Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia

British Journal of Cancer

Volumn 102, Issue 7, 2010, Pages 1129-1136

  Daayana, S ^a,b   Elkord, E ^b   Winters, U ^a,b   Pawlita, M ^c   Roden, R ^d   Stern, P L ^b   Kitchener, H C ^a  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^d JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Imiquimod; T regulatory cells; Therapeutic HPV vaccination; Vulval intraepithelial neoplasia (VIN)

Indexed keywords

IMIQUIMOD; WART VIRUS VACCINE;

ADULT; AGED; ARTICLE; CANCER CHEMOTHERAPY; CANCER PATIENT; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DENSITY; CLINICAL ARTICLE; CLINICAL TRIAL; DRUG EFFECT; FEMALE; HISTOLOGY; HUMAN; HUMAN PAPILLOMAVIRUS TYPE 16; HUMAN TISSUE; IMMUNE RESPONSE; IMMUNOFLUORESCENCE; LYMPHOCYTE PROLIFERATION; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PUNCH BIOPSY; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TREATMENT DURATION; VACCINATION; VULVA CANCER; VULVAL INTRAEPITHELIAL NEOPLASIA;

ADOLESCENT; ADULT; AGED; AMINOQUINOLINES; ANTIGENS, VIRAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CANCER VACCINES; CARCINOMA IN SITU; DRUG TOLERANCE; FEMALE; HUMAN PAPILLOMAVIRUS 16; HUMANS; MIDDLE AGED; PAPILLOMAVIRUS VACCINES; VULVAR NEOPLASMS; YOUNG ADULT;

EID: 77950370339     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/sj.bjc.6605611     Document Type: Article

References (43)

1. Abdel-Hady ES, Martin-Hirsch P, Duggan-Keen M, Stern PL, Moore JV, Corbitt G, Kitchener HC, Hampson IN (2001) Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. Cancer Res 61: 192-196
2. Akerman G, Dussour C, Haddad B, Paniel BJ, Rouzier R (2007)[Epidemiology of vulvar intra-epithelial neoplasias]. Gynecol Obstet Fertil 35: 1251-1256
3. Castano AP, Mroz P, Hamblin MR (2006) Photodynamic therapy and anti-tumour immunity. Nat Rev Cancer 6: 535-545
4. Chuang CM, Hoory T, Monie A, Wu A, Wang MC, Hung CF (2009) Enhancing therapeutic HPV DNA vaccine potency through depletion of CD4+CD25+ T regulatory cells. Vaccine 27: 684-689
5. Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, Zhang A, Dahm P, Chao N, Gilboa E, Vieweg J (2005) Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest 115: 3623-3633
6. Davidson EJ, Boswell CM, Sehr P, Pawlita M, Tomlinson AE, McVey RJ, Dobson J, Roberts JS, Hickling J, Kitchener HC, Stern PL (2003a Immunological and clinical responses in women with vulval intraepithelial neoplasia vaccinated with a vaccinia virus encoding human papillomavirus 16/18 oncoproteins. Cancer Res 63: 6032-6041
7. Davidson EJ, Davidson JA, Sterling JC, Baldwin PJ, Kitchener HC, Stern PL (2003b) Association between human leukocyte antigen polymorphism and human papillomavirus 16-positive vulval intraepithelial neoplasia in British women. Cancer Res 63: 400-403
8. Davidson EJ, Faulkner RL, Sehr P, Pawlita M, Smyth LJ, Burt DJ, Tomlinson AE, Hickling J, Kitchener HC, Stern PL (2004) Effect of TA-CIN (HPV 16 L2E6E7) booster immunisation in vulval intraepithelial neoplasia patients previously vaccinated with TA-HPV (vaccinia virus encoding HPV 16/18 E6E7). Vaccine 22: 2722-2729
9. de Jong A, O'Neill T, Khan AY, Kwappenberg KM, Chisholm SE, Whittle NR, Dobson JA, Jack LC, Clair Roberts JA, Offringa R, van der Burg SH, Hickling JK (2002) 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
10. de Jong A, Van Poelgeest MI, van der Hulst JM, Drijfhout JW, Fleuren GJ, Melief CJ, Kenter G, Offringa R, van der Burg SH (2004) Human papillomavirus type 16-positive cervical cancer is associated with impaired CD4+ T-cell immunity against early antigens E2 and E6. Cancer Res 64: 5449-5455
11. De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S (2009) Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 124: 1626-1636
12. Dermime S, Armstrong A, Hawkins RE, Stern PL (2002) Cancer vaccines and immunotherapy. Br Med Bull 62: 149-162
13. Duong TH, Flowers LC (2007) Vulvo-vaginal cancers: risks, evalua-tion, prevention and early detection. Obstet Gynecol Clin North Am 34: 783-802, x
14. Fahey LM, Raff AB, Da Silva DM, Kast WM (2009) Reversal of human papillomavirus-specific T cell immune suppression through TLR agonist treatment of Langerhans cells exposed to human papillomavirus type 16. J Immunol 182: 2919-2928
15. Farhat S, Nakagawa M, Moscicki AB (2009) Cell-mediated immune responses to human papillomavirus 16 E6 and E7 antigens as measured by interferon gamma enzyme-linked immunospot in women with cleared or persistent human papillomavirus infection. Int J Gynecol Cancer 19: 508-512
16. Fehr MK, Hornung R, Schwarz VA, Simeon R, Haller U, Wyss P (2001) Photodynamic therapy of vulvar intraepithelial neoplasia III using topically applied 5-aminolevulinic acid. Gynecol Oncol 80: 62-66
17. Gravitt PE, Peyton CL, Apple RJ, Wheeler CM (1998) Genotyping of 27 human papillomavirus types by using L1 consensus PCR products by a single-hybridization, reverse line blot detection method. J Clin Microbiol 36: 3020-3027
18. Gul N, Ganesan R, Luesley DM (2004) Characterizing T-cell response in low-grade and high-grade vulval intraepithelial neoplasia, study of CD3, CD4 and CD8 expressions. Gynecol Oncol 94: 48-53
19. Jones RW, Rowan DM, Stewart AW (2005) Vulvar intraepithelial neoplasia: aspects of the natural history and outcome in 405 women. Obstet Gynecol 106: 1319-1326
20. Karanam B, Gambhira R, Peng S, Jagu S, Kim DJ, Ketner GW, Stern PL, Adams RJ, Roden RB (2009) Vaccination with HPV16 L2E6E7 fusion protein in GPI-0100 adjuvant elicits protective humoral and cell-mediated immunity. Vaccine 27: 1040-1049
21. Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, Essahsah F, Fathers LM, Offringa R, Drijfhout JW, Wafelman AR, Oostendorp J, Fleuren GJ, van der Burg SH, Melief CJ (2009) Vaccination against HPV-16 oncoproteins for vulvar intraepithe-lial neoplasia. N Engl J Med 361: 1838-1847
22. Kobayashi A, Greenblatt RM, Anastos K, Minkoff H, Massad LS, Young M, Levine AM, Darragh TM, Weinberg V, Smith-McCune KK (2004) Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection. Cancer Res 64: 6766-6774
23. Kondratiev S, Sabo E, Yakirevich E, Lavie O, Resnick MB (2004) Intratumoral CD8+ T lymphocytes as a prognostic factor of survival in endometrial carcinoma. Clin Cancer Res 10: 4450-4456
24. Le T, Menard C, Hicks-Boucher W, Hopkins L, Weberpals J, Fung-Kee-Fung M (2007) Final results of a phase 2 study using continuous 5% imiquimod cream application in the primary treatment of high-grade vulva intraepithelial neoplasia. Gynecol Oncol 106: 579-584
25. Likes WM, Stegbauer C, Tillmanns T, Pruett J (2007) Correlates of sexual function following vulvar excision. Gynecol Oncol 105: 600-603
26. Martin-Hirsch PL, Whitehurst C, Buckley CH, Moore JV, Kitchener HC (1998) Photodynamic treatment for lower genital tract intraepithelial neoplasia. Lancet 351: 1403
27. Mathiesen O, Buus SK, Cramers M (2007) Topical imiquimod can reverse vulvar intraepithelial neoplasia: a randomised, double-blinded study. Gynecol Oncol 107: 219-222
28. Olejek A, Kozak-Darmas I, Biniszkiewicz T, Kellas-Sleczka S, Sieron A (2008)[Photodynamic therapy in vulvar intraepithelial neoplasia]. Ginekol Pol 79: 276-280
29. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K (2005) Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 102: 18538-18543
30. Schon MP, Schon M (2007) Imiquimod: mode of action. Br J Dermatol 157(Suppl 2): 8-13
31. Sherman JF, Mount SL, Evans MF, Skelly J, Simmons-Arnold L, Eltabbakh GH (2008) Smoking increases the risk of high-grade vaginal intraepithe-lial neoplasia in women with oncogenic human papillomavirus. Gynecol Oncol 110: 396-401
32. Shylasree TS, Karanjgaokar V, Tristram A, Wilkes AR, MacLean AB, Fiander AN (2008) Contribution of demographic, psychological and disease-related factors to quality of life in women with high-grade vulval intraepithelial neoplasia. Gynecol Oncol 110: 185-189
33. Smyth LJ, Van Poelgeest MI, Davidson EJ, Kwappenberg KM, Burt D, Sehr P, Pawlita M, Man S, Hickling JK, Fiander AN, Tristram A, Kitchener HC, Offringa R, Stern PL, van der Burg SH (2004) Immunological responses in women with human papillomavirus type 16 (HPV-16)-associated anogenital intraepithelial neoplasia induced by heterologous prime-boost HPV-16 oncogene vaccination. Clin Cancer Res 10: 2954-2961
34. Stanley M (2008) Immunobiology of HPV and HPV vaccines. Gynecol Oncol 109: S15-S21
35. Stern PL (2005) Immune control of human papillomavirus (HPV) associated anogenital disease and potential for vaccination. J Clin Virol 32(Suppl 1): S72-S81
36. Thuesen B, Andreasson B, Bock JE (1992) Sexual function and somatopsychic reactions after local excision of vulvar intra-epithelial neoplasia. Acta Obstet Gynecol Scand 71: 126-128
37. Tristram A, Fiander A (2005) Clinical responses to Cidofovir applied topically to women with high grade vulval intraepithelial neoplasia. Gynecol Oncol 99: 652-655
38. van der Burg SH, Piersma SJ, de Jong A, van der Hulst JM, Kwappenberg KM, van den HM, Welters MJ, Van Rood JJ, Fleuren GJ, Melief CJ, Kenter GG, Offringa R (2007) Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens. Proc Natl Acad Sci USA 104: 12087-12092
39. Van Poelgeest MI, van Seters M, van Beurden M, Kwappenberg KM, Heijmans-Antonissen C, Drijfhout JW, Melief CJ, Kenter GG, Helmer-horst TJ, Offringa R, van der Burg SH (2005) Detection of human papillomavirus (HPV) 16-specific CD4+ T-cell immunity in patients with persistent HPV16-induced vulvar intraepithelial neoplasia in relation to clinical impact of imiquimod treatment. Clin Cancer Res 11: 5273-5280
40. van Seters M, van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, Kagie MJ, Meijer CJ, Aaronson NK, Kleinjan A, Heijmans-Antonissen C, Zijlstra FJ, Burger MP, Helmerhorst TJ (2008) Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med 358: 1465-1473
41. Vilmer C, Havard S, Cavelier-Balloy B, Pelisse M, Dubertret L, Leibowitch M (1998) Failure of isotretinoin and interferon-alpha combination therapy for HPV-linked severe vulvar dysplasia. A report of two cases. J Reprod Med 43: 693-695
42. Winters U, Daayana S, Lear JT, Tomlinson AE, Elkord E, Stern PL, Kitchener HC (2008) Clinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia. Clin Cancer Res 14: 5292-5299
43. Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E, Deibl M, Gastl G, Gunsilius E, Marth C (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11: 8326-8331