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A possible role for human papillomaviruses in head and neck cancer

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Abstract

Human papillomaviruses (HPVs) cause benign tumors in the respiratory tract. Mounting evidence suggests that they also play a role in the etiology of a subset of head and neck cancers. Carcinomas in patients with a history of recurrent respiratory papillomatosis clearly are caused by persisting HPV interacting with one or more carcinogenic agents. Verrucous carcinomas of the oral cavity, tonsillar and tongue carcinomas are strongly linked with HPVs, based on molecular epidemiologic data. Tonsillar cancers have been shown to express HPV RNA, presumed necessary to induce and maintain a carcinoma, supporting a viral etiology. This paper reviews the molecular and cellular basis for considering HPVs as causttive agents of cancer, and reviews the literature that considers the possible role of HPVs in head and neck cancer.

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References

  1. Pfister H: Papillomaviruses and Human Cancer. CRC Press, Boca Raton, 1990, pp 1–9

    Google Scholar 

  2. Chiang CM, Ustav M, Stenlund A, Ho TF, Broker TR, Chow LT: Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. Proc Natl Acad Sci USA 89: 5799–5803, 1992

    Google Scholar 

  3. Remm M, Brain R, Jenkins JR: The E2 binding sites determine the efficiency of replication for the origin of human papillomavirus type 18. Nucleic Acids Res 20: 6015–6021, 1992

    Google Scholar 

  4. Del Vecchio AM, Romanczuk H, Howley PM, Baker CC: Transient replication of human papillomavirus DNAs. J Virol 66: 5949–5958, 1992

    Google Scholar 

  5. Kuo SR, Liu JS, Broker TR, Chow LT: Cell-free replication of the human papillomavirus DNA with homologous viral E1 and E2 proteins and human cell extracts. J Biol Chem 269: 24058–24065, 1994

    Google Scholar 

  6. McBride AA, Romanczuk H, Howley PM: The papilloma-virus E2 regulatory proteins. J Biol Chem 266: 18411–18414, 1991

    Google Scholar 

  7. Chin MT, Hirochika R, Hirochika H, Broker TR, Chow LT: Regulation of human papillomavirus type 11 enhancer and E6 promoter by activating and repressing proteins from the E2 open reading frame: Functional and biochemical studies. J Virol 62: 2994–3002, 1988

    Google Scholar 

  8. Tan SH, Gloss B, Bernard HU: During negative regulation of the human papillomavirus-16 E6 promoter, the viral E2 protein can displace Sp1 from a proximal promoter element. Nucleic Acids Res 20: 251–256, 1992

    Google Scholar 

  9. Woodworth CD, Bowden PE, Doniger J, Pirisi L, Barnes W, Lancaster WD, DiPaolo JA: Characterization of normal human exocervical epithelial cells immortalized in vitro by papillomavirus types 16 and 18 DNA. Cancer Res 48: 4620–4628, 1988

    Google Scholar 

  10. Barbosa MS, Schlegel R: The E6 and E7 genes of HPV-18 are sufficient for inducing two-stage in vitro transformation of human keratinocytes. Oncogene 4: 1529–1532, 1989

    Google Scholar 

  11. 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 67: 4521–4532, 1993

    Google Scholar 

  12. Brandsma JL: Animal models of human-papillomavirus-associated oncogenesis. Intervirology 37: 189–200, 1994

    Google Scholar 

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

    Google Scholar 

  14. Chow LT, Broker TR: Papillomarivus DNA replication. Intervirology 37: 150–158, 1994

    Google Scholar 

  15. Fuchs PG, Pfister H: Transcription of papillomavirus genomes. Intervirology 37: 159–167, 1994

    Google Scholar 

  16. Chow LT, Nasseri M, Wolinsky SM, Broker TR: Human papillomavirus types 6 and 11 mRNAs from genital condylomata acuminata. J Virol 61: 2581–2588, 1987

    Google Scholar 

  17. Smotkin D, Prokoph H, Wettstein FO: Oncogenic and non-oncogenic human genital papillomaviruses generate the E7 mRNA by different mechanisms. J Virol 63: 1441–1447, 1989

    Google Scholar 

  18. Ward P, Mounts P: Heterogeneity in mRNA of human papillomavirus type-6 subtypes in respiratory tract lesions. Virology 168: 1–12, 1989

    Google Scholar 

  19. Nasseri M, Hirochika R, Broker TR, Chow LT: A human papillomavirus type 11 transcript encoding an E1-E4 protein. Virology 159: 433–439, 1987

    Google Scholar 

  20. Doorbar J, Parton A, Hartley K, Banks L, Crook T, Stanley M, Crawford L: Detection of novel splicing patterns in a HPV 16-containing keratinocyte cell line. Virology 178: 254–262, 1990

    Google Scholar 

  21. Rotenberg MO, Chow LT, Broker TR: Characterization of rare human papillomavirus type 11 mRNAs coding for regulatory and structural proteins, using the polymerase chain reaction. Virology 172: 489–497, 1989

    Google Scholar 

  22. Miller SJ, Sun TT, Lavker RM: Hair follicles, stem cells, and skin cancer. J Invest Dermatol 100: 288S-294S, 1993

    Google Scholar 

  23. Stanley MA: Virus-keratinocyte interactions in the infectious cycle. In: Stern PL, Stanley M (eds) Human papillo-maviruses and Cervical Cancer. Biology and Immunology, Oxford University Press, Oxford, 1994, pp 116–145

    Google Scholar 

  24. Zhou J, Sun XY, Stenzel DJ, Frazer IH: Expression of vaccinia recombinant HPV 16 L1 and L2 ORF proteins in epithelial cells is sufficient for assembly of HPV virion-like particles. Virology 185: 251–257, 1991

    Google Scholar 

  25. Steinberg BM, Auborn KJ, Brandsma JL, Taichman LB: Tissue site-specific enhancer function of the upstream regulatory region of human papillomavirus type 11 in cultured keratinocytes. J Virol 63: 957–960, 1989

    Google Scholar 

  26. Maran A, Amella CA, DiLorenzo TP, Auborn KJ, Taichman LB, Steinberg BM: Human papillomarivus type 11 transcripts are present at low abundance in latently infected respiratory tissues. Virology 212: 285–294, 1995

    Google Scholar 

  27. Meyers C, Harry J, Lin YL, Wettstein FO: Identification of three transforming proteins encoded by cottontail rabbit papillomavirus. J Virol 66: 1655–1664, 1992

    Google Scholar 

  28. Brandsma JL, Yang ZH, Barthold SW, Johnson EA: Use of a rapid, efficient inoculation method to induce papillomas by cottontail rabbit papillomavirus DNA shows that the E7 gene is required. Proc Natl Acad Sci USA 88: 4816–4820, 1991

    Google Scholar 

  29. Stoler MH, Whitbeck A, Wolinsky SM, Broker TR, Chow LT, Howett MK, Kreider JW: Infectious cycle of human papillomavirus type 11 in human foreskin xenografts in nude mice. J Virol 64: 3310–3318, 1990

    Google Scholar 

  30. Steinberg BM, Topp WC, Schneider PS, Abramson AL: Laryngeal papillomavirus infection during clinical remission. N Engl J Med 308: 1261–1264, 1983

    Google Scholar 

  31. Ferenczy A, Mitao M, Nagai N, Silverstein SJ, Crum CP: Latent papillomavirus and recurring genital warts. N Engl J Med 313: 784–788, 1985

    Google Scholar 

  32. Toon PG, Arrand JR, Wilson LP, Sharp DS: Human papillomavirus infection of the uterine cervix of women without cytological signs of neoplasia. Br Med J Clin Res Ed 293: 1261–1264, 1986

    Google Scholar 

  33. Amtmann E, Volm M, Wayss K: Tumour induction in the rodent Mastomys natalensis by activation of endogenous papillomavirus genomes. Nature 308: 291–292, 1984

    Google Scholar 

  34. Siegsmund M, Wayss K, Amtmann E: Activation of latent papillomavirus genomes by chronic mechanical irritation. J Gen Virol 72: 2787–2789, 1991

    Google Scholar 

  35. Amella CA, Lofgren LA, Ronn AM, Nouri M, Shikowitz MJ, Steinberg BM: Latent infection induced with cottontail rabbit papillomavirus: A model for human papillomavirus latency. Am J Pathol 144: 1167–1171, 1994

    Google Scholar 

  36. Campo MS, Jarrett WFH, O'Neil W, Barron RJ: Latent papillomavirus infection in cattle. Res Vet Sci 56: 151–157, 1994

    Google Scholar 

  37. Benton C, Shahidullah H, Hunter JAA: Human papillomavirus in the immunosuppressed. Papillomavirus Rep 3: 23–26, 1992

    Google Scholar 

  38. Haglund S, Lundquist PG, Cantell K, Strander H: Interferon therapy in juvenile laryngeal papillomatosis. Arch Otolaryngol 107: 327–332, 1981

    Google Scholar 

  39. Auborn KJ, Steinberg BM: Therapy of papillomavirus-induced lesions. In: Pfister H (ed.) Papillomavirus and Human Cancer. CRC Press, Boca Raton, 1990, pp 203–223

    Google Scholar 

  40. Abramson AL, Steinberg BM, Winkler B: Laryngeal papillomatosis: clinical, histopathologic and molecular studies. Laryngoscope 97: 678–685, 1987

    Google Scholar 

  41. Steinberg BM, Meade R, Kalinowski S, Abramson AL: Abnormal differentiation of human papillomavirus-induced laryngeal papillomas. Arch Otolaryngol Head Neck Surg 116: 1167–1171, 1990

    Google Scholar 

  42. Iftner T, Oft M, Bohm S, Wilczynski SP, Pfister H: Transcription of the E6 and E7 genes of human papillomavirus type 6 in anogenital condylomata is restricted to undifferentiated cell layers of the epithelium. J Virol 66: 4639–4646, 1992

    Google Scholar 

  43. Stoler MH, Wolinsky SM, Whitbeck A, Broker TR, Chow LT: Differentiation-linked human papillomavirus type 6 and 11 transcription in genital condylomata revealed by in situ hybridization with message-specific RNA probes. Virology 172: 331–340, 1989

    Google Scholar 

  44. Durst M, Glitz D, Schneider A, zur Hausen H: Human papillomavirus type 16 (HPV16) gene expression and DNA replication in cervical neoplasia: Analysis by in situ hybridization. Virology 189: 132–140, 1992

    Google Scholar 

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

    Google Scholar 

  46. Lack EE, Jenson AB, Smith HG, Healy GB, Pass F, Vawter GF: Immunoperoxidase localization of human papillomavirus in laryngeal papillomas. Intervirology 14: 148–154, 1980

    Google Scholar 

  47. Chang F, Syrjanen S, Kellokoski J, Syrjanen K: Human papillomavirus (HPV) infection and their associations with oral disease. J Oral Pathol Med 20: 305–317, 1991

    Google Scholar 

  48. Loning T, Reichart P, Staquet MJ, Becker J, Thivolet J: Occurrence of papillomavirus structural antigens in oral papillomas and leukoplakias. J Oral Pathol 13: 155–165, 1984

    Google Scholar 

  49. Ward KA, Napier SS, Winter PC, Maw RD, Dinsmore WW: Detection of human papillomavirus DNA sequences in oral squamous cell papillomas by the polymerase chain reaction. Oral Surg Oral Med Oral Path Oral Radiol 80: 63–66, 1995

    Google Scholar 

  50. Pfister H, Hettich I, Runne U, Gissmann L, Chilf GN: Characterization of human papillomavirus type 13 from focal epithelial hyperplasia Heck lesions. J Virol 47: 363–366, 1983

    Google Scholar 

  51. Beaudenon S, Praetorius F, Kremsdorf D, Lutzner M, Worsaae N, Pehau-Arnaudet G, Orth G: A new type of human papillomavirus associated with oral focal epithelial hyperplasia. J Invest Dermatol 88: 130–135, 1987

    Google Scholar 

  52. Sarkar FH, Visscher DW, Kintanar EB, Zarbo RJ, Crissman JD: Sinonasal Schneiderian papillomas: human papillomavirus typing by polymerase chain reaction. Mod Pathol 5: 329–332, 1992

    Google Scholar 

  53. Brandsma J, Abramson A, Sciubba J, Shah K, Barrezueta N, Galli R: Papillomavirus infection of the nose. In: Steinberg BM, Brandsma JL, Taichman LB (eds) Cancer Cells 5: Papillomaviruses. Cold Spring Harbor Press. Cold Spring Harbor, 1987, pp 301–308

    Google Scholar 

  54. Judd R, Zaki SR, Coffield LM, Evatt BL: Sinonasal papillomas and human papillomavirus: human papillomavirus 11 detected in fungiform Schneiderian papillomas by in situ hybridization and the polymerase chain reaction. Hum Pathol 22: 550–556, 1991

    Google Scholar 

  55. Buchwald C, Franzmann M-B, Jacobsen GK, Lindeberg H: Human papillomavirus (HPV) in sinonasal papillomas: a study of 78 cases using in situ hybridization and polymerase chain reaction. Laryngoscope 105: 66–71, 1995

    Google Scholar 

  56. Fu YS, Hoover L, Franklin M, Cheng L, Stoler MH: Human papillomavirus identified by nucleic acid hybridization in concomitant nasal and genital papillomas. Laryngoscope 102: 1014–1019, 1992

    Google Scholar 

  57. Beck JC, McClatchey KD, Lesperance MM, Esclamado RM, Carey TE, Bradford CR: Presence of human papillomavirus predicts recurrence of inverted papilloma. Otolaryngol Head Neck Surg 113: 49–55, 1995

    Google Scholar 

  58. Wu T-C, Trujillo JM, Kashima HK, Mounts P: Association of human papillomavirus with nasal neoplasia. Lancet 341: 522–524, 1993

    Google Scholar 

  59. Steinberg BM: Laryngeal papillomas: Clinical aspects and in vitro studies. In: Salzman NP, Howley PM (eds) The Papovaviridae, Vol 2, The Papillomaviruses. Plenum Press, New York, 1987, pp 265–292

    Google Scholar 

  60. Mounts P, Shaw KV, Kashima H: Viral etiology of juvenile and adult onset squamous papilloma of the larynx. Proc Natl Acad Sci USA 79: 5425–5429, 1982

    Google Scholar 

  61. Rihkanen H, Aatonen L-M, Syrjanen SM: Human papillomavirus in laryngeal papillomas and in adjacent normal epithelium. Clin Otolaryngol 18: 470–474, 1993

    Google Scholar 

  62. Pignatari S, Smith EM, Gray SD, Shive C, Turek LP: Detection of human papillomavirus infection in diseased and non-diseased sites of the respiratory tract in recurrent respiratory papillomatosis patients by DNA hybridization. Ann Otol Rhinol Laryngol 101: 408–412, 1992

    Google Scholar 

  63. De Villiers E-M, Gissmann L, zur Hausen H: Molecular cloning of viral DNA from human genital warts. J Virol 40: 932–935, 1981

    Google Scholar 

  64. Gissmann L, Diehl V, Schultz-Coulon H-J, zur Hausen H: Molecular cloning and characterization of human papillomavirus DNA derived from a laryngeal papilloma. J Virol 44: 393–400, 1982

    Google Scholar 

  65. Dickens P, Srivastava G, Loke SL, Larkin S: Human papillomavirus 6,11, and 16 in laryngeal papillomas. J Pathol 165: 243–246, 1991

    Google Scholar 

  66. Strong MS, Vaughan CW, Healy B, Cooperband SR, Clemente MA: Recurrent respiratory papillomatosis: management with the CO2 laser. Ann Otol Rhinol Laryngol 85: 508–516, 1976

    Google Scholar 

  67. Lindeberg H, Elbrond O: Laryngeal papillomas: the epidemiology in a Danish subpopulation 1965–1984. Clin Otolaryngol 15: 125–131, 1990

    Google Scholar 

  68. Cook TA, Brunschwig JP, Butel JS, Cohn AM, Goepfert H, Rawls WE: Laryngeal papilloma: etiologic and therapeutic considerations. Ann Otol Rhinol Laryngol 82: 649–655, 1973

    Google Scholar 

  69. Quick CA, Watts SL, Krzyzek RA, Faras AJ: Relationship between condylomata and laryngeal papillomata. Clinical and molecular virological evidence. Ann Otol Rhinol Laryngol 89: 467–471, 1980

    Google Scholar 

  70. Shah K, Kashima H, Polk BF, Shah F, Abbey H, Abramson A: Rarity of cesarean delivery in cases of juvenile onset respiratory papillomatosis. Obstet Gynecol 68: 795–799, 1986

    Google Scholar 

  71. Brandsma JL, Abramson AL: Association of papillomavirus with cancers of the head and neck. Arch Otolaryngol Head Neck Surg 115: 621–625, 1989

    Google Scholar 

  72. Rikhanen H, Peltomaa J, Syrjanen S: Prevalence of human papillomavirus (HPV) DNA in vocal cords without laryngeal papillomas. Acta Otolaryngol (Stockh) 114: 348–351, 1994

    Google Scholar 

  73. Kellokoski J, Syrjanen S, Yliskoski M, Syrjanen K: Dot blot hybridization in detection of human papillomavirus (HPV) infections in the oral cavity of women with genital HPV infections. Oral Microbiol Immunol 7: 19–23, 1992

    Google Scholar 

  74. Abramson AL, Shikowitz MJ, Mullooly VM, Steinberg BM, Hyman RB: Variable light dose effect on photodynamic therapy for laryngeal papillomas. Arch Otolaryngol Head Neck Surg 120: 852–855, 1994

    Google Scholar 

  75. Lofgren LA, Ronn AM, Abramson AL, Shikowitz MJ, Nouri M, Lee CJ, Batti J, Steinberg BM: Photodynamic therapy using meso-tetra(hydroxyphenyl) chlorin: An animal model. Arch Otolaryngol Head Neck Surg 120: 1355–1362, 1994

    Google Scholar 

  76. Altmann A, Jochmus I, Rosl F: Intra-and extracellular control mechanisms of human papillomavirus infection. Intervirology 37: 180–188, 1994

    Google Scholar 

  77. Connor ME, Stern PL: Loss of MHC class-I expression in cervical carcinomas. Int J Cancer 46: 1029–1034, 1990

    Google Scholar 

  78. Cromme FV, Airey J, Heemels MT, Ploegh HL, Keating PJ, Stern PL, Meijer CJLM, Walboomers JMM: Loss of transporter protein, encoded by the Tap-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. J Exp Med 179: 335–340, 1994

    Google Scholar 

  79. Bonagura VR, Siegal FP, Abramson AL, Santiago-Schwarz F, O'Reilly ME, Shah K, Drake D, Steinberg BM: Enriched HLA-DQ3 phenotype and decreased class I major histocompatibility complex antigen expression in recurrent respiratory papillomatosis. Clin Diag Lab Immunol 1: 357–360, 1994

    Google Scholar 

  80. Wank R, Thomssen C: High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. Nature 352: 723–725, 1991

    Google Scholar 

  81. Glew SS, Stern PL, Davidson JA, Dyer PA: HLA antigens and cervical carcinoma. Nature 356: 22, 1992

    Google Scholar 

  82. Asselineau D, Prunieras M: Reconstruction of ‘simplified’ skin: control of fabrication. Br J Dermatol 111 (Suppl 27): 219–222, 1984

    Google Scholar 

  83. Dollard SC, Wilson JL, Demeter LM, Bonnez W, Reichman RC, Broker TR, Chow LT: Production of human papillomavirus and modulation of the infectious program in epithelial raft cultures. Genes Dev 6: 1131–1142, 1992

    Google Scholar 

  84. Mendelsohn MG, DiLorenzo TP, Abramson AL, Steinberg BM: Retinoic acid regulates, in vitro, the two normal pathways of differentiation of human laryngeal keratinocytes. In Vitro Cell Dev Biol 27A: 137–141, 1991

    Google Scholar 

  85. Reppucci AD, DiLorenzo TP, Abramson AL, Steinberg BM: In vitro modulation of human laryngeal papilloma cell differentiation by retinoic acid. Otolaryngol Head Neck Surg 105: 528–532, 1991

    Google Scholar 

  86. DiLorenzo TP, Steinberg BM: Differential regulation of human papillomavirus type 6 and 11 early promoters in cultured cells derived from laryngeal papillomas. J Virol 69: 6865–6872, 1995

    Google Scholar 

  87. Vambutas A, DiLorenzo TP, Steinberg BM: Laryngeal papilloma cells have high levels of epidermal growth factor receptor and respond to epidermal growth factor by a decrease in epithelial differentiation. Cancer Res 53: 910–914, 1993

    Google Scholar 

  88. Galloway TC, Soper GR, Elsen G: Carcinoma of the larynx after irradiation of papilloma. Arch Otolaryngol 72: 289–294, 1960

    Google Scholar 

  89. Majoros M, Devine KD, Parkhill EM: Malignant transformation of benign laryngeal papillomas in children after radiation therapy. Surg Clin North Am 43: 1049–1061, 1963

    Google Scholar 

  90. Brach BB, Klein RC, Mathews AJ, Cook EW: Papillomatosis of the respiratory tract: upper airway obstruction and carcinoma. Arch Otolaryngol 104: 413–416, 1978

    Google Scholar 

  91. Schnadig VJ, Clark WD, Clegg TJ, Yao CS: Invasive papillomatosis and squamous carcinoma complicating juvenile laryngeal papillomatosis. Arch Otolaryngol Head Neck Surg 112: 966–971, 1986

    Google Scholar 

  92. Zarod AP, Rutherford JD, Corbitt G: Malignant progression of laryngeal papilloma associated with human papilloma virus type 6 (HPV 6) DNA. J Clin Pathol 41: 280–283, 1988

    Google Scholar 

  93. Byrne JC, Tsao M-S, Fraser RS, Howley PM: Human papillomavirus-11 DNA in a patient with chronic laryngotracheobronchial papillomatosis and metastatic squamous-cell carcinoma of the lung. N Engl J Med 317: 873–878, 1987

    Google Scholar 

  94. DiLorenzo TP, Tamsen A, Abramson AL, Steinberg BM: Human papillomavirus type 6a DNA in the lung carcinoma of a patient with recurrent laryngeal papillomatosis is characterized by a partial duplication. J Gen Virol 73: 423–428, 1992

    Google Scholar 

  95. Yoder MG, Batsakis JG: Squamous cell carcinoma in solitary laryngeal papilloma. Otolaryngol Head Neck Surg 88: 745–748, 1980

    Google Scholar 

  96. Singh B, Ramsaroop R: Clinical features of malignant transformation in benign laryngeal papillomata. J Laryngol Otol 108: 642–648, 1994

    Google Scholar 

  97. Kashima H, Wu T-C, Mounts P, Heffner D, Cachay A, Hyams V: Carcinoma ex-papilloma: histologic and virologic studies in whole-organ sections of the larynx. Laryngoscope 98: 619–624, 1988

    Google Scholar 

  98. Lindeberg H, Syrjanen S, Karja J, Syrjanen K: Human papillomavirus type 11 DNA in squamous cell carcinomas and pre-existing multiple laryngeal papillomas. Acta Otolaryngol (Stockh) 107: 141–149, 1989

    Google Scholar 

  99. Rosen M, Auborn K: Duplication of the upstream regulatory sequences increases the transformation potential of human papillomavirus type 11. Virology 185: 484–487, 1991

    Google Scholar 

  100. Brandsma JL, Steinberg BM, Abramson AL, Winkler B: Presence of human papillomavirus type 16 related sequences in verrucous carcinoma of the larynx. Cancer Res 46: 2185–2188, 1986

    Google Scholar 

  101. Bryan RL, Bevan IS, Crocker J, Young LS: Detection of HPV 6 and 11 in tumours of the upper respiratory tract using the polymerase chain reaction. Clin Otolaryngol 15: 177–180, 1990

    Google Scholar 

  102. Perez-Ayala M, Ruiz-Cabello F, Esteban F, Concha A, Redondo M, Oliva MR, Cabrera T, Garrido T: Presence of HPV 16 sequences in laryngeal carcinomas. Int J Cancer 46: 8–11, 1990

    Google Scholar 

  103. Fliss DM, Noble-Topham SE, McLachlin M, Freeman JL, Noyek AM, van Nostrand AWP, Hartwick RW: Laryngeal verrucous carcinoma: A clinicopathologic study and detection of human papillomavirus using polymerase chain reaction. Laryngoscope 104: 146–152, 1994

    Google Scholar 

  104. Noble-Topham SE, Fliss DM, Hartwick WJ, McLachlin CM, Freeman JL, Noyek AM, Andrulis IL: Detection and typing of human papillomavirus in verrucous carcinoma of the oral cavity using the polymerase chain reaction. Arch Otolaryngol Head Neck Surg 119: 1299–1304, 1993

    Google Scholar 

  105. Adler-Storthz K, Newland JR, Tessin BA, Yeudall WA, Shillitoe EJ: Human papillomavirus type 2 DNA in oral verrucous carcinoma. J Oral Pathol 15: 472–475, 1986

    Google Scholar 

  106. Roman A, Fife K: Human papillomaviruses: are we ready to type? Clin Microbiol Rev 2: 166–190, 1989

    Google Scholar 

  107. Shibata DK, Arnheim N, Martin WJ: Detection of human papilloma virus in paraffin-embedded tissue using the polymerase chain reaction. J Exp Med 167: 225–230, 1988

    Google Scholar 

  108. Kwok S, Higuchi R: Avoiding false positives with PCR. Nature 339: 237–238, 1989

    Google Scholar 

  109. Beyer-Finkler E, Pfister H, Girardi F: Anti-contamination primers to improve specificity of polymerase chain reaction in human papillomavirus screening. Lancet 335: 1289–1290, 1990

    Google Scholar 

  110. Morrison EAB, Goldberg GL, Kadish AS, Burk RD: Polymerase chain reaction detection of human papillomavirus: Quantitation may improve clinical utility. J Clin Microbiol 30: 2539–2543, 1992

    Google Scholar 

  111. De Villiers E-M, Weidauer H, Otto H, zur Hausen H: Papillomavirus DNA in human tongue carcinomas. Int J Cancer 36: 575–578, 1985

    Google Scholar 

  112. Brachman DG, Graves D, Vokes E, Beckett M, Haraf D, Montag A, Dunphy E, Mick R, Yandell D, Weichselbaum RR: Occurrence of p53 gene deletions and human papilloma virus infection in human head and neck cancer. Cancer Res 52: 4832–4836, 1992

    Google Scholar 

  113. Ogura H, Watanabe S, Fukushima K, Masuda Y, Fujiwara T, Yabe Y: Human papillomavirus DNA in squamous cell carcinomas of the respiratory and upper digestive tracts. Jpn J Clin Oncol 23: 221–225, 1993

    Google Scholar 

  114. Shindoh M, Sawada Y, Kohgo T, Amemiya A, Fujinaga K: Detection of human papillomavirus DNA sequences in tongue squamous-cell carcinoma utilizing the polymerase chain reaction method. Int J Cancer 50: 167–171, 1992

    Google Scholar 

  115. Snijders PJF, Cromme FV, van den Brule AJC, Schrijnemakers PJF, Snow GB, Meijer CJLM, Walboomers JMM: Prevalence and expression of human papillomavirus in tonsillar carcinomas, indicating a possible viral etiology. Int J Cancer 51: 845–850, 1992

    Google Scholar 

  116. Snijders PJF, Steenbergen RDM, Top B, Scott SD, Meijer CJLM, Walboomers JMM: Analysis of p53 status in tonsillar carcinomas associated with human papillomavirus. J Gen Virol 75: 2769–2775, 1994

    Google Scholar 

  117. Brandwein M, Zeitlin J, Nuovo GJ, MacConnell P, Bodian C, Urken M, Biller H: HPV detection using ‘hot start’ polymerase chain reaction in patients with oral cancer: a clinicopathological study of 64 patients. Mod Pathol 7: 720–727, 1994

    Google Scholar 

  118. Balaram P, Nalinakumari KR, Abraham E, Balan A, Hareendran NK, Bernard H-U, Chan S-Y: Human papillomaviruses in 91 oral cancers from indian betel quid chewershigh prevalence and multiplicity of infections. Int J Cancer 61: 450–454, 1995

    Google Scholar 

  119. Chang KW, Chang CS, Lai KS, Chou MJ, Choo KB: High prevalence of human papillomavirus infection and possible association with betel quid chewing and smoking in oral epidermoid carcinomas in Taiwan. J Med Virol 28: 57–61, 1989

    Google Scholar 

  120. Thomas SJ, MacLennan R: Slaked lime and betel nut cancer in Papua New Guinea. Lancet 340: 577–578, 1992

    Google Scholar 

  121. Syrjanen S, Happonen R-P, Virolainen E, Siivonen L, Syrjanen K: Detection of human papillomavirus (HPV) structural antigens and DNA types in inverted papillomas and squamous cell carcinomas of the nasal cavities and paranasal sinuses. Acta Otolaryngol (Stockh) 104: 334–341, 1987

    Google Scholar 

  122. Hording U, Winther HW, Daugaard S, Albeck H: Human papillomavirus types 11 and 16 detected in nasopharyngeal carcinomas by the polymerase chain reaction. Laryngoscope 104: 99–102, 1994

    Google Scholar 

  123. Dickens P, Srivastava G, Liu YT: Human papillomavirus 16/18 and nasopharyngeal carcinoma. J Clin Pathol 45: 81–82, 1992

    Google Scholar 

  124. Furuta Y, Takasu T, Asai T, Shinohara T, Sawa H, Nagashima K, Inuyama Y: Detection of human papillomavirus DNA in carcinomas of the nasal cavities and paranasal sinuses by polymerase chain reaction. Cancer 69: 353–357, 1992

    Google Scholar 

  125. Judd R, Zaki SR, Coffield LM, Evatt BL: Human papillomavirus type 6 detected by the polymerase chain reaction in invasive sinonasal papillary squamous cell carcinoma. Arch Pathol Lab Med 115: 1150–1153, 1991

    Google Scholar 

  126. Tyan Y-S, Liu S-T, Ong W-R, Chen M-L, Shu C-H, Chang Y-S: Detection of Epstein-Barr virus and human papillomavirus in head and neck tumors. J Clin Microbiol 31: 53–56, 1993

    Google Scholar 

  127. Lawson W, Le Benger J, Som P, Bernard PJ, Biller HF: Inverted papilloma: an analysis of 87 cases. Laryngoscope 99: 1117–1124, 1989

    Google Scholar 

  128. MacDonald MR, Le KT, Freeman J, Hui MF, Cheung RK, Dosch H-M: A majority of inverted sinonasal papillomas carries Epstein-Barr virus genomes. Cancer 75: 2307–2312, 1995

    Google Scholar 

  129. Salam MA, Rockett J, Morris A: General primer-mediated polymerase chain reaction for simultaneous detection and typing of human papillomavirus DNA in laryngeal squamous cell carcinomas. Clin Otolaryngol 20: 84–88, 1995

    Google Scholar 

  130. Hoshikawa T, Nakajima T, Uhara H, Gotoh M, Shimosato Y, Tsutsumi K, Ono I, Ebihara S: Detection of human papillomavirus DNA in laryngeal squamous cell carcinomas by polymerase chain reaction. Laryngoscope 100: 647–650, 1990

    Google Scholar 

  131. Nunez DA, Astley SM, Lewis FA, Wells M: Human papilloma viruses: a study of their prevalence in the normal larynx. J Laryngol Otol 108: 319–320, 1994

    Google Scholar 

  132. Stremlau A, Gissmann L, Ikenberg H, Stark M, Bannasch P, zur Hausen H: Human papillomavirus type 16 related DNA in an anaplastic carcinoma of the lung. Cancer 55: 1737–1740, 1985

    Google Scholar 

  133. Kahn T, Schwarz E, zur Hausen H: Molecular cloning and characterization of the DNA of a new human papillomavirus (HPV 30) from a laryngeal carcinoma. Int J Cancer 37: 61–65, 1986

    Google Scholar 

  134. Yousem SA, Ohori NP, Sonmez-Alpan E: Occurrence of human papillomavirus DNA in primary lung neoplasms. Cancer 69: 693–697, 1992

    Google Scholar 

  135. Shamanin V, Delius H, de Villiers E-M: Development of a broad spectrum PCR assay for papillomaviruses and its application in screening lung cancer biopsies. J Gen Virol 75: 1149–1156, 1994

    Google Scholar 

  136. Zur Hausen H, Schneider A: The role of papillomaviruses in human anogenital cancer. In: Salzman NP, Howley PM (eds) The Papovaviridae, Vol. 2. Plenum Press. New York, 1987, pp 245–263

    Google Scholar 

  137. Pirisi L, Yasumoto S, Feller M, Doniger J, DiPaolo JA: Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA. J Virol 61: 1061–1066, 1987

    Google Scholar 

  138. 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 1: 251–256, 1987

    Google Scholar 

  139. Park NH, Min BM, Li SL, Huang MZ, Cherick HM, Doniger J: Immortalization of normal human oral keratinocytes with type 16 human papillomavirus. Carcinogenesis 12: 1627–1631, 1991

    Google Scholar 

  140. Band V, Zajchowski D, Kulesa V, Sager R: Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements. J Virol 87: 463–467, 1990

    Google Scholar 

  141. Kaur P, McDougall JK: Characterization of primary human keratinocytes transformed by human papillomavirus type 18. J Virol 62: 1917–1924, 1988

    Google Scholar 

  142. Schlegel R, Phelps WC, Zhang Y-L, Barbosa M: Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma. EMBO J 7: 3181–3187, 1988

    Google Scholar 

  143. Pecoraro G, Morgan D, Defendi V: Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells. Proc Natl Acad Sci USA 86: 563–567, 1989

    Google Scholar 

  144. Munger K, Phelps WC, Bubb V, Howley PM, Schlegel R: The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol 63: 4417–4421, 1989

    Google Scholar 

  145. Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT: HPV 16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO J 8: 3905–3910, 1989

    Google Scholar 

  146. Hudson JB, Bedell MA, McCance DJ, Laimins LA: Immortalization and altered differentiation of human keratinocytes in vitro by the E6 and E7 open reading frames of human papillomavirus type 18. J Virol 64: 519–526, 1990

    Google Scholar 

  147. Choo K-B, Pan C-C, Han S-H: Integration of human papillomavirus type 16 into cellular DNA of cervical carcinoma: preferential deletion of the E2 gene and invariable retention of the long control region and the E6/E7 open reading frames. Virology 161: 259–261, 1987

    Google Scholar 

  148. Smotkin D, Wettstein FO: Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proc Natl Acad Sci USA 83: 4680–4684, 1986

    Google Scholar 

  149. Shirasawa H, Tomita Y, Kubota K, Kasai T, Sekiya S, Takamizawa H, Simizu B: Transcriptional differences of the human papillomavirus type 16 genome between precancerous lesions and invasive carcinomas. J Virol 62: 1022–1027, 1988

    Google Scholar 

  150. Schwarz E, Freese UK, Gissmann L, Mayer W, Roggenbuck B, Stremlau A, zur Hausen H: Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314: 111–114, 1985

    Google Scholar 

  151. Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM: Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol 61: 962–971, 1987

    Google Scholar 

  152. Seedorf K, Oltersdorf T, Krammer G, Rowekamp W: Identification of early proteins of the human papilloma viruses type 16 (HPV 16) and type 18 (HPV 18) in cervical carcinoma cells. EMBO J 6: 139–144, 1987

    Google Scholar 

  153. Androphy EJ, Hubbert NL, Schiller JT, Lowy DR: Identification of the HPV-16 E6 protein from transformed mouse cells and human cervical carcinoma cell lines. EMBO J 6: 989–992, 1987

    Google Scholar 

  154. Smotkin D, Wettstein FO: The major human papillomavirus protein in cervical cancers is a cytoplasmic phospho-protein. J Virol 61: 1686–1689, 1987

    Google Scholar 

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

    Google Scholar 

  156. Munger K, Werness BA, Dyson N, Phelps WC, Harlow E, Howley PM: Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J 8: 4099–4105, 1989

    Google Scholar 

  157. Riley DJ, Lee EY-HP, Lee W-H: The retinoblastoma protein: more than a tumor suppressor. Annu Rev Cell Biol 10: 1–29, 1994

    Google Scholar 

  158. Nevins JR: E2F: A link between the Rb tumor suppressor protein and viral oncoproteins. Science 258: 424–429, 1992

    Google Scholar 

  159. Arroyo M, Bagchi S, Raychaudhuri P: Association of the human papillomavirus type 16 E7 protein with the S-phase-specific E2F-cyclin A complex. Mol Cell Biol 13: 6537–6546, 1993

    Google Scholar 

  160. Dyson N, Guida P, Munger K, Harlow E: Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J Virol 66: 6893–6902, 1992

    Google Scholar 

  161. Tommasino M, Adamczewski JP, Carlotti F, Barth CF, Manetti R, Contorni M, Cavalieri F, Hunt T, Crawford L: HPV 16 E7 protein associated with the protein kinase p33CDK2 and cyclin A. Oncogene 8: 195–202, 1993

    Google Scholar 

  162. Werness BA, Levine AJ, Howley PM: Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248: 76–79, 1990

    Google Scholar 

  163. Huibregtse JM, Scheffner M, Howley PM: Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins. Mol Cell Biol 13: 4918–4927, 1993

    Google Scholar 

  164. Harris CC: p53: At the crossroads of molecular carcinogenesis and risk assessment. Science 262: 1980–1981, 1993

    Google Scholar 

  165. Pines J: Arresting developments in cell-cycle control. Trends Biochem Sci 19: 143–145, 1994

    Google Scholar 

  166. De Villiers E-M, Schneider A, Miklaw H, Papendick U, Wagner D, Wesch H, Wahrendorf J, zur Hausen H: Human papillomavirus infections in women with and without abnormal cervical cytology. Lancet 2: 703–706, 1987

    Google Scholar 

  167. Zur Hausen H: Intracellular surveillance of persisting viral infections. Human genital cancer results from deficient cellular control of papillomavirus gene expression. Lancet 2: 489–491, 1986

    Google Scholar 

  168. Kim MS, Shin K-H, Baek J-H, Cherrick HM, Park N-H: HPV-16, tobacco-specific N-Nitrosamine, and N-methyl-N′-nitro-N-nitrosoguanidine in oral carcinogenesis. Cancer Res 53: 4811–4816, 1993

    Google Scholar 

  169. Pecoraro G, Lee M, Morgan D, Defendi V: Evolution of in vitro transformation and tumorigenesis of HPV 16 and HPV 18 immortalized primary cervical epithelial cells. Am J Pathol 138: 1–8, 1990

    Google Scholar 

  170. Hurlin PJ, Kaur P, Smith PP, Perez-Reyes N, Blanton RA, McDougall JK: Progression of human papillomavirus type 18-immortalized human keratinocytes to a malignant phenotype. Proc Natl Acad Sci USA 88: 570–574, 1991

    Google Scholar 

  171. Garrett LR, Perez-Reyes N, Smith PP, McDougall JK: Interaction of HPV-18 and nitrosomethylurea in the induction of squamous cell carcinoma. Carcinogenesis 14: 329–332, 1993

    Google Scholar 

  172. Klingelhutz AJ, Smith PP, Garrett LR, McDougall JK: Alteration of the DCC tumor-suppressor gene in tumorigenic HPV-18 immortalized human keratinocytes transformed by nitrosomethylurea. Oncogene 8: 95–99, 1993

    Google Scholar 

  173. Klingelhutz AJ, Hedrick L, Cho KR, McDougall JK: The DCC gene suppresses the malignant phenotype of transformed human epithelial cells. Oncogene 10: 1581–1586, 1995

    Google Scholar 

  174. DiPaolo JA, Woodworth CD, Popescu NC, Notario V, Doniger J: Induction of human cervical squamous cell carcinoma by sequential transfection with human papillomavirus 16 DNA and viral Harvey ras. Oncogene 4: 395–399, 1989

    Google Scholar 

  175. Riou G, Barrois M, Sheng ZM, Duvillard P, Lhomme C: Somatic deletions and mutations of c-Ha-ras gene in human cervical cancers. Oncogene 3: 329–333, 1988

    Google Scholar 

  176. DiPaolo JA, Woodworth CD, Popescu NC, Koval DL, Lopez JV, Doniger J: HSV-2-induced tumorigenicity in HPV 16-immortalized human genital keratinocytes. Virology 177: 777–779, 1990

    Google Scholar 

  177. Von Knebel Doeberitz M, Rittmuller C, Aengeneyndt F, Jansen-Durr P, Spitkovsky D: Reversible repression of papillomavirus oncogene expression in cervical carcinoma cells: consequences for the phenotype and E6-p53 and E7-pRB interactions. J Virol 68: 2811–2821, 1994

    Google Scholar 

  178. Von Knebel Doeberitz M, Rittmuller C, zur Hausen H, Durst M: Inhibition of tumorigenicity of cervical cancer cells in nude mice by HPV E6–E7 anti-sense RNA. Int J Cancer 51: 831–834, 1992

    Google Scholar 

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Steinberg, B.M., DiLorenzo, T.P. A possible role for human papillomaviruses in head and neck cancer. Cancer Metast Rev 15, 91–112 (1996). https://doi.org/10.1007/BF00049489

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