STDS ? HPV and the vaccine.
Introduction
Genital HPV infections are a sexually transmitted disease (STD) that is caused by the Human Papillomavirus (HPV). Human Papillomavirus is the name of a group of viruses that includes more than 100 different strains.1 More than 30 of these viruses is sexually transmitted. 2 Many of the epidemiological and experimental studies have shown a distinct link between HPV and the development of cervical cancer.3 The World Health Organisation claim over 99% of cervical cancers contain HPV DNA and four specific types (16, 18, 31 and 45) cause at least 80% of diagnosed cervical carcinomas.4
From epidemiological studies, the world wide prevalence is suggested to be between 9 and 13%, which equates to approximately 630 million people infected with HPV.5
HPV is very contagious in its nature and this means that approximately two thirds of all people who have sexual contact with an infected person will develop an HPV infection within three months. 6 It is also known that 70% of genital HPV infections are sub clinical and so will not progress on to a disease status.7 However, in a small minority of women who have been diagnosed with persistent pre- malignant cervical intraepithelial neoplasia (CIN) 8, cervical cancer will almost certainly develop but it usually appears more than ten years after the initial infection. 9 The HPV virus infects basal epithelial layers in the region of metaplasia and the transformation zone on the cervix consisting of the ecto and endo cervix, where the most susceptible cells are found. As a sexually transmitted disease, HPV infection occurs mostly in younger women, often those <40 years of age.27 Syrjanen et al. observed that progression rates from HPV detection to dysplasias ranged from 15% to 30% for HPV types 18 and 16, compared with 5% to 25% for types 6 and 11. Regression rates were 30% for all viral types.28
Cervical cancer is second only to breast cancer when it comes to disease incidence in women.10 A cost effective long term strategy to reduce the cervical cancer incidences, particularly in developing countries when a cervical cancer screening programme is not available would be a vaccine to prevent oncogenic HPV infection, or pre malignant cervical lesions would be a great advantage to many women. There has been very encouraging experimental data obtained through the clinical trials of vaccine preparations in animal models. This has prompted the public and commercial institutions to pursue the clinical development of a vaccine. Recombinant DNA technology is being used to produce vaccines against HPV and this vaccine seems to be a priority in this field for many pharmaceutical and biotechnology companies. Furthermore, both prophylactic and therapeutic are under current development.
In viral like particle vaccines (VLPs) recombinant L1 capsid protein from HPV has the property of self assembling into viral particles and so the L1 capsid protein has been targeted for neutralizing-antibody formation using a DNA or polynucleotide vaccine in the Cottontailed Rabbit Papilloma Virus model.29 These particles do not contain any DNA material and therefore are non infectious.11 Most importantly these particles stimulate the production of antibodies that bind and neutralise the HPV virion. Human trials have been carried out and the reported results were very encouraging, excellent tolerability and high immunogenicity was reported in each of the trials. Other vaccine candidates based on the expression of viral early antigens as fusion proteins, or synthetic peptides which correspond to the epitopes of the virus protein, have been designed to have therapeutic properties to treat women already infected with the HPV virus. In pre malignant lesions and cervical carcinomas the E6 and E7 oncoproteins of HPV are selectively expressed, and so these are an attractive vaccine target.12 In experimental models these kinds of vaccines have the ability to induce anti tumour responses. So far three fusion proteins and several peptides are being tested in human clinical trials as potential therapeutic vaccines but as yet they have not been proven to be safe. However their immunogenicity and efficacy has not yet been fully characterised. Live recombinant vaccinia viruses have been engineered to express the HPV types 16 and 18 genes, as these are the most common viruses associated with cervical cancer.13 Phase I and II of the clinical trials have been conducted and the results are very encouraging. The studies have been very successful and have demonstrated that the vaccine induces no serious side effects. However, the initial sample group was too small to fully evaluate the clinical efficacy. Also live attenuated vectors, such as salmonella, are being investigated as potential second-generation vaccines. Merck & CO have come up with a vaccine called Gardasil, which is a genetically engineered vaccine that blocks HPV 16 and 18.14 During the final phase of the study included 10,559 sexually active women within an age range of 16 to 26 in The United States of America who had not been previously infected with HPV 16 or 18. Plus women from 12 other countries who were not infected with HPV 16 and 18.15 Half were given 3 vaccine doses over a period of 6 months and half were given placebo shots. The subjects who remained virus free after the 6 months, none who received the vaccine went on to develop cervical cancer or pre cancerous lesions over an average of two years of follow up, compared to 21 who received the placebo.
A second analysis was carried out which included hundreds of women who were participating in the ongoing study, it was shown that after just one dose the vaccine was 97% effective. It was found that just one of the 5736 women who received the vaccine went on to develop cervical cancer or pre cancerous lesions in comparison to the 36 among the 5766 who received the placebo. 16 It was concluded that administration of the HPV16 vaccine reduced the incidences of both HPV16 infection and HPV 16 associated CIN. Immunising negative women against HPV 16 may eventually reduce the incidence of cervical cancer.17
It was reported by the New Scientist late 2004 that it may even be possible to combat cervical cancer in its early stages by applying a gel to the cervix, instead of removing abnormal cells surgically.18 A team of scientists from the University of York (led by Jo Milner) have been developing the gel and have been carrying out trials in the UK. It is proposed that similar gels maybe become accessible for treatment of cancers with accessible surfaces.19 The problem with siRNA?s is the delivery, as they are destroyed very quickly in the vascular system, within minutes of injection.20 However as cervical cancer develops on or near to the surface of the cervix, there shouldn?t be any need to inject siRNA?s. So the gel that is being developed contains siRNA?s encased in liposomes, and it is these liposomes that assist their passage into the cells. However, it is not yet clear whether the liposomes would be able to penetrate deeply enough into the cervix to destroy any early stage cancers. It is also hoped that even if the gel doesn?t get into all of the cells, it will kill off enough cells just to tip the balance in favour of the immune system.
Other research has been going on into the viral DNA, as occasionally it inserts itself the host cells genome via the cervix surface which boosts the production of E6 and E7 which alters and prevent apoptosis.21 Research shows that if the production of the E6 and 7 proteins is blocked, the cultured cervical cancer cells can undergo apoptosis, whilst neighbouring normal cells are untouched.22 Using RNA interference can block these proteins and exploit the natural defence mechanisms we have against viruses. So if short interfering RNA?s (siRNA?s) are introduced into cells the RNA copies of that gene will be blocked preventing any protein from being made.23
There has also been research into the correlation between HPV and colo-rectal carcinomas. In colo-rectal cancer, however, the role of HPV infection remains unresolved. Although several previous studies have reported detection of HPV DNA in colo-rectal cancer tissues, there are some concerns about assay sensitivity and cross-contamination of tissue samples limit their conclusiveness. The current report is a retrospective; it was a controlled study to determine the presence of HPV DNA in the colo-rectal tissues of cancer patients vs. healthy individuals. Employing various methods to exclude the possibilities of any cross-contamination, the researchers surgically removed colo-rectal cancers and tissues adjacent to the cancers from 55 colo-rectal cancer patients. Normal colo-rectal tissues were sampled from 10 individuals who died accidentally provided the required negative controls. These results suggested that colo-rectal HPV infection, particularly with HPV16, is common in patients with colo-rectal cancer and that HPV infection may play a role in colo-rectal carcinogenesis. With HPV vaccines currently in development, these and other reports linking HPV to colo-rectal cancer may significantly impact future strategies for colo-rectal cancer prevention and treatments. Furthermore, these results, if confirmed, may shed light on how colo-rectal cancer develops and alter approaches to treating the disease. 24 Such vaccines are urgently needed and ultimately may be an important preventive measure. 25
Conclusion
HPV is a sexually transmitted disease; the virus responsible is the Human Papilloma Virus. This group of viruses includes more than 100 different types of HPV strain and more than 30 of them are sexually transmitted. It has been scientifically proven that over 99% of cervical cancers contain DNA from HPV and that 80% of diagnosed cervical cancers contain HPV DNA of 4 specific gene types 16, 18, 31 and 45.
The long term strategy to reduce the numbers of cervical cancer incidences is the development of an HPV vaccine is the way forward. This will be especially beneficial in developing countries where perhaps a cervical cancer screening programme is not available. There have been quite a few clinical trials for new HPV vaccines and so far the results are looking very promising, and hopefully within the next year or two they may be available to young teenage women and possibly also in young boys.
References
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14 Merck & co webpages
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29 Donnelly JJ, Martinez D, Jansen KU et al. Protection against papillomavirus with a polynucleotide vaccine. J Infect Dis 1996; 173: 314?320
Stanimirovic B, Kuljic-Kapulica N, Antic N, Stanimirovic V, Vasiljevic M, Popovic-Lazic J. HPV typing in cervical squamous intraepithelial lesions(SIL)-our experience after 1000 studied patiens. Archiv Oncol 7: 43?48.
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Oct 11, 2005 @ 10:25:42
my cat has a wierd name too its Piepuss lol he also looks like he has 4 white socks on coz his paws are all white lol
Is it an STD or not. 
