Skip to main content

Advertisement

SpringerLink
Log in

Immune Escape and Immunotherapy of HPV-Related Oropharyngeal Cancer: Has the Future Arrived?

  • HPV in Head and Neck Cancer (J. Rocco, Section Editor)
  • Published:
Current Otorhinolaryngology Reports Aims and scope Submit manuscript

Abstract

The epidemiology of human papillomavirus (HPV)-associated cancers indicates dramatically increased rates for HPV-related oropharyngeal squamous cell carcinoma (OPSCC) over the past two decades. This development accounts for the increasing significance and research focus in the fields of immunology, oncology, and otolaryngology. In this review, we provide an overview of the most important and recent developments in pathogenesis and therapy in HPV-related OPSCC with a focus on the disease’s immune escape mechanisms and strategies for their reversal. In order to introduce the therapeutic approaches that are currently used and under development, we summarize the viral pathway, genomic alterations, and functional carcinogenesis in relation to antiviral immunity. The different viral strategies to evade the host immune system and their influence in carcinogenesis provide a unique tumor microenvironment that is not completely understood. Immunotherapies under development aim to prevent viral and tumor immunoevasion and may provide new insights into why—despite manifold immunoevasion strategies—an improved clinical outcome can be observed in HPV-related OPSCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118(12):3030–44. doi:10.1002/ijc.21731.

    Article  CAS  PubMed  Google Scholar 

  2. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294–301. doi:10.1200/jco.2011.36.4596.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Koshkareva Y, Branstetter BFT, Gaughan JP, Ferris RL. Predictive accuracy of first post-treatment PET/CT in HPV-related oropharyngeal squamous cell carcinoma. Laryngoscope. 2014;124(8):1843–7. doi:10.1002/lary.24617.

    Article  PubMed  Google Scholar 

  4. Maxwell JH, Mehta V, Wang H, Cunningham D, Duvvuri U, Kim S, et al. Quality of life in head and neck cancer patients: impact of HPV and primary treatment modality. Laryngoscope. 2014;124(7):1592–7. doi:10.1002/lary.24508.

    Article  PubMed  Google Scholar 

  5. Shope RE, Hurst EW. Infectious papillomatosis of rabbits: with a note on histopathology. J Exp Med. 1933;58(5):607–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Rous P, Beard JW. The progression to carcinoma of virus-induced rabbit papillomas (Shope). J Exp Med. 1935;62(4):523–48.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Rous P, Kidd JG, Beard JW. Observations on the relation of the virus causing rabbit papillomas to the cancers deriving therefrom: I. The influence of the host species and the pathogenic activity and concentration of the virus. J Exp Med. 1936;64(3):385–400.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Franceschi S, Munoz N, Bosch XF, Snijders PJ, Walboomers JM. Human papillomavirus and cancers of the upper aerodigestive tract: a review of epidemiological and experimental evidence. Cancer Epidemiol Biomark Prev. 1996;5(7):567–75.

    CAS  Google Scholar 

  9. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709–20.

    Article  CAS  PubMed  Google Scholar 

  10. Dogan S, Hedberg ML, Ferris RL, Rath TJ, Assaad AM, Chiosea SI. Human papillomavirus and Epstein-Barr virus in nasopharyngeal carcinoma in a low-incidence population. Head Neck. 2014;36(4):511–6. doi:10.1002/hed.23318.

    Article  PubMed  Google Scholar 

  11. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. New Engl J Med. 2003;348(6):518–27. doi:10.1056/NEJMoa021641.

    Article  PubMed  Google Scholar 

  12. Halec G, Alemany L, Lloveras B, Schmitt M, Alejo M, Bosch FX, et al. Pathogenic role of the eight probably/possibly carcinogenic HPV types 26, 53, 66, 67, 68, 70, 73 and 82 in cervical cancer. J Pathol. 2014;234(4):441–51. doi:10.1002/path.4405.

    Article  CAS  PubMed  Google Scholar 

  13. Zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2(5):342–50. doi:10.1038/nrc798.

    Article  CAS  PubMed  Google Scholar 

  14. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. New Engl J Med. 2010;363(1):24–35. doi:10.1056/NEJMoa0912217.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Scheurer ME, Tortolero-Luna G, Adler-Storthz K. Human papillomavirus infection: biology, epidemiology, and prevention. Int J Gynecol Cancer. 2005;15(5):727–46. doi:10.1111/j.1525-1438.2005.00246.x.

    Article  CAS  PubMed  Google Scholar 

  16. Bodily J, Laimins LA. Persistence of human papillomavirus infection: keys to malignant progression. Trends Microbiol. 2011;19(1):33–9. doi:10.1016/j.tim.2010.10.002.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Raff AB, Woodham AW, Raff LM, Skeate JG, Yan L, Da Silva DM, et al. The evolving field of human papillomavirus receptor research: a review of binding and entry. J Virol. 2013;87(11):6062–72. doi:10.1128/jvi.00330-13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Munger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, et al. Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004;78(21):11451–60. doi:10.1128/jvi.78.21.11451-11460.2004.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Zhou Q, Zhu K, Cheng H. Ubiquitination in host immune response to human papillomavirus infection. Arch Dermatol Res. 2011;303(4):217–30. doi:10.1007/s00403-011-1141-0.

    Article  CAS  PubMed  Google Scholar 

  20. Bernard BA, Bailly C, Lenoir MC, Darmon M, Thierry F, Yaniv M. The human papillomavirus type 18 (HPV18) E2 gene product is a repressor of the HPV18 regulatory region in human keratinocytes. J Virol. 1989;63(10):4317–24.

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Phelps WC, Howley PM. Transcriptional trans-activation by the human papillomavirus type 16 E2 gene product. J Virol. 1987;61(5):1630–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Bedell MA, Hudson JB, Golub TR, Turyk ME, Hosken M, Wilbanks GD, et al. Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation. J Virol. 1991;65(5):2254–60.

    PubMed Central  CAS  PubMed  Google Scholar 

  23. Genther SM, Sterling S, Duensing S, Munger K, Sattler C, Lambert PF. Quantitative role of the human papillomavirus type 16 E5 gene during the productive stage of the viral life cycle. J Virol. 2003;77(5):2832–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Doorbar J, Ely S, Sterling J, McLean C, Crawford L. Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature. 1991;352(6338):824–7. doi:10.1038/352824a0.

    Article  CAS  PubMed  Google Scholar 

  25. Sirianni N, Ha PK, Oelke M, Califano J, Gooding W, Westra W, et al. Effect of human papillomavirus-16 infection on CD8 + T-cell recognition of a wild-type sequence p53264-272 peptide in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res. 2004;10(20):6929–37. doi:10.1158/1078-0432.ccr-04-0672.

    Article  CAS  PubMed  Google Scholar 

  26. Ferris RL, Martinez I, Sirianni N, Wang J, Lopez-Albaitero A, Gollin SM, et al. Human papillomavirus-16 associated squamous cell carcinoma of the head and neck (SCCHN): a natural disease model provides insights into viral carcinogenesis. Eur J Cancer. 2005;41(5):807–15. doi:10.1016/j.ejca.2004.11.023 (Oxford, England : 1990).

    Article  CAS  PubMed  Google Scholar 

  27. Thomas M, Glaunsinger B, Pim D, Javier R, Banks L. HPV E6 and MAGUK protein interactions: determination of the molecular basis for specific protein recognition and degradation. Oncogene. 2001;20(39):5431–9. doi:10.1038/sj.onc.1204719.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Kumar A, Zhao Y, Meng G, Zeng M, Srinivasan S, Delmolino LM, et al. Human papillomavirus oncoprotein E6 inactivates the transcriptional coactivator human ADA3. Mol Cell Biol. 2002;22(16):5801–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Gewin L, Galloway DA. E box-dependent activation of telomerase by human papillomavirus type 16 E6 does not require induction of c-myc. J Virol. 2001;75(15):7198–201. doi:10.1128/jvi.75.15.7198-7201.2001.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Zerfass-Thome K, Zwerschke W, Mannhardt B, Tindle R, Botz JW, Jansen-Durr P. Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein. Oncogene. 1996;13(11):2323–30.

    CAS  PubMed  Google Scholar 

  31. Cam H, Dynlacht BD. Emerging roles for E2F: beyond the G1/S transition and DNA replication. Cancer Cell. 2003;3(4):311–6.

    Article  CAS  PubMed  Google Scholar 

  32. Duensing S, Munger K. Mechanisms of genomic instability in human cancer: insights from studies with human papillomavirus oncoproteins. Int J Cancer. 2004;109(2):157–62. doi:10.1002/ijc.11691.

    Article  CAS  PubMed  Google Scholar 

  33. Spanos WC, Nowicki P, Lee DW, Hoover A, Hostager B, Gupta A, et al. Immune response during therapy with cisplatin or radiation for human papillomavirus-related head and neck cancer. Arch Otolaryngol Head Neck Surg. 2009;135(11):1137–46. doi:10.1001/archoto.2009.159.

    Article  PubMed  Google Scholar 

  34. Sirianni N, Wang J, Ferris RL. Antiviral activity of Cidofovir on a naturally human papillomavirus-16 infected squamous cell carcinoma of the head and neck (SCCHN) cell line improves radiation sensitivity. Oral Oncol. 2005;41(4):423–8. doi:10.1016/j.oraloncology.2004.11.003.

    Article  CAS  PubMed  Google Scholar 

  35. •• Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res. 2013;73(1):128–38. doi:10.1158/0008-5472.can-12-2606. The authors contribute to a new understanding of PD-1-positive—infiltrating T cells in HPV-associated Head and Neck Cancer and the roles of immune checkpoint receptors in clinical outcome.

  36. Davis KS, Vargo JA, Ferris RL, Burton SA, Ohr JP, Clump DA, et al. Stereotactic body radiotherapy for recurrent oropharyngeal cancer—influence of HPV status and smoking history. Oral Oncol. 2014;50(11):1104–8. doi:10.1016/j.oraloncology.2014.08.004.

    Article  PubMed  Google Scholar 

  37. Stanley MA, Pett MR, Coleman N. HPV: from infection to cancer. Biochem Soc Trans. 2007;35(Pt 6):1456–60. doi:10.1042/bst0351456.

    Article  CAS  PubMed  Google Scholar 

  38. O’Brien PM, Saveria Campo M. Evasion of host immunity directed by papillomavirus-encoded proteins. Virus Res. 2002;88(1–2):103–17.

    Article  PubMed  Google Scholar 

  39. Stanley M. Immunobiology of HPV and HPV vaccines. Gynecol Oncol. 2008;109(2 Suppl):S15–21. doi:10.1016/j.ygyno.2008.02.003.

    Article  CAS  PubMed  Google Scholar 

  40. Tindle RW. Immune evasion in human papillomavirus-associated cervical cancer. Nat Rev Cancer. 2002;2(1):59–65. doi:10.1038/nrc700.

    Article  CAS  PubMed  Google Scholar 

  41. Kanodia S, Fahey LM, Kast WM. Mechanisms used by human papillomaviruses to escape the host immune response. Curr Cancer Drug Targets. 2007;7(1):79–89.

    Article  CAS  PubMed  Google Scholar 

  42. Bhat P, Mattarollo SR, Gosmann C, Frazer IH, Leggatt GR. Regulation of immune responses to HPV infection and during HPV-directed immunotherapy. Immunol Rev. 2011;239(1):85–98. doi:10.1111/j.1600-065X.2010.00966.x.

    Article  CAS  PubMed  Google Scholar 

  43. Frazer IH. Interaction of human papillomaviruses with the host immune system: a well evolved relationship. Virology. 2009;384(2):410–4. doi:10.1016/j.virol.2008.10.004.

    Article  CAS  PubMed  Google Scholar 

  44. Alcocer-Gonzalez JM, Berumen J, Tamez-Guerra R, Bermudez-Morales V, Peralta-Zaragoza O, Hernandez-Pando R, et al. In vivo expression of immunosuppressive cytokines in human papillomavirus-transformed cervical cancer cells. Viral Immunol. 2006;19(3):481–91. doi:10.1089/vim.2006.19.481.

    Article  CAS  PubMed  Google Scholar 

  45. Nees M, Geoghegan JM, Hyman T, Frank S, Miller L, Woodworth CD. Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive genes and upregulate proliferation-associated and NF-kappaB-responsive genes in cervical keratinocytes. J Virol. 2001;75(9):4283–96. doi:10.1128/jvi.75.9.4283-4296.2001.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Zhou Q, Zhu K, Cheng H. Toll-like receptors in human papillomavirus infection. Archivum Immunologiae et Therapiae Experimentalis. 2013;61(3):203–15. doi:10.1007/s00005-013-0220-7.

    Article  CAS  PubMed  Google Scholar 

  47. Vu HL, Sikora AG, Fu S, Kao J. HPV-induced oropharyngeal cancer, immune response and response to therapy. Cancer Lett. 2010;288(2):149–55. doi:10.1016/j.canlet.2009.06.026.

    Article  CAS  PubMed  Google Scholar 

  48. Gildener-Leapman N, Ferris RL, Bauman JE. Promising systemic immunotherapies in head and neck squamous cell carcinoma. Oral Oncol. 2013;49(12):1089–96. doi:10.1016/j.oraloncology.2013.09.009.

    Article  PubMed  Google Scholar 

  49. Stanley M, Gissmann L, Nardelli-Haefliger D. Immunobiology of human papillomavirus infection and vaccination—implications for second generation vaccines. Vaccine. 2008;26(Suppl 10):K62–7. doi:10.1016/j.vaccine.2008.05.066.

    Article  CAS  PubMed  Google Scholar 

  50. Stanley M, Pinto LA, Trimble C. Human papillomavirus vaccines–immune responses. Vaccine. 2012;30(Suppl 5):F83–7. doi:10.1016/j.vaccine.2012.04.106.

    Article  CAS  PubMed  Google Scholar 

  51. •• Albers A, Abe K, Hunt J, Wang J, Lopez-Albaitero A, Schaefer C et al. Antitumor activity of human papillomavirus type 16 E7-specific T cells against virally infected squamous cell carcinoma of the head and neck. Cancer Res. 2005;65(23):11146–55. doi:10.1158/0008-5472.can-05-0772. This report showed that HPV E7-specific cellular immunity exists but that the antiviral T cells are terminally differentiated effector cells, likely reflecting an “exhausted” dysfunctional state.

  52. Beachler DC, Weber KM, Margolick JB, Strickler HD, Cranston RD, Burk RD, et al. Risk factors for oral HPV infection among a high prevalence population of HIV-positive and at-risk HIV-negative adults. Cancer Epidemiol Biomark Prev. 2012;21(1):122–33. doi:10.1158/1055-9965.epi-11-0734.

    Article  CAS  Google Scholar 

  53. Denny LA, Franceschi S, de Sanjose S, Heard I, Moscicki AB, Palefsky J. Human papillomavirus, human immunodeficiency virus and immunosuppression. Vaccine. 2012;30(Suppl 5):F168–74. doi:10.1016/j.vaccine.2012.06.045.

    Article  CAS  PubMed  Google Scholar 

  54. D’Souza G, Carey TE, William WN, Nguyen ML Jr, Ko EC, Riddell JT, et al. Epidemiology of head and neck squamous cell cancer among HIV-infected patients. J Acquir Immune Defic Syndr (1999). 2014;65(5):603–10. doi:10.1097/qai.0000000000000083.

    Article  Google Scholar 

  55. Madkan VK, Cook-Norris RH, Steadman MC, Arora A, Mendoza N, Tyring SK. The oncogenic potential of human papillomaviruses: a review on the role of host genetics and environmental cofactors. Br J Dermatol. 2007;157(2):228–41. doi:10.1111/j.1365-2133.2007.07961.x.

    Article  CAS  PubMed  Google Scholar 

  56. Scott M, Nakagawa M, Moscicki AB. Cell-mediated immune response to human papillomavirus infection. Clin Diagn Lab Immunol. 2001;8(2):209–20. doi:10.1128/cdli.8.2.209-220.2001.

    PubMed Central  CAS  PubMed  Google Scholar 

  57. Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker T, et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res. 2015;21(3):632–41. doi:10.1158/1078-0432.ccr-13-3310.

    Article  CAS  PubMed  Google Scholar 

  58. Gollin SM. Cytogenetic alterations and their molecular genetic correlates in head and neck squamous cell carcinoma: a next generation window to the biology of disease. Genes Chromosom Cancer. 2014;53(12):972–90. doi:10.1002/gcc.22214.

    Article  CAS  PubMed  Google Scholar 

  59. • Lyford-Pike S, Peng S, Young GD, Taube JM, Westra WH, Akpeng B et al. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res. 2013;73(6):1733–41. doi:10.1158/0008-5472.can-12-2384. The authors describe the role of PD-1 and PD-L1 interaction for the infection and subsequent adaptive immune resistance in HPV-associated cancers. While HPV-negative cancers were initially reported to be PD-L1+ in < 30 % of patients, as opposed to 65 % of HPV+ patients, other more recent reports indicated that PD-L1 positivity is seen roughly equally in 60 % of both tumor subtypes.

  60. Khoury JD, Tannir NM, Williams MD, Chen Y, Yao H, Zhang J, et al. Landscape of DNA virus associations across human malignant cancers: analysis of 3,775 cases using RNA-Seq. J Virol. 2013;87(16):8916–26. doi:10.1128/jvi.00340-13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Martinez I, Wang J, Hobson KF, Ferris RL, Khan SA. Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer. 2007;43(2):415–32. doi:10.1016/j.ejca.2006.09.001 (Oxford, England : 1990).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Best SR, Niparko KJ, Pai SI. Biology of human papillomavirus infection and immune therapy for HPV-related head and neck cancers. Otolaryngol Clin North Am. 2012;45(4):807–22. doi:10.1016/j.otc.2012.04.005.

    Article  PubMed Central  PubMed  Google Scholar 

  63. Lyford-Pike S, Peng S, Young GD, Taube JM, Westra WH, Akpeng B, et al. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res. 2013;73(6):1733–41. doi:10.1158/0008-5472.can-12-2384.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Pai SI. Adaptive immune resistance in HPV-associated head and neck squamous cell carcinoma. Oncoimmunology. 2013;2(5):e24065. doi:10.4161/onci.24065.

    Article  PubMed Central  PubMed  Google Scholar 

  65. Ferris RL, Lu B, Kane LP. Too much of a good thing? Tim-3 and TCR signaling in T cell exhaustion. J Immunol. 2014;193(4):1525–30. doi:10.4049/jimmunol.1400557.

    Article  CAS  PubMed  Google Scholar 

  66. Quezada SA, Peggs KS. Exploiting CTLA-4, PD-1 and PD-L1 to reactivate the host immune response against cancer. Br J Cancer. 2013;108(8):1560–5. doi:10.1038/bjc.2013.117.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. King EV, Ottensmeier CH, Thomas GJ. The immune response in HPV oropharyngeal cancer. Oncoimmunology. 2014;3(1):e27254. doi:10.4161/onci.27254.

    Article  PubMed Central  PubMed  Google Scholar 

  68. Nasman A, Romanitan M, Nordfors C, Grun N, Johansson H, Hammarstedt L, et al. Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer. PLoS One. 2012;7(6):e38711. doi:10.1371/journal.pone.0038711.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Jie HB, Gildener-Leapman N, Li J, Srivastava RM, Gibson SP, Whiteside TL, et al. Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients. Br J Cancer. 2013;109(10):2629–35. doi:10.1038/bjc.2013.645.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Schiller JT, Castellsague X, Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine. 2012;30(Suppl 5):F123–38. doi:10.1016/j.vaccine.2012.04.108.

    Article  CAS  PubMed  Google Scholar 

  71. Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Penny ME, Aranda C, et al. Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. New Engl J Med. 2011;364(5):401–11. doi:10.1056/NEJMoa0909537.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Steinau M, Saraiya M, Goodman MT, Peters ES, Watson M, Cleveland JL, et al. Human papillomavirus prevalence in oropharyngeal cancer before vaccine introduction, United States. Emerg Infect Dis. 2014;20(5):822–8. doi:10.3201/eid2005.131311.

    Article  PubMed Central  PubMed  Google Scholar 

  73. Joura EA, Ault KA, Bosch FX, Brown D, Cuzick J, Ferris D, et al. Attribution of 12 high-risk human papillomavirus genotypes to infection and cervical disease. Cancer Epidemiol Biomark Prev. 2014;23(10):1997–2008. doi:10.1158/1055-9965.epi-14-0410.

    Article  Google Scholar 

  74. van Seters M, van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, et al. Treatment of vulvar intraepithelial neoplasia with topical imiquimod. New Engl J Med. 2008;358(14):1465–73. doi:10.1056/NEJMoa072685.

    Article  PubMed  Google Scholar 

  75. Sin JI, Kim JM, Bae SH, Lee IH, Park JS, Ryoo HM. Adoptive transfer of human papillomavirus E7-specific CTL enhances tumor chemoresponse through the perforin/granzyme-mediated pathway. Mol Ther. 2009;17(5):906–13. doi:10.1038/mt.2009.32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Peralta-Zaragoza O, Bermudez-Morales VH, Perez-Plasencia C, Salazar-Leon J, Gomez-Ceron C, Madrid-Marina V. Targeted treatments for cervical cancer: a review. Onco Targets Ther. 2012;5:315–28. doi:10.2147/ott.s25123.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Sewell DA, Pan ZK, Paterson Y. Listeria-based HPV-16 E7 vaccines limit autochthonous tumor growth in a transgenic mouse model for HPV-16 transformed tumors. Vaccine. 2008;26(41):5315–20. doi:10.1016/j.vaccine.2008.07.036.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Brun JL, Dalstein V, Leveque J, Mathevet P, Raulic P, Baldauf JJ, et al. Regression of high-grade cervical intraepithelial neoplasia with TG4001 targeted immunotherapy. Am J Obstet Gynecol. 2011;204(2):169 e1–8. doi:10.1016/j.ajog.2010.09.020.

    Article  PubMed  Google Scholar 

  79. Gildener-Leapman N, Lee J, Ferris RL. Tailored immunotherapy for HPV positive head and neck squamous cell cancer. Oral Oncol. 2014;50(9):780–4. doi:10.1016/j.oraloncology.2013.09.010.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The design of figures was aided by materials from ScienceSlides (http://www.visiscience.com) and Microsoft PowerPoint 2007 (www.microsoft.com).

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany

    Benjamin A. Kansy

  2. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA

    Nicole C. Schmitt & Robert L. Ferris

  3. Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Benjamin A. Kansy, Nicole C. Schmitt & Robert L. Ferris

  4. Hillman Cancer Center Research Pavilion, 5117 Centre Avenue, Room 2.26b, Pittsburgh, PA, 15213-1863, USA

    Robert L. Ferris

Authors
  1. Benjamin A. Kansy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicole C. Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert L. Ferris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert L. Ferris.

Additional information

This article is part of the Topical Collection on HPV in Head and Neck Cancer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kansy, B.A., Schmitt, N.C. & Ferris, R.L. Immune Escape and Immunotherapy of HPV-Related Oropharyngeal Cancer: Has the Future Arrived?. Curr Otorhinolaryngol Rep 3, 63–72 (2015). https://doi.org/10.1007/s40136-015-0079-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40136-015-0079-8

Keywords

Search

Navigation