Viruses+and+Cancer

__**I. Viruses**__
Viruses according to science.yourdictionary.com, are defined as extremely small, disease causing particles consisting of a particle, the viron[|(1)] which contains a segment of RNA or DNA within a protein coat named a capsid[|(1)]. Viruses on a technical level are not defined as living organisms because they do not carry out biological processes such as metabolism and respiration and they are unable to reproduce independently, i.e outside of a living cell. Viruses reproduce by injecting their genetic material into the host cell, or by entering the living cell and shedding their protein coats. Their genetic material is then incorporated into the cell's own genome or it can remain in the cytoplasm of the cell. After this process viruses then instruct the cell's genes to produce the viruses' progeny which often causes the cell to die when the viruses eventually exit the cell.Viruses are thought to have evolved from 'rogue' pieces of cellular nucleic acids(1). Articleon PreCancer of the h uman cervix
 * Figure 1:** How Viruses transform themselves into normal cells

II. Cancer and Viruses
Cervical cancer is amongst the many diseases caused by viruses. The virus we are focusing on, the Human Papillomavirus (HPV) is classified as a DNA tumor virus and is in the same class as mouse polyomavirus and SV40 which all fall under the Papillomovirus class of viruses (Hanahan, Weinberg). (For more info on this topic please click this link. According to a 2001 article published by the NIH, cervical cancer is the 3rd most prevalent cancer globally. 80% of the cases of cervical cancer occur in developing countries. In 2001, the estimate of women who succumb to mortality via this cancer was at 190,000 women annually. The disease is most prevalent in sub Saharan Africa, Central America, and Melanesia. Unlike most cancers however, cervical cancer is preventable. This can be done by preventing infection of the HPV virus. Primary prevention of the HPV virus can be challenging however. Unlike other cases of sexually transmitted infections, HPV- infected women are usually asymptomatic and there are no therapies that actually work to eliminate the underlying infections caused by HPV. Primary prevention of HPV is usually in the form of vaccines against HPV, and secondary prevention against cervical cancer involves utilizing cheap screening and treatment technologies to detect dysplasia before it develops into an invasive form of cancer. We were intrigued to find out what factors contribute to high HPV prevalence in developing countries and the correlation between the virus and cervical cancer in women of developing countries. How viruses induce cancer is through oncogenes and they specify specific proteins called oncoproteins. Viruses that are cancer causing are known as oncoviruses, oncogenes of these viruses undergo mutations or disregulation in order to be converted into v-oncogenes which are cancerous. In the case of the Human Papillomavirus, HPV is recognized as the absolute cause of cervical cancer in women(2). In fact, according to Weinberg, on a global scale, "5% of cancer mortality [is from cervical cancer which is] largely attributable to human papillomavirus (HPV) infections."(Cancer Bio, Weinberg)

III. HPV OVERALL

 * Figure 2:** 3-D diagram representing the model of the Human Papillomavirus (HPV).

3-D Model of the HPV Virus above.

HPV, also known as the Human Papilloma Virus, is a virus that has its particles mobilized in a DNA genome, and it is protected in a protein coat (Hanahan, Weinberg). The HPV virus is known to affect cells within the vicinity of the cervix and to induce cellular changes in these cells which eventually lead to cervical cancer in some cases. HPV is a prominent virus amongst sexually active people in particular, the virus can be easily spread through skin-to-skin contact during the processes of vaginal, anal, and oral sex. Sexually transmitted HPV's are classified into two groups, low risk HPV's and high-risk (oncogenic) HPV's. Low-risk HPV's do not result in cancer but they do lead to the onset of warts in the areas of the genitalia, mouth, and anus. High risk HPV's can eventually lead to the onset of cancer. HPV's 16 and 18 in particular are responsible for the majority of HPV associated cancers (NCI).
 * What is HPV:**

Table 1 below illustrates the strains/types of the HPV Virus and their associated cancers.
 * **Disease** || **HPV Type** ||
 * Plantar warts || 1, 2, 4 ||
 * Common warts || 1, 2, 4, 26, 27, 29, 41, 57 ||
 * Flat warts || 3, 10, 27, 28, 41, 49 ||
 * Genital Warts || 6, 11, 30, 40-45, 51, 54 ||
 * Cervical cancer || 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 ||
 * Precancerous changes || 16, 18, 34, 39, 42, 55 ||
 * Laryngeal papillomas || 6, 11, 30 ||

High-risk HPV infection is responsible for roughly 5% of all cancers worldwide. It is however important to note that most High-risk HPV infections do occur with no manifested symptoms and may usually go away within 1 to 2 years from the time of infection. In such cases, such HPV's are not responsible for cancer. Unfortunately, some HPV's cause infection that can perpetuate for several years. These perpetual infections associated with High-risk HPV cases often result in grave cytological developments and lesions which, if left untreated, then have the potential and ability to advance and transform into cancer. A few of the cancers associated with HPV are, anal,cervical, vaginal, vulvar, penile, oropharynx and throat cancers.(cancer.gov)

Some Factors that increase the risk of an individual developing HPV and that HPV turning into cancer include:

-**Smoking**. According to Robert A. Weinberg, mutagenic carcinogens like those present in the tar found in tobacco for example, stimulate the activation of previously dormant retroviruses derived from within the organism in question. The resulting viral matter begins to proliferate rapidly and then go on to cause cancer. A separate study found that, women who smoked while simultaneously being affected by HPV increased their risk for cervical cancer by up to 27-fold.((Cancer Epidemiol Biomarkers Prev. 2006;15:2141-2147)hcplive.com)

-**Having a weakened immune system** (HIV) A study found that HIV activates dormant HPV cells which the go on to lead to the complications of HPV related disease, additionally, because HIV is accompanied by the suppression of the immune system, the immune system becomes less efficient at destroying tumor cells because HIV weakens the immune systems's ability to control the HPV virus. Furthermore, individuals with weakened immune systems risk contracting the HPV virus, via long term stress, and immune system-suppressing drugs, a few other examples of factors that contribute to the weakening of the immune system. (Mayo Clinic) .Furthermore, in a study conducted in the Kiambu district of Central Kenya, between June 2009 and September 2010, HIV infected women visiting the ART clinic at the Nazareth Hospital in the district were studied in order to assess their disposition towards precancerous cervical cancer lesions. The women were inbetween the ages of 18 and 69 years of age. In 1993, cervical cancer was proclaimed an acquired immunodeficiency syndrome(AIDS) defining illness. HIV positivity implies, higher prevalence and incidences of cervical cancer in positive women than in HIV negative women. The study notes that HIV positive women have a 2 to 4 fold greater rate of HPV infection as well. HPV prevalence amongst HIV positive women is often associated with low CD47 counts vital for the immune system.

-**Having many sexual partners**; mayo clinic has pointed out a relationship between the number of sexual partners an individual has and his/ her chances of contracting HPV, the more partners one has, the greater his/ her chances of contractng HPV are.

-**Having too many children:** Another possible cause is related to multiple child births in women. Developing countries are synonymous with high birth rates. This can be tied in to multiple sex partners which infers, higher risks of contracting HPV, which increases risks for cervical cancer. Studies show that women who have had 7 or more children have doubled their risk then those who had only had 1-2 children. Other research has observed that having a baby before the age of 17 doubles the risk compared to having your first child around 25 years old or older.


 * -Long Term oral contraceptive use:** The results are unclear as too why this increases risk, however, studies do show that the risk of cervical cancer begins to decrease when the patient stops taking the pill. After 10 years the risk stabilizes to when it was as if you never had taken the pill.

-**Poor hygiene** ( linked to oropharyngeal and cervical cancer as it worsens the effects of HPV infection, see section V, under hygiene, for more details). @http://www.cancer.gov/cancertopics/factsheet/Risk/HPV

Research has shown that women with HPV who shower or bath up to six or more times a week cut their risk factors for cervical cancer in half. There is however no solid research to pinpoint what exactly it is about hygiene that reduces the effects of the HPV virus. It is however not a surprising observation, in the past, hygiene has been known to play a role in treating yeast infections and bacterial vaginosis. Good oral hygiene is also thought to alleviate chances and cases of HPV contracted via o
 * -Hygiene and HPV:**

We will be focusing on HPV types 16 and 18, strains of HPV known to be the most carcinogenic strains of the virus in the scientific world. -HPV 16 is a strain of HPV characterized as a high risk strain of HPV that induces transformations in the cells of the human cervix. These changes are viewed as unusual on pap smear results. In some cases, HPV 16 can disappear on its own, however, in some cases, it causes transformations that may lead to cervical cancer. Usually, this happens when such manifestations of HPV 16 in the cervix are not treated. HPV 16 is one of the largest contributors to cervical cancer. HPV 16 sometimes manifests itself in flat warts, termedcondyloma planum, or as warts that somewhat resemble cauliflower under the skin. HPV 16 can hibernate (lie dormant) in the human corpus for a lengthy period before developing into cancer of the cervix. The average length for women is about 7-11 years. According to the CDC, HPV 16 is more prevalent in women than in men and in sexually active individuals. HPV 18 is like a sister to HPV 16, they both cause similar cancers and are usually classified together in terms of the diseases they cause. The major difference between the two types of HPV lies in the fact that HPV 16 is associated with squamous differentiation, while HPV 18 is associated with adenosquamous or adenomatous differentiation after infection or transformation of cells via HPV into cancerous ones.(NIH)
 * HPV Strains related to Cancer:**

IV. Specifically focus on HPV - cervical cancer cases
The HPV virus targets cervical epithelial cells, and causes chronic infection in these tissues. Epithelial cells are usually organized cells that line the inside and outside of the body including the skin, the throat, the cervix, the genital tract, and the anus. HPV's do not enter cells via the blood stream, therefore, having an HPV infection in one part of the body, usually does not cause an infection in another part. Once an HPV virus penetrates epithelial cells, it commences the production of proteins. High risk HPV's make proteins that disrupt the normal functionality of epithelial cells, enabling the cells to proliferate in an untamed manner and to evade apoptosis-programed cell death, a vital hallmark of cancer (Hanahan, Weinberg). After this process, the cancer can now advance and proliferate freely.(NCI) Usually, the immune system is very good at recognizing these cancerous cells and eliminating them, but not all cells are destroyed in this process. Cancer cells are very dynamic, they find ways of proliferating and evading immune system destruction (Hanahan, Weinberg). Researchers believe that 10-20 years lie in between the time of HPV infection and the time when tumors develop in the human body. (NCI), (Weinberg, Cancer Bio, 455).


 * Figure 3 :** diagram representing how the HPV virus causes cancer (cervical cancer in this case) in the long term.



__**V. Is this a geographical/physical/environmental disease?**__
====**//Is there something, like the climate, that makes HPV related cancer more prevalent in these countries, or is there a specific gene prevalent in certain ethnicity's that make it easier for HPV to become cancer, or is the state of the nation, developing vs. developed, the reason for the rates per population?//**====

When looking at maps that took a census of HPV cases in the world against a map with a census of Cervical Caner, there seemed to be a striking correlation.
 * Geographically**



Figure 4. Geographic Distribution of HPV prevalence in 2005 The map above illustrates the widespread prevalence of HPV in especially in Africa, South America, and various parts of Asia.

Figure 5 above,(5)shows the superior reign of cervical cancer in some African (mostly subsaharan Africa), South American (Brazil, Peru, Bolivia, Paraguay,etc) and Asian (India, Thailand, Cambodia, Nepal, Bhutan,etc) regions.
 * Figure 5**: Global distribution of Cervical Cancer prevalence in 2005.

A 2010 study on Examining attitudes and knowledge about HPV and cervical cancer risk among female clinic attendees in Johannesburg, South Africa, notes that developing countries account for 85% of the approximate 500,000 cases per year of cervical cancer globally. Approximately 250,000 of these deaths occur in Sub Saharan Africa, South Asia and Latin America as the data below also proves. There definitely appears to be an apparent correlation between HPV and cervical cancer in developing countries. In developing countries, for example African countries like South Africa and Zambia cervical cancer is highly prominent amongst women and almost always, it can be traced back to the HPV virus which is not surprising considering the lack of the vaccination against the HPV virus and sexual education in some developing countries. There also appears to be a significant correlation between HIV and the development of precancerous cervical cancer lesions.

Interesting link between HIV and HPV and Cervical cancer in women Examining attitudes and knowledge about HPV and cervical cancer risk among female clinic attendees in Johannesburg, South Africa Zambia has second highest incidence of Cervical cancer in Africa(Lusaka Times) **Oral infection by the Human Papilloma Virus in women with cervical lesions at a prison in São Paulo, Brazil.**
 * Case study's:**

Map of Global HIV Prevalence:
 * Figure 6**: Global distribution of HIV prevalence.

This map above rules out the link between HIV, HPV and cervical cancer in Asian and South American countries, however, the correlation can very much still be maintained for African countries (especially subsaharan African countries), where the most stubborn prevalence of HIV, can be observed as illustrated by the map above.

One suggested cause for the high rates of cervical cancer in developing countries may be attributed to the lack of efficient methods of screening for and treating HPV and cervical cancer. According to the WHO, cervical cancer is treatable, but many women in developing countries do not have access to effective screening programs, thus explaining the high incidences of cancer in developing countries. Furthermore, according to studies published by the NIH in 2001, incidences of cervical cancer are so high in developing countries primarily because of the lack of effective screening programs aimed at detecting and then treating precancerous conditions. In the study, an estimated 5% of females in developing countries had been screened for cervical dysplasia in 5 sequential years, where as in developed nations at least 40%-50% of the women had been screened for cervical dysplasia. Furthermore, while developing nations do offer pap smear services, in many cases, these tests are only available to a small number of women, via private health care. In short lack of technology, lack of follow up diagnostics and treatments are largely to blame for the high incidences and prevalence of cervical cancer in developing nations. Furthermore, in a 2010 study, 86 women aged 18-44 with at least one offspring were enlisted to take part in a survey which aimed to understand the attitudes towards and knowledge about HPV, cervical cancer and the HPV vaccine in South African women. The results reflected that the significant portion of the participants were not familiar with HPV, cervical cancer, and the vaccine. The women were however concerned about the risk to both them and their offspring of acquiring HPV and cervical cancer. The study also reflected the fact that many of these women faced barriers towards receiving screening for cervical cancer but were willing to get their offspring vaccinated.This study reflects the need for education in developing nations such as South Africa about HPV, how it is contracted and how it can lead to cancer. Such invaluable knowledge could offer a major break through in terms of reducing incidences of cervical cancer in the developing nations. Below is a sample of some of the questions asked and some of the results from the survey and study:
 * -Technology, Sexual Education and Wealth:**

Table 2. Women's knowledge of HPV.
 * ~ Question ||~ Participants’ response ||
 * < C1. Have you ever heard of HPV infection ||< 29% (// n // = 86) yes ||
 * < C2. HPV is a sexually transmitted disease/infection ||< 79% answered true ||
 * < C3. There is no cure for HPV but it can be controlled ||< 33% answered true ||
 * < C4. Having HPV puts one at risk for cervical cancer ||< 67% answered true ||
 * < C5. HPV is an infection that only affects women ||< 17% answered false ||
 * < C6. HPV is spread through sexual contact ||< 71% answered true ||
 * < C7. Condoms offer some protection from HPV ||< 75% answered true ||


 * Figure 7**: Cervical cancer mortality rates in both developed and developing countries.



So what is going on in the various continents, there seem to be multiple contributors to HPV as the data above suggests.

In South Asia, cervical cancer is the number one killer amongst women. In a study, cytological samples were obtained and tested for HPV infection and analyzed in order to better understand the associated risk factors for HPV in mainland China. The two areas of study were Hong Kong(HK) and Guangzhou(GZ) all locations in mainland china. 1570 individuals had their samples collected from HK, and 1369 individuals from GZ had their samples collected by researchers. HPV types 16 & 52 were observed in the samples from both HK and GZ. The study also found that age was consistent with HPV infection in HK while in GZ HPV infection was consistent with the number of sexual partners one had. HPV prevalence after being studied in 4 continents, Asia, Africa, Europe, and South America, is known to vary as much as 20 times in some cases amongst populations of various geographic locations. Within Chinese populations, researchers found that HPV prevalence and subtype distribution in cervical lesions and invasive cancer varied amongst different geographical areas of mainland China. For example, in HK, the HPV 16 found from the samples had close resemblance to Asian and European lineages, while that found in Sichuan, China had close similarity to Asian American and Asian lineages. One suggested reason for the difference is that HK is a British colony and it once was the portal for trade with the West for hundreds of years, thus explaining the prevalence of European HPV variants present in the area. Furthermore, the study found that In HK mortality due to cervical cancer increased in young women especially those residing in urban areas, this reflected that there was a shift in sexual behaviors also evident by the increase in STD's in the area in the 1990's. On the same note, due to economical growth, and better transportation, it is easier to go to and from HK and GZ, there has thus been more intermarriages between the two regions and like wise, more 'efficient' transmission of infectious diseases across the borders of the two regions.
 * CASE STUDY 1:**
 * -Contributors to HPV infection; cervical cancer in Main land China (South Asia).**


 * Figure 8:**
 * The prevalence of type-specific HPV infection in women with normal cytology in the HK and GZ cohorts. **

=Table 3 =

** The prevalence of type-specific HPV infection in women with normal cytology in the HK and GZ cohorts. ***Statistically significant at 0.05 level of significance by Holm's procedure that accounts for the multiple comparisons.**Adjusted for the stratified sampling design.** ** †† The seven commonest HPV high-risk types in the HK cohort. ‡‡ The seven commonest HPV high-risk types in the GZ cohort. **
 * |||| Hong Kong |||| Guangzhou ||  ||
 * HPV type || No. of positive case || Prevalence [|**] (95%CI) || No. of positive case || Prevalence [|**] (95%CI) || P value [|*] ||
 * 16 [|†][|‡] || 25 || 1.24% (0.75–1.73) || 21 || 1.19% (0.63–1.76) || 0.901 ||
 * 18 [|†][|‡] || 20 || 0.99% (0.56–1.43) || 9 || 0.68% (0.22–1.15) || 0.339 ||
 * 31 [|‡] || 0 || 0 || 27 || 1.16% (0.67–1.66) || ** <0.001 ** [|*] ||
 * 33 [|†][|‡] || 5 || 0.25% (0.03–0.47) || 10 || 0.59% (0.2–0.98) || 0.136 ||
 * 35 || 0 || 0 || 1 || 0.07% (0.0–0.21) || 0.317 ||
 * 39 || 1 || 0.04% (0.0–0.12) || 6 || 0.32% (0.03–0.6) || 0.07 ||
 * 45 [|†] || 3 || 0.15% (0.0–0.31) || 3 || 0.24% (0.0–0.54) || 0.577 ||
 * 51 || 0 || 0 || 2 || 0.14% (0.0–0.35) || 0.198 ||
 * 52 [|†][|‡] || 23 || 1.16% (0.68–1.64) || 40 || 2.62% (1.75–3.48) || ** 0.004 ** [|*] ||
 * 56 || 0 || 0 || 4 || 0.27% (0.0–0.54) || 0.058 ||
 * 58 [|†][|‡] || 20 || 1.03% (0.58–1.48) || 18 || 1.07% (0.53–1.62) || 0.905 ||
 * 59 || 2 || 0.09% (0.0–0.21) || 2 || 0.15% (0.0–0.37) || 0.619 ||
 * 68 [|†][|‡] || 5 || 0.23% (0.03–0.44) || 7 || 0.39% (0.06–0.72) || 0.428 ||
 * In concluding the study, researchers found that the main risk factors for the acquisition of HPV in both regions included, i) the number of lifetime sexual partners, ii) contraceptive use, iii) smoking and iv) having previous STD history, v) age. The researchers also concluded that the best way to combat cervical cancer in Southern Chinese women was to i) provide population education, and ii) to provide effective cancer screening.**

CASE STUDY 2:** In Jingan County of China, a study consisting of 16,767 women over the age of 25 or more where followed during the 1974-1985 within the framework of a program for cervical screening. At the beginning of the experiment women were interviewed with standard questions that gave the research insight into the women's demographic information, their menstrual cycle, fertility and reproductive history up to that point, family history, and marital/partner status. At the end of the study, between 1984-1985, the women were gathered again to answer questions about personal habits, hygiene, sexual behaviors, partners sexual behavior. This was done so that the researchers could rule out other known factors so they may focus on just geography. 99% of cases confirmed invasive squamous cell carcinomas were found after the end of the study.



FIG.9 The results of the experiment measured as relative risk rate or the odds of getting the disease as well as a 95% confidence interval.

Their conclusion was that the incidence rates were notably higher for women who lived in the mountain area, moderate for those in the hills, and low for the women who lived in the plain regions. The rest of the study did look at the other factors related to cervical cancer and it was reflective of what was already known about those factors, again establishing the risk of normal life choices on HPV related cervical cancer.

www.ncbi.nlm.nih.gov/pmc/articles/PMC1060214

Treatments:
-Surgery -Radiation Terapy -Chemotherapy -Vaccines against HPV. E.g- gardasil.

Table 3: Pros and Cons of vaccines that take a prophylactic approach to treating and detaining HPV.

Characteristics of prophylactic HPV vaccine approaches.(NIH) Different immunological properties of viruses Wide variety of vectors available Can potentially be engineered to express cytokines or other stimulatory molecules || Risk of toxicity in using live viruses Potential pre-existing immunity Inhibited repeat immunization Immunodominance of viral vector antigens over HPV tumor antigens || Can deliver either engineered plasmids or HPV tumor proteins to antigen-presenting cells Wide variety of vectors available || Risk of toxicity in using live bacteria Potential pre-existing immunity Inhibited repeat immunization || Can combine multiple epitopes Can enhance peptides for MHC binding || Low immunogenicity Must determine epitopes Must match patient’s [|HLA] || Multiple known adjuvants No [|HLA] restriction || Usually better induction of antibody response than CTL response || Versatility in ability to add targeting and/or co-stimulatory genes Capable of multiple immunizations Variety of delivery methods (i.e., direct injection, gene gun, intranasal, biojector) Sustained expression of antigen on MHC-peptide complex (compared with peptide/protein vaccines) || Intrinsically weak immunogenicity Concern of integration into genome or cellular transformation || Capable of multiple immunizations RNA replicons replicate within the cell to enhance antigen expression Multiple vectors are available || Difficult to store and handle Labor-intensive preparation Difficult to prepare large amounts || Methods are available to generate large numbers of DCs Multiple methods of antigen loading available Potency can be enhanced by gene transduction or cytokine treatment || Labor intensive, costly, // ex vivo //, individualized cell processing Variable quality control and a lack of standard criteria for quality of vaccines Do not necessarily home to draining lymph nodes Possibility of tolerization by immature DCs || Potency can be enhanced by gene transduction or cytokine treatment Likely to express relevant tumor antigens || Safety concerns about injecting tumor cells into patients Labor-intensive procedure Weak antigen presentation by tumor cells Requires availability of tumor cell lines or autologous tumor cells || *DC: Dendritic cell; HPV: Human Papillomavirus.
 * ~ Vaccine approach ||~ Advantages ||~ Disadvantages ||
 * Viral-vector-based (i.e., vaccinia, adenovirus, alphavirus) || High immunogenicity
 * Bacterial-vector-based (i.e., // Listeria //,// Salmonella //, // Lactococcus //) || High immunogenicity
 * Peptide based || Stable, easy to produce, safe
 * Protein based || Stable, easy to produce, safe
 * DNA || Easy to produce, store and transport
 * RNA || Non-infectious, transient; no risk of chromosomal integration or cellular transformation
 * DC based || High immunogenicity; uses the most potent antigen-presenting cells
 * Tumor cell based || Useful if tumor antigen unknown


 * Figure 9** above below illustrates how vaccines with a therapeutic approach would deal with HPV infection. We propose that such a drug be developed to treat HPV and HPV-Related Cervical Cancer.



**Other preventative measures to take:**

 * -Routine Screenings:** Developing nations are unable to provide or receive the routine screenings or even the proper screenings as they do not have the resources for it, nor the knowledge to get one.
 * -Maintaining one sex partner:** People in developing countries don't understand the risk of having multiple partners.
 * -Sexual education:** Many people in developing countries are unaware of the risks as there are less educational resources for them to get in contact with in order to prevent HPV related cancer.
 * -Lifestyle**: According to Sophia Chernikova from Stanford diet and lifestyles play key roles in the development of cancer in individuals. For example, cancer is on the rise in developing countries due to unhealthy dietary and exercise habits.

VIII. Conclusion
HPV related cervical cancer is extremely common and transmittable, causing it to be one of the leading reasons as to the severity of the cancer as well as its enormity as a world wide disease. There are many risk factors that are known to increase the risk of HPV becoming cervical cancer and as many of them are every common actions of life, it is important that people monitor their life choices. As for the case of those living in developed countries, many of them do not realize or are unaware of HPV and its causing them to be further unaware of their chances of cervical cancer. Many of the cases that are seen in these developed countries are due to lack of education in both HPV and in cervical cancer, which this lack of knowledge is considered the leading cause to the high rates of HPV cervical cancer. Because of these, we feel that there should be preventative measures made available to the people in these countries in order to avoid HPV, such as education in the disease and how to get it/treat it. We also feel that the people should be made aware of the possibility of HPV becoming cervical cancer and that there should be accessibility to treatment centers that can help screen and test patients for both HPV and cervical cancer. We would be curious to see the rate of decline in these countries after such measures were taken, as we predict the high levels of HPV cervical cancer would drastically decrease possibly to the same rates seen in developed countries. However, we do also realize that this would be respectively as the care would still not be at the same availability level or unfortunately the same quality that is accessible by developed nations.

However, because of the research we have seen, there seems to be a possibility that geography places a role in HPV related cervical cancer. Although the two cases studies conducted in China were contradictory they both express promise in the idea of geography as a risk factor. We believe that a study should be conducted world wide, analyzing both developed and developing countries to observe if a correlation between geography and the disease does in fact exist and acts as an amplifier for HPV becoming cervical cancer. This needs to be on a global scale and done in the same fashion as the Jingan study, as to ensure that the only factor tested was geography. There would be a lot of problems that could occur with this study such as people moving therefore moving to other regions contaminating the data, so if this test was conducted over 10-20 years, the evidence could be considered inconclusive. Nonetheless, a study like this could show that where you live affects your chance of HPV related cancers and by doing so would allow people to factor it into how to best treat cervical cancer induced by HPV.


 * Bibliography:**


 * "HPV and Cancer." //HPV and Cancer- National Cancer Institute//. National Cancer Institute, 15 March 2012. Web. 13 Jun 2012.
 * "HPV infection ." //HPV infection :Risk factors-Mayo Clinic//. Mayo Clinic, 24 May 2012. Web. 13 Jun 2012. .
 * . "HPV Infection plus Cigarette Smoking-A Deadly Combination." //HPV Infection plus Cigarette Smoking-A Deadly Combination//. HCPLive, 5 May 2007. Web. 13 Jun 2012.
 * "HPV and HIV." //HPV and HIV- TheBody.com//. The Body, March 2003. Web. 13 Jun 2012. .
 * Pontén, J., and Z. Guo. "Precancer of the human cervix."//NCBI//. (1998): 32,201-29. Web. 13 Jun. 2012.
 * Sherris, Jacqueline, Cristina Herdman, Christopher Elias, et al. "Cervical cancer in the developing world."//NCBI//. 175.4 (2001): 231-233. Web. 13 Jun.
 * "Types of HPV." //Types of HPV//. MedTV, 2006. Web. 13 Jun 2012. .
 * "Virus-Science Definition." //Virus-Science Definition//. Houghton Mifflin Harcourt Publishing Company, 2012. Web. 13 Jun 2012. .
 * ** Hung, Chien-Fu, Barbara Ma, et al. "Therapeutic human papillomavirus vaccines: current clinical trials and future directions." NCBI. 8.4 (2011): 421-439. **
 * ** Liu, Stephanie Si, Kelvin Yuen Kwong Chan, et al. "Prevalence and Risk Factors of Human Papillomavirus (HPV) Infection in Southern **
 * ** http://www.prn.org/images/uploads/hpv_3d_high.jpg **