Cancer and Metastasis Reviews

, Volume 5, Issue 2, pp 139–165 | Cite as

Interferons in the treatment of human papillomavirus diseases

  • Phillip K. Weck
  • Janet L. Brandsma
  • John K. Whisnant
Article

Abstract

A variety of epithelioproliferative benign neoplasms, both trivial and life-threatening, are caused by subtypes of human papillomaviruses. Interferons objectively regress HPV-induced warty disease and affect the regrowth of the transformed epithelium. Interferons effectively control the most serious and potentially life-threatening papillomavirus associated diseases, respiratory papillomatosis and genital warts, but not without the anticipated side effects associated with this potent biological weapon. It is entirely possible and even likely that individual species of interferons act preferentially on certain cells, tissues or organs in response to particular viruses. Combined therapies, such as surgery in combination with interferon, or podophyllin in conjunction with interferon alfa-nl, may prove most efficacious.

Key words

respiratory papillomatosis verruca condylomata viral genetics interferon dysplasia warts 

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References

  1. 1.
    Celsus AC, quoted by Bunny M. Viral Warts: Their Biology and Treatment. Oxford Medical Publications, Oxford University Press, 1982Google Scholar
  2. 2.
    Variot G: Un Cas d'inoculation experimentale des verrues de l'enfant a l'homme. J Clin Therap Infant 2: 529–534, 1894Google Scholar
  3. 3.
    Licht C de F: Om Vorters Smitsomhed. Ugeskrift Laeger 1: 368–369, 1894Google Scholar
  4. 4.
    Cuiffo G: Innesto positivo confiltrato di verruca volgare. Giorn Ital Mal Venereal 48: 12–17, 1907Google Scholar
  5. 5.
    Ullman EV: On the aetiology of the laryngeal papilloma. Acta Oto-Laryngol 5: 317–334, 1923Google Scholar
  6. 6.
    Ishikawa K: Klinishche and experimentelle Untersuchungen uber die Entstehungsussachen der Papillome. Fukoka Acta Med 29: 87–88, 1936Google Scholar
  7. 7.
    Richart RM: Cervical intraepithelial neoplasia. In Somers SC (ed): ‘Genital and Mammary Pathology Decennial’ 1966–1975. New York, Appleton-Century-Crofts, pp. 1–28, 1975Google Scholar
  8. 8.
    Duff TB: Laryngeal papillomatosis. J Laryngol Otol 85: 947–956, 1971Google Scholar
  9. 9.
    Cook TA: Laryngeal papilloma: etiologic and therapeutic considerations. Ann Otol 82: 649–655, 1973Google Scholar
  10. 10.
    Centers for Disease Control. Condyloma acuminatum — United States, 1966–1981, MMWR 32: 306–308, 1983Google Scholar
  11. 11.
    Arnold W: Atiologische Aspekte zur Frage der Entstehung der Larynxpapillome. Laryngol Rhinol Otol 55: 102–111Google Scholar
  12. 12.
    Mounts P, Shah K: Respiratory papillomatosis: etiological relation to genital tract papillomaviruses. In: Melnick JL (ed): Progress in Medical Virology Vol. 29 S. Karger Publishers, Basel, Switzerland, pp. 90–114, 1984Google Scholar
  13. 13.
    Ruiter M, Van Mullem PJ: Behavior of virus in malignant degeneration of skin lesions in epidermodysplasia verruciformis. J Invest Dermatol 54: 324–331, 1970Google Scholar
  14. 14.
    zur Hausen H, Gissmann L, Steiner W, Dippold W and Dregger I: Human papillomaviruses and cancer. Bibl Haematol 43: 569–571, 1975Google Scholar
  15. 15.
    zur Hausen H: Human papillomaviruses and their possible role in squamous cell carcinomas. Curr Top Microbiol Immunol 78: 1–30, 1978Google Scholar
  16. 16.
    Singleton GT, Adkins WY: Cryosurgical treatment of juvenile laryngeal papillomatosis. An eight year experience. Ann Otol 81: 784–789, 1972Google Scholar
  17. 17.
    Fisher AA: Severe systemic and local reactions to topical podophyllin resin. Cutis 28: 233, 236, 242, 1981Google Scholar
  18. 18.
    Dedo HH and Jackler RK: Laryngeal papilloma: results of treatment with the CO2 laser and podophyllum. Ann Otol Rhinol Laryngol 91: 425–430, 1982Google Scholar
  19. 19.
    Biberstein H: Immunization therapy of warts. Arch Dermatol Syphilol 50: 12–22, 1944Google Scholar
  20. 20.
    Holinger PH, Shipkowitz NA, Holper JC et al.: Studies of laryngeal papilloma and an autogenous papilloma vaccine. Acta Otolaryngol (Stockh) 65: 63–69, 1968Google Scholar
  21. 21.
    Strauss MJ, Shaw EW, Bunting H and Melnick J: ‘Crystalline’ virus-like particles from skin papillomas characterized by intranuclear inclusion bodies. Proc Soc Exper Biol & Med 72: 46–50, 1949Google Scholar
  22. 22.
    zur Hausen H, Meinhof W, Scheiber W and Bornkamm GW: Attempts to detect virus-specific DNA in human tumors. I. Nucleic acid hybridizations with complementary RNA of human wart virus. Int J Cancer 13: 650–656, 1974Google Scholar
  23. 23.
    Gissmann J and zur Hausen H: Human papilloma viruses: physical mapping and genetic heterogeneity. Proc Natl Acad Sci USA 73: 1310–1313, 1976Google Scholar
  24. 24.
    Jensen AB, Rosenthal JD, Onson C et al.: Immunological relatedness of papillomaviruses from different species. J Nat Ca Inst 64: 495–500, 1980Google Scholar
  25. 25.
    Heilman CA, Law M-F, Israel MA et al.: Cloning of human papilloma virus genomic DNAs and analysis of homologous polynucleotide sequence. J Virol 36: 395–407, 1980Google Scholar
  26. 26.
    Isaacs A and Lindemann J: Virus interference: I. The interferon. Proc Royal Soc Biol 147: 258, 1957Google Scholar
  27. 27.
    Scott GM and Tyrrell DAJ: Antiviral effects of interferons in man. In: Finter NB and Oldham RK (eds): Interferon: In Vitro and Clinical Studies. Vol. 4 Elsevier Science Publishers, Amsterdam, 1985Google Scholar
  28. 28.
    Ikic D, Maricic Z, Oresic V, Rode B, Nola P, Smudj K, Khezevic M, Jusic D and Soos E: Application of human leukocyte interferon in patients with urinary bladder papillomatosis, breast cancer and melanoma. Lancet 1: 1022–1024, 1981Google Scholar
  29. 29.
    Ikic D, Brodorec I, Padovan I, Knezevic M and Soos E: Application of human leukocyte interferon in patients with tumors of the head and neck. Lancet 1: 1025–1027, 1981Google Scholar
  30. 30.
    Ikic D, Kirhmajer V, Maricic A, Jusic D, Krusic J, Knezevic M, Rode B and Soos E: Application of human leukocyte interferon in patients with carcinoma of the uterine cervix. Lancet 1: 1027–1030, 1981Google Scholar
  31. 31.
    Maricic Z, Nola P, Ikic D, Smudj K, Oresic V, Knezevic M, Rode B, Jusic D and Soos S: Human Leukocyte interferon in therapy of patients with urinary bladder papillomatosis, breast cancer and melanoma. J Cancer Res Clin Oncol 101: 317–323, 1981Google Scholar
  32. 32.
    Ikic D, Krusic J, Cupak K et al.: The use of human leukocyte interferon in patients with cervical cancer and basocellular cancer of the skin. Proc Symp Clinical Use of Interferon. 9th Int Immunobiol Symp Yugoslav Acad Sci Arts. Zagreb, pp. 239–243, 1972Google Scholar
  33. 33.
    Krusic J, Ikic D, Knezevic M, Soos E, Rode B, Jusic D and Maricic Z: Clinical and histological findings after local application of human leukocyte interferon in patients with cervical cancer. Pro Symp Clinical Use of Interferon. 11th Int Immunobiol Symp Yugoslav Acad Sci Arts. Zagreb, pp. 167–177, 1972Google Scholar
  34. 34.
    Stander H, Cantell K: Studies on antiviral and antitumor effects of human leukocyte interferon in vitro and in vivo. In: Waymouth C (ed): The Production and Use of Interferon for the Treatment and Prevention of Human Virus Infections. Rockville, MD Tissuc Culture Association, 1974, pp. 49–56Google Scholar
  35. 35.
    Haglund S, Lundquist PG, Cantell K and Strander H: Interferon therapy in juvenile laryngeal papillomatosis. Arch Otolaryngol 107: 327–332, 1981Google Scholar
  36. 36.
    Pazin GJ, Ho M, Haverkos HW, Armstrong JA, Breinig MD, Wechsler HL, Arvin A, Merigan TC, Cantell K: Effects of interferon-alpha on human warts. J Interferon Res 2: 235–243, 1982Google Scholar
  37. 37.
    Goeddel DV, Yelverton D, Ullrich A, Heynekker HL, Miozarri G, Holmes W, Seeburg PH, Dull T, May L, Stebbing N, Crea R, Maeda S, McCandliss R, Sloma A, Tabor JM, Gross M, Familletti PC and Pestka S: Human leukocyte interferon produced by E. coli is biologically active. Nature (Lond) 287: 411–416, 1980Google Scholar
  38. 38.
    Nagata S, Taira H, Hall A, Johnsbrud L, Streuli H, Escodi J, Bull W, Cantell K and Weissmann K: Synthesis in E. coli of a polypeptide with human leukocyte interferon activity. Nature (Lond) 284: 316–320, 1980Google Scholar
  39. 39.
    Zoon KC, Hu RQ, ZurNedden D, Nguyen NY: The purification and characterization of multiple species of human lymphoblastoid interferon alpha. In: Kirchmer H and Schellehus H (eds). The Biology of the Interferon System. Elsevier Science Publishers, Amsterdam, 1984, pp. 61–68Google Scholar
  40. 40.
    Zoon KC and Hu R: Further studies on the purification and partial characterization of multiple species of human lymphoblastoid interferon alphas. In: Kirchner H and Schellekens H (eds): The Biology of the Interferon System. Elsevier Science Publishers, AmsterdamGoogle Scholar
  41. 41.
    Liang C and Herren S: Analysis of antibody response in patients receiving recombinant E. coli derived human interferon gamma. Clin Immunol & Immunopathol 36: 95–100, 1985Google Scholar
  42. 42.
    Taguchi T: Clinical studies of recombinanat interferon alpha-2a (Roferon A) in cancer patients. Cancer 57: 1705–1708, 1986Google Scholar
  43. 43.
    Jones GJ and Itri LM: Safety and tolerance of recombinant interferon alpha 2a (Roferon A) in cancer patients. Cancer 57: 1709–1715, 1986Google Scholar
  44. 44.
    Weck PK, Apperson S, May L, Stebbing N: Comparison of the antiviral activities of various cloned human interferon alpha subtypes in mammalian cell cultures. J gen Virol 57: 233–237, 1981Google Scholar
  45. 45.
    Ransehoff RM, Maroney PA, Nayak DP, Chambers TM and Nilsen TW: Effect of human alpha A interferon on influenza virus replication in MDBK cells. J Virol 56: 1049–1052, 1985Google Scholar
  46. 46.
    Turek LP, Byrne JC, Lowy DR, Dvoretzky I, Friedman RM and Howley PM: Interferon induces morphologic reversion with elimination of extrachromosomal viral genomes in bovine papillomavirus-transformed mouse cells. Proc Natl Acad Sci 79: 7914–7918, 1982Google Scholar
  47. 47.
    Steinberg BM, Abramson AL and Horowitz B: Effects of alpha interferon on cultured laryngeal papilloma cells. Papilloma Viruses: Molecular and Clinical Aspects. UCLA Symposia on Molecular and Cellular Biology, New Series Volume 32, Howley PM and Broker TR (eds), Alan R. Liss, Inc., pp. 413–426, 1985Google Scholar
  48. 48.
    Yamazaki S: Current status of clinical interferon research in Japan. J Med Sci Biol 36: 261–271, 1983Google Scholar
  49. 49.
    Gall SA, Hughes CE, Mounts P, Segreti A, Weck PK and Whisnant JK: The efficacy of human lymphoblastoid interferon in the therapy of resistant condylomata acuminata. Obstet Gynecol 67: 643–651, 1986Google Scholar
  50. 50.
    Gall SA, Hughes CE, Trofatter K, Whisnant J and Weck PK: Lymphoblastoid interferon for the therapy of condylomata acuminata: an inter-study comparison of two dose regimens. Papilloma Viruses: Molecular and Clinical Aspects. UCLA Symposia on Molecular and Cellular Biology. New Series Volume 32, Howley PM and Broker TR (eds), Alan R. Liss, Inc., pp. 201–216, 1985Google Scholar
  51. 51.
    Whisnant J, Kashima H, Leventhal B: Interferon treatment of juvenile laryngeal papillomatosis: the design of a cooperative trial with Wellferon. The Biology of the Interferon System, H. Kirchner and H. Schellekens (eds), Elsevier Science Publishers BV, pp. 601–609, 1984Google Scholar
  52. 52.
    Healy GB and Trowbridge AL: Interferon in recurrent respiratory papillomatosis — a multicenter controlled clinical trial. Papilloma Viruses: Molecular and Clinical Aspects. UCLA Symposia on Molecular and Cellular Biology, New Series Volume 32, Howley PM and Broker TR (eds), Alan R. Liss. Inc., pp. 181–182, 1985Google Scholar
  53. 53.
    Baglioni C: Interferon induced enzymatic activities and their role in the antiviral state. Cell 17: 255–264, 1979Google Scholar
  54. 54.
    Lengyl P: Biochemistry of interferons and their actions. Ann Rev Biochem 51: 251–282, 1982Google Scholar
  55. 55.
    McMahon M and Kerr IM: The biochemistry of the antiviral state. In: Interferons: From Molecular Biology to Clinical Applications, DC Burke and AG Morris (eds), Cambridge University Press, 1983, pp. 89–108Google Scholar
  56. 56.
    Strong MS, Vaughan CW, Healy GB et al.: Recurrent respiratory papillomatosis — management with the CO2 laser. Ann Otol Rhinol Laryngol 85: 508–516, 1976Google Scholar
  57. 57.
    Steinberg BM, Topp WC, Schneider PS: Laryngeal papillomavirus infection during clinical remission. N Engl J Med 308: 121–1264, 1983Google Scholar
  58. 58.
    Goepfert H, Sessions RB, Gutterman JU et al.: Leukocyte interferon in patients with juvenile laryngeal papillomatosis. Ann Otol Rhinol Laryngol 91: 431–436, 1982Google Scholar
  59. 59.
    Sessions RB, Goepfert H, Donovan DT et al.: Further observations on the treatment of recurrent respiratory papillomatosis with interferon: a comparison of sources. Ann Otol Rhinol Laryngol 92: 456–461, 1983Google Scholar
  60. 60.
    McCabe BF, Clark KF: Interferon and laryngeal papillomatosis. The Iowa experience. Ann Otol Rhinol Laryngol 92: 2–7, 1983Google Scholar
  61. 61.
    Bomholt A: Interferon therapy for laryngeal papillomatosis in adults. Arch Otolaryngol 109: 550–552, 1983Google Scholar
  62. 62.
    Schouten TJ, Weimar W, Bos JH et al.: Treatment of juvenile laryngeal papillomatosis with two types of interferon. Laryngoscope 92: 686–688, 1982Google Scholar
  63. 63.
    Gobel U, Arnold W, Wahn V, Treuner J, Jurgens H and Cantell K: Comparison of human fibroblast and leukocyte interferon in the treatment of severe laryngeal papillomatosis in children. Eur J Pediatr 137: 175, 1981Google Scholar
  64. 64.
    Weck PK, Kashima H, Leventhal B, Tuttle RL, Whisnant JK: Evaluation of human lymphoblastoid interferon in juvenile laryngeal papillomatosis. Antiviral Res Abstr 1: 17, 1983Google Scholar
  65. 65.
    Mounts P and Kashima HK: Association of human papillomavirus subtype and clinical course in respiratory papillomatosis. Laryngoscope 94: 28, 1984Google Scholar
  66. 66.
    Von Krogh G: Topical treatment of penile condylomata acuminata with podophyllin, podophyllotoxin and colchicine. Acta Dermatol (Stockholm) 58: 163–169, 1978Google Scholar
  67. 67.
    Ikic D, Bosnic N, Smerdel S: Double-blind clinical study with human leukocyte interferon in the therapy of condylomata acuminata. Proc Symp Clinical Use of Interferon. Zagreb, pp. 239–233, 1975Google Scholar
  68. 68.
    Ikic D, Orescanin J, Krusic Z: Preliminary study of the effect of human leukocyte interferon on condylomata acuminata in women. Proc Symp Clinical Use of Interferon. Zagreb, pp. 233–238, 1975Google Scholar
  69. 69.
    Scott GM, Csonka GW: Effect of injections of small doses of human fibroblast interferon into geni al warts. A pilot study. Br J Vener Dis 55: 442–445, 1979Google Scholar
  70. 70.
    Marcovici R, Peretz BA, Poldi E: Human fibroblast interferon therapy in patients with condyloma acuminata. Isr J Sci 19: 104, 1983Google Scholar
  71. 71.
    Schonfield A, Nitke S, Schattner A, Wallach D, Crespi M, Hahn T, Levavi H, Yarden O, Schoham J, Doerner T, Revel M: Intramuscular human interferon-beta injections in treatment of condylomata acuminata. Lancet 1: 1038, 1984Google Scholar
  72. 72.
    Gross G, Ikenberg H and Gissmann L: Bowenoid dysplasia in human papillomavirus-16 DNA positive flat condylomas during interferon-beta treatment. Lancet 1: 1467–1468, 1984Google Scholar
  73. 73.
    Geffen JR, Klein RJ, Friedman-Kein AE: Intralesional administration of large doses of human leukocyte interferon for the treatment of condyloma acuminata. J Inf Dis 150: 612, 1984Google Scholar
  74. 74.
    Einhorn N, Ling P and Strander H: Systemic interferon alpha treatment of human condyloma acuminata. Acta Obstet Gynecol Scand 62: 285, 1983Google Scholar
  75. 75.
    Reichman RG, Micha J, Bonnez W, Trofatter K, Weck P, Gall S: A multicenter study of interferon alfa-nl (Wellferon®) treatment for refractory condyloma acuminatum. Abstract #96 Proc Intersci Conf Antimicrobial Agents Chemother 106, 1985Google Scholar
  76. 76.
    Trofatter KF, Olsen EA, Kucera PR, Sheets EE, Britt PH, Wold D, Weck PK: Combination of NSAID and WELL-FERON: A controlled clinical trial in genital warts. In: Stewart WE and Schellekens H (eds): The Biology of the Interferon System. Elsevier Science Publishers, Amsterdam, 1985Google Scholar
  77. 77.
    Gottlieb A, Mills J, Britt P, Weck P: Interferon alfa-nl for the treatment of severe perianal and rectal condylomata acuminata. Second World Congress on Sexually Transmitted Diseases. Paris, June 25–28, 1986Google Scholar
  78. 78.
    Gibson JR, Harvey SG: Interferon in the treatment of persistant viral warts. Dermatologica 169: 47–48, 1984Google Scholar
  79. 79.
    Androphy EJ, Dvoretzky I, Maluish AE, Wallace HJ and Lowy DR: Response of warts in epidermodysplasia verruciformis to treatment with systemic and intralesional alpha interferon. J Am Acad Dermatol 11: 197–202, 1984Google Scholar
  80. 80.
    Beral V: Cancer of the cervix: a sexually transmitted infection. Lancet 1: 1037, 1974Google Scholar
  81. 81.
    Rotkin IA: A comparison review of key epidemiologic studies in cervical cancer related to current searches for transmissible agents. Cancer Res 33: 1353, 1973Google Scholar
  82. 82.
    Terris M, Wilson F, Nelson JHJr: Comparative epidemiology of invasive carcinoma of the cervix, carcinoma in situ, and cervical dysplasia. Am J Epidemiol 112: 253, 1980Google Scholar
  83. 83.
    Gissmann L: Papillomaviruses and their association with cancer in animals and man. Cancer Surveys. 1984Google Scholar
  84. 84.
    Durst M, Gissmann L, Ikenberg H and zur Hausen H: A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci USA 80: 3812–3815, 1983Google Scholar
  85. 85.
    Crum CP, Ikenberg H, Richart R and Gissmann L: Human papillomavirus type 16 and early cervical neoplasia. N E J M 310: 880–883, 1984Google Scholar
  86. 86.
    Gissmann L, Boshart M, Durst M, Ikenberg H, Wagner D and zur Hausen H: Presence of human papillomavirus in genital tumors. J Invest Dermatol 83 (1 Suppl): 26s-28s, 1984Google Scholar
  87. 87.
    Crum CP, Fu YS, Levine, Ryu, Richart RM, Townsend DE, Fenoglio DM: Intraepithelial squamous lesions of the vulva: biologic and histologic criteria for the distinction of condylomas from vulvar intraepithelial neoplasia. Am J Obstet Gynecol 144: 77, 1982Google Scholar
  88. 88.
    Winkler B, Crum CP, Fujii T, Ferenczy A, Boon M, Braun L, Lancaster WD, Richart RM: Koilocytotic lesions of the cervix: the relationship of mitotic abnormalities to nuclear DNA content. Cancer 53: 1081, 1984Google Scholar
  89. 89.
    De Palo G, Stefanon B, Rilke F, Pilotti S, Ghione M: Human fibroblast interferon in cervical and vulvar intraepithelial neoplasia associated with papillomavirus infection. Int J Tiss Reac VI: 523–527, 1984Google Scholar
  90. 90.
    Lerner AM and Bailey EJ: Differential sensitivity of herpes simplex virus types 1 and 2 to human interferon: Antiviral effects of interferon plus 9-B-D-arabinofuranosyladenine. J Infect Dis 134: 400, 1976Google Scholar
  91. 91.
    Bryson YJ and Kronenberg: Combined antiviral effects of interferon, adenine arabinoside, hypozanthine arabinoside, and adenine arabinoside-5′-monophosphate in human fibroblast cultures. Antimicrob Agents Chemother 11: 299, 1977Google Scholar
  92. 92.
    Levin MJ and Leary PL: Inhibition of human herpes viruses by combinations of acyclovir and human leukocyte interferon. Infect Immun 32: 995, 1981Google Scholar
  93. 93.
    Stanwick TL, Schinazi RF, Campbell DE and Nahmias AJ: Combined antiviral effect of interferon and acyclovir on herpes simplex viruses types 1 and 2. Antimicrob Agents Chemother 19: 672, 1981Google Scholar
  94. 94.
    Reichman RC, Bonnez W, Greisberger C, Whitley RJ, Tyring S, Miller L et al.: Treatment of condyloma acuminatum with intralesionally administered interferons: a multicentered, placebo-controlled trial. Clin Res 34 (2): 531A, 1986Google Scholar

Copyright information

© Martinus Nijhoff Publishers 1986

Authors and Affiliations

  • Phillip K. Weck
    • 1
    • 2
  • Janet L. Brandsma
    • 1
    • 2
  • John K. Whisnant
    • 1
    • 2
  1. 1.Department of Immunology and OncologyBurroughs Wellcome Co.Research Triangle ParkUSA
  2. 2.Long Island Jewish Medical CenterNew Hyde ParkUSA

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