Hpv vaccines will they prevent cervical cancer - Free Essay Example

Sample details Pages: 33 Words: 9883 Downloads: 5 Date added: 2017/06/26 Category Statistics Essay Did you like this example? HPV Vaccines: Will They Prevent Cervical cancer Introduction Human papilloma viruses (HPV) belong to the papillomaviridae family, they are double stranded DNA viruses. HPV is the most common sexually transmitted infection (STI) in the world (Urman et al. 2008). Don’t waste time! Our writers will create an original "Hpv vaccines: will they prevent cervical cancer" essay for you Create order HPV is strongly associated with cervical cancer; more than 99% what are the other causes/factors please of cervical cancer cases are positive for HPV DNA and indeed, cervical cancer is the second most common malignancy in the world (Wang et al. 2007). In developed countries the incidence of cervical cancer has been reduced significantly by the introduction of a cervical screening programme. In developing countries where 83% of mortalities due to cervical cancer occur, there are no such programmes (Parkin et al. 2006). Can the introduction of a vaccine against HPV further reduce globally the incidence of cervical cancer? Many diseases caused by viruses are controlled in the developed world by ongoing successful vaccination programmes; Polio, Measles, Mumps and Rubella are a few examples. Smallpox caused by Variola virus was eradicated in 1979 through a successful worldwide vaccination programme. The factors that affect the Polio and MMR vaccine programmes success and those that affected the successful smallpox programme may also be contributory to the success of the HPV vaccination program. Vaccination of HPV is complex and multi factorial. This investigation studies a number of factors including: * Vaccine efficacy * Vaccine Cost/affordability/practicality of administration * Production and Distribution * Government backing and financial commitment * Other support organisations such as the WHO, UNICEF, Gates Foundation, * Social factors * Media effects * Public awareness * Safety, and perceived fears Currently two prophylactic vaccines against HPV types 16 and 18, the most prevalent causes of HPV have been approved by the food and drug administration (FDA). Many developed countries have already introduced vaccination programmes using one of these vaccines. Can the vaccines and programme prevent cervical cancer? In order to effectively understand the implication of such a vaccination programme we must first fully examine the causative agent (HPV) and the consequential potential diseases including the biology, history and prevalence. Human Papillomavirus Approximately 200 types of HPV are identified of which around 40 infect the genital tract (McCance 2004). The majority of HPV types cause no symptoms, some types can cause warts and a minority may lead to cancer. Genital HPVs are transmitted via sexual contact, mainly intercourse, with an infected individual, and the risk of developing an HPV infection generally increases with the number of sexual partners, the sexual history of that partner or the introduction of a new sexual partner. Studies have shown that at least one type of HPV infection occurs soon after sexual debut, with around 30% of women infected with at least one high risk type within two years (Winer et al 2003; Winer et al 2008). HPVs are classified as either high risk or low risk, on the basis of association with cervical cancer. There are 15 types classified as high risk and three as probable high risk. High risk types include 16,18,31,33,35,39,,45,51,52,56,58,59,68,73,probable high risk types include 26,53,66 Low risk types include 6,11,40,42,43,54,61,70,72,81 and CP6108. More than 99% of cervical cancers are associated with HPV, of these 70% are associated with HPV type 16 and 18, with HPV 16 causing 50% and HPV 18 causing more than 15% in Europe (Smith et al..2007). HPV 16 is thus the single, most common high risk HPV. Interestingly HPV types 16 and 18 also cause 80% of anal cancer and 30% of vaginal and why the difference in % oper area research needed here.vulvar cancer and are associated with cancers of the, oropharynx and some rare cancers of the head and neck. (add reference form cervical cancer burden worldwide paper) The majority of HPV infections are asymptomatic, self limiting, and transient, with 70% of new HPV high risk type infections cleared within one year (with the median duration of an infection at 8 months) and 90% within two years (Ho et al 1998). The transient infection usually causes no clinical problems. A small proportion of high risk type infections persist due to host immune evasion, an evasion that results not only from restriction of HPVs to sites that are relatively inaccessible to host defences but also due to several mechanisms of preventing immune response what are these mechanisms please (a sk Dick if this is what he means . This persistence is the most important factor in the development of pre cancerous and cancerous lesions. The time span between infection by HPV and the development of pre cancerous lesions or cervical carcinoma varies from one to ten years (Moscicki et al 2006) and up to 20 years from other sources. HPV show little evidence of dramatic adaptability with phylogenic studies suggesting that the biology of HPVs has remained the same for over 200,000 years (Halpren et al 2000). While HPVs show historically the influence of point mutations, inserts, deletions and duplications, the predominant pattern of mutation within a given type is point mutation, with large scale rearrangements within the most conserved genes of HPVs such as L1 being rare (Myers et al 1996). Intra patient variation within HPV types is uncommon due to their low mutation rate. This low mutation rate is directly linked to the HPV replication strategy that requires host cell machinery, which has stringent proof reading mechanisms that avoid the incorporation of errors, conferring slow mutagenesis. All HPVs exhibit extreme specificity for infection of epithelial cells and do not infect or express their gene products in the underlying dermis. Although the mechanism of infection is not fully understood, the HPV epitheliotrophy resides for the most part in the interaction of specific transcription factors with the viral regulatory region known as the long control region (LCR). Infection with HPV can result in hyperproliferation of the host cell, and with certain high risk HPV types it may lead to transformation and immortalization. This is because high risk HPVs express two or more protein products (E6, E7 and E5) that transiently disrupt the cell cycle and stimulate cell division, knocking out at the same time the cellular mechanisms for growth inhibition. For a productive infection, HPVs require terminally differentiated cells. This HPV biology feature has impeded studies on the full reproduction life cycle because of the lack of highly efficient models of epithelial terminal di fferentiation in vitro. Most of the different stages in the HPV life cycle have been established using genetic engineering and molecular biology strategies. The dsDNA of HPV exists in a non enveloped icosahedral shaped virion 52-55 nm in diameter. The dsDNA genome is circularised and around 8000base pairs in length (Fig1). The genome encodes eight proteins, six early E1, E2, E4, E5, E6, E7, and two late structural proteins L1 and L2 and the previously mentioned noncoding LCR. Fig 1 HPV type 16 Genome structure, gene and functional domain location https://www.dnachip-link.com/Eng/library/HPV.aspusg 15/11/20009 Fig 1 shows the dsDNA genome of HPV type 16, and the location of the early and late genes along with the LCR that contains the origin of replication. An initial infection requires the access of infectious particles to the basal layer of the epithelium. Some HPVs require a break in the stratified epithelium to achieve this. Such breaks are not necessarily obvious and may occur under conditions where the skin is exposed to water or abraded, or subjected to an environment where micro traumas may occur such as possibly in aswiming pool or ect (must put an example)(in fig 2 shows as a cut). Following infection and uncoating it is thought that the virus maintains its genome as an episome in low copy numbers within basal cells of the epithelium. Although the pattern of gene expression in these cells is not well understood, it is generally thought that viral proteins E1 and E2 are expressed to maintain the viral DNA episome (Wilson et al.2002) and possibly to facilitate the segregation of genomes during cell division (You et all.2004). It is not known whether viral transformation proteins E6 and E7 are also expressed in the basal layer, but it does appear that initial infection is followed by a proliferative phase that results in the increase in the number of basal cells harbouring viral episomes. In normal uninfected epithelium, basal cells leave the cell cycle soon after migration into the superbasal cell layers where they undergo a process of terminal differentiation. During infection E6 and E7 are expressed in these cells stopping normal differentiation (Sherman et all.1997). E6 and E7 are believed to work together to achieve this and in lesions caused by high risk HPV types. During a natural infection the ability of E7 to stimulate S-phase progression is limited to a subset of differentiated cells with low levels of p21/p27, or which express high enough levels of E7 to overcome the block in S-phase entry. The viral E6 protein is thought to prevent apoptosis in response to unscheduled S-phase entry brought on by E7. The association of E6 with p53 and the inactivation of p53 mediated growth suppression and apoptosis is well documented, E6 may also associate with other pro-apoptotic proteins including bak (Thomas and Banks,1998) and bax (Li and Dou,2000). E6 is thus considered a predisposing factor in the development of HPV associated cancers, allowing the accumulation of chance errors in host DNA to go unchecked. Furthermore the E6 protein of high risk HPVs can stimulate cell proliferation independently of E7 via a c-terminal PDZ ligand binding domain. E6 PDZ is enough to mediate superbasal cell proliferation and may contribute to the formation of metastatic tumours by disrupting normal cell adhesion (Nguyen et al.2003) Amplification of the viral genome and the ability to package these genomes into infectious particles is essential for the production of infectious virions. For most HPV types this occurs in the mid or upper epithelial layers following an increase in activity of the late promoter. The late promoter gene is located within the E7 open reading frame, and the upregulation of the late promoter is thought to lead to increased expression of proteins involved in viral DNA replication, without directly affecting the expression of E6 or E7 necessary for S-phase entry. The amplification of the viral genome begins in a subset of cells in the proliferative compartment and requires the expression of all viral early gene products, these include E4 and E5 whose role in replication is not yet clearly understood. Binding of E2 to the HPV upstream regulator region is essential for viral DNA replication that is dependent on the differentiated state of epithelial cells. E2 recruits the E1 DNA helicase to the viral origin of replication. Throughout the virus life cycle, the relative levels of viral proteins are controlled by promoter usage and by differential splice site selection, with an increase in E1 and E2 allowing an increase in viral copy numbers in the upper epithelial layers. Current models suggest that a small increase in promoter activation during differentiation may lead to an increase in the level of E1 and E2 and a subsequent increase in genome copy number. The newly replicated genome could then serve as a further template for expression of E1 and E2, facilitating the amplification of viral genome and in turn further expression of E1 and E2 replication proteins. Viral DNA remains latent (not integrated) in basal cells of benign lesions. Replication occurs in the differentiating cells where capsid proteins and viral particles are found. Viral DNA is integrated in cancer cells, which contain no replicating virus. Once viral genome replication is completed, the expression of two virally encoded structural proteins, expressed in the upper layers of infected epithelia may occur. L1 the major capsid protein is expressed after L2 in a sub set of cells that express E4 (fig 2), this allows the assembly of infectious particles in the upper layers of the epithelium (Florin et al.,2002). A successful infection requires the virus to escape from the infected skin cell and survive extracellularly prior to re-infection. HPVs are non-lytic and are as such not released until the infected cells reach the epithelial surface. The intracellular retention of HPV antigen until the cell reaches the uppermost epithelial layers may contribute the compromised immune detection, especially as the virus has molecular mechanisms that limit the presentation of viral epitopes to the immune system in the lower epithelial layers (Ashrafi et al 2002). What are these mechanisms Figure 2 Papillomavirus type 16 Life Cycle and gene expression location within epithelium Taken from, The papillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Figure 2 diagrammatic representation of the skin with HPV type 16 gene expression incorporated, colour of arrows are representative of genes expressed within epithelial cells. The frequent detection of high risk HPV DNA in cervical lesions in the absence of any obvious disease, may be explained by the presence of the virus in a latent state, with only very few cells able to support the productive virus life cycle during epithelial cell differentiation. Following immune regression, HPV DNA is thought to remain in the basal epithelial cells waiting to be reactivated once levels of immune surveillance decline there are conflicting opinions (Zhang et al.1999). If regression is not achieved lesions may persist and in some instances progress to cancer. The number of lesion that progress to cancer is very low when compared to the prevalence of high risk HPV infection in the general public. The Progression of productive lesion to high grade lesions may result from the deregulation ( what happen to allow thes proteins to be deregulated intergrattion loss of E2 adn p53 association, be specific add biochemistry here please. in the expression of transforming proteins E6 and E7. The inability of a cell to support the whole virus life cycle is often associated with the development of cancerous lesions. The transformation zone (Fig 3) is particularly susceptible to cervical cancer; it appears that high risk types of HPV such as type 16 cannot complete their life cycle at this site Progression from CIN3 to cancer usually occurs in lesions that contain integrated copies of the viral genome in which E7 expression is elevated. Suggesting that retention of E6 and E7genes and the loss of E2 and E4 genes (that exert negative effect on cell growth) usually accompanies the development of invasive cancer. (reference) Remember for CIN refer to in that section or here but Cin must be corrulated with what causes the cancer and with whats happening with the virus that causes the change in CIN or the causes in CIN to occur. Cervical cancerisa considerable contributor to morbidity and mortality. Being the second most common cancer worldwide and the twelfth most common cancer in women in the UK. Cervical cancer in 2002 was the cause of 274,000 deaths worldwide (the most current data available)REF THIS FIGURE and continues to causes more than 1000 deaths in the UK each year. There are two main types of cervical cancer squamous cell cancer (the most common) and adenocarcinoma, although they are often mixed. They are named after the types of cell that become cancerous through neoplasia. Squamous cells are flat cells covering the cervix; adenomatous cells are found in the passageway from the cervix to the womb. Other rarer cancers of the cervix include small cell cancer. Deaths from cervical cancer in the UK have fallen over the last 20 years mainly because of the NHS cervical screening programme that reduced the mortality rates by 62% between 1987-2006. Screening may detect changes in the cells of the cervix at a pre-cancerous stage. Fig 3 TITTLE Showing location of transformation zone. Cell samples are examined for abnormalities, these abnormality are described in a standard format covering cytology and/or histology. What are these standard format CIN 1 CIN2 CIN3 LISL LGSIL HSIL HGSIL USE FIG 4 and explain whats happening with the proteins expressed and genome intergration where CIN number progression is concerned please. MUST DO From Lowy Schiller, J Clin Invest, 116:1167-73, 2006 Low grade squamous intraepithelial lesion (LSIL or LGSIL) indicates possiblecone biopsy, or laser ablation. High grade squamous intraepithelial lesion (HSIL or HGSIL) indicates moderate or severeCIN 2 or CIN3 (fig 3). While cervical screening has reduced the mortality significantly in the developed world cervical cancer is still a significant burden worldwide. Fig 4 Taken from, The popillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Fig. 5. CIN 1 resembles productive infections caused by other HPV types and as such is the most benign form of cervical intraepithelial neoplasia , it is confined to the basal 1/3 of the epithelium, CIN 2 Moderate dysplasia confined to the basal 2/3 of the epithelium,CIN3 Sever dysplasia that spans more than 2/3 of the epithelium, and may involve the full thickness. INCIDENCE An estimated 493,000 new cases and 274,000 deaths in 2002 were caused by cervical cancer. The vast majority, some 83% of these cases, occur in developing countries, where cervical cancer amounts to 15% of female cancers with a risk before age 65 of 1.5%. In developed countries cervical cancer accounts for only 3.6%, with a risk of 0.8% before age 65. REF The highest incidence rates are observed in Sub-Saharan Africa, Melanesia, Latin America and the Caribbean, South-Central Asia, and South East Asia (fig 6) Fig 6 Worldwide Burden of HPV related Cervical Cancer Figures from 2002. Parkin MD et al 2006 The burden of HPV-related cervical cancers The vast majority of cervical cancers are squamous cell carcinoma adenocarcinomas being less common (fig 6). Generally the proportion of adenocarcinoma cases is higher in areas with low incidence of cervical cancer, accounting for up to 25% of cases in western countries (fig 6). This higher incidence of adenocarcinoma may be partially explained by cytological screening, which historically, had little effect in reducing the risk of adenocarcinoma of the cervix, because these cancers, and their precursors, occur within the cervical canal, and were not readily sampled by scraping of the epithelium of the ectocervix. Fig 5 Fig 5 showing the higher % of adenocarcinoma in counties that have screening programmes such as the UK and Denmark What is this showing? Make it clear.do you really need it. MORTALITY RATES Mortality rates are substantially lower than incidence rates. Worldwide 55% (could you double chek that this is the case please misses) of all those that develop the disease die, the figures vary significantly from the developed to the developing world. Low risk regions of the west such as Europe have a death rate of 37% while in developing countries where many cases present at relatively advanced stages, death rates are significantly higher increasing to 70%. Cervical screening programmes in the developed world identify pre-cancerous lesions at a stage where they can be easily treated accounting for the difference in mortality rates. TITTLE IF and figure number staying and refer to in text As cervical cancer affects a relatively high number of young women, it is a significant cause of years of life lost (YLL) in the developing world. Yang et al 2004 found that cervical cancer was responsible for the 2.7 million (age weighted) years of lives lost world wide in 2000, and that it is the single biggest cause of years of life lost from cancer in the developing world. In Latin America, Eastern Europe and the Caribbean, cervical cancer makes a greater contribution to YLL than disease such as Tuberculosis or AIDS. HPV is also associated with many other forms of cancer that could possibly be prevented with use of HPV vaccines; cancers of the penis, anus, vulva, vagina, oropharynx and some rare cancers of the head and neck are included. However cancer of the cervix is by far the most significant, in terms of incidence and mortality (table 1). Cancer of the vulva and vagina have a significantly lower incidence rate compared to cervical cancer, however since 80% of the incidence are caused by HPV types 16 or 18 women vaccinated against these types would also be protected against these forms of cancer. Incidence of squamous cell carcinoma of the anus are twice as common in females as males with HPV types 16 and 18 accounting for 83% of all cases. There is a particularly high incidence of anal cancer among homosexual males, shown by the high incidence rate in populations such as Sanfransisco, where gay incidence are higher than average (fig 7). Globally cancer of the penis is relatively rare accounting for 0.5% of cancers in men (table 1). HPV DNA is detectable in 40-50% of all penile cancers and serological studies have confirmed the role of HPV 16 and 18 (IARC 2005). Cancers of the mouth and oropharynx caused by HPV are very low at 0.06% of all cancers with 0.05% being caused by HPV types 16/18. Due to the small size of most studies and the absence of comparable measurements of prevalence of infection in normal subjects conducted for cancers of the vulva, vagina, penis and anus true prevalence is difficult to quantify. The figures shown in table 1, imply that we are dealing with a virus that discriminates primarily through disease aginst women, in particular young women. Gay men, however are also clearly an at risk group. Currently only young women are vaccinated aginst HPV types 16 and 18, however the JCVI (joint committee on vaccination and immunisation) have noted that the vaccines has not been conclusively trialled on men, and that there is insufficient evidence that the vaccine available would protect against anal, penile or head and neck cancer. However when more data becomes available they will consider vaccinating, high risk groups such as men who have sex with men. Add what this implies for prophylactic use of vaccine with other cancers cause by HPV And what you think about the ue of vaccine on highrisk men and its effectivity against other cancers caused by HPV types 16 and 18. Fig 7 TITTLE add Figure 6 showing that cancer of the anus are more prevalent in women than men with the major noted exception being San Francisco, where the increased incidence can be explained by a large number of homosexual men. HPV INFECTION-ATTRIBUTABLE CANCER IN 2002: BY SEX AND HPV TYPE Table 1 MALES SITE ATTRIBUTABEL TO HPV % OF WHICH HPV TYPES 16 AND/OR 18 % TOTAL CANCERS ATTRIBUTABLE TO HPV ATTRIBUTABLE TO HPV THYPES 16/18 CERVIX 100 70 0 0 0 PENIS 40 63 26,300 10,500 6600 VULVA/VAGINA 40 80 0 0 0 ANUS 90 92 14,500 13,000 12,000 MOUTH 3 95 175,900 5200 5000 OROPHARYNX 12 89 42,500 5100 4500 ALLL SITES 5,801,800 33,900 28,100 Table 2 FEMALES SITE ATTRIBUTABEL TO HPV % OF WHICH HPV TYPES 16 AND/OR 18 % TOTAL CANCERS ATTRIBUTABLE TO HPV ATTRIBUTABLE TO HPV THYPES 16/18 CERVIX 100 70 492,800 492,800 344,900 PENIS 40 63 0 0 0 VULVA/VAGINA 40 80 40,000 16,000 12,800 ANUS 90 92 15,900 14,300 13,100 MOUTH 3 95 98,400 2,900 2,800 OROPHARYNX 12 89 9,600 1,100 1,000 ALLL SITES 5,060,700 527,200 374,700 Table 3 BOTH SEXES TOTAL CANCERS ATTRIBUTABLE TO HPV % OF ALL CANCERS ATTRIBUTABLE TO HPV TYPES 16/18 % OF ALL CANCERS 492,800 492,800 4.54 344,900 3.18 26,300 10,500 0.10 6600 0.06 40,000 16,000 0.15 12,800 0.12 30,400 27,300 0.25 25,100 0.23 274,300 8,200 0.08 7,800 0.07 52,100 6,200 0.06 5,500 0.05 10,862,500 561,100 5.17 402,900 3.71 VACCINATION An effective vaccine should stimulate a suitable range of immune responses, mimic or improve on the protection gained from a wild type infection with little side effects. Critically the vaccine should be inexpensive, easily administered, transported and stored to further reduce cost and maximise convenience, this is especially relevant in the case of HPV vaccine as those that are not protected by the screening programmes of the developed world would benefit the most, ease of administration and storage is paramount in the developing world as stability and healthcare is more sporadic, and people are often more remote. There are many different kinds of vaccines available, and different vaccines have a variety qualities and limitations. Live attenuated vaccines contain a version of the pathogenic microbe that is avirulent, they often elicit an excellent cellular and antibody response with good longevity that can be lifelong with few doses. However there is always the possibility that the vaccine may revert to its virulent form, causing disease. For this reason a live attenuated vaccine is not appropriate for use against oncogenic HPV types. Recombinant vaccines can include one or more proteins that may illicit an immune response. A process has been developed to allow the removal of the genome from an attenuated or avirulent viral vector allowing the insertion of selected genetic material or proteins from another virus. The carrier viruses then ferry that viral DNA into host cells where the genes are expressed. Recombinant vaccines closely mimic a natural infection and therefore illicit a strong immune system. Inactivated vaccines are produced by killing the disease causing microbe by chemical (formaldehyde eg just double check), heat or radioactive means. These vaccines are more stable than live vaccines, and as there is no risk of reversion to virulence. They are also safer than live vaccines. Most inactivated vaccines stimulate a weaker immune response than live vaccines and several doses or boosters may be required to maintain immunity. DNA vaccines dispense with both the whole organism and its parts. They only include the essential part of the microbes genetic material. In particular, DNA vaccines use the genes that code for immunogens. Researchers have found that when the genes for a microbes antigens are introduced into the body, some cells will take up that DNA. The DNA then instructs those cells to make the antigen molecules. The cells secrete the antigens and display them on their surfaces. In other words, the bodys own cells become vaccine-making factories, creating the antigens necessary to stimulate the immune system. A DNA vaccine against a microbe would evoke a strong antibody response to the free antigen secreted by cells, and also stimulate a strong cellular response against the microbial antigens displayed on cell surfaces. The DNA vaccine is unable to cause disease because it does not contain the microbe, only copies of a few of its genes. In addition, DNA vaccines are relatively easy and inexpensive to design and produce. It is likely that several doses or boosters would be required to maintain immunity. DNA vaccine are still in development and currently no one are licensed for use although they show great promisedouble check please. A subunit vaccine includes only the antigens that best stimulate the immune system. In some cases the vaccine uses epitopes. Subunit vaccines do not contain whole microbes or genetic information, reducing the chances of an adverse response significantly. Sub unit vaccines may include several antigens. In the case of Cervarix two different subunits are included, and in the case of Gardasil four different subunits are included. Identifying which antigen best stimulates the immune system can be problematic, once achieved subunit vaccine can be, made in one of 2 ways: 1)The microbe can be grown in the lab to high titres; chemicals (what chemicals)are used to break the microbe apart allowing the gathering of the relevant antigen. 2)Antigen molecules can be manufactured form the microbe using recombinant DNA technology. Vaccines produced in this way are called recombinant subunit vaccines Both Cervarix and Gardasil are recombinant subunit vaccines. WHAT are VLPs discuss these please And the process of making Cervarix and Gardasil Biochemical detail to include explanation of bacalovirus system and wehat genes they insert and how they do it. Full explanation please misses x x VACCINE USE Insert table of available vaccines There are several examples of diseases that have been controlled through successful vaccination programs (table 2) , the most successful and the only disease to have been eradicated is smallpox. Table 2 TITTLE Virus Administered Attenuated Inactivated Recombinant/Sub-unit Hepatitis A im X Hepatitis B im/sc X Influenza im X Japanese Bencephalitis sc X Measles, Mumps, Rubella (MMR) im X Poliovirus o/im X X Rabies im X (X) Smallpox sc X Tick-borne encephalitis im X Varicella-Zoster im X Yellow fever sc X Papilloma virus (16,18) im X Rotavirus oral X Refferncve source is DIDcks lectures can I really do this The vaccine for smallpox is a live virus preparation of vaccinia virus. The antibodies produced by/against vaccinia are cross reactive for smallpox. Vaccinia virus infection is very mild and is typically asymptomatic in healthy individuals check ther are someside effects. Live vaccinia virus vaccine can not cause small pox infections as it does not contain small pox DNA, so the risk that comes with a live attenuated vaccine does not apply here as the vaccine cannot revert to virulence. Estimated vaccine cost per vaccination in developing countries was 10 cents per vaccination, this very low cost allowed worldwide access. Freeze dried vaccine was mass produced in many countries reducing the risk of vaccine shortages, and the potency and stability of the vaccine was essential in the success of the programme. Novel administration techniques helped drive down the cost and expertise required; development of a new type of needle that could be reused after boiling contributed significantly. Success of the small pox eradication programme was also related to political commitment and leadership in the form of the World Health Organisation (WHO) and the Centres for Disease Control (CDC). Organisation of people on the ground by the WHO maintained motivation and focus, with small numbers of highly committed knowledgeable people, able to motivate large numbers of staff successfully, even in unstable areas and the poorest countries. This would have been more of a challenge without the backing received from many governments. Fig 8 TITTLE PLEASE When eliminated from more developed countries, public awareness was a key factor, with posters (fig 8) and leaflets used to educate the public about the dangers of small pox and encourage them to take up the vaccine. A combination of good science, outstanding organisation, focused monitoring, international commitment through governments, the WHO and CDC, coupled with high public awareness and low cost, easy administration of the vaccine was critical in the success of the smallpox eradication programme. There are elements directly linked to the smallpox virus that also helped in the eradication. Could say this bit in red more scientificallySmallpox has no zoonotic reservoir and as such only needed to be eradicated from humans to completely eradicate the disease. There is also only one strain of the virus that mutates very slowly, giving us the opportunity to succeed with the eradication before significant mutagenesis could occur. POLIO The introduction of a polio vaccine reduced the worldwide incidence of polio from an estimated 350,000 cases in 1988 to 1,652 cases in 2007. There are two vaccines used against polio, an oral live attenuated vaccine and an inactivated vaccine administer intramuscularly. The oral vaccine is easy and cheap to administered, an oral polio vaccine (OPV) is also advantageous in this case, as the virus replicates primarily in the gut, mimicking a true infection successfully. The attenuated strain of the vaccine may also be transmitted from person to person within the community providing wider protection than just those vaccinated. In regions without wildtype poliovirus, inactivated polio vaccine is the vaccine of choice. In regions with higher incidence of polio, and thus a different relative risk between efficacy and reversion of the vaccine to a virulent form, live vaccine is still used. The live virus also has stringent requirements for transport and storage which are a problem in some hot or remote areas. As with other live-virus vaccines, immunity initiated by OPV is likely to be lifelong. Is POLIO vaccine expensive? Poliovirus has no zoonotic reservoir and survival of the virus in the environment for an extended period of time is remote. Therefore similarly to smallpox, interruption of person-to person transmission of the virus by vaccination is the critical step in global polio eradication. These two vaccines and the implementation of their programmes haveeradicated poliofrom most previously endemic countries of the world. Public awareness was raised by poster, leaflets, radio, television and personal appearance of the character Well bee (fig 9) at public events in the United States. Fig 9 Public awareness poster for Polio Vaccination https://en.wikipedia.org/wiki/File:Polio_vaccine_poster.jpg Fig 9 poster of the CDC Well bee used in the US in the 1960s to raise public awareness of the polio vaccine The WHO in conjunction with UNICEF are hoping to eradicate polio as they did with smallpox, their campaign is ongoing. Only a handful of endemic countries remain; Afghanistan, India, Nigeria and Pakistan. The proposed deadline for eradication has been revised on a number of occasions due to financial and logistical issues surrounding the task. Measles Mumps Rubella (MMR) The MMR vaccination is given as part of the government immunisation programme in the UK. The MMR vaccine is a live attenuated vaccine that protects against Measles Mumps and Rubella. The fact that the vaccine is a combination vaccine means reduced administration costs. Even though the vaccine is given in the UK as a matter of course to children, when concerns surrounding its safety were raised and claims of connections between the vaccine and autism were made, a significant impact was seen on the uptake rate of the vaccine. In turn this meant increased incidence disease especially where measles is concerned. MMR is a good example of how a vaccination programme can be hit hard due to the public perception of risk and safety, even when the cost of vaccine and administration is low, government support and strategy of administration is well established, and efficacy of vaccine is high. There are posters and leaflets available for information on the safety and efficacy of the MMR vaccine. However it may take a significant amount of time to restore public faith in the MMR vaccine. Unfortunately the perceived safety of all vaccines can be adversely affected by media coverage, whether they are based on founded or unfounded data. THE VACCINES Insert introductory paragraph about why we need teh vaccine all you have said so far Is teh evidence for this. Must also describe The way in which they produce the vaccine background to development must also be included. Plenty of data on both Cervarix and Gardasil on your desk topo including info about how its made and the clinical trials and production of the vaccine C and P According to WHO, there were 510000 cases of cervical cancer in the world resulting in 288000 deaths each year. India has a higher burden with 130000 new cases and 75000 deaths each year due to cervical cancer. India has 25% of the global cervical cervical cancer burden by number of patients and deaths. Recent CDC data indicates that over 20 million Americans are already infected with human papilloma virus and 6.2 million new cases are detected every year. Each year 11000 cases of cervical cancer resulting in 4000 deaths in the US. Over 70 % of cervical cancer is caused by 2 strains of HPV 16 and 18 and 90% of anogenital warts are caused by 2 strains of HPV, 6 and 11, all four of these strains can be prevented by a quadrivalent vaccine Gardasil. About 1% of sexually active men have genital warts and over 10,000 women develop other types of genitalcancer due toHPV infectionseach year. Genital contact favors HPV transmission and spreads infection. In most of the cases (70-90%)our immun e system can overcome HPV infection and eliminate infected cells. Herald zur Hausen in Heidelberg during the 1977-1980 period, first isolated the HPV type 6 in human genital warts and later detected the presence of HPV 16 in 50% of cervical cancer cells and HPV 18 in 17-20% of cancer cells. The advent of PCR resulted in rapid detection of the HPV types in cervical cancer and so far over 106 types of viruses have been described. A pharmaceutical company turned down zur Hausen request to develop a vaccine in 1984. It was only in 1991 that the idea of HP virus as a leading cause of cervical vaccine was accepted and industry started development of HPV vaccine. The Nobel Laureate in his recent lectures has mentioned 500000 deaths per year from cervical cancer and 21% of global cancer burden due to chronic infections. https://knol.google.com/k/cervarix-glaxo-smith-kline-vaccine-for-cervical-cancer# Cervarix produced by Glaxo Smith Kline (GSK) and Gardasil produced by Merck are the two currently approved vaccines. Both are recombinant subunit vaccines made from the major capsid protein L1. Cervarix is a bivalent vaccine that targets HPV 16 and HPV 18 collectively responsible for 70% of cervical cancers. Gardasil is a Quadrivalent vaccine that targets HPV 16 and HPV 18, plus HPV type 6 and 11 responsible for more than 80% of genital warts. Both vaccines have been shown to be effective in preventing persistent infection with the targeted HPV types and in preventing cervical intraepithelial lesions. Virus like particles that form from the recombinant L1 protein mimic the native virus structure, but contain none of the viral DNA, meaning they cant infect cells or replicate within them. NOT enough information here refer to above HPV vaccines are highly effective; in clinical trials both Cervarix and Gardasil were over 99% effective at preventing pre cancerous and cancerous lesions caused by types 16/18 in young women (Harper et al 2006). How do we know how effective they are, how were they measured clinical trial information is on your desktop use this please. Both vaccines prevent infection by generating neutralizing antibodies against L1, blocking incidence infection. The vaccines use different adjuvants; Cervarix uses a new type of adjuvant, which GSK believes enhances its effectiveness, while Gardasil uses a more conventional adjuvant. Mention different adjuvants and different imunnogenicity as a result in your fuller explanation of the vaccines and their composition how they are made and their efficacy please my lovely. Both vaccines are very effective at protecting from incident infection with types 16 and 18. Although research funded by Gsk showed in a head to head trial that included more than 1100 women aged 18-45 that women who receive Cervarix had higher levels of antibodies than those receiving Gardasil 1 month after the final dose. Type 16 showed that levels induced by Cervarix were twice as high as Gardasil and for type 18 were more than 6 times higher. GSK claim that the new type of adjuvant used in their vaccine is partially responsible for the enhanced immune response. Several studies conducted with Cervarix showed more than 90% efficacy against incident infection (Harper.D.M et al 2004), (Harper.D.M et al 2006),100% efficacy against persistent infection (Harper.D.M et al 2004 )(Harper.D.M et al 2006), and 90.4% to 100% efficacy against HPV types 16 and 18 related CIN (Harper.D.M et al 2006).The vaccine was shown to be highly immunogenic with more than 98% seropositivity after 4.5 years (Harper.D.M et al 2006) now extended by Gsk to 7.3 years of sustained protection in women aged 15-25. Cross protection against incident infection with high risk HPV types 45 and 31 (types 16/18/31/45 account for more than 90% of cervical cancer cases) has also been seen with Cervarix (Harper.D.M et al 2006). As longevity of protection is not yet fully elucidated the need for a booster injection and its frequency if need is yet to be established; phase four trials are ongoing. For Gardasil estimations are that the vaccine is between 70 and 100% effective, with the life time risk of cervical cancer reduced to 47% and 30% respectively, compared to 86% risk with the current screening programme alone (Doling TS 2008). The duration of efficacy of Gardasil is not yet known but studies show good efficacy for at least 5 years(Wang KL 2007). Similarly to Cervarix it has not yet been determined whether booster doses are required for Gardasil. Both vaccines were shown to be most effective when administered before sexual debut and subsequent initial infection. The history of HPV infection and cervical cancer development in younger populations is is well understood, this is not so for older women. Although the highest incident of infection is seen in adolescents and early adulthood followed by a gradual decline with age, there is still a significant risk of new infection in sexually active women of all ages. We know that the introduction of new sexual partner is an increased risk and this can happen at any age. When women developed antibodies against a natural infection, the level at peak are generally very low (Vicidi RP et al 2004). Data from phase three Gardasil trials, showed that of the women aged 24-45 only a very small percentage, 0.35% had serological or DNA evidence of all types covered by the vaccine. A study has shown that women seropositive had the same risk of subsequent infection as seronegative women after 5-7 years (Vicidi et al 2004). Another study found that the risk of acquiring a new HPV type does not decrease among those with prior infection by a related or unrelated type. Although higher levels of antibody titer were seen in the younger vaccinated women it appears that there is only a very small proportion of women, those who are seroposative for all types conferred by the vaccine that would not benefit by receiving a vaccination. Even those seroposative for all type protected against after five years would have little protection from a natural infection. The decision to only vaccinate young women seems to have been decided by the high cost of the vaccine. DEVLOOPMENT AND DISTRIBUTION section must be added Include polyvalent vaccine in the pipe line Therapeutic vaccines and combination vacines Growth vectors technology/plants ect to reduce cost This is not inthe correct location fit it in somewhere more appropriate. Both Cervarix and Gardasil (the two currently available vaccines) fail to meet some of the criteria seen to aid in the success of past and current vaccination programmes. Both are very expensive at a cost of more than ÂÂ £300 in total for all three doses when compared to the low cost of vaccines such as the MMR or the vaccine against polio. The high cost of the vaccine currently rules out its use in developing countries. The administration strategy for both is also more complicated with three doses required over 6 months. With all three doses required to achieve maximum efficacy, ensuring that all three are given is important and logistically complicate in developed countries, in developing countries especially those that have a high population migration due to public unrest this will be nearly impossible to achieve. As neither vaccine are live the longevity of immunity may also be in question in years to c ome, as of yet there is no answer to whether a booster vaccination will be required. Incudes portical for both vaccine administration MUST DO Both vaccines are very effective, but an effective vaccine is not enough on its own to prevent disease. Public awareness of the efficacy and safety of the vaccine has to be raised by education through health care professionals, schools, posters, and leaflets as seen with succesfull and ongoing vaccination progemmes for smallpox, polio and MMR. Say they are using Cervarix please The vaccination programme followed in the UK was devised and implemented following advice from the joint committee of vaccination and immunisation (JCVI). Vaccine groups were originally split into two separate cohorts: Routine and Catch up The routine cohort is 12-13 year old females (born between 1 September 1995 and 31st August 1996) The catch up cohort is 17-18 year old females (born between September 1st1990 and 31st August 1991). Vaccination uptake figuers for those aged 14-18 are yet to be released as the vaccination campaign is ongoing, and should be completed by the end of the academic year 2009/2010 and therefore this aged group is excluded from this investigation. An overlap for the catchup cohort exsits due to the moving forward of those aged 17-18 to be vaccinated in 2008-2009 to include greater numbers of young women. Vaccination for both routine and catch up cohorts was implemented for the academic year 2008-2009. A high uptake rate is important where vaccines are concerned with regard to achineving herd immunity. In this case as the vaccine is only being given to young girls herd immunity cannot be achived consequently a high uptake rate is even more important, as reservoir of high risk HPV types exists in men and older women. Vaccination uptake in both cohorts was monitored carefully. This monitoring will allow the Department of Health (DOH) to facilitate the effective management of HPV programmes at all levels. Most importantly it will allow in the future the ability to analyse the benefit of the vaccination programme against what may be falling cervical cancer rates. The vaccination was given as per protocol and the uptake figures achieved could improve, especially where those who did not complete the course are given another oppertuninty for vaccination in the academic year 2009-2010. Several factors have already been seen to affect the uptake rate of the vaccine. FACTORS AFFECTING UPTAKE RATE stop think about what your trying to show here before you re arrange and edit, how much detail do you need. What you need to cover Location Choice over-under 16 Canhge of dates ofr cathcup cohort The setting in which the vaccination was given had a significant effect on the uptake rate. (fig 8). Both cohorts were vaccinated in a number of different settings including the school environment, the local general practitioner (where letters were sent to invite for vaccination appendix 1) and in some STI clinics. This will be less of an issue once the catch up programme is complete as vaccination will mostly be given in the school environment where the highest uptake rates were achieved check and change figures number please Fig 8 http:[emailprotected]/* */[emailprotected]/* */[emailprotected]/* *//documents/digitalasset/dh_111676.pdf Fig 8 showing a high uptake rate in the school environment, graph shows that of the PCTs with higher uptake % the vast majority of the vaccines were given in the school environment. The third dose uptake rate seen is much lower (fig 9); perhaps due to the lesser convenience, or possibly due to the availability of less information to allow an informed decision to be made. Those over 16 do not require parental consent and as such may make their own decision; this too may have a significant bearing on the uptake rate. Fig 9 http:[emailprotected]/* */[emailprotected]/* */[emailprotected]/* *//documents/digitalasset/dh_111676.pdf Fig 9 Catch up cohort shows a much lower uptake rate with those in the higher % over 40% being given mainly in the school environment. The differnce in uptake rate was particullary noticable where the third dose of vaccine is concerned. Whys that then? A direct comparison between school based doses 1, 2 and 3 and GP based doses 1, 2 and 3 shows a greater coverage rate achieved by the school based programme when compared to the GP based programme. Lower uptake rate for doses 2 and 3 in the catch up cohort may be partially explained by a change in the dates for beginning the programme; dates were pushed forward to 2008/2009 form 2009/2010. PCTs were only notified in June 2008 that the programme had been pushed forward given them little time to prepare, this my partially explain the lower figures but not fully. Letters were sent (example letters in the appendix) to all girls registered within a PCTS that were eligible but could not receive the vaccine at school, as they had left or because the school was not offering it. Non compliant patients were sent second letters asking them to confirm or decline their interest (example letters in appendix). Second letters were also sent to all patients who had dose 1 but not dose 2 and 3 (appendix). Table 4 Annual UK HPV vaccine coverage for females aged 12-13 years by country, 2008/09 HPV vaccine uptake % Country Dose1 Doses 1 and 2 All three doses NI 89.6 85.9 83.9 Scotland 93.7 92.7 89.4 Wales 87.9 87.0 78.8 England 88.1 86.0 80.1 UK 88.6 86.6 80.9 Across the UK 80.9% of those 12-13 years eligible for the vaccine received all three doses (table 4), with the highest percentages reached in Scotland where a more school based strategy for administration affected their overall uptake rate favourably. When uptake rates are compared with other developed countries the UK with regard to teh routine cohort compares favourably (table 5) , however as teh figures for those aged 14-18 years are not complete it is unfair to make a full comparison with other countries that have include wider age group. Table 5 International HPV vaccine uptake Country Third dose uptake % Delivery method Start date Evaluation period UK 80.9 Schools-based delivery to 12-13- year-olds Sept 2008 Sept 08 to Aug 09 USA 17.9* Through general practice to 13-17-year-olds Jan 2008 Jan 08 to Dec 08 Belgium 44** Schools-based programme to 12-15-year-olds Nov 2007 Nov 07 to Nov 08 Australia 66.3*** Schools-based programme to 12-18-year-olds Apr 2007 Apr 07 to Mar 08 Belongs with factors affecting the vaccination uptake rate Ethnicity religion and English as a first language are associated with acceptability of the vaccine in the UK. Girls form Muslim, Hindu or /Sikh backgrounds are less likely to have the vaccine. Support for this comes from studies of ethnic minority attitudes to HPV testing; where some women felt it reflected non-traditional cultural or religious practices concerning sex and monogamy and form ethnic differences in the use of sexual health services, where a major barrier for south Asian and African minorities is the cultural taboo around discussion of sexual matters. Perceived susceptibility, benefits and barriers were also associated with acceptability. Perceived risk of HPV within the ethnic minority groups was low because of their religious beliefs about sexual abstinence until marriage (Marlow LAV 2009). Another study has shown that ethnic minority parents are more likely to believe that HPV vaccination will result in an increase in risky sexual behaviour, a belief that has been sh own to be a barrier to HPV. A reduction in risk perception was also correlated with less likely hood of vaccine uptake in lowest income families, lack of education around the high risk of HPV and cervical cancer was seen as the reason. (Ref) Also seen was a correlation in safety fears surrounding the vaccine, with those parents less convinced that the vaccine is safe not consenting to is administration. As the vaccine is newly approved and phase four trials are still ongoing questions surrounding long term safety cannot be fully answered. While long term safety remains an important issue adolescent HPV vaccines coverage may; similarly to the MMR vaccine struggle to reach full coverage. Over 16s were seen to have some similar beliefs surrounding the vaccine with lower uptake rate seen in ethnic minorities. This is a worrying trend as it is suspected that those that do not take the vaccine would also be part of the 20% of total invited that do not take up their cervical screening appointment, putting them at extreme risk (appendix). The vaccine in the UK is given to young girls aged 12-13, parental consent is therfore applicable. Thus looking at the limiting factors of uptake rate diffetnt for for this demographic than it does for the catch-up cohort where the majority are over 16 and do not require parental consent. In the long term this will not be a consideration as the administration of the vaccine to those over 16 is time limited. Vaccines in the public eye Natalie Morton In excess of a million single doses of Cervarix have been given in the UK, only one was thought to be associated with the death of a young girl, Natalie Morton. It was quickly established that the real cause of death was a large and previously undetected tumour in Natalies chest that could have killed her at any moment; not from the Cervarix vaccine, this confirmed by the DOH appendix 2). Natalies death on 28/10/09 was covered extensively in the media and the vaccine batch in question was withdrawn and tested by two independent bodies and GSK, no abnormalities were found. Given the extent that the uptake of the MMR vaccine was adversely affected based on unfounded evidence, it is likely that this event will have some effect on the uptake of this vaccine. Data is yet to be published on the vaccination rates for 2009-2010 but information from a nurse working in the Warwikshire PCT (appendix3?) shows that three schools in Coventry (Natalies local area) have withdrawn from the vaccination programme. Since the evidence has shown that the best uptake rates are achieved when vaccinations are given in the school environment; implications for lower uptake rates due to Natalies death, even though unrelated, are already evident. Information surrounding the safety of this vaccine must be made clear to all possible recipients and their parents to allow informed decision rather than rash decisions to be made. The percentage of women screened for cervical abnormalities within the last 5 years has been falling slightly over the last decade, mainly in lower age groups. Data for 2006-2007 show that this is the second year it has dropped below 80% since the early 1990 (appendix 4). This is a concern as there is strong evidence that the death rate is lower in women first screened at a young age. This is clearly evident in developing countries with no screening programme, where the YLL due to cervical cancer are much greater than those of developed countries that do have screening programmes. The effect of the media with regard to Jade Goody, who famously and publicly died of cervical cancer on the 22 March 2009 at the age of 27 was significant. The public nature of her death prompted an increase in the number of women wanting information about cervical cancer and those attending cervical screening. Having interviewed a nurse who works for Warwickshire PCT and discussed with her the impact of the Jade Goody death her estimates were that for the two months following Jades death the screening rate doubled. However she was concerned that after this two month period the rate reverted back to its previous standings. Cancer research also experienced a significant increase in activity on their website. On the day that Jades diagnosis went public the figure increased from the usual 2-3000 to 32,000. They also claim that since then (August 2008) the number of hits per day is sustained at double the level they were before the public diagnosis (Correct to Feb 2009). The increase in the number of women being screened and the increase in information sought; shows that the influence of the media can both raise public awareness and prompt the general public into action. Stories such as those of Jade have had a huge impact. The level of raised awareness surrounding both the dangers of cervical cancer and the benefits of the vaccine must be sustained for the vaccination programme to be truly successful. People need to be encouraged to discuss any fears they have with a health care professional before making the decision to have the vaccination. CONCLUSION HPV vaccines; can they prevent cervical cancer? Go through one at time then delete this bit * Vaccine efficacy * Vaccine Cost/affordability/practicality of administation * Production and Distribution * Government backing and financial commitment * Other support organisations such as the WHO, UNICEF, Gates Foundation, Rotary International * Social factors * Media effects/Public awareness * Safety, and perceived fears Vaccine efficacy/longevity. The efficacy in preventing incident infection in types 16 and 18 for both vaccines is shown to be very high. Cervarix does have some increased protection against HPV types 31 and 45. The concern here is that both vaccines only protect against 70% of HPVs causing cervical cancer, what of the remaining 30%? Is it possible that the remaining high risk HPV types will become more prevalent in the absence of HPV type 16 and 18? There is not enough current data to compare population prevalence of other high risk types of HPV with the prevelence of HPV types 16 and 18 to allow this question to be answered. As we know cervical cancer is uncommon in women under 25 and is highest in women over 40 and as the oldest of the vaccinated cohort are 18 it will be several years before any real figures can be analysed. Screening will need to continue along with HPV typing for all cases of cervical cancer to allow monitoring of the possible success of the vaccine, to monitor for cervical cancer caused by the high risk types that are not covered by the vaccine, and to protect those that did not take up the vaccine or were not of eligible age. Cost affordability/practicality Both vaccines are very expensive, limiting use to more developed countries. Novel growth vectors are being explored in an attempt to lower the cost making the vaccine more widely available. A multivalent vaccine that protects against all types of high risk HPV would also be advantageous. There is a polyvalent vaccine in development that protects against nine high risk HPVs. If the cost of the vaccine was lowered to be affordable for developing countries the current regime of 3 doses over 6 months would not be practical. In the UK where the population is stable and also has easy access to healthcare the uptake rate of the third dose is significantly lower than that of the first two doses; adding our relevant limiting factors to the public unrest, mass migration, and sporadic healthcare in some developing countries it is clear to see that the current programme would be almost unattainable under these circumstances. Development/distribution Multiple therapeutic vaccines are in early development that may be more appropriate for those already exposed to high risk HPV types. Combination vaccines that are both therapeutic and prophylactic are also in development. DISTRIBUTION Support, governments/WHO/CDC/UNICEF The governments of many developed countries have shown support for the vaccine through the introduction of national immunization programmes. With the vaccines safety under question after the unrelated death of Natalie Morton greater effort needs to be made to publicise the well established safety of the vaccine. Media effects Public Awareness Can be good or bad but as they are free to publish only selected information they naturally select what will sell their products rather than report the full facts. This is unfortunate but in our free society is an inevitability that we have to work around as Jade Goody did Public awareness leaflets, posters and education are all important factors in maintaining a high uptake rate. Minorities that are more reluctant to have the vaccine should be targeted specifically with information pertaining to the dangers of cervical cancer and the benefits of the vaccine. MEDIA Safety Safety of the vaccines must be shown along with the few side effects seen after administration, this is critical to achieve a high uptake rate as was seen with MMR and more than likely due to the tragic death of Natalie Morton, if is question is raised regarding safety the take up rate could be reduced dramatically. Al current data indicates that the current HPV vaccines should prevent some incidence of cervical cancer by preventing incident infection of HPV types 16 and 18, new more novel vaccination will need to be developed to prevent cervical cancers caused by all HPV types. The long term efficacy of the current vaccine will also need to be monitored to establish if a booster is required at a later date to maintain protection. The Vaccination of other high risk group should also be considered. MORE Older women MEN ERADICATION is this a possibilityNO As the vaccine is only given to girls there is not protection by herd immunity as in essence men will continue to be a reservoir for HPV types 16 and 18, for this reason the uptake rate in women need to be as high as possible, no vaccine no protection at all. Could the vaccine be used to protect against other kinds of cancer? Yes more than likely however with the incidence of other cancers caused by HPV types 16 and 18 is so small that the vaccination programme at the current vaccination cost would not be cost effective. If there becomes available a multi valent vaccine that protects against more HPV types a t a significantly lower cost they could be given to men. Then possibly eradication, if the virus has no zoontic reservoir. Could the vaccine be used to protect against other kinds of cancer? Yes more than likely however with the incidence of other cancers caused by HPV types 16 and 18 is so small that the vaccination programme at the current vaccination cost would not be cost effective. If there becomes available a multi valent vaccine that protects against more HPV types a t a significantly lower cost they could be given to men. Will we ever eradicate HPV unlikely, will we ever eradicate oncogenic HPV. Who knows!!!!!! As of yet there is little evidence due to the newness of the vaccine to show that the vaccines will prevent cervical cancer at all. There is ample evidence that the vaccine prevents incident infection and that antibody levels are consistent for up to 7 years, Is the elimination of oncogenic HPV realistic Not with the current vaccines and not at the current cost Im afraid. My opinion Women of all ages should be able to take an informed decision when considering an HPV vaccination, 1 | Page

Gender Roles in Literature - 1573 Words

Gender roles play a significant part in all literature. Throughout history men and women have been represented in a variety of different ways. In some tales men and women are equals, while in others men are seen as superior to females. Their roles in the stories have to do with the cultural aspect of the society the story was written during, and when the story is supposed to take place. Examples of the importance of gender roles can be seen in Bram Stoker’s Dracula and Jeremias Gotthelf’s The Black Spider. The role of the sexes is a main theme throughout the both plots. These works were written in two completely different time periods, as such the role of women, meaning what was expected of them, were significantly different. This is a one of the main differences in the pieces. Though they were written during different times both Dracula and The Black Spider were written with strong female characters. Also these female characters undergo a significant change. These cha nges were, predominantly, not for the better. From these works it could be suggested that if women hold independent and strong roles, they are often seen as evil or brought down by temptation. Comparing these two works by looking at both texts it is clear how much time changes the perception of women. This paper will focus on the role of women in both pieces of literature, how they are similar and how they are different. In Bram Stoker’s Dracula, the roles given to each gender are extremely important andShow MoreRelatedGender Roles in Childrens Literature2226 Words   |  9 PagesGender Bias in Literature Men Fix ThingsÂ…Girls Have Dolls -Shirley B. Ernst I have thought about many different ways to organize this paper and have come to the conclusion that the best way to approach the topic is on a book-by-book basis. 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As society has changed, so has the typical role that eachRead MoreEssay Gender Roles in Childrens Literature1876 Words   |  8 Pages| | |Gender Roles in Children’s Literature | | | |Kate Moore | |11/22/2010 Read More Gender Roles In Childrens Literature Essay2194 Words   |  9 PagesGender Bias in Literature nbsp;nbsp;nbsp;nbsp;nbsp;I have thought about many different ways to organize this paper and have come to the conclusion that the best way to approach the topic is on a book-by-book basis. My perceptions of the gender biases in these books vary greatly and I did not want to begin altering my views on each so that they would fit into certain contrived connections. 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Introduction to Statistics and Graphical Descriptive Measures

Questions: A. politician who is running for the office of mayor of a city with 55,000 registered voters commissions a survey. In the survey, 52% of the 250 registered voters interviewed said they plan to vote for her.i. Describe the population of interest? ii. Describe the sample? iii. Is the value 52% a parameter or a statistic? Explain your answer.B. At the Eastern Suburbs Community College, administrators want to determine the average commuting distance for their students. They randomly select 350 students who commute and ask them the distance of their commute to campus. From this group a mean of 15.5km has been calculated.i. Describe the parameter.ii. Describe the statistic. iii. Describe the population.Question 2 a. Define each of the following Types of Data: i. Nominalii. Ordinaliii. Intervalb. For each of the following, identify the data type as Nominal, Ordinal, or Interval. i. The size of an order of fries (small, medium, large) purchased by a fast food customer.ii. The reading of the odometer of a motor vehicleiii. The marital status of respondents in a Customer Satisfaction Surveyiv. The extent to which a Customer agrees (Strongly Agrees, Agrees, Neutral, Disagrees, StronglyDisagrees to a Statement regarding the Companys refund policy is fairv. A students STAT201A Mid-Trimester Examination result as a percentagevi. A students STAT201A Mid-Trimester Examination result as a Grade (Fail, Pass, Credit, Distinction, High Distinction)Question 3 To help determine the need for more Golf Courses, a survey was undertaken. A sample of 60 self-declared Golfers we asked how many rounds of golf they played last year. The data collected is as follows: 18 15 25 18 29 28 23 20 13 26 29 24 3 13 28 26 18 30 24 23 9 20 30 26 17 18 30 28 18 19 35 18 14 25 19 28 28 12 30 36 31 13 14 14 42 30 29 20 18 27 25 36 31 29 24 36 23 24 16 22 a. Draw /Construct a correctly labelled Histogram b. Draw /Construct a correctly labelled Stem-and-Leaf Display c. Draw /Construct a correctly labelled Pie Chart Answers: A.i. The population of interest in the given question is the total number of registered voters in the city i.e. 55,000.ii. The sample in the given case is the number of people chosen from the population to be interviewed i.e. 250.iii. 52% is a statistic and not a parameter since it describes about the characteristic of the sample and not the population. This is apparent since the given information clearly states that 52% of those interviewed (i.e. sample of 250) would vote.B.i. The parameter in the given case is not calculated since parameter is derived from the population i.e. all the students at the Eastern Suburbs Community College but the research confines to only a sample of 350 students.ii. The statistic in the given case is 15.5 km since it summaries the information based on the sample of 350 students at the Eastern Suburbs Community College.iii. The population in the given case would constitute all those students who are commuting and studying at the Eastern Suburbs Community College. However this figure is not given in the given case.2. A. Nominal data are commonly use to depict data which cannot be quantified and thus primarily requires labelling such as sex, marital status etc.Ordinal data is normally used to denote different degrees or orders of a particular value where the exact difference between the various degrees cannot be exactly quantified. For instance, the level of satisfaction can be low, moderate or high but the exact difference between these three cannot be accurately quantified or defined.Interval data is used to denote those numeric values where the various degrees are known and additionally the exact difference between the various degrees can also be exactly quantified. For instance the values on a speedometer can be classified as interval data.B.i. Data type is Ordinal since the given data since the exact difference is not known.ii. Data type is interval since the reading of the odometer can be easily quantified in the form of interv als.iii.Data type is nominal since the data cannot be quantified and would primarily involve the use of labels such married, unmarried and divorced.iv. Data type is ordinal since the given data measures the degree of satisfaction where the difference between various satisfaction degrees cannot be exactly quantified.v. Data type is interval since the result in % is quantifiable and thus can be grouped into intervals.vi. Data type is interval since the given data primarily presents labels represent the performance of the student which can be quantified as the pass , fail depend on particular range of marks.3. i. The histogram for the given data is shown below. 1. The stem leaf plot is as shown below. Stem Leaf 0 3,9 1 2,3,3,3,4,4,4,5,6,7,8,8,8,8,8,8,8,9,9 2 0,0,0,2,3,3,3,4,4,4,4,5,5,5,6,6,6,7,8,8,8,8,8,9,9,9,9 3 0,0,0,0,0,1,1,5,6,6,6 4 2 iii. The relative frequency table of the given data is shown below. Value Frequency Relative Frequency 0 to 5 1 1.67% 5 to 10 1 1.67% 10 to 15 7 11.67% 15 to 20 12 20.00% 20 to 25 11 18.33% 25 to 30 16 26.67% 30 to 35 7 11.67% 35 to 40 4 6.67% 40 to 45 1 1.67% Total 60 100.00% The pie chart corresponding to the above is shown below.

Women in music videos an Example by

Women in music videos The objectification of women in music video industry has become increasingly rampant since the inception of the entertainment medium. The era of music videos has heralded the demeaning of women by reducing them to an object of male visual appreciation. The music industry thrives on the level of viewer-ship that can be attracted to any given video, and it seems to be the dominant belief that the less clothing a woman wears in a video, the more likely it is to be viewed. Such channels as MTV, BET and VH-1three of the largest music video cable channelsthrive on the broadcast of videos that are filled with sexual images portraying women as scantily clad. These images are present in order to fuel the sexual fantasies of men, and highlight women as having the primary purpose of fulfilling those desires. Many videos are also filled with women being touched by men, as We only want to see males if theyre doing things to females (Burrowes, 2002). Therefore, while women are made objects in a lo t of videos, the primary purpose of the male in such videos is usually to act out the fantasies that place women in the position of sexual object. Need essay sample on "Women in music videos" topic? We will write a custom essay sample specifically for you Proceed This paper addresses the problem with media portrayal of women as objects by arguing that not only does it harm the image that women have of themselves, but it also adversely alters the image that is fostered in the minds of males as they grow within the society. With respect to the study and practice of communication, such media objectification has the potential also to adversely affect the treatment of women in workplaces. It may also hinder the commencement or advancement of their careers in the corporate world. Such portrayal of women as objects in music videos makes it difficult for a woman to be taken seriously in any communications setting within and beyond the interpersonal level. Possible sources for this research include Philip Burrowes A new era of scantily-clad women, Robin Roberts Ladies First: women in music videos, and Hedy Frys Round table on the portrayal of women in the media. While some have argued that it is women who allow themselves to be portrayed in that way, but the pressure that such videos place upon them is largely responsible for influencing their behaviors and their subordinate role in society. References Burrowes, Philip. (2002). A new era of scantily-clad women. The Tech. 122(8). Fry, H. (1997). Round table on the portrayal of young women in the media. Status of Women: Canada. Vancouver. Roberts, R. (1996). Ladies first: women in music videos. Jackson: University Press of Mississippi.

Ethnic Stratification, Prejudice, Discrimination Hispanics

Ethnicity and race have been a topic of immense concern in the United States of America since it has a wide range of ethnic and racial entities in this country, having a broad historical background of origin. The author of this paper discusses the effects of ethnic stratification on the Hispanics/Latinos, and how prejudice and discrimination are relevant to this ethnic group.Advertising We will write a custom essay sample on Ethnic Stratification, Prejudice, Discrimination: Hispanics specifically for you for only $16.05 $11/page Learn More Ethnic Stratification Ethnic stratification has resulted in differences in the distribution of resources according to hierarchical positions. The most powerful/dominant ethnic group enjoys most benefits as long as resource distribution is concerned. In the US, stratification was done based on physical appearance and religion. The white Protestants are top in the hierarchy followed by the Jews, white Catholics and Asian s. The bottom in the hierarchy includes the blacks, Indian Americans, some Asians and Hispanics or Latinos. This has changed since there have been several conversions from one culture to another. Currently, stratification is done using two main ways i.e. biological characteristics and ethnic background. To the Hispanic, what has mostly influenced their placement in the hierarchy is their ethnic background. Given their unclear origin these citizens are usually treated as non-Americans. They are currently ranked lower than the blacks especially in employment, housing and education. The Latinos are thus discriminated because of their position in the ethnic hierarchy. In fact, stratification is the main reason for racialism and racism among the American population. Prejudice and discrimination The disparity in ethnic class resulting from the social stratification in the American society has resulted to uncontained prejudice and discrimination. Price (2012) defines prejudice as peoplesâ €™ perception towards people of other cultures whose traits they consider negative because of their cultural background, religion or color (Price 802). Discrimination, on the other hand, is one’s act of prejudice on another person or a group (Price 802).Advertising Looking for essay on ethnicity studies? Let's see if we can help you! Get your first paper with 15% OFF Learn More According to different surveys (Gk-survey, Pew Research poll), the Hispanics are ranked second after African Americans among those who face discrimination in the United States of America. The Hispanics are mostly discriminated against finding adequate and good housing (US Census Bureau, para 7). The pew research poll indicated a shocking statistics that three of ten Latino employees have been discriminated at least once a week at their work place. About 12% of the interviewed Hispanics in the US Census Bureau Survey believe that at one time, they had been fired from work due to prejud ice. Moreover, one in ten Hispanic men report going into prison at least once in their life due to prejudice and discrimination (US census bureau para. 6). This discrimination extends to other extremely valuable services like education, health services and leadership. The children and youth are the most affected by the discrimination though adults also phase their position of prejudice and discrimination. The discrimination has had lots of influence on the perception of the Hispanics on life and other vital activities (Price 801). The Hispanics are reported to be less motivated in life at work, low education standard and high unemployment rates. These are all results of prejudice and discrimination that they face. Policy measures to reduce the discrimination bears no evident fruit, campaigns for equality to bears no fruits. It is forecast that with the increase in Hispanic immigrants into the US, perceptions against the Hispanics increases and thus discrimination worsens. The bid to reduce this prejudice has thus to be heightened to save the situation. Works Cited Price, Patricia L. â€Å"Race and ethnicity: Latino immigrants and emerging geographies of race and place in the USA.† Progress in Human Geography 36.6 ( 2012): 800-809. Print. US census bureau, 2010, Web. www.census.gov.Advertising We will write a custom essay sample on Ethnic Stratification, Prejudice, Discrimination: Hispanics specifically for you for only $16.05 $11/page Learn More This essay on Ethnic Stratification, Prejudice, Discrimination: Hispanics was written and submitted by user Brody L. to help you with your own studies. You are free to use it for research and reference purposes in order to write your own paper; however, you must cite it accordingly. You can donate your paper here.

Qualitative Data Definition and Examples

Qualitative Data Definition and Examples In statistics, qualitative data- sometimes referred to as categorical data- is data that can be arranged into categories based on physical traits, gender, colors or anything that does not have a number associated with it. The hair colors of players on a football team, the color of cars in a parking lot, the letter grades of students in a classroom, the types of coins in a jar, and the shape of candies in a variety pack are all examples of qualitative data so long as a particular number is not assigned to any of these descriptions. Qualitative data is contrasted with  quantitative data  wherein quantitative  data sets have numbers associated with them that evaluate the quantity of an object or objects with shared features. Oftentimes, quantitative data is used to analyze qualitative data sets. Qualitative vs. Quantitative Data Its pretty easy to understand the difference between qualitative and quantitative data: the former doesnt include numbers in its definition of traits of an object or group of objects while the latter does. Still, it can get confusing when thinking in terms of statistical attributes, which include size and dimensions, which are quantitative and not qualitative data. In order to better understand these concepts, its best to observe examples of particular datasets and how they can be defined. Observe which are qualitative and which are quantitative data sets in the following examples: The cats have orange, brown, black, or white fur (qualitative).The boys have brown, black, blonde, and red hair (qualitative).There are four black cats and five orange cats (quantitative).The cake was 50 percent chocolate and 50 percent vanilla (quantitative). Even when a particular feature or attribute of an object is qualitative, such as chocolate for the cake or black for the cats, the inclusion of a number in the data set makes it a quantitative one, though this interplay is important for the study of statistics as it provides categories for which mathematicians  can then compare numerically. The Importance of Qualitative Data Whereas quantitative data is important in determining the particular frequency of traits or characteristics, the sizes, and dimensions of objects, and that sort of information about a given topic, qualitative data like the color of hair or skin of employees in a company or the healthiness of a pets coat can be important in statistical analysis, especially when paired with quantitative data about these qualitative features. Essentially, qualitative data is important because it allows statisticians to form parameters through which to observe larger sets of data. For instance, a company that wanted to determine the diversity of its workforce would want to look at a set of qualitative data like race and ethnicity of its employees as well as the quantitative data of the frequency of employees to belong to those races and ethnicities. Qualitative data provides the means for which observers can quantify the world around them- there are three blondes, two brunettes, and three black-haired women at the table or there are 16  freshmen and 15 sophomores attending the annual band trip.

Performance Review Takes a Page from Facebook Research Paper

Performance Review Takes a Page from Facebook - Research Paper Example It is because of this that this essay seeks to establish the reality on these matters. It is very untenable to posit that regular conversations with employees and familiarity with their stand can overwrite the need for performance evaluation. First, it is likely that these regular conversations also include both formal and informal discourse. Informal discourse does no constitute the frameworks of performance evaluation. Conversely, taking regular conversations and an employees’ acquaintance with their stand is akin to taking an individual’s words for a fact. What an employee says he has done is not what may be the reality. Many are the cases when employees have assured their bosses that they have finished a project, to save face, and with the hope of finishing the project before the boss asks for it. Performance evaluation also factors several measures and frameworks that conversations and familiarity may not capture, the degree of regularity and familiarity notwithsta nding. First, performance evaluation should be carried out on regular basis (for instance, at the end of a fiscal year) and should be facilitated by the human resources (HR) management or a supervisor. It is debatable if the boss will follow through the frameworks that entail performance evaluation, due to the impromptu nature of a conversation. In a closely related wavelength, performance evaluation becomes only meaningful with a performance target in mind or at hand. Even if the boss may have this in mind, it is a fact that his mind will not contain all the specific frameworks of performance evaluation. It is very unlikely that the employer or the boss will keep every employee’s performance target, in order to make sensible performance appraisal. Performance evaluation also meaningful if it factors it is followed up with proper correctional action. Because there would be no proper performance appraisal, it follows that such conversations will not capture proper correctional measures such as workshop drives and training programs, or the degree to which they should be carried out. Question 2 When one looks at the possible effectiveness of the social network performance review to veterans, baby boomers, Gen X, and Gen Y, one realizes that there are changes that have taken place. For the veterans and the baby boomers, it is clear that conventional type of social network performance was used, in lieu of the online social networks. This is because the world had not yet become acquainted to the Worldwide Web. Generation Y and X began using social networks to perpetuate organizational goals, earlier and more frequently than the baby boomers and the veterans due to age. For instance, the veterans (1922-1943) always value clarity and consistency in respect to rules, performance standards and decision making processes. This generation may therefore need clarification on what it is actually expect of it, when introducing social network performance. Baby boomers ( 1944-60) in turn will also realize positive social network performance reviews since this group likes being in control. Generation X (1961-1980) may also register positive social network performance review since it has the ability to flexibly balance work arrangements and work balance. This group also has ready access to exciting and meaningful work choices. Generation Y (1981-2000) may also register pleasing social network performance review since it has a knack for teamwork, fast decision making and self-motivation. Question 3: Justification