Cervical cancer human papillomavirus

Cervical cancer, human papillomaviruses (HPVs) and, 22 Channel catfish virus, 381 CHEF sheet, 128... 

A new subunit recombinant vaccine is Gardasil it is a tetravalent vaccine against human papillomavirus (HPV) implicated in cervical cancer. See Exhibit 4.5 for details. 

Gardasil is a noninfectious recombinant vaccine consisting of capsid proteins from four different human papillomaviruses (HPVs) of types 6,11, 16, and 18. HPV causes squamous cell cervical cancer and cervical adenocarcinoma, as well as 35-50% of vulvar and vaginal cancers. 

Grinstein E, Wernet P, Snijders PJ, Rosl F, Weinert I, Jia W, Kraft R, Schewe C, Schwabe M, Hauptmann S, Dietel M, Meijer CJ, Royer HD (2002) Nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer. J Exp Med 196 1067-1078 Grisendi S, Bernard R, Rossi M, Cheng K, Khandker L, Manova K, Pandolfi PP (2005) Role of nucleophosmin in embryonic development and tumorigenesis. Nature 437 147-153 Hanakahi LA, Bu Z, Maizels N (2000) The C-terminal domain of nucleolin accelerates nucleic acid annealing. Biochemistry 39 15493-15499... 

Human papillomavirus (HPV) infection is a necessary factor in the development of nearly all cases of cervical cancer. A recently approved HPV vaccine, Gardasil, that blocks initial infection with several of the most common sexually transmitted HPV types may lead to significant decreases in the incidence of HPV-induced cancer (see Lowy et ah, 2006). 

Human papillomavirus (HPV) is the causative agent of virtually all cases of cervical cancer and one of the most common of the sexually transmitted diseases. Cervical cancer remains a main cause of cancer-related death in many developing countries. Current vaccines are too expensive... 

The occurrence of malignant tumors in patients taking oral contraceptives has been studied extensively. It is now clear that these compounds reduce the risk of endometrial and ovarian cancer. The lifetime risk of breast cancer in the population as a whole does not seem to be affected by oral contraceptive use. Some studies have shown an increased risk in younger women, and it is possible that tumors that develop in younger women become clinically apparent sooner. The relation of risk of cervical cancer to oral contraceptive use is still controversial. It should be noted that a number of recent studies associate the use of oral contraceptives by women who are infected with human papillomavirus with an increased risk of cervical cancer. 

Muderspach, L., Wilczynski, S., Roman, L., et al. (2000) A phase I trial of a human papillomavirus (HPV) peptide vaccine for women with high-grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive. Clin. Cancer Res. 6, 3406-3416. 

Several DNA viruses are associated with, and are important in, the etiology of certain human cancers. For example, chronic infection with hepatitis B or C virus (HBV, HCV) is associated with liver cancer, infection with human papillomavirus (HPV) type 16 and type 18 is associated with cervical cancer, and infection with Epstein-Barr virus (EBV) is associated with Burkitt s lymphoma. About one-fifth of human cancer worldwide is associated with DNA oncogenic viruses. In 2006, the FDA approved a vaccine against HPV 16 and 18, which are responsible for about 70% of cervical cancer cases. 

Molecular risk biomarkers could detect systemic or local changes indicating that the carrier of this specific biomarker is at higher risk for disease development in the future. Examples include the presence of human papillomavirus in the cervix, which is associated with a higher risk for the development of cervical cancer, the association between Hdicohacterpylori and gastric cancer as well as EBV and nasopharyngeal carcinoma. The drawback of these markers is that they are not helpful for the detection of early disease. 

Papillomavirus infections usually cause benign epithelial papillomas, but a subset of human papillomaviruses is associated with cervical cancer [137]. More than 90% of cervical cancers are associated with sexually transmitted genital human papillomavirus. Because of this high degree of association and the high mortality rate of cervical cancer, it is of great importance to understand the mechanism of antibody-mediated neutralization to facilitate vaccine development. 

Jansen AM, Peto J, et al. Prevalence of human papillomavirus in cervical cancer a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Nad Cancer Inst 1995 87 796-802. 

Gissmann L, Wolnik L, Ikenberg H, Koldovsky U, Schnurch HG, zur Hausen H. Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papniomas and in some cervical cancers. Proc Natl Acad Sci, USA 1983 80 560-3. 

Walboomers JM, Jacobs MV, Manos MM, Bosch EX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999 189 12-9. 

Zhang MQ, El-Mofty SK, Davila RM. Detection of human papillomavirus-related squamous cell carcinoma cytologically and by in situ hybridization in fine-needle aspiration biopsies of cervical metastasis a tool for identifying the site of an occult head and neck primary. Cancer. 2008 114(2) 118-123. 

Another manifestation of genetic instability is an abnormal number of centro-somes. Centrosomes can be stained and quantified in an assay using anti-centrin antibodies. Both, genetic instability and loss of genomic integrity, are often posttransformation events. However, under certain circumstances they can contribute to cellular transformation directly. An example is the transformation by the human papillomavirus (HPV) E7 protein. The HPV E7 and E6 proteins are the two HPV oncogenes found in 99.3% of all cervical cancers. 

In a chapter Infection Unmasked, Drexler first underscores the point that some 70% of all deaths are due to lingering or chronic illnesses rather than to the abrupt severity of acute afflictions. Furthermore, there is the statement that today, a growing number of researchers claim that these disabling conditions may be caused by infection. Thus, more than 90% of cervical cancer cases are caused by the human papillomavirus, and more than 60% of liver cancer cases result from the hepatitis B virus. The retrovirus HTLV-1 is the precursor for adult T cell lymphoma, with the cancerous condition occurring decades after the infection. The Epstein-Barr virus, a herpes-type virus causing mononucleosis, also has an effect on people with malaria, producing a cancer known as Burkitt s lymphoma, the leading cause of childhood cancer deaths worldwide. Kaposi s sarcoma, known as a comphcation of AIDS, is said to be caused by human herpesvirus 8. 

Merck s Gardasil, recently approved by FDA for the prevention of two types of human papillomavirus (HPV) that can lead to cervical cancer, is expected to be quite profitable, and money and some liability protection have become available in recent years in light of potential bioterrorist threats like anthrax. For more on the future profitability of vaccines, see Ginsberg, T. Making vaccines worth it. Philadelphia Enquirer, September 24, 2006. 

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