**1. Introduction**

Cervical cancer was formerly the second most common cancer killer of women worldwide. Following widespread adoption of Papanicolau cytologic screening (Pap test) for cervical cancer in the 1950s, this began to change. Today, advanced cervical cancer is rare in screened populations. Although an uncommon disease in developed nations, internationally about 500,000 women annually are diagnosed with cervical cancer, and about half of those women will die of their disease. In global terms, this ranks second only to breast cancer as a cause of cancer-specific mortality. Over the past three decades the scientific community has witnessed spectacular advances in the understanding of the underlying pathophysiology of cervical cancer, with the most profound discovery being in 1983 of the identification of the human papillomavirus (HPV) within cervical cancer (a discovery that earned Harold Zur-Hausen, M.D the Nobel prize for Medicine and Physiology in 2008). A viral etiology for cervical cancer implied that it may be possible to eradicate cervical cancer through vaccination. This promise was partially fulfilled in 2006 when the United States Food and Drug Administration approved an HPV vaccine for the prevention of HPV-induced cervical dysplasia and/or cancer. These advances, profound though they are, have yet to eradicate cervical cancer. Furthermore, due to the pervasiveness of HPV infection and the timeline of disease progression, it will be a few decades before we will be able to determine the impact preventive practices are having on cancer incidence and prevalence. In addition, those for whom preventative measures are not a solution, including HIV+ individuals as well as women already infected with HR-HPV, await an answer.

Over the past several years, developments in innovative imaging, superior surgical technolo‐ gies, immunotherapies, and molecular therapies have surfaced, making the eradication of

© 2013 Evans et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

cervical cancer a much more achievable goal than in the past. Several areas of cervical cancer research continue to address the challenges posed by the need for appropriate therapeutic alternatives, and progress is occurring at each level of clinical management ranging from detection to the development of small molecule antiviral leads. Because the field is evolving rapidly in all directions and related disciplines, it is helpful to summarize the status of our growth, and to recognize those pioneering efforts that may ultimately contribute to achieving our goal of eliminating cervical cancer. This review seeks to survey the current understanding of cervical cancer etiology and treatment and to review areas requiring additional progress.

UNESCO (United Nations Educational, Scientific, and Cultural Organization) has demon‐ strated the effectiveness of sex education in the global fight against HIV/AIDs. Although HPV does not currently compare to HIV/AIDs in terms of mortality and global magnitude, the need for HPV awareness has grown tremendously and it is speculated that such a plan may prove useful here as well. An increase in consciousness may decrease sexual risk behaviors if populations at high-risk for contracting HPV were actively targeted for education [16, 17]. However, it should be considered that gender inequalities experienced by women in locations like Sub-Saharan Africa, as reported by the Global Health Corps and UNESCO, may negatively impact these initiatives. Furthermore, the cost of such programs compared to other interven‐ tional methods has not been determined. But in general, education can be used as a powerful tool in preventing HPV-mediated diseases such as cervical cancer. Ideally, these programs would emphasize risk-perception in both men and women leading to lifestyle modifications, and a further reduction in the incidence of HPV-mediated carcinoma might be realized.

Modern Molecular and Clinical Approaches to Eradicate HPV-Mediated Cervical Cancer

http://dx.doi.org/10.5772/55810

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*Prophylactic Immune Strategies:* Presently, the most effective protective factor against the most prevalent and high-risk types of HPV infection is prophylactic vaccination [18]. It has been seven years since the introduction of the first HPV vaccine [19]. Since then, two vaccines, Gardasil and Cervarix, have been made available to the public to protect against the more common HPV strains [20]. The vaccines induce the production of neutralizing antibodies against HPV L1 capsid virus-like proteins (VLPs), which do not contain virus genetic material. The quadrivalent vaccine, Gardasil, protects against low- and high-risk HPV (LR- and HR-HPV, respectively) types 6, 11, 16, and 18 following full vaccination of all three doses at 0, 1, 2 and 6 months. Alternatively, the bivalent vaccine, Cervarix, prevents infection by HR-HPV types 16 and 18. Both vaccines have been documented to possess compelling prophy‐ lactic efficacy in preventing cervical, genital, and anal diseases. This protection is expected to persist for 7 years, or at least during the years of high infection risk for most individuals

HPV infections of types other than the four mentioned above are not reliably prevented by vaccination. Also, studies are warranted regarding the vaccine's long-term effects and how they might impact the occurrence of infections by other HPV types. It has already been noted that quadrivalent and bivalent vaccines may exhibit cross-protection against HPV 31 and other types by 75 to 80 percent [23]. However, concerns are emerging that relate to HPV typereplacement. Type-replacement is an increased prevalence of other HPV strains that are not included in the vaccines, while vaccine-type HPV prevalence is decreased. It was recently reported that vaccine-type HPV has been reduced in vaccinated and nonvaccinated women, while nonvaccine-type HPV has slightly increased overall [24]. Researchers do not expect typereplacement to occur frequently. However, studies are becoming more attentive to changes in the prevalence of various HPV types, which are expected to surface first within the sexually experienced population. Such discoveries could encourage the research community to continue seeking multivalent solutions to as many HPV types as possible without eliciting additional harmful results. To date, clinical trials have revealed that the most common adverse response to both vaccines are injection site reactions, which occur more frequently in vaccine

groups rather than in participants given placebos [25].

[20-22].
