlands is cost effective or not. Many girls must be vaccinated to prevent deaths in the long term, even if the longer term immunity also persists. Data on the duration of the efficacy after more than ten years are not yet known.

The Minister has taken the advice of the Health Council and the end of 2008 to the second Chamber that human papillomavirus vaccine in 2009 in the national vaccination programme comes. Also it was decided to organize a ' catching-up ' campaign in 2009 for girls who were born on or after 1 January 1993 to 31 december 1996. Related to the pandemic of the swine flu, vaccination of 12-year-old girls delayed until spring 2010. In 2012 are girls who were born in 1999 invited to the human papillomavirus vaccination.

Side effects of vaccines

In the United States, the United States Centers for Disease Control and Prevention received since the introduction of Gardasil 7,800 complaints about potential side effects of a total of more than 40 million vaccines. The CDC Gardasil therefore are safe. In the Netherlands Cervarix is used in the National Immunisation Programme.

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