Human papillomaviruses as therapeutic targets in human cancer

Journal of Clinical Oncology

Volumn 29, Issue 13, 2011, Pages 1785-1794

  Hellner, Karin ^a,b   Münger, Karl ^a,b  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEIN E2; PROTEIN E6; PROTEIN E7; PROTEIN P53; WART VIRUS VACCINE;

ANUS CANCER; CANCER RISK; CANCER SCREENING; CONDYLOMA; CONDYLOMA ACUMINATUM; DISEASE ASSOCIATION; DIZZINESS; DRUG TARGETING; HEAD AND NECK CARCINOMA; HEADACHE; HIGH RISK PATIENT; HUMAN; HUMAN PAPILLOMAVIRUS TYPE 11; HUMAN PAPILLOMAVIRUS TYPE 16; HUMAN PAPILLOMAVIRUS TYPE 18; HUMAN PAPILLOMAVIRUS TYPE 6; HYPERSENSITIVITY REACTION; INFECTION PREVENTION; INFECTION RISK; INJECTION SITE REACTION; MOUTH CANCER; NAUSEA; NEOPLASM; NONHUMAN; OROPHARYNX CANCER; PAPANICOLAOU TEST; PAPILLOMATOSIS; PAPILLOMAVIRUS INFECTION; PENIS CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SKIN CANCER; URTICARIA; UTERINE CERVIX CARCINOMA; VAGINA CANCER; VIRUS TRANSMISSION; VULVA CANCER; WART VIRUS;

FEMALE; HEAD AND NECK NEOPLASMS; HUMANS; MALE; NEOPLASMS; PAPILLOMAVIRUS INFECTIONS; PAPILLOMAVIRUS VACCINES; UTERINE CERVICAL NEOPLASMS;

EID: 79955600307     PISSN: 0732183X     EISSN: 15277755     Source Type: Journal    
DOI: 10.1200/JCO.2010.28.2186     Document Type: Review

References (109)

1. Howley PM, Lowy DR: Papillomaviruses, in Knipe DM, Howley PM (eds): Fields Virology. Philadelphia, PA, Wolters Kluwer/Lippincott Williams & Wilkins, 2007, pp 2299-2354
2. Lee C, Laimins L: The differentiationdependent life cycle of human papillomaviruses in keratinocytes, in Garcea RL, DiMaio D (eds): The Papillomaviruses. New York, NY, Springer, pp 45-68, 2007
3. de Villiers EM, Fauquet C, Broker TR, et al: Classification of papillomaviruses. Virology 324:17-27, 2004 (Pubitemid 38737395)
4. Burchell AN, Winer RL, de Sanjose S, et al: Chapter 6: Epidemiology and transmission dynamics of genital HPV infection. Vaccine 24:S3/52-61, 2006 (suppl 3)
5. Winer RL, Lee SK, Hughes JP, et al: Genital human papillomavirus infection: Incidence and risk factors in a cohort of female university students. Am J Epidemiol 157:218-226, 2003 (Pubitemid 36152435)
6. Ferenczy A, Bergeron C, Richart RM: Human papillomavirus DNA in fomites on objects used for the management of patients with genital human papillomavirus infections. Obstet Gynecol 74:950-954, 1989 (Pubitemid 20003293)
7. Roden RB, Lowy DR, Schiller JT: Papillomavirus is resistant to desiccation. J Infect Dis 176: 1076-1079, 1997 (Pubitemid 27411055)
8. Nielson CM, Flores R, Harris RB, et al: Human papillomavirus prevalence and type distribution in male anogenital sites and semen. Cancer Epidemiol Biomarkers Prev 16:1107-1114, 2007 (Pubitemid 46984945)
9. Gray RH, Serwadda D, Kong X, et al: Male circumcision decreases acquisition and increases clearance of high-risk human papillomavirus in HIV-negative men: A randomized trial in Rakai, Uganda. J Infect Dis 201:1455-1462, 2010
10. Castellsague X, Bosch FX, Munoz N, et al: Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med 346:1105-1112, 2002 (Pubitemid 34984600)
11. Shields TS, Brinton LA, Burk RD, et al: A casecontrol study of risk factors for invasive cervical cancer among U.S. women exposed to oncogenic types of human papillomavirus. Cancer Epidemiol Biomarkers Prev 13:1574-1582, 2004 (Pubitemid 39331877)
12. Buck CB, Thompson CD, Roberts JN, et al: Carrageenan is a potent inhibitor of papillomavirus infection. PLoS Pathog 2:e69, 2006
13. Roberts JN, Buck CB, Thompson CD, et al: Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan. Nat Med 13:857-861, 2007 (Pubitemid 47038188)
14. Smedts F, Ramaekers F, Troyanovsky S, et al: Basal-cell keratins in cervical reserve cells and a comparison to their expression in cervical intraepithelial neoplasia. Am J Pathol 140:601-612, 1992
15. Tsutsumi K, Sun Q, Yasumoto S, et al: In vitro and in vivo analysis of cellular origin of cervical squamous metaplasia. Am J Pathol 143:1150-1158, 1993
16. Martens JE, Arends J, Van der Linden PJ, et al: Cytokeratin 17 and p63 are markers of the HPV target cell, the cervical stem cell. Anticancer Res 24:771-775, 2004 (Pubitemid 38625020)
17. Pagliusi SR, Dillner J, Pawlita M, et al: Chapter 23: International Standard reagents for harmonization of HPV serology and DNA assays: An update. Vaccine 24:S3/193-200, 2006 (suppl 3)
18. Baseman JG, Koutsky LA: The epidemiology of human papillomavirus infections. J Clin Virol 32: S16-24, 2005 (suppl 1)
19. Dunne EF, Unger ER, Sternberg M, et al: Prevalence of HPV infection among females in the United States. JAMA 297:813-819, 2007 (Pubitemid 46333946)
20. Munoz N, Castellsague X, de Gonzalez AB, et al: Chapter 1: HPV in the etiology of human cancer. Vaccine 24:S3/1-10, 2006 (suppl 3)
21. Kumar V, Fausto N, Mitchell R: The female genital system and breast, in Kumar V, Abbas AK, Fausto N, et al (eds): Robbins Basic Pathology (ed 8). Philadelphia, PA, Saunders, pp 679-718, 2007
22. Bosch X, Harper D: Prevention strategies of cervical cancer in the HPV vaccine era. Gynecol Oncol 103:21-24, 2006 (Pubitemid 44399804)
23. Beutner KR, Ferenczy A: Therapeutic approaches to genital warts. Am J Med 102:28-37, 1997 (Pubitemid 127695957)
24. Frega A, Stentella P, Tinari A, et al: Giant condyloma acuminatum or buschke-Lowenstein tumor: Review of the literature and report of three cases treated by CO2 laser surgery: A long-term follow-up. Anticancer Res 22:1201-1204, 2002 (Pubitemid 34836174)
25. Rady PL, Schnadig VJ, Weiss RL, et al: Malignant transformation of recurrent respiratory papillomatosis associated with integrated human papillomavirus type 11 DNA and mutation of p53. Laryngoscope 108:735-740, 1998
26. Stamataki S, Nikolopoulos TP, Korres S, et al: Juvenile recurrent respiratory papillomatosis: Still a mystery disease with difficult management. Head Neck 29:155-162, 2007 (Pubitemid 46167783)
27. Durst M, Gissmann L, Ikenberg H, et al: A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A 80:3812-3815, 1983 (Pubitemid 13063146)
28. Boshart M, Gissmann L, Ikenberg H, et al: A new type of papillomavirus DNA and its prevalence in genital cancer biopsies and in cell lines derived from cervical cancer. The EMBO Journal 3:1151-1157, 1984
29. WHO/ICO Information Center on HPV and Cervical Cancer. http://www.who.int/hpvcentre/statistics/en/
30. Smith JS, Lindsay L, Hoots B, et al: Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A metaanalysis update. Int J Cancer 121:621-632, 2007 (Pubitemid 46986496)
31. Schiffman M, Castle PE, Jeronimo J, et al: Human papillomavirus and cervical cancer. Lancet 370:890-907, 2007 (Pubitemid 47371147)
32. Stanley M: Immune responses to human papillomavirus. Vaccine 24:S16-22, 2006 (suppl 1)
33. Plummer M, Schiffman M, Castle PE, et al: A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis 195:1582-1589, 2007 (Pubitemid 46799215)
34. Schiffman M, Herrero R, Desalle R, et al: The carcinogenicity of human papillomavirus types re- flects viral evolution. Virology 337:76-84, 2005 (Pubitemid 40725441)
35. Khan MJ, Castle PE, Lorincz AT, et al: The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst 97: 1072-1079, 2005 (Pubitemid 41417924)
36. Castle PE, Solomon D, Schiffman M, et al: Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities. J Natl Cancer Inst 97:1066-1071, 2005 (Pubitemid 41417923)
37. Franco EL, Harper DM: Vaccination against human papillomavirus infection: A new paradigm in cervical cancer control. Vaccine 23:2388-2394, 2005 (Pubitemid 40341489)
38. Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2009. CA Cancer J Clin 59:225-249, 2009
39. Parkin DM, Bray F: Chapter 2: The burden of HPV-related cancers. Vaccine 24:S3/11-25, 2006 (suppl 3)
40. Solomon D, Breen N, McNeel T: Cervical cancer screening rates in the United States and the potential impact of implementation of screening guidelines. CA Cancer J Clin 57:105-111, 2007 (Pubitemid 46535710)
41. American Cancer Society: ACS Cancer Statistics, Cases and Deaths by Site, State 2009, http:// www.cancer.org/docroot/PRO/content/PRO-1-1-Cancer-Facts- Figures-Suppl-Data-2009.asp
42. Gillison ML: Human papillomavirusassociated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol 31:744-754, 2004
43. Gillison ML, D'Souza G, Westra W, et al: Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 100:407-420, 2008 (Pubitemid 351480511)
44. Gillison ML, Koch WM, Capone RB, et al: Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709-720, 2000 (Pubitemid 30365531)
45. D'Souza G, Kreimer AR, Viscidi R, et al: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356:1944-1956, 2007
46. D'Souza G, Agrawal Y, Halpern J, et al: Oral sexual behaviors associated with prevalent oral human papillomavirus infection. J Infect Dis 199:1263-1269, 2009
47. Syrjanen S: Human papillomavirus (HPV) in head and neck cancer. J Clin Virol 32:S59-66, 2005 (suppl 1)
48. Andrews E, Seaman WT, Webster-Cyriaque J: Oropharyngeal carcinoma in non-smokers and non-drinkers: A role for HPV. Oral Oncol 45:486-491, 2009
49. Hobbs CG, Sterne JA, Bailey M, et al: Human papillomavirus and head and neck cancer: A systematic review and meta-analysis. Clin Otolaryngol 31: 259-266, 2006 (Pubitemid 44141088)
50. Gillison ML, Shah KV: Role of mucosal human papillomavirus in nongenital cancers. J Natl Cancer Inst Monogr 57-65, 2003
51. Talbert-Slagle K, DiMaio D: The bovine papillomavirus E5 protein and the PDGF beta receptor: It takes two to tango. Virology 384:345-351, 2009
52. DiMaio D, Mattoon D: Mechanisms of cell transformation by papillomavirus E5 proteins. Oncogene 20:7866-7873, 2001 (Pubitemid 33135313)
53. Krawczyk E, Suprynowicz FA, Liu X, et al: Koilocytosis: A cooperative interaction between the human papillomavirus E5 and E6 oncoproteins. Am J Pathol 173:682-688, 2008
54. Munger K, Howley PM, DiMaio D: Human papillomavirus E6 and E7 oncogenes, in Garcea RL, DiMaio D (eds): The Papillomaviruses. New York, NY, Springer, 2007, pp 195-251
55. McCance DJ, Kopan R, Fuchs E, et al: Human papillomavirus type 16 alters human epithelial cell differentiation in vitro. Proc Natl Acad Sci U S A 85:7169-7173, 1988
56. Arbeit JM, Howley PM, Hanahan D: Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice. Proc Natl Acad Sci U S A 93:2930-2935, 1996 (Pubitemid 26114341)
57. Thierry F, Yaniv M: The BPV1-E2 trans-acting protein can be either an activator or a repressor of the HPV18 regulatory region. Embo J 6:3391-3397, 1987
58. McLaughlin-Drubin ME, Munger K: The human papillomavirus E7 oncoprotein. Virology 384: 335-344, 2009
59. White AE, Livanos EM, Tlsty TD: Differential disruption of genomic integrity and cell cycle regulation in normal human fibroblasts by the HPV Oncoproteins. Genes Dev 8:666-677, 1994 (Pubitemid 24116761)
60. Duensing S, Lee LY, Duensing A, et al: The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proc Natl Acad Sci U S A 97:10002-10007, 2000
61. Crum CP, Ikenberg H, Richart RM, et al: Human papillomavirus type 16 and early cervical neoplasia. N Engl J Med 310:880-883, 1984 (Pubitemid 14173180)
62. Nguyen CL, Hayakawa H, Munger K: Activities of human papillomavirus oncoproteins that contribute to genomic instability and malignant progression, in Norrild B (ed): Human Paillomavirus Gene Regulation and Transformation. Trivandrum, India, Transworld Research Network, 2007, pp 139-164
63. Chen W, Li F, Mead L, et al: Human papillomavirus causes an angiogenic switch in keratinocytes which is sufficient to alter endothelial cell behavior. Virology 367:168-174, 2007 (Pubitemid 47418936)
64. Hellner K, Mar J, Fang F, et al: HPV16 E7 oncogene expression in normal human epithelial cells causes molecular changes indicative of an epithelial to mesenchymal transition. Virology 391: 57-63, 2009
65. Zwerschke W, Mazurek S, Massimi P, et al: Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc Natl Acad Sci U S A 96:1291-1296, 1999 (Pubitemid 29098444)
66. Uyar DS, Eltabbakh GH, Mount SL: Positive predictive value of liquid-based and conventional cervical Papanicolaou smears reported as malignant. Gynecol Oncol 89:227-232, 2003 (Pubitemid 36457869)
67. Bernstein SJ, Sanchez-Ramos L, Ndubisi B: Liquid-based cervical cytologic smear study and conventional Papanicolaou smears: A metaanalysis of prospective studies comparing cytologic diagnosis and sample adequacy. Am J Obstet Gynecol 185:308-317, 2001 (Pubitemid 32769428)
68. Wright TC Jr: Cervical cancer screening in the 21st century: Is it time to retire the PAP smear? Clin Obstet Gynecol 50:313-323, 2007
69. Clavel C, Masure M, Bory JP, et al: Human papillomavirus testing in primary screening for the detection of high-grade cervical lesions: A study of 7932 women. Br J Cancer 84:1616-1623, 2001 (Pubitemid 32612492)
70. Lie AK, Risberg B, Borge B, et al: DNAversus RNA-based methods for human papillomavirus detection in cervical neoplasia. Gynecol Oncol 97:908-915, 2005 (Pubitemid 40824665)
71. Mayrand MH, Duarte-Franco E, Rodrigues I, et al: Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med 357:1579-1588, 2007 (Pubitemid 47598400)
72. Ordi J, Garcia S, del Pino M, et al: P16 INK4a immunostaining identifies occult CIN lesions in HPVpositive women. Int J Gynecol Pathol 28:90-97, 2009
73. Klaes R, Friedrich T, Spitkovsky D, et al: Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer 92:276-284, 2001 (Pubitemid 32225381)
74. Khan AM, Singer A: Biomarkers in cervical precancer management: The new frontiers. Future Oncol 4:515-524, 2008
75. Giannini SL, Hanon E, Moris P, et al: Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine 24:5937-5949, 2006 (Pubitemid 44080367)
76. Huh WK, Roden RB: The future of vaccines for cervical cancer. Gynecol Oncol 109:S48-56, 2008
77. Koutsky LA, Harper DM: Chapter 13: Current findings from prophylactic HPV vaccine trials. Vaccine 24:S3/114-121, 2006 (suppl 3)
78. Paavonen J, Naud P, Salmeron J, et al: Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): Final analysis of a double-blind, randomised study in young women. Lancet 374:301-314, 2009
79. Kjaer SK, Sigurdsson K, Iversen OE, et al: A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (types 6/11/16/ 18) vaccine against high-grade cervical and external genital lesions. Cancer Prev Res 2:868-878, 2009
80. Frazer IH: Measuring serum antibody to human papillomavirus following infection or vaccination. Gynecol Oncol 118:S8-11, 2010
81. Kines RC, Thompson CD, Lowy DR, et al: The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding. Proc Natl Acad Sci U S A 106: 20458-20463, 2009
82. Fraser C, Tomassini JE, Xi L, et al: Modeling the long-term antibody response of a human papillomavirus (HPV) virus-like particle (VLP) type 16 prophylactic vaccine. Vaccine 25:4324-4333, 2007 (Pubitemid 46635934)
83. Olsson SE, Villa LL, Costa RL, et al: Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine 25:4931-4939, 2007 (Pubitemid 46843434)
84. Smith JF, Brownlow M, Brown M, et al: Antibodies from women immunized with Gardasil cross-neutralize HPV 45 pseudovirions. Hum Vaccin 3:109-115, 2007 (Pubitemid 47501028)
85. Slade BA, Leidel L, Vellozzi C, et al: Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA 302: 750-757, 2009
86. Agorastos T, Chatzigeorgiou K, Brotherton JM, et al: Safety of human papillomavirus (HPV) vaccines: A review of the international experience so far. Vaccine 27:7270-7281, 2009
87. Slupetzky K, Gambhira R, Culp TD, et al: A papillomavirus-like particle (VLP) vaccine displaying HPV16 L2 epitopes induces cross-neutralizing antibodies to HPV11. Vaccine 25:2001-2010, 2007
88. Jagu S, Karanam B, Gambhira R, et al: Concatenated multitype L2 fusion proteins as candidate prophylactic pan-human papillomavirus vaccines. J Natl Cancer Inst 101:782-792, 2009
89. Gambhira R, Karanam B, Jagu S, et al: A protective and broadly cross-neutralizing epitope of human papillomavirus L2. J Virol 81:13927-13931, 2007
90. von Knebel Doeberitz M, Rittmuller C, zur Hausen H, et al: Inhibition of tumorigenicity of cervical cancer cells in nude mice by HPV E6-E7 anti-sense RNA. Int J Cancer 51:831-834, 1992
91. Butz K, Ristriani T, Hengstermann A, et al: SiRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells. Oncogene 22:5938-5945, 2003 (Pubitemid 37175872)
92. Chung SH, Lambert PF: Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists. Proc Natl Acad Sci U S A 106:19467-19472, 2009
93. Kaelin WG Jr: Synthetic lethality: A framework for the development of wiser cancer therapeutics. Genome Med 1:99, 2009
94. Luo J, Emanuele MJ, Li D, et al: A genomewide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 137:835-848, 2009
95. Scholl C, Frohling S, Dunn IF, et al: Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 137:821-834, 2009
96. Baldwin A, Li W, Grace M, et al: Kinase requirements in human cells: II. Genetic interaction screens identify kinase requirements following HPV16 E7 expression in cancer cells. Proc Natl Acad Sci U S A 105:16478-16483, 2008
97. Baldwin A, Grueneberg DA, Hellner K, et al: Kinase requirements in human cells: V. Synthetic lethal interactions between p53 and the protein kinases SGK2 and PAK3. Proc Natl Acad Sci U S A 107:12463-12468, 2010
98. Frazer IH: Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol 4:46-54, 2004
99. Cid-Arregui A: Therapeutic vaccines against human papillomavirus and cervical cancer. Open Virol J 3:67-83, 2009
100. de Jong 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 HPV16 L2E7E6 fusion protein vaccine. Vaccine 20:3456-3464, 2002
101. Einstein MH, Kadish AS, Burk RD, et al: Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III. Gynecol Oncol 106:453-460, 2007 (Pubitemid 47302460)
102. Goldstone SE, Palefsky JM, Winnett MT, et al: Activity of HspE7, a novel immunotherapy, in patients with anogenital warts. Dis Colon Rectum 45:502-507, 2002 (Pubitemid 34407728)
103. Welters MJ, Kenter GG, Piersma SJ, et al: Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin Cancer Res 14:178-187, 2008 (Pubitemid 351377994)
104. Kenter GG, Welters MJ, Valentijn AR, et al: Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 361:1838-1847, 2009
105. Trimble CL, Frazer IH: Development of therapeutic HPV vaccines. Lancet Oncol 10:975-980, 2009
106. 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 8:3676-3685, 2002 (Pubitemid 35424757)
107. Fiander AN, Tristram AJ, Davidson EJ, et al: Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: Clinical results from a multicenter phase II trial. Int J Gynecol Cancer 16:1075-1081, 2006 (Pubitemid 43886729)
108. Kuck D, Leder C, Kern A, et al: Efficiency of HPV 16 L1/E7 DNA immunization: Influence of cellular localization and capsid assembly. Vaccine 24: 2952-2965, 2006
109. Kaufmann AM, Nieland JD, Jochmus I, et al: Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3). Int J Cancer 121:2794-2800, 2007 (Pubitemid 350136429)