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ABSTRACT RESULTS AND DISCUSSION

INTRODUCTION

CONCLUSIONS

A SYSTEMATIC OVERVIEW: THE EFFICACY OF HPV VACCINCATIONS IN PREVENTING CERVICAL

CANCER By: Blayne Clarke and Camika Parkes

Faculty of Health Sciences, University of Ottawa

METHODOLOGY

REFERENCES

Figure 1. Age-specific prevalence of HPV among women with normal cytology, by world region5. Figure 2. HPV prevalence in HPV-associated cancers5.

Figure 3. Carcinogenic mechanism of HPV (top) and A Schematic representation of the HPV genome (bottom)5.

Figure 4. The Multistep process of cervical carcinogenesis5.

Figure 5. Role of E6 and E7 in the HPV-induced carcinogenesis of cervical cancer5.

Figure 6. Anti-HPV vaccines efficacy in preventing cervical infections from HPV-166.

Figure 7. Anti-HPV bivalent and tetravalent vaccines efficacy in preventing persistent cervical infections from HPV-166.

Figure 8. Anti-HPV bivalent and tetravalent efficacy in preventing persistent cervical infections from HPV 186.

Figure 6 shows the reduction of HPV 16 infection risk. The relative risk was 0.10 (95% CI: 0.07-0.15) with a 10 times decrease in the risk of becoming infected in the vaccinated group.

Figure 7 shows a relative risk of 0.13 (95% CI: 0.09-0.20) which therefore signifies an 8 times decrease of risk of infection from HPV 16 for women who have been vaccinated with bivalent and tetravalent vaccines.

Figure 8 shows a relative risk of 0.22 (95% CI: 0.13-0.38) which therefore signifies a 4.5 times reduction of risk of infection from HPV 18 vaccination in women.

Vaccines against HPV 16 and 18 could significantly reduce the HPV-related cervical disease burden.

The tetravalent and bivalent vaccines pooled efficacy is 87% (95% CI: 80-91%) and 78% (95% CI: 62-87) in preventing cervical infections from HPV 16 and HPV 18 respectively.

Similar techniques for HPV DNA was used in the different trials therefore the potential for misclassification bias was reduced.

All the studies used were pooled analyses of clinical trials with common study outcomes. Therefore confounders and selection bias were reduced.

Although there are several studies on HPV vaccine efficacy, most of them have a short follow-up stage therefore it was decided that vaccine efficacy in preventing infection and not invasive carcinoma was evaluated.

Since there is a dearth of studies with long follow-up phases, it makes it impossible to evaluate the long-term vaccine efficacy/duration of immunization and therefore HPV screening is still necessary.

30% of cervical cancers are related to HPV types that are not targeted by the vaccines. Therefore vaccination does not eliminate the need to screen women.

BACKGROUND: Cervical cancer is a malignant tumour development that starts in the cervix. This cancer is a significant problem for women worldwide. Infection with the human papilloma virus (HPV) is necessary for the development of cervical cancer. HPV vaccination has been shown to be effective in reducing infection caused by the vaccine-associated HPV types 16 and 18. METHODS: To gauge the potential impact of HPV vaccines on incidence rates of cervical cancer, a systematic review was conducted on accessible data from randomized controlled trials on the efficacy of HPV vaccines. Research was primarily based upon the findings and publication of online electronic databases. 42 articles were screened and 8 which demonstrated a more evidence-based approach were included in this review. RESULTS: Meta-analysis indicates that the two available HPV vaccines, Gardasil and Cervarix, seem to be highly efficacious in preventing precancerous cervical lesions and the development of HPV infections, which have the ability to lead to cervical cancer in women between the ages of 14 and 26. The HPV vaccines proved to be most efficient amongst women who had not previously been infected with HPV strains. CONCLUSION: HPV vaccinations are extremely efficient in preventing persistent HPV 16 and 18 cervical infections. The use of HPV vaccinations show great promise to reduce the incidence of HPV-induced cervical cancers in the future.

Cervical cancer is a malignant tumour development that starts in the cervix. Globally, cervical cancer is the third leading type of cancer in women. It is estimated that 371 000 new cases of invasive cervical cancers are diagnosed yearly. Women in areas such as the Caribbean, South and Central America as well as Eastern Africa, have the highest risk for cervical cancer. In Canada, the highest incidence rates of cervical cancer are in Newfoundland, Nova Scotia, and Prince Edward Island. Cervical cancer also has a high prevalence rate in Aboriginal, Hispanic and Black populations. The mortality rate of cervical cancer has decreased over the past 50 years with the help of Papanicolaou smear screening programs. Studies have long established that there is a strong positive correlation between cervical cancer and the Human Papilloma Virus (HPV). There are currently two vaccinations: Gardasil (tetravalent) and Cervarix (bivalent), which have been FDA approved for use in females aged 9-26. RESEARCH QUESTION: How efficient are HPV vaccinations in reducing the incidence of HPV-induced cervical cancers?

Research was primarily based upon the findings and publications of online electronic databases. Listed below are the steps that were followed in a consecutive sequence. A) Literature Search: The electronic databases used for the search were PubMed, Google Scholar and Web of Science. All of these vast databases helped in the ‘collection of articles’ process. English language key terms such as “Papillomavirus”, “HPV vaccine”, “Cervical Cancer”, and “Randomized Control Trial” were typed into these databases separately and in combination, in order to find various articles.B) Quality Assessment and Study Selection: Only data on randomized clinical trials were selected. Inclusion criteria also included those studies that focused on the efficacy of the HPV vaccine, as well as studies that were carried out on women. Exclusion criteria included any studies that did not focus on the efficacy of the HPV vaccine in preventing cervical cancer, studies that were carried out solely on males, those that were not randomized clinical trials, studies evaluating the therapeutic efficacy of HPV vaccines, and studies which investigated HPV vaccine efficacy in preventing invasive cervical carcinoma.C) Statistical Analysis: The studies were examined by two separate researchers. Meta-analysis was performed on studies found to be suitable for research objective.  

HPV is not only the most common of sexually transmitted diseases, but it is also responsible for more than 70% of cervical cancers worldwide. It takes many years for precancerous HPV lesions to develop into invasive cervical cancer and because of this, it will probably be another decade, before people can be certain that this vaccine will result in a reduction in the incidence of HPV-induced cervical cancers using data from those vaccinated. However, results from clinical trials show a very promising future. HPV vaccinations are extremely efficient in reducing HPV 16 and 18 infection risk, both of which can lead to cervical cancer. Despite controversy, these vaccines have very high efficacy, and its’ efficiency will only continue to improve.

1. American Society of Clinical Oncology. (2010). HPV Vaccination for Cervical Cancer: Ask an Expert. Retrieved March 30, 2011, from http://www.cancer.net/patient/All+About+Cancer/Cancer.Net+Feature+Articles.2. Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski, B, Roteli-Martins CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006;367(9518):1247–55.3. Hong No, J., Kim, M., Jeon, Y., Kim, Y., & Song, Y. (2011). Human papillomavirus   vaccine: Widening the scope for cancer prevention. Molecular Carcinogenesis, 50(1), 244-253.4. Koutsky, L., et. Al. (2002). A Controlled trial of a human papillomavirus type 16 vaccine. New England Journal of Medicine. Retrieved April 1, 2011, from PubMed database.

5. La Torre, G., de Waure, G., Chiaradia, G., Mannocci, A., & Ricciardi, W. (2007). HPV vaccine efficacy in preventing persistent cervical HPV infection: A systematic review and meta-analysis. Vaccine, 25(1), 8352-8358.6. Paavonen J, Jenkins D, Bosch FX, Naud P, Salmer´on J, Wheeler CM, et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-likeparticle vaccine against infection with human papillomavirus types 16 and 18 in youngwomen: an interim analysis of a phase III double-blind, randomized controlled trial. Lancet 2007;369(9580):2161–70. 7. Rambout, L., Hopkins, L., Hutton, B. & Fergusson, D. (2009). Prophylactic vaccination against human papillomavirus infection and disease in women: A systematic review of randomized controlled trials. Canadian Medical Association Journal. Retrieved March 30, 2011, from PubMed database.8. Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen OE, et al. High sustained efficacy of a prophylactic quadrivalent humanpapillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer 2006;95(11):1459–66.