Head and Neck Pathology

, Volume 6, Supplement 1, pp 104–120 | Cite as

Human Papillomavirus in Non-Oropharyngeal Head and Neck Cancers: A Systematic Literature Review

  • Tatyana Isayeva
  • Yufeng Li
  • Daniel Maswahu
  • Margaret Brandwein-GenslerEmail author
Invited Review


Perhaps one of the most important developments in head and neck oncology of the past decade is the demonstration that patients with human papillomavirus (HPV)-mediated oropharyngeal cancers have significantly improved outcomes, compared to HPV-negative counterpart patients. This has become the basis for clinical trials investigating the impact on “treatment deintensification” for patients with HPV-mediated oropharyngeal cancers. Unfortunately, the significance of HPV in non-oropharyngeal head and neck cancers is much less certain. Our goal is to systematically review the published data regarding the role HPV in carcinomas of the oral cavity, larynx, sinonasal tract and nasopharynx with respect to HPV detection frequency, viral activity, and association with outcome. We also present preliminary data on HPV16/18 transcriptional status in oral cavity carcinomas, as well as salivary gland neoplasia, as determined by nested reverse transcription PCR for HPV E6/E7 RNA. The weighted prevalence (WP) of HPV DNA detection in 4,195 oral cavity cancer patients is 20.2 %, (95 % CI 16.0 %, 25.2 %). HPV16 is the most common type detected. Importantly, no data currently demonstrates a significant association between the presence of HPV DNA and improved outcome. The WP of HPV DNA in 1,712 laryngeal cancer patients is 23.6 %, (95 % CI 18.7 %, 29.3 %). Similarly, no association has yet been demonstrated between HPV DNA status and outcome. The WP of HPV DNA detection in 120 sinonasal cancer patients is 29.6 % (95 % CI 17.8 %, 44.9 %), and in 154 nasopharyngeal carcinoma patients is 31.1 %, (95 % CI 20.3 %, 44.5 %). Recent preliminary data also suggests an association between HPV and certain salivary gland neoplasms. The clinical significance of these findings is unclear. The published data strongly support the need for studies on patients with oral and laryngeal carcinomas that will be powered to find any differences in clinical outcome with respect to HR-HPV and p16 overexpression.


HPV Squamous carcinoma Oral cavity Laryngeal Larynx Mucoepidermoid carcinoma Salivary 


  1. 1.
    Manjarrez ME, Ocadiz R, Valle L, et al. Detection of human papillomavirus and relevant tumor suppressors and oncoproteins in laryngeal tumors. Clin Cancer Res. 2006;12:6946–51.PubMedGoogle Scholar
  2. 2.
    Venuti A, Badaracco G, Rizzo C, et al. Presence of HPV in head and neck tumours: high prevalence in tonsillar localization. J Exp Clin Cancer Res. 2004;23:561–6.PubMedGoogle Scholar
  3. 3.
    Badaracco G, Rizzo C, Mafera B, et al. Molecular analyses and prognostic relevance of HPV in head and neck tumours. Oncol Rep. 2007;17:931–9.PubMedGoogle Scholar
  4. 4.
    Szarka K, Tar I, Fehér E, et al. Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential. Oral Microbiol Immunol. 2009;24:314–8.PubMedGoogle Scholar
  5. 5.
    Fehér E, Gáll T, Murvai M, et al. Investigation of the occurrence of torque tenovirus in malignant and potentially malignant disorders associated with human papillomavirus. J Med Virol. 2009;81:1975–81.PubMedGoogle Scholar
  6. 6.
    van Houten VM, Snijders PJ, van den Brekel MW, et al. Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas. Int J Cancer. 2001;93:232–5.PubMedGoogle Scholar
  7. 7.
    Braakhuis BJ, Snijders PJ, Keune WJ, et al. Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst. 2004;96:998–1006.PubMedGoogle Scholar
  8. 8.
    Morshed K, Polz-Dacewicz M, Szymański M, Polz D. Short-fragment PCR assay for highly sensitive broad-spectrum detection of human papillomaviruses in laryngeal squamous cell carcinoma and normal mucosa: clinico-pathological evaluation. Eur Arch Otorhinolaryngol. 2008;265:S89–96.PubMedGoogle Scholar
  9. 9.
    Morshed K. Association between human papillomavirus infection and laryngeal squamous cell carcinoma. J Med Virol. 2010;82:1017–23.PubMedGoogle Scholar
  10. 10.
    Smith EM, Summersgill KF, Allen J, et al. Human papillomavirus and risk of laryngeal cancer. Ann Otol Rhinol Laryngol. 2000;109:1069–76.PubMedGoogle Scholar
  11. 11.
    Smith EM, Rubenstein LM, Ritchie JM, et al. Does pretreatment seropositivity to human papillomavirus have prognostic significance for head and neck cancers? Cancer Epidemiol Biomarkers Prev. 2008;17:2087–96.PubMedGoogle Scholar
  12. 12.
    Smith EM, Wang D, Rubenstein LM, et al. Association between p53 and human papillomavirus in head and neck cancer survival. Cancer Epidemiol Biomarkers Prev. 2008;17:421–7.PubMedGoogle Scholar
  13. 13.
    Smith EM, Rubenstein LM, Hoffman H, et al. Human papillomavirus, p16 and p53 expression associated with survival of head and neck cancer. Infect Agent Cancer. 2010;5:4.Google Scholar
  14. 14.
    Almadori G, Cadoni G, Cattani P, et al. Human papillomavirus infection and epidermal growth factor receptor expression in primary laryngeal squamous cell carcinoma. Clin Cancer Res. 2001;7:3988–93.PubMedGoogle Scholar
  15. 15.
    Anderson CE, McLaren KM, Rae F, et al. Human papillomavirus in squamous carcinoma of the head and neck: a study of cases in south east Scotland. J Clin Pathol. 2007;60:439–41.PubMedGoogle Scholar
  16. 16.
    Báez A, Almodóvar JI, Cantor A, et al. High frequency of HPV16-associated head and neck squamous cell carcinoma in the Puerto Rican population. Head Neck. 2004;26:778–84.PubMedGoogle Scholar
  17. 17.
    Bagan JV, Jimenez Y, Murillo J, et al. Lack of association between proliferative verrucous leukoplakia and human papillomavirus infection. J Oral Maxillofac Surg. 2007;65:46–9.PubMedGoogle Scholar
  18. 18.
    Balderas-Loaeza A, Anaya-Saavedra G, Ramirez-Amador VA, et al. Human papillomavirus-16 DNA methylation patterns support a causal association of the virus with oral squamous cell carcinomas. Int J Cancer. 2007;120:2165–9.PubMedGoogle Scholar
  19. 19.
    Barwad A, Sood S, Gupta N, et al. Human papilloma virus associated head and neck cancer: a PCR based study. Diagn Cytopathol. 6 Apr 2011. doi: 10.1002/dc.21667.
  20. 20.
    Baumann JL, Cohen S, Evjen AN, et al. Human papillomavirus in early laryngeal carcinoma. Laryngoscope. 2009;119:1531–7.PubMedGoogle Scholar
  21. 21.
    Boscolo-Rizzo P, Da Mosto MC, Fuson R, et al. HPV-16 E6 L83 V variant in squamous cell carcinomas of the upper aerodigestive tract. J Cancer Res Clin Oncol. 2009;135:559–66.PubMedGoogle Scholar
  22. 22.
    Bouda M, Gorgoulis VG, Kastrinakis NG, et al. “High risk” HPV types are frequently detected in potentially malignant and malignant oral lesions, but not in normal oral mucosa. Mod Pathol. 2000;13:644–53.PubMedGoogle Scholar
  23. 23.
    Boy S, Van Rensburg EJ, Engelbrecht S, et al. HPV detection in primary intra-oral squamous cell carcinomas–commensal, aetiological agent or contamination? J Oral Pathol Med. 2006;35:86–90.PubMedGoogle Scholar
  24. 24.
    Correnti M, Rivera H, Cavazza ME. Detection of human papillomaviruses of high oncogenic potential in oral squamous cell carcinoma in a Venezuelan population. Oral Dis. 2004;10:163–6.PubMedGoogle Scholar
  25. 25.
    Dahlgren L, Dahlstrand HM, Lindquist D, et al. Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients. Int J Cancer. 2004;112:1015–9.PubMedGoogle Scholar
  26. 26.
    Deng Z, Hasegawa M, Matayoshi S, et al. Prevalence and clinical features of human papillomavirus in head and neck squamous cell carcinoma in Okinawa, southern Japan. Eur Arch Otorhinolaryngol. 2011;268:1625–31.PubMedGoogle Scholar
  27. 27.
    Dong SM, Sun DI, Benoit NE, et al. Epigenetic inactivation of RASSF1A in head and neck cancer. Clin Cancer Res. 2003;9:3635–40.PubMedGoogle Scholar
  28. 28.
    D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356:1944–56.PubMedGoogle Scholar
  29. 29.
    Duray A, Descamps G, Arafa M, et al. High incidence of high-risk HPV in benign and malignant lesions of the larynx. Int J Oncol. 2011;39:51–9.PubMedGoogle Scholar
  30. 30.
    Elango KJ, Suresh A, Erode EM, et al. Role of human papilloma virus in oral tongue squamous cell carcinoma. Asian Pac J Cancer Prev. 2011;12:889–96.PubMedGoogle Scholar
  31. 31.
    El-Mofty SK, Lu DW. Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil, and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol. 2003;27:1463–70.PubMedGoogle Scholar
  32. 32.
    Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100:261–9.PubMedGoogle Scholar
  33. 33.
    Fischer M, von Winterfeld F. Evaluation and application of a broad-spectrum polymerase chain reaction assay for human papillomaviruses in the screening of squamous cell tumours of the head and neck. Acta Otolaryngol. 2003;123:752–8.PubMedGoogle Scholar
  34. 34.
    Fujita S, Senba M, Kumatori A, et al. Human papillomavirus infection in oral verrucous carcinoma: genotyping analysis and inverse correlation with p53 expression. Pathobiology. 2008;75:257–64.PubMedGoogle Scholar
  35. 35.
    Furniss CS, McClean MD, Smith JF, et al. Human papillomavirus 16 and head and neck squamous cell carcinoma. Int J Cancer. 2007;120:2386–92.PubMedGoogle Scholar
  36. 36.
    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. 2000;92:709–20.PubMedGoogle Scholar
  37. 37.
    González JV, Gutiérrez RA, Keszler A, et al. Human papillomavirus in oral lesions. Medicina (B Aires). 2007;67(4):363–8.Google Scholar
  38. 38.
    Gudleviciene Z, Smailyte G, Mickonas A, Pikelis A. Prevalence of human papillomavirus and other risk factors in Lithuanian patients with head and neck cancer. Oncology. 2009;76:205–8.PubMedGoogle Scholar
  39. 39.
    Güvenç MG, Midilli K, Ozdoğan A, et al. Detection of HHV-8 and HPV in laryngeal carcinoma. Auris Nasus Larynx. 2008;35:357–62.PubMedGoogle Scholar
  40. 40.
    Ha PK, Pai SI, Westra WH, et al. Real-time quantitative PCR demonstrates low prevalence of human papillomavirus type 16 in premalignant and malignant lesions of the oral cavity. Clin Cancer Res. 2002;8:1203–9.PubMedGoogle Scholar
  41. 41.
    Halimi M, Morshedi Asl S. Human papillomavirus infection in lung vs. oral squamous cell carcinomas: a polymerase chain reaction study. Pak J Biol Sci. 2011;14:641–6.PubMedGoogle Scholar
  42. 42.
    Hansson BG, Rosenquist K, Antonsson A, et al. Strong association between infection with human papillomavirus and oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Acta Otolaryngol. 2005;125:1337–44.PubMedGoogle Scholar
  43. 43.
    Harris SL, Thorne LB, Seaman WT, et al. Association of p16(INK4a) overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue. Head Neck. 2011;33:1622–7.PubMedGoogle Scholar
  44. 44.
    Hassumi-Fukasawa MK, Miranda-Camargo FA, Guimarães MC, et al. Possible implication of Mdm2 as a prognostic marker in invasive laryngeal carcinoma. Eur Arch Otorhinolaryngol. 5 Feb 2012. [Epub ahead of print] PubMed PMID: 22310835.Google Scholar
  45. 45.
    Herrero R, Castellsagué X, Pawlita M, et al. IARC Multicenter Oral Cancer Study Group. Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst. 2003;95:1772–83.PubMedGoogle Scholar
  46. 46.
    Hoffmann M, Kahn T, Goeroegh T, et al. Tracing human papillomavirus DNA in nasal polyps by polymerase chain reaction. Acta Otolaryngol. 2000;120:872–5.PubMedGoogle Scholar
  47. 47.
    Hoffmann M, Klose N, Gottschlich S, et al. Detection of human papillomavirus DNA in benign and malignant sinonasal neoplasms. Cancer Lett. 2006;239:64–70.PubMedGoogle Scholar
  48. 48.
    Ibieta BR, Lizano M, Fras-Mendivil M, et al. Human papilloma virus in oral squamous cell carcinoma in a Mexican population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;99:311–5.PubMedGoogle Scholar
  49. 49.
    Jalouli J, Ibrahim SO, Mehrotra R, et al. Prevalence of viral (HPV, EBV, HSV) infections in oral submucous fibrosis and oral cancer from India. Acta Otolaryngol. 2010;130:1306–11.PubMedGoogle Scholar
  50. 50.
    Jimenez C, Correnti M, Salma N, et al. Detection of human papillomavirus DNA in benign oral squamous epithelial lesions in Venezuela. J Oral Pathol Med. 2001;30:385–8.PubMedGoogle Scholar
  51. 51.
    Kaminagakura E, Villa LL, Andreoli MA, et al. High-risk human papillomavirus in oral squamous cell carcinoma of young patients. Int J Cancer. 2012;130:1726–32.PubMedGoogle Scholar
  52. 52.
    Kansky AA, Seme K, Maver PJ, et al. Human papillomaviruses (HPV) in tissue specimens of oral squamous cell papillomas and normal oral mucosa. Anticancer Res. 2006;26:3197–201.PubMedGoogle Scholar
  53. 53.
    Kleist B, Bankau A, Lorenz G, et al. Different risk factors in basaloid and common squamous head and neck cancer. Laryngoscope. 2004;114:1063–8.PubMedGoogle Scholar
  54. 54.
    Klozar J, Kratochvil V, Salakova M, et al. HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer. Eur Arch Otorhinolaryngol. 2008;265:S75–82.PubMedGoogle Scholar
  55. 55.
    Klussmann JP, Weissenborn SJ, Wieland U, et al. Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer. 2001;92:2875–84.PubMedGoogle Scholar
  56. 56.
    Koppikar P, deVilliers EM, Mulherkar R. Identification of human papillomaviruses in tumors of the oral cavity in an Indian community. Int J Cancer. 2005;113:946–50.PubMedGoogle Scholar
  57. 57.
    Koskinen WJ, Chen RW, Leivo I, et al. Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck. Int J Cancer. 2003;107:401–6.PubMedGoogle Scholar
  58. 58.
    Koskinen WJ, Brøndbo K, Mellin Dahlstrand H, et al. Alcohol, smoking and human papillomavirus in laryngeal carcinoma: a Nordic prospective multicenter study. J Cancer Res Clin Oncol. 2007;133:673–8.PubMedGoogle Scholar
  59. 59.
    Kraft M, Simmen D, Casas R, Pfaltz M. Significance of human papillomavirus in sinonasal papillomas. J Laryngol Otol. 2001;115:709–14.PubMedGoogle Scholar
  60. 60.
    Kristoffersen AK, Enersen M, Kverndokk E, et al. Human papillomavirus subtypes in oral lesions compared to healthy oral mucosa. J Clin Virol. 2012;53:364–6.PubMedGoogle Scholar
  61. 61.
    Laco J, Vosmikova H, Novakova V, et al. The role of high-risk human papillomavirus infection in oral and oropharyngeal squamous cell carcinoma in non-smoking and non-drinking patients: a clinicopathological and molecular study of 46 cases. Virchows Arch. 2011;458:179–87.PubMedGoogle Scholar
  62. 62.
    Liu B, Lu Z, Wang P, et al. Prevalence of high-risk human papillomavirus types (HPV-16, HPV-18) and their physical status in primary laryngeal squamous cell carcinoma. Neoplasma. 2010;57:594–600.PubMedGoogle Scholar
  63. 63.
    Lopes V, Murray P, Williams H, et al. Squamous cell carcinoma of the oral cavity rarely harbours oncogenic human papillomavirus. Oral Oncol. 2011;47:698–701.PubMedGoogle Scholar
  64. 64.
    Luo CW, Roan CH, Liu CJ. Human papillomaviruses in oral squamous cell carcinoma and pre-cancerous lesions detected by PCR-based gene-chip array. Int J Oral Maxillofac Surg. 2007;36:153–8.PubMedGoogle Scholar
  65. 65.
    Major T, Szarka K, Sziklai I, et al. The characteristics of human papillomavirus DNA in head and neck cancers and papillomas. J Clin Pathol. 2005;58:51–5.PubMedGoogle Scholar
  66. 66.
    McKay SP, Grégoire L, Lonardo F, et al. Human papillomavirus (HPV) transcripts in malignant inverted papilloma are from integrated HPV DNA. Laryngoscope. 2005;115:1428–31.PubMedGoogle Scholar
  67. 67.
    Migaldi M, Pecorari M, Forbicini G, et al. Low prevalence of human Papillomavirus infection in the healthy oral mucosa of a Northern Italian population. J Oral Pathol Med. 2012;41:16–20.PubMedGoogle Scholar
  68. 68.
    Montaldo C, Mastinu A, Zorco S, et al. Distribution of human papillomavirus genotypes in Sardinian patients with oral squamous cell carcinoma. Open Virol J. 2010;4:163–8.PubMedGoogle Scholar
  69. 69.
    Mork J, Lie AK, Glattre E, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 2001;344:1125–31.PubMedGoogle Scholar
  70. 70.
    Nemes JA, Deli L, Nemes Z, Márton IJ. Expression of p16(INK4A), p53, and Rb proteins are independent from the presence of human papillomavirus genes in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:344–52.PubMedGoogle Scholar
  71. 71.
    de Oliveira DE, Bacchi MM, Macarenco RS, et al. Human papillomavirus and Epstein-Barr virus infection, p53 expression, and cellular proliferation in laryngeal carcinoma. Am J Clin Pathol. 2006;126:284–93.PubMedGoogle Scholar
  72. 72.
    Pannone G, Rodolico V, Santoro A, et al. Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 immunohistochemistry, consensus PCR HPV-DNA, and in situ hybridization. Infect Agent Cancer. 2012;7:4. doi: 10.1186/1750-9378-7-4.
  73. 73.
    Pintos J, Black MJ, Sadeghi N, et al. Human papillomavirus infection and oral cancer: a case-control study in Montreal, Canada. Oral Oncol. 2008;44:242–50.PubMedGoogle Scholar
  74. 74.
    Popović B, Jekić B, Novaković I, et al. Cancer genes alterations and HPV infection in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2010;39:909–15.PubMedGoogle Scholar
  75. 75.
    Reidy PM, Dedo HH, Rabah R, et al. Integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer. Laryngoscope. 2004;114:1906–9.PubMedGoogle Scholar
  76. 76.
    Ribeiro KB, Levi JE, Pawlita M, et al. Low human papillomavirus prevalence in head and neck cancer: results from two large case-control studies in high-incidence regions. Int J Epidemiol. 2011;40:489–502.PubMedGoogle Scholar
  77. 77.
    Ringström E, Peters E, Hasegawa M, et al. Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res. 2002;8:3187–92.PubMedGoogle Scholar
  78. 78.
    Ritchie JM, Smith EM, Summersgill KF, et al. Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer. 2003;104:336–44.PubMedGoogle Scholar
  79. 79.
    Saghravanian N, Ghazvini K, Babakoohi S, et al. Low prevalence of high risk genotypes of human papilloma virus in normal oral mucosa, oral leukoplakia and verrucous carcinoma. Acta Odontol Scand. 2011;69:406–9.PubMedGoogle Scholar
  80. 80.
    Sand L, Jalouli J, Larsson PA, Hirsch JM. Human papilloma viruses in oral lesions. Anticancer Res. 2000;20(2B):1183–1188.Google Scholar
  81. 81.
    Schlecht NF, Brandwein-Gensler M, Nuovo GJ, et al. A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer. Mod Pathol. 2011;24:1295–305.PubMedGoogle Scholar
  82. 82.
    Seraj JM, Yazdani N, Ashtiani ZO, et al. TP53 gene expression in HPV-positive oral tongue SCC and its correlation with nodal metastasis. Pathol Res Pract. 2011;207:758–61.PubMedGoogle Scholar
  83. 83.
    Sethi S, Ali-Fehmi R, Franceschi S, et al. Characteristics and survival of head and neck cancer by HPV status: a cancer registry-based study. Int J Cancer. 23 Oct 2011. doi: 10.1002/ijc.26500.
  84. 84.
    Slebos RJ, Yi Y, Ely K, et al. Gene expression differences associated with human papillomavirus status in head and neck squamous cell carcinoma. Clin Cancer Res. 2006;12:701–9.PubMedGoogle Scholar
  85. 85.
    Smeets SJ, Hesselink AT, Speel EJ, et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer. 2007;121:2465–72.PubMedGoogle Scholar
  86. 86.
    Snietura M, Piglowski W, Jaworska M, et al. Impact of HPV infection on the clinical outcome of p-CAIR trial in head and neck cancer. Eur Arch Otorhinolaryngol. 2011;268:721–6.PubMedGoogle Scholar
  87. 87.
    Soderberg C, Perez DS, Ukpo OC, et al. Differential loss of expression of common fragile site genes between oral tongue and oropharyngeal squamous cell carcinomas. Cytogenet Genome Res. 2008;121:201–10.PubMedGoogle Scholar
  88. 88.
    Stephen JK, Chen KM, Shah V, et al. Human papillomavirus outcomes in an access-to-care laryngeal cancer cohort. Otolaryngol Head Neck Surg. 20 Jan 2012. [Epub ahead of print] PubMed PMID: 22267491.Google Scholar
  89. 89.
    Sugiyama M, Bhawal UK, Kawamura M, et al. Human papillomavirus-16 in oral squamous cell carcinoma: clinical correlates and 5-year survival. Br J Oral Maxillofac Surg. 2007;45:116–22.PubMedGoogle Scholar
  90. 90.
    Szládek G, Juhász A, Kardos G, et al. High co-prevalence of genogroup 1 TT virus and human papillomavirus is associated with poor clinical outcome of laryngeal carcinoma. J Clin Pathol. 2005;58:402–5.PubMedGoogle Scholar
  91. 91.
    Tachezy R, Klozar J, Saláková M, et al. HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic. Oral Dis. 2005;11:181–5.PubMedGoogle Scholar
  92. 92.
    Torrente MC, Ampuero S, Abud M, Ojeda JM. Molecular detection and typing of human papillomavirus in laryngeal carcinoma specimens. Acta Otolaryngol. 2005;125:888–93.PubMedGoogle Scholar
  93. 93.
    van Monsjou HS, van Velthuysen ML, van den Brekel MW, et al. Human papillomavirus status in young patients with head and neck squamous cell carcinoma. Int J Cancer. 2012;130:1806–12.PubMedGoogle Scholar
  94. 94.
    Venuti A, Manni V, Morello R, et al. Physical state and expression of human papillomavirus in laryngeal carcinoma and surrounding normal mucosa. J Med Virol. 2000;60:396–402.PubMedGoogle Scholar
  95. 95.
    Vlachtsis K, Nikolaou A, Markou K, et al. Clinical and molecular prognostic factors in operable laryngeal cancer. Eur Arch Otorhinolaryngol. 2005;262:890–8.PubMedGoogle Scholar
  96. 96.
    Zhang ZY, Sdek P, Cao J, Chen WT. Human papillomavirus type 16 and 18 DNA in oral squamous cell carcinoma and normal mucosa. Int J Oral Maxillofac Surg. 2004;33:71–4.PubMedGoogle Scholar
  97. 97.
    Alos L, Moyano S, Nadal A, et al. Human papillomaviruses are identified in a subgroup of sinonasal squamous cell carcinomas with favorable outcome. Cancer. 2009;115:2701–9.PubMedGoogle Scholar
  98. 98.
    Maxwell JH, Kumar B, Feng FY, et al. HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans. Head Neck. 2010;32:562–7.PubMedGoogle Scholar
  99. 99.
    Lo EJ, Bell D, Woo JS, et al. Human papillomavirus and WHO type I nasopharyngeal carcinoma. Laryngoscope. 2010;120:1990–7.PubMedGoogle Scholar
  100. 100.
    Laantri N, Attaleb M, Kandil M, et al. Human papillomavirus detection in Moroccan patients with nasopharyngeal carcinoma. Infect Agent Cancer. 2011;6:3.Google Scholar
  101. 101.
    Smith EM, Rubenstein LM, Haugen TH, et al. Complex etiology underlies risk and survival in head and neck cancer human papillomavirus, tobacco, and alcohol: a case for multifactor disease. J Oncol. 2012;2012:571862.Google Scholar
  102. 102.
    Westra WH, Taube JM, Poeta ML, et al. Inverse relationship between human papillomavirus-16 infection and disruptive p53 gene mutations in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2008;14:366–9.PubMedGoogle Scholar
  103. 103.
    Smith EM, Swarnavel S, Ritchie JM, et al. Prevalence of human papillomavirus in the oral cavity/oropharynx in a large population of children and adolescents. Pediatr Infect Dis J. 2007;26:836–40.PubMedGoogle Scholar
  104. 104.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedGoogle Scholar
  105. 105.
    Bonagura VR, Hatam LJ, Rosenthal DW, et al. Recurrent respiratory papillomatosis: a complex defect in immune responsiveness to human papillomavirus-6 and -11. APMIS. 2010;118:455–70.PubMedGoogle Scholar
  106. 106.
    Lawson W, Schlecht NF, Brandwein-Gensler M. The role of the human papillomavirus in the pathogenesis of schneiderian inverted papillomas: a critical review of the evidence. Head Neck Pathol. 2008;2:49–59.PubMedGoogle Scholar
  107. 107.
    Singhi AD, Califano J, Westra WH. High-risk human papillomavirus in nasopharyngeal carcinoma. Head Neck. 2012;34:213–8.PubMedGoogle Scholar
  108. 108.
    Punwaney R, Brandwein MS, Zhang DY, et al. Human papillomavirus may be common within nasopharyngeal carcinoma of Caucasian Americans: investigation of Epstein-Barr virus and human papillomavirus in eastern and western nasopharyngeal carcinoma using ligation-dependent polymerase chain reaction. Head Neck. 1999;21:21–9.PubMedGoogle Scholar
  109. 109.
    Bleyer A. Cancer of the oral cavity and pharynx in young females: increasing incidence, role of human papilloma virus, and lack of survival improvement. Semin Oncol. 2009;36:451–9.PubMedGoogle Scholar
  110. 110.
    Vageli D, Sourvinos G, Ioannou M, et al. High-risk human papillomavirus (HPV) in parotid lesions. Int J Biol Markers. 2007;22:239–44.PubMedGoogle Scholar
  111. 111.
    Boland JM, McPhail ED, García JJ, et al. Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck. Mod Pathol. 2012;25:529–36.PubMedGoogle Scholar
  112. 112.
    Zehbe I, Wilander E. Two consensus primer systems and nested polymerase chain reaction for human papillomavirus detection in cervical biopsies: a study of sensitivity. Hum Pathol. 1996;27:812–5.PubMedGoogle Scholar
  113. 113.
    Kreimer AR, Cifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:467–75.PubMedGoogle Scholar
  114. 114.
    Termine N, Panzarella V, Falaschini S, et al. HPV in oral squamous cell carcinoma vs. head and neck squamous cell carcinoma biopsies: a meta-analysis (1988–2007). Ann Oncol. 2008;19:1681–90.PubMedGoogle Scholar
  115. 115.
    Syrjänen S, Lodi G, von Bültzingslöwen I, et al. Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review. Oral Dis. 2011;17(Suppl 1):58–72.PubMedGoogle Scholar
  116. 116.
    Torrente MC, Rodrigo JP, Haigentz M Jr, et al. Human papillomavirus infections in laryngeal cancer. Head Neck. 2011;33:581–6.PubMedGoogle Scholar
  117. 117.
    Hobbs CG, Sterne JA, Bailey M, et al. Human papillomavirus and head and neck cancer: a systematic review and meta-analysis. Clin Otolaryngol. 2006;31:259–66.PubMedGoogle Scholar
  118. 118.
    Laco J, Slaninka I, Jirásek M, et al. High-risk human papillomavirus infection and p16INK4a protein expression in laryngeal lesions. Pathol Res Pract. 2008;204:545–52.PubMedGoogle Scholar
  119. 119.
    El-Mofty SK, Lu DW. Prevalence of high-risk human papillomavirus DNA in nonkeratinizing (cylindrical cell) carcinoma of the sinonasal tract: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol. 2005;29:1367–72.PubMedGoogle Scholar
  120. 120.
    Jo VY, Mills SE, Stoler MH, Stelow EB. Papillary squamous cell carcinoma of the head and neck: frequent association with human papillomavirus infection and invasive carcinoma. Am J Surg Pathol. 2009;33:1720–4.PubMedGoogle Scholar
  121. 121.
    Stasikowska-Kanicka O, Wągrowska-Danilewicz M, Danilewicz M. Effect of human papillomavirus on cell cycle-related proteins p16INK4A, p21waf1/cip1, p53 and cyclin D1 in sinonasal inverted papilloma and laryngeal carcinoma. An in situ hybridization study. Folia Histochem Cytobiol. 2011;49:34–40.PubMedGoogle Scholar
  122. 122.
    Wadsworth B, Bumpous JM, Martin AW, et al. Expression of p16 in sinonasal undifferentiated carcinoma (SNUC) without associated human papillomavirus (HPV). Head Neck Pathol. 2011;5:349–54.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Tatyana Isayeva
    • 1
  • Yufeng Li
    • 2
  • Daniel Maswahu
    • 1
    • 2
  • Margaret Brandwein-Gensler
    • 3
    Email author
  1. 1.Department of PathologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Preventative MedicineUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Surgical Pathology Section, Division Anatomic Pathology, NP 3545University of Alabama at BirminghamBirminghamUSA

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