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Prevention and Treatment of Cervical Cancer by Vaccination

  • Chapter
Molecular Pathology of Gynecologic Cancer

Part of the book series: Current Clinical Oncology ((CCO))

Abstract

Causality requires a judgment based on scientific evidence from human and experimental studies, as strict causality studies are often not appropriate in humans. Evidence linking certain human papillomavirus (HPV) genotypes to cervical carcinoma is extensive and compelling. More than two decades of research has led to the fulfillment of criteria, as proposed by Hill, to establish a causal link between high risk HPV infection and cervical cancer (Table 1). HPV DNA was first isolated from biopsies of cervical cancer more than 30 years ago (1, 2). HPV DNA is detected in 99.7% of cervical carcinomas worldwide. The evidence overwhelmingly demonstrates that persistent high risk HPV infection is a necessary but not sufficient cause of this cancer (3).

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References

  1. zur Hausen H, Meinhof W, Scheiber W, Bornkamm GW. Attempts to detect virus-secific DNA in human tumors. I. Nucleic acid hybridizations with complementary RNA of human wart virus. Int J Cancer 1914; 13(5): 650–656.

    Google Scholar 

  2. Gissmann L, Boshart M, Durst M, Ikenberg H, Wagner D, zur Hausen H. Presence of human papillomavirus in genital tumors. J Invest Dermatol 1984; 83(Suppl 1): 26S–28S.

    PubMed  CAS  Google Scholar 

  3. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189(1): 12–19.

    PubMed  CAS  Google Scholar 

  4. Schwarz E, Freese UK, Gissmann L, et al. Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 1985; 314(6006): 111–114.

    PubMed  CAS  Google Scholar 

  5. Human papillomaviruses. WHO/IARC, Lyon, France, 1995. Volume 64, 1–6.

    Google Scholar 

  6. Kreider JW, Howett MK, Wolfe SA, et al. Morphological transformation in vivo of human uterine cervix with papillomavirus from condylomata acuminata. Nature 1985; 317(6038): 639–641.

    PubMed  CAS  Google Scholar 

  7. Durst M, Dzarlieva-Petrusevska RT, Boukamp P, Fusenig NE, Gissmann L. Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus type 16 DNA. Oncogene 1987; 1(3): 251–256.

    PubMed  CAS  Google Scholar 

  8. Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT. HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. Embo J 1989; 8(12): 3905–3910.

    PubMed  CAS  Google Scholar 

  9. Strickler HD, Dillner J, Schiffman MH, et al. A seroepidemiologic study of HPV infection and incident cervical squamous intraepithelial lesions. Viral Immunol 1994; 7(4): 169–177.

    PubMed  CAS  Google Scholar 

  10. Jha PK, Beral V, Peto J, et al. Antibodies to human papillomavirus and to other genital infectious agents and invasive cervical cancer risk. Lancet 1993; 341(8853): 1116–1118.

    PubMed  CAS  Google Scholar 

  11. Koutsky LA, Ault KA, Wheeler CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002; 347(21): 1645–1651.

    PubMed  CAS  Google Scholar 

  12. deVilliers EM. Human pathogenic papillomavirus types: an update. Curr Top Microbiol Immunol 1994; 186: 1–12.

    PubMed  Google Scholar 

  13. Centers for Disease Control and Prevention (CDC). MMWR Morb. Mortal. Wkly. Rep. 2006; 55(41): 1118–1120.

    Google Scholar 

  14. Koutsky LA, Galloway DA, Holmes KK. Epidemiology of genital human papillomavirus infection. Epidemiol Rev 1988; 10: 122–163.

    PubMed  CAS  Google Scholar 

  15. Munoz N, Bosch FX, deSanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348(6): 518–527.

    PubMed  Google Scholar 

  16. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics 2002. CA Cancer J Clin 2005; 55(2): 74–108.

    PubMed  Google Scholar 

  17. Clifford GM, Gallus S, Herrero R, et al. Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet 2005; 366(9490): 991–998.

    PubMed  CAS  Google Scholar 

  18. Baker C, Calef C. Maps of Papillomavirus mRNA Transcripts. HPV Compendium 1997. III–3.

    Google Scholar 

  19. Baker TS, Newcomb WW, Olson NH, Cowsert LM, Olson C, Brown JC. Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J 1991; 60(6): 1445–1456.

    PubMed  CAS  Google Scholar 

  20. Modis Y, Trus BL, Harrison SC. Atomic model of the papillomavirus capsid. Embo J 2002; 21(18): 4754–4762.

    PubMed  CAS  Google Scholar 

  21. Finnen RL, Erickson KD, Chen XS, Garcea RL. Interactions between papillomavirus LI and L2 capsid proteins. J Virol 2003; 77(8): 4818–4826.

    PubMed  CAS  Google Scholar 

  22. You J, Croyle JL, Nishimura A, Ozato K, Howley PM. Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 2004; 117(3): 349–360.

    PubMed  CAS  Google Scholar 

  23. Doorbar J, Campbell D, Grand RJ, Gallimore PH. Identification of the human papilloma virus-la E4 gene products. Embo J 1986; 5(2): 355–362.

    PubMed  CAS  Google Scholar 

  24. Kawana Y, Kawana K, Yoshikawa H, Taketani Y, Yoshiike K, Kanda T. Human papillomavirus type 16 minor capsid protein 12 N-terminal region containing a common neutralization epitope binds to the cell surface and enters the cytoplasm. J Virol 2001; 75(5): 2331–2336.

    PubMed  CAS  Google Scholar 

  25. Patterson NA, Smith JL, Ozbun MA. Human papillomavirus type 31b infection of human keratinocytes does not require heparan sulfate. J Virol 2005; 79(11): 6838–6847.

    PubMed  CAS  Google Scholar 

  26. Yang R, Day PM, Yutzy WHT, Lin KY, Hung CF, Roden RB. Cell surface-binding motifs of L2 that facilitate papillomavirus infection. J Virol 2003; 77(6): 3531–3541.

    PubMed  CAS  Google Scholar 

  27. Richards RM, Lowy DR, Schiller JT, Day PM. Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proc Natl Acad Sci USA 2006; 103(5): 1522–1527.

    PubMed  CAS  Google Scholar 

  28. Bossis I, Roden RB, Gambhira R, et al. Interaction of tSNARE syntaxin 18 with the papillomavirus minor capsid protein mediates infection. J Virol 2005; 79(11): 6723–6731.

    PubMed  CAS  Google Scholar 

  29. Yang R, Yutzy WH, Viscidi RP, Roden RB. Interaction of L2 with beta-actin directs intracellular transport of papillomavirus and infection. J Biol Chem 2003; 278(14): 12,546–12,553.

    PubMed  CAS  Google Scholar 

  30. Day PM, Roden RB, Lowy DR, Schiller JT. The papillomavirus minor capsid protein, L2, induces localization of the major capsid protein, LI, and the viral transcription/replication protein, E2, to PML oncogenic domains. J Virol 1998; 72(1): 142–150.

    PubMed  CAS  Google Scholar 

  31. Day PM, Baker CC, Lowy DR, Schiller JT. Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression. Proc Natl Acad Sci USA 2004; 101(39): 14,252–14,257.

    PubMed  CAS  Google Scholar 

  32. Hildesheim A, Schiffman MH, Gravitt PE, et al. Persistence of type-specific human papillomavirus infection among cytologically normal women. J Infect Dis 1994; 169(2): 235–240.

    PubMed  CAS  Google Scholar 

  33. Ho GY, Studentsov YY, Bierman R, Burk RD. Natural history of human papillomavirus type 16 virus-like particle antibodies in young women. Cancer Epidemiol Biomarkers Prev 2004; 13(1): 110–116.

    PubMed  CAS  Google Scholar 

  34. Ferenczy A, Franco E. Persistent human papillomavirus infection and cervical neoplasia. Lancet Oncol 2002; 3(1): 11–16.

    PubMed  CAS  Google Scholar 

  35. Ali SZ, Steinberg DM, Rosenthal DL, Chan TY, Burroughs F. Cytopathology Tutorial: The Johns Hopkins University School of Medicine Department of Pathology Division of Cytopathology, 2002. http://pathology2.jhu.edu/cyto_tutorial/Atlas/Index.cfm

  36. Holowaty P, Miller AB, Rohan T, To T. Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 1999; 91(3): 252–258.

    PubMed  CAS  Google Scholar 

  37. Marchetti B, Ashrafi GH, Dornan ES, Araibi EH, Ellis SA, Campo MS. The E5 protein of BPV-4 interacts with the heavy chain of MHC class I and irreversibly retains the MHC complex in the Golgi apparatus. Oncogene 2006; 25(15): 2254–2263.

    PubMed  CAS  Google Scholar 

  38. Barnard P, McMillan NA. The human papillomavirus E7 oncoprotein abrogates signaling mediated by interferon-alpha. Virology 1999; 259(2): 305–313.

    PubMed  CAS  Google Scholar 

  39. Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ. Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem 2000; 275(10): 6764–6769.

    PubMed  CAS  Google Scholar 

  40. Trimble CL, Piantadosi S, Gravitt P, et al. Spontaneous regression of high-grade cervical dysplasia: effects of human papillomavirus type and HLA phenotype. Clin Cancer Res 2005; 11(13): 4717–41723.

    PubMed  CAS  Google Scholar 

  41. Ross GL. Oral contraceptives and cervical cancer. Lancet 2002; 360(9330): 409; author reply 409.

    PubMed  Google Scholar 

  42. Brinton LA. Oral contraceptives and cervical neoplasia. Contraception 1991; 43(6): 581–595.

    PubMed  CAS  Google Scholar 

  43. Horomonal contraception and post-menopausal hormonal therapy. International Agency for Research on Cancer, Lyon, France, 1999. IARC Monegraph vol 721–660

    Google Scholar 

  44. Brinton LA, Reeves WC, Brenes MM, et al. Parity as a risk factor for cervical cancer. Am J Epidemiol 1989; 130(3): 486–496.

    PubMed  CAS  Google Scholar 

  45. Parazzini F, Chatenoud L, LaVecchia C, Negri E, Franceschi S, Bolis G. Determinants of risk of invasive cervical cancer in young women. Br J Cancer 1998; 77(5): 838–841.

    PubMed  CAS  Google Scholar 

  46. Moreno V, Bosch FX, Munoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet 2002; 359(9312): 1085–1092.

    PubMed  CAS  Google Scholar 

  47. Berrington A, Jha P, Peto J, Green J, Hermon C. Oral contraceptives and cervical cancer. Lancet 2002; 360(9330): 410.

    PubMed  Google Scholar 

  48. Deacon JM, Evans CD, Yule R, et al. Sexual behaviour and smoking as determinants of cervical HPV infection and of CIN3 among those infected: a case-control study nested within the Manchester cohort. Br J Cancer 2000; 83(11): 1565–1572.

    PubMed  CAS  Google Scholar 

  49. Munoz N, Franceschi S, Bosetti C, et al. Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. Lancet 2002; 359(9312): 1093–1101.

    PubMed  Google Scholar 

  50. Brabin L, Barr F. Oral contraceptives and cervical cancer. Lancet 2002; 360(9330): 409–410.

    PubMed  Google Scholar 

  51. Skegg DC. Oral contraceptives, parity, and cervical cancer. Lancet 2002; 359(9312): 1080–1081.

    PubMed  Google Scholar 

  52. Dong G, Broker TR, Chow LT. Human papillomavirus type 11 E2 proteins repress the homologous E6 promoter by interfering with the binding of host transcription factors to adjacent elements. J Virol 1994; 68(2): 1115–1127.

    PubMed  CAS  Google Scholar 

  53. Dostatni N, Lambert PF, Sousa R, Ham J, Howley PM, Yaniv M. The functional BPV-1 E2 transactivating protein can act as a repressor by preventing formation of the initiation complex. Genes Dev 1991; 5(9): 1657–1671.

    PubMed  CAS  Google Scholar 

  54. Dowhanick JJ, McBride AA, Howley PM. Suppression of cellular proliferation by the papillomavirus E2 protein. J Virol 1995; 69(12): 7791–7799.

    PubMed  CAS  Google Scholar 

  55. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990; 63(6): 1129–1136.

    PubMed  CAS  Google Scholar 

  56. Dyson N, Howley PM, Munger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 1989; 243(4893): 934–937.

    PubMed  CAS  Google Scholar 

  57. Zerfass K, Levy LM, Cremonesi C, et al. Cell cycle-dependent disruption of E2F-plO7 complexes by human papillomavirus type 16 E7. J Gen Virol 1995; 76(Pt 7): 1815–1820.

    PubMed  CAS  Google Scholar 

  58. Cellular proteins. HPV Compendium 1997. IV-1–IV-4

    Google Scholar 

  59. Hebner CM, Laimins LA. Human papillomaviruses: basic mechanisms of pathogenesis and oncogenicity. Rev Med Virol 2006; 87(11): 3183–3193.

    CAS  Google Scholar 

  60. Moodley M. Update on pathophysiologic mechanisms of human papillomavirus. Curr Opin Obstet Gynecol 2005; 17(1): 61–64.

    PubMed  Google Scholar 

  61. Motoyama S, Ladines-Llave CA, Luis Villanueva S, Maruo T. The role of human papilloma virus in the molecular biology of cervical carcinogenesis. Kobe J Med Sci 2004; 50(1-2): 9–19.

    PubMed  CAS  Google Scholar 

  62. Hagensee ME, Yaegashi N, Galloway DA. Self-assembly of human papillomavirus type 1 capsids by expression of the L1 protein alone or by coexpression of the LI and L2 capsid proteins. J Virol 1993; 67(1): 315–322.

    PubMed  CAS  Google Scholar 

  63. Kirnbauer R, Booy F, Cheng N, Lowy DR, Schiller JT. Papillomavirus LI major capsid protein selfassembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci USA 1992; 89(24): 12,180–12,184.

    PubMed  CAS  Google Scholar 

  64. Kirnbauer R, Taub J, Greenstone H, et al. Efficient self-assembly of human papillomavirus type 16 LI and L1-L2 into virus-like particles. J Virol 1993; 67(12): 6929–6936.

    PubMed  CAS  Google Scholar 

  65. Schiller JT and Nardelli-Haefliger. chapter 17: second generation HPV vaccines to prevent cervical cancer (2006) vaccine vol 24,supplement 3 pages, S147–S153.

    Google Scholar 

  66. Nardelli-Haefliger D, Lurati F, Wirthner D, et al. Immune responses induced by lower airway mucosal immunisation with a human papillomavirus type 16 virus-like particle vaccine. Vaccine 2005; 23(28): 3634–3641.

    PubMed  CAS  Google Scholar 

  67. Mao C, Koutsky LA, Ault KA, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol 2006; 107(1): 18–27.

    PubMed  Google Scholar 

  68. Herrero R, Hildesheim A, Bratti C, et al. Rationale and design of the NCI-Costa Rica HPV 16 vaccine trial. 19th International Papillomavirus Conference Florianopolis, Brazil, 2001, pp. 94.

    Google Scholar 

  69. Ruiz W, McClements WL, Jansen KU, Esser MT. Kinetics and isotype profile of antibody responses in rhesus macaques induced following vaccination with HPV 6, 11, 16 and 18 Ll-virus-like particles formulated with or without Merck aluminum adjuvant. J Immune Based Ther Vaccines 2005; 3(1): 2.

    PubMed  Google Scholar 

  70. GlaxoSmithKline. 22nd International Papillomavirus Conference 2005.

    Google Scholar 

  71. Roden RB, Greenstone HL, Kirnbauer R, et al. In vitro generation and type-specific neutralization of a human papillomavirus type 16 virion pseudotype. J Virol 1996; 70(9): 5875–5883.

    PubMed  CAS  Google Scholar 

  72. Munoz N, Bosch FX, Castellsague X, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 2004; 111(2): 278–285.

    PubMed  CAS  Google Scholar 

  73. Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent LI virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364(9447): 1757–1765.

    PubMed  CAS  Google Scholar 

  74. Villa LL, Costa RL, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) LI virus-like particle vaccine in young women: a randomised double-blind placebocontrolled multicentre phase II efficacy trial. Lancet Oncol 2005; 6(5): 271–278.

    PubMed  Google Scholar 

  75. Roden RB, Yutzy WHt, Fallon R, Inglis S, Lowy DR, Schiller JT. Minor capsid protein of human genital papillomaviruses contains subdominant, cross-neutralizing epitopes. Virology 2000; 270(2): 254–257.

    PubMed  CAS  Google Scholar 

  76. Embers ME, Budgeon LR, Culp TD, Reed CA, Pickel MD, Christensen ND. Differential antibody responses to a distinct region of human papillomavirus minor capsid proteins. Vaccine 2004; 22(5-6): 670–680.

    PubMed  CAS  Google Scholar 

  77. HPV and animal PV nucleic acid sequences. HPV Compendium 1997. http://npv-web.lanl.gov/std-gen/virus/hpv/compendium/htdocs/.

  78. Chen XS, Casini G, Harrison SC, Garcea RL. Papillomavirus capsid protein expression in Escherichia coli purification and assembly of HPV11 and HPV16 LI. J Mol Biol 2001; 307(1): 173–182.

    PubMed  CAS  Google Scholar 

  79. Yuan H, Estes PA, Chen Y, et al. Immunization with a pentameric LI fusion protein protects against papillomavirus infection. J Virol 2001; 75(17): 7848–7853.

    PubMed  CAS  Google Scholar 

  80. Giles M, Garland S. Chapter 21: HPV Vaccines. In: Papillomavirus Research (Campo MS, ed.), Norfolk, England: Caister Academic Press, 2006: 341–356.

    Google Scholar 

  81. Kawana K, Yasugi T, Kanda T, et al. Neutralizing antibodies against oncogenic human papillomavirus as a possible determinant of the fate of low-grade cervical intraepithelial neoplasia. Biochem Biophys Res Commun 2002; 296(1): 102–105.

    PubMed  CAS  Google Scholar 

  82. Halpert R, Fruchter RG, Sedlis A, Butt K, Boyce JG, Sillman FH. Human papillomavirus and lower genital neoplasia in renal transplant patients. Obstet Gynecol 1986; 68(2): 251–258.

    PubMed  CAS  Google Scholar 

  83. Laga M, Icenogle JP, Marsella R, et al. Genital papillomavirus infection and cervical dysplasia— opportunistic complications of HIV infection. Int J Cancer 1992; 50(1): 45–48.

    PubMed  CAS  Google Scholar 

  84. Schafer A, Friedmann W, Mielke M, Schwartlander B, Koch MA. The increased frequency of cervical dysplasia-neoplasia in women infected with the human immunodeficiency virus is related to the degree of immunosuppression. Am J Obstet Gynecol 1991; 164(2): 593–599.

    PubMed  CAS  Google Scholar 

  85. Sun XW, Kuhn L, Ellerbrock TV, Chiasson MA, Bush TJ, Wright TC Jr. Human papillomavirus infection in women infected with the human immunodeficiency virus. N Engl J Med 1997; 337(19): 1343–1349.

    PubMed  CAS  Google Scholar 

  86. Coleman N, Birley HD, Renton AM, et al. Immunological events in regressing genital warts. Am J Clin Pathol 1994; 102(6): 768–774.

    PubMed  CAS  Google Scholar 

  87. Ressing ME, vanDriel WJ, Brandt RM, et al. Detection of T helper responses, but not of human papillomavirus-specific cytotoxic T lymphocyte responses, after peptide vaccination of patients with cervical carcinoma. J Immunother 2000; 23(2): 255–266.

    PubMed  CAS  Google Scholar 

  88. vanDriel WJ, Ressing ME, Kenter GG, et al. Vaccination with HPV16 peptides of patients with advanced cervical carcinoma: clinical evaluation of a phase I-II trial. Eur J Cancer 1999; 35(6): 946–952.

    PubMed  Google Scholar 

  89. Steller MA, Gurski KJ, Murakami M, et al. Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7. Clin Cancer Res 1998; 4(9): 2103–2109.

    PubMed  CAS  Google Scholar 

  90. Muderspach L, Wilczynski S, Roman L, et al. 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 2000; 6(9): 3406–3416.

    PubMed  CAS  Google Scholar 

  91. Adams M, Borysiewicz L, Fiander A, et al. Clinical studies of human papilloma vaccines in preinvasive and invasive cancer. Vaccine 2001; 19(17-19): 2549–2556.

    PubMed  CAS  Google Scholar 

  92. Borysiewicz LK, Fiander A, Nimako M, et al. A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. Lancet 1996; 347(9014): 1523–1527.

    PubMed  CAS  Google Scholar 

  93. Kaufmann AM, Stern PL, Rankin EM, et al. Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer. Clin Cancer Res 2002; 8(12): 3676–3685.

    PubMed  CAS  Google Scholar 

  94. Baldwin PJ, van der Burg SH, Boswell CM, et al. Vaccinia-expressed human papillomavirus 16 and 18 e6 and e7 as a therapeutic vaccination for vulval and vaginal intraepithelial neoplasia. Clin Cancer Res 2003; 9(14): 5205–5213.

    PubMed  CAS  Google Scholar 

  95. Davidson EJ, Boswell CM, Sehr P, et al. Immunological and clinical responses in women with vulval intraepithelial neoplasia vaccinated with a vaccinia virus encoding human papillomavirus 16/18 oncoproteins. Cancer Res 2003; 63(18): 6032–6041.

    PubMed  CAS  Google Scholar 

  96. Corona Gutierrez CM, Tinoco A, Navarro T, et al. Therapeutic vaccination with MVA E2 can eliminate precancerous lesions (CIN 1, CIN 2, and CIN 3) associated with infection by oncogenic human papillomavirus. Hum Gene Ther 2004; 15(5): 421–431.

    PubMed  CAS  Google Scholar 

  97. Klencke B, Matijevic M, Urban RG, et al. Encapsulated plasmid DNA treatment for human papillomavirus 16-associated anal dysplasia: a Phase I study of ZYC101. Clin Cancer Res 2002; 8(5): 1028–1037.

    PubMed  CAS  Google Scholar 

  98. Sheets EE, Urban RG, Crum CP, et al. Immunotherapy of human cervical high-grade cervical intraepithelial neoplasia with microparticle-delivered human papillomavirus 16 E7 plasmid DNA. Am J Obstet Gynecol 2003; 188(4): 916–926.

    PubMed  CAS  Google Scholar 

  99. Garcia F, Petry KU, Muderspach L, et al. ZYClOla for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol 2004; 103(2): 317–326.

    PubMed  CAS  Google Scholar 

  100. deJong A, O’Neill T, Khan AY, et al. Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV 16 L2E7E6 fusion protein vaccine. Vaccine 2002; 20(29-30): 3456–3464.

    PubMed  Google Scholar 

  101. Meyers C, Frattini MG, Hudson JB, Laimins LA. Biosynthesis of human papillomavirus from a continuous cell line upon epithelial differentiation. Science 1992; 257(5072): 971–973.

    PubMed  CAS  Google Scholar 

  102. Staler MH, Rhodes CR, Whitbeck A, Wolinsky SM, Chow LT, Broker TR. Human papillomavirus type 16 and 18 gene expression in cervical neoplasias. Hum Pathol 1992; 23(2): 117–128.

    Google Scholar 

  103. Hu G, Liu W, Hanania EG, Fu S, Wang T, Deisseroth AB. Suppression of tumorigenesis by transcription units expressing the antisense E6 and E7 messenger RNA (mRNA) for the transforming proteins of the human papilloma virus and the sense mRNA for the retinoblastoma gene in cervical carcinoma cells. Cancer Gene Ther 1995; 2(1): 19–32.

    PubMed  Google Scholar 

  104. Chen G, Stenlund A. The El initiator recognizes multiple overlapping sites in the papillomavirus origin of DNA replication. J Virol 2001; 75(1): 292–302.

    PubMed  CAS  Google Scholar 

  105. Hughes FJ, Romanos MA. El protein of human papillomavirus is a DNA helicase/ATPase. Nucleic Acids Res 1993; 21(25): 5817–5823.

    PubMed  CAS  Google Scholar 

  106. Conger KL, Liu JS, Kuo SR, Chow LT, Wang TS. Human papillomavirus DNA replication. Interactions between the viral El protein and two subunits of human dna polymerase alpha/primase. J Biol Chem 1999; 274(5): 2696–2705.

    PubMed  CAS  Google Scholar 

  107. Frattini MG, Laimins LA. Binding of the human papillomavirus El origin-recognition protein is regulated through complex formation with the E2 enhancer-binding protein. Proc Natl Acad Sci USA 1994; 91(26): 12,398–12,402.

    PubMed  CAS  Google Scholar 

  108. Frattini MG, Hurst SD, Lim HB, Swaminathan S, Laimins LA. Abrogation of a mitotic checkpoint by E2 proteins from oncogenic human papillomaviruses correlates with increased turnover of the p53 tumor suppressor protein. Embo J 1997; 16(2): 318–331.

    PubMed  CAS  Google Scholar 

  109. Doorbar J, Ely S, Sterling J, McLean C, Crawford L. Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature 1991; 352(6338): 824–827.

    PubMed  CAS  Google Scholar 

  110. Raj K, Berguerand S, Southern S, Doorbar J, Beard P. El empty set E4 protein of human papillomavirus type 16 associates with mitochondria. J Virol 2004; 78(13): 7199–7207.

    PubMed  CAS  Google Scholar 

  111. Crusius K, Auvinen E, Steuer B, Gaissert H, Alonso A. The human papillomavirus type 16 E5-protein modulates ligand-dependent activation of the EGF receptor family in the human epithelial cell line HaCaT. Exp Cell Res 1998; 241(1): 76–83.

    PubMed  CAS  Google Scholar 

  112. Straight SW, Hinkle PM, Jewers RJ, McCance DJ. The E5 oncoprotein of human papillomavirus type 16 transforms fibroblasts and effects the downregulation of the epidermal growth factor receptor in keratinocytes. J Virol 1993; 67(8): 4521–4532.

    PubMed  CAS  Google Scholar 

  113. Genther Williams SM, Disbrow GL, Schlegel R, Lee D, Threadgill DW, Lambert PF. Requirement of epidermal growth factor receptor for hyperplasia induced by E5, a high-risk human papillomavirus oncogene. Cancer Res 2005; 65(15): 6534–6542.

    Google Scholar 

  114. Cohen BD, Goldstein DJ, Rutledge L, et al. Transformation-specific interaction of the bovine papillomavirus E5 oncoprotein with the platelet-derived growth factor receptor transmembrane domain and the epidermal growth factor receptor cytoplasmic domain. J Virol 1993; 67(9): 5303–5311.

    PubMed  CAS  Google Scholar 

  115. Gardiol D, Kuhne C, Glaunsinger B, Lee SS, Javier R, Banks L. Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation. Oncogene 1999; 18(40): 5487–5496.

    PubMed  CAS  Google Scholar 

  116. Tong X, Howley PM. The bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton. Proc Natl Acad Sci USA 1997; 94(9): 4412–4417.

    PubMed  CAS  Google Scholar 

  117. Tong X, Boll W, Kirchhausen T, Howley PM. Interaction of the bovine papillomavirus E6 protein with the clathrin adaptor complex AP-1. J Virol 1998; 72(1): 476–482.

    PubMed  CAS  Google Scholar 

  118. Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 1996; 380(6569): 79–82.

    PubMed  CAS  Google Scholar 

  119. Matthews K, Leong CM, Baxter L, et al. Depletion of Langerhans cells in human papillomavirus type 16-infected skin is associated with E6-mediated down regulation of E-cadherin. J Virol 2003; 77(15): 8378–8385.

    PubMed  CAS  Google Scholar 

  120. Ronco LV, Karpova AY, Vidal M, Howley PM. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 1998; 12(13): 2061–2072.

    PubMed  CAS  Google Scholar 

  121. Joyce JG, Tung JS, Przysiecki CT, et al. The LI major capsid protein of human papillomavirus type 11 recombinant virus-like particles interacts with heparin and cell-surface glycosaminoglycans on human keratinocytes. J Biol Chem 1999; 274(9): 5810–5822.

    PubMed  CAS  Google Scholar 

  122. Roden RB, Kirnbauer R, Jenson AB, Lowy DR, Schiller JT. Interaction of papillomaviruses with the cell surface. J Virol 1994; 68(11): 7260–7266.

    PubMed  CAS  Google Scholar 

  123. Harro CD, Pang YY, Roden RB, et al. Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 LI virus-like particle vaccine. J Natl Cancer Inst 2001; 93(4): 284–292.

    PubMed  CAS  Google Scholar 

  124. Pinto LA, Castle PE, Roden RB, et al. HPV-16 LI VLP vaccine elicits a broad-spectrum of cytokine responses in whole blood. Vaccine 2005; 23(27): 3555–3564.

    PubMed  CAS  Google Scholar 

  125. Pinto LA, Edwards J, Castle PE, et al. Cellular immune responses to human papillomavirus (HPV)16 LI in healthy volunteers immunized with recombinant HPV-16 LI virus-like particles. J Infect Dis 2003; 188(2): 327–338.

    PubMed  CAS  Google Scholar 

  126. Ault KA, Giuliano AR, Edwards RP, et al. A phase I study to evaluate a human papillomavirus (HPV) type 18 LI VLP vaccine. Vaccine 2004; 22(23-24): 3004–3007.

    PubMed  CAS  Google Scholar 

  127. Kawana K, Yasugi T, Kanda T, et al. Safety and immunogenicity of a peptide containing the crossneutralization epitope of HPV16 L2 administered nasally in healthy volunteers. Vaccine 2003; 21(27-30): 4256–4260.

    PubMed  CAS  Google Scholar 

  128. Hallez S, Simon P, Maudoux F, et al. Phase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein-based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia. Cancer Immunol Immunother 2004; 53(7): 642–650.

    PubMed  CAS  Google Scholar 

  129. Santin AD, Bellone S, Gokden M, Cannon MJ, Parham GP. Vaccination with HPV-18 E7-pulsed dendritic cells in a patient with metastatic cervical cancer. N Engl J Med 2002; 346(22): 1752–1753.

    PubMed  Google Scholar 

  130. Santin AD, Bellone S, Palmieri M, et al. HPV16/18 E7-pulsed dendritic cell vaccination in cervical cancer patients with recurrent disease refractory to standard treatment modalities. Gynecol Oncol 2006; 100(3): 469–478.

    PubMed  CAS  Google Scholar 

  131. Bosch FX, Lorincz A, Murioz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer, J Clin Pathol 2002; 55: 244–265.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD

    Hannah H. Alphs BS

  2. Departments of Pathology, Oncology, Obstetrics and Gynecology, and Molecular Microbiology and Immunology, The Johns Hopkins Medical Institutions, Baltimore, MD

    T-C Wu MD, PhD

  3. Departments of Pathology, Gynecology-Obstetrics, and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD

    Richard B. S. Roden PhD

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  1. Hannah H. Alphs BS
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  2. T-C Wu MD, PhD
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  3. Richard B. S. Roden PhD
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Editor information

Editors and Affiliations

  1. Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA

    Antonio Giordano MD, PhD  & Alessandro Bovicelli MD, PhD  & 

  2. Departments of Human Pathology and Oncology, University of Siena, Siena, Italy

    Antonio Giordano MD, PhD

  3. Department of Obstetrics and Gynecology, University of Bologna, Bologna, Italy

    Alessandro Bovicelli MD, PhD

  4. Departments of Gynecology-Obstetrics and Pathology, Johns Hopkins University, Baltimore, MD

    Robert J. Kurman MD, PhD

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© 2007 Humana Press Inc., Totowa, NJ

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Alphs, H.H., Wu, TC., Roden, R.B.S. (2007). Prevention and Treatment of Cervical Cancer by Vaccination. In: Giordano, A., Bovicelli, A., Kurman, R.J. (eds) Molecular Pathology of Gynecologic Cancer. Current Clinical Oncology. Humana Press. https://doi.org/10.1007/978-1-59745-346-2_9

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  • DOI: https://doi.org/10.1007/978-1-59745-346-2_9

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