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Nicholas Kirkby

on 14 July 2014

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Transcript of HPV

(Human Pappilomavirus)
The HPV Virion is encased in the capsid proteins L1 and L2 which (when the virus has entered through a small abrasion or tear in the outer skin) interact with a6ß4 Integrin, a component of the hemidesmosomes, which regulates cell migration in response to wound healing. Through this interaction with a6ß4 Integrin, the virus is integrated into the basal squamous epithelial cells which constitute the bottom layer of the squamous epithelial. (Immunopaedia.org, 2010)
HPV is an extremely common sexually transmitted virus that can lead to genital warts and cancer. However, it is usually defeated by the body's immune system before these conditions develop. (CDC, 2014)
Once inside the basal epithelial cells, the HPV infection has mechanisms to ensure it is not detected. HPV will only produce minimal levels of viral protein. HPV is importantly not cytolytic and the virus replication and assembly only occurs in cells that are already destined for destruction by anoikis (death by natural causes). This results in an absence of HPV in the bloodstream and thus there is little exposure to the acquired immune system resulting in a significantly reduced production of antibodies in response. (Immunopaedia.org, 2010)
The primary method of viral immune evasion is most likely the reduction of antigen presentation. This is achieved through the methods already mentioned, as well as through specific non-structural proteins that inhibit the cell's signalling mechanisms and the expression of IRF-1 which is an essential intermediate transcription control factor for the production of interferon induced effectors. (I. Frazer, 2009)
Through antigen presentation, the immune system is made aware of the pathogen's presence and is then able to mount an appropriate response. With antigen presentation compromised, the immune system's response is significantly reduced. (I. Frazer, 2009)
The production of effector cells is inhibited by the HPV virus.
With less antigens produced, most of the HPV virus does not have antigens attached which results in a reduced production of lymphocytes and no inflammatory response.
HPV actively suppresses the production of antigens in response to its presence.
Without antigens attached to the HPV virus, the immune system is unable to respond effectively.
HPV in this way can exist passively in the epithelial cells for years without an adequate response from the immune system.
HPV is cleared in 90% of cases by the immune system.
If HPV gives rise to cancer however the immune system is able to respond to this new threat faster than in response to HPV infection.
While HPV is difficult to be cleared by the immune system due to its ability to evade it, if it develops cancerous cells the immune system is capable of dealing with those cancerous cells effectively through the use of dendritic cells.
Luckily, immunisation to HPV can be achieved through vaccination (Note: only for the high risk forms of HPV that are known to cause cancer: 6, 11, 16 and 18) (CC, 2013)
The HPV prophylactic vaccine releases the L1 capsid proteins that would be found surrounding the HPV virus rather than the actual virus itself like many other vaccines.
The HPV virus is vulnerable to antibodies during the complex multi-step process of its integration into the basal squamous epithelial cells. The vaccine which promotes a strong immunological response to the presence of L1 proteins thus allows the body to destroy HPV before it is fully integrated and reproduced. (M. Stanley, 2010)
The vaccine is also composed of immunostimulant 3-O-desacyl-4'-monophosphoryl lipid A and aluminium hydroxide which together elicit an increased frequency of HPV L1 protein specific memory cells for up to 7 months after vaccination. (Tino Schwartz, 2008) The production of these memory cells is vital to immunity as it is these memory cells which will look specifically for HPV and produce antibodies faster when HPV is detected.
Ethical Issues:
There is a concern amongst the community in relation to the administration of the HPV vaccination at the early ages of 11 and 12. There is the perception that giving a child this vaccine for a sexually transmitted disease is giving them permission to have unsafe sex. This however is not founded on any evidence and research indicates that the sexual activity of younger persons is not influenced by STI's in general at all. (T. Donahau, 2013)

Another ethical issue in relation to HPV vaccination is that it only prevents 70% of cervical cancer cases and it has been proposed that "some women may develop a false sense of security and forego the recommended screening." (T. Donahau, 2013) This would result in a decline in pap testing and as a consequence an increase of cervical cancer.
HPV is usually cleared by the immune system in 90% of cases (Luciano Mariani, 2010) although it can take extended periods of time (months to years). The immune system responds to HPV infection by releasing type-specific antibodies to the most accessible epitopes (recognisable sections of the virus such as E6 and E7 proteins) which in turn are recognised by T-cells (including cytotoxic T-cells and T-helper cells which signal production of macrophages and antibodies) which work to destroy both the virus-infected cells and the internalised pathogens using macrophages. (Davidson College DOB, 2006)
Health Issues:
There are no major health issues associated with the HPV vaccine however like all vaccines the HPV vaccine may have certain side effects (NPS, 2013) such as:
Soreness, redness and swelling at the injection site
Mild Headache
Mild Nausea
Muscle and Joint Pain
Note: These side effects are in reaction to the extra chemicals within the vaccine and not the L1 capsid protein fragments (NPS, 2013).
Importance of HPV vaccination for herd immunity
Firstly: What is herd immunity?
"Herd immunity is a form of immunity that occurs when the vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immunity." (Vaccines Today, 2013)
Importance of HPV vaccination for herd immunity
Herd immunity through the use of vaccination helps to inhibit the spread of the HPV virus as there are less people who are susceptible to being carriers of the virus. There is only a very small chance of an outbreak because those few that are susceptible to the HPV virus are 'protected' by those who are immune to the HPV virus. (Vaccines.gov, 2013)
1. Immunopaedia.org 2010, Immunology, Infections: Human Papiloma Virus (HPV), available at http://immunopaedia.org.za/index.php?id=799 [accessed on: 10/07/2014]
2. Swiss Institute of Bioinformatics (SIB) 2010, General: Alphapapillomavirus, available at http://viralzone.expasy.org/all_by_species/187.html [accessed on: 10/07/2014]
3. Centers for Disease Control and Prevention (CDC) 2014, Sexually Transmitted Diseases (STDs), Human Papillomavirus (HPV), Facts & Brochures, available at http://www.cdc.gov/std/hpv/stdfact-hpv.htm [accessed on: 10/07/2014]
4. STDealWithIt.com 2012, STD treatment reviews, available at: http://stdealwithit.com/genital-warts-symptoms [accessed on: 10/07/2014]
5. Interaction of human papillomaviruses with the host immune system: A well evolved relationship by Ian Fraser 2009, available at: http://www.sciencedirect.com/science/article/pii/S0042682208006624 [accessed on: 11/07/2014]
6. Davidson College Department of Biology 2001, HPV, Cellular Response, available at: http://www.bio.davidson.edu/people/sosarafova/assets/bio307/emmccracken/page%2004.html [accessed on: 11/07/2014]
7. HPV vaccine: an overview of immune response, clinical protection, and new approaches for the future by Luciana Mariani and Aldo Venuti 2010, available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988719/ [accessed on: 11/07/2014]
8. National Cancer Institute (NCI) 2005a, Understanding Cancer Series, available at: http://www.cancer.gov/cancertopics/understandingcancer/HPV-vaccine/AllPages [accessed on: 10/07/2014]
9. National Cancer Institute (NCI) 2005b, Understanding Cancer Series, available at: http://www.cancer.gov/cancertopics/understandingcancer/immunesystem/page34 [accessed on: 11/07/2014]
10. Cancer Council (CC) 2013, HPV Vaccine Fact Sheet, available at: http://www.cancercouncil.com.au/1060/cancer-information/cancer-risk-and-prevention/screening-and-early-detection/cervical-cancer-vaccine-fact-sheet/ [accessed on: 11/04/2014]
11. AS04-adjuvanted Human Papillomavirus-16/18 Vaccination: Recent Advances in Cervical Cancer Prevention by Tino Schwartz 2008, available at: http://www.medscape.com/viewarticle/584810_2 [accessed on: 11/07/2014]
12. HPV - immune response to infection and vaccination
by Margaret Stanley 2010, available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161350/ [accessed on: 11/07/2014]
HPV Vaccine Controversy: Ethics, Economics, and Equality
by Tanya Donahau 2013, available at: http://www.bu.edu/themovement/files/2012/06/HPV-Controversy-Tanya-Donahou.pdf [accessed on: 12/07/2014]
14. NPS MedicineWise 2013, Vaccines & Immunisation, Human Papillomavirus (HPV) Vaccine, available at: http://www.nps.org.au/medicines/immune-system/vaccines-and-immunisation/for-individuals/vaccines-a-z/human-papillomavirus-hpv [accessed on: 12/07/2014]
15. Vaccines Today The Blog 2013, available at: http://www.vaccinestoday.eu/vaccines/what-is-herd-immunity/ [accessed on: 12/07/2014]
16. Vaccines.gov 2013, Basics, Protection, Community Immunity ("Herd Immunity"), available at: http://www.vaccines.gov/basics/protection/ [accessed on: 12/07/2014]
(Immunopaedia.org, 2010)
(Immunopaedia.org, 2010)
(SIB, 2010)
STDealWithIt.com (2012)
(NexiImmune, 2014)
(Influenza Report, 2009)
(NCI, 2005b)
NCI, 2005a
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