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Treatment Paradigms in HPV-Associated SCCHN

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Part of the book series: Current Cancer Research ((CUCR))

Abstract

The primary risk factor for development of HPV-related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is oral HPV infection, most frequently by HPV type 16. The most clinically relevant features of HPV+ disease is the significantly increased incidence worldwide, improved response to chemotherapy and radiation and overall prognosis, as well as distinct patterns of failure in comparison to their HPVnegative brethren. As a result, the AJCC Cancer Staging Manual 8th edition has introduced significant changes from the seventh edition, recognizing the prognostic power of newly validated pathologic features of some primary tumors and of cervical lymph node metastases and differentiating high-risk human papilloma virus (HR-HPV)-associated oropharyngeal cancer from OPSCC with other causes. In addition, considerable thought has been directed toward reevaluating historic treatment paradigms. Recent efforts pursue treatment deintensification to reduce long-term toxicities in this relatively younger patient cohort. This also includes minimally invasive surgery techniques and the substitution or elimination of standard cytotoxic chemotherapy with biologic agents and immunotherapies. Overall, HPV-related cancers are now recognized as a distinct entity. This has resulted in a reexamination of the core principles of head and neck cancer treatment developed decades ago, with the goals of obtaining high cure rates simultaneously with meanigful reductions in long-term toxicity and improved quality of life.

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References

  1. Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum. 2007;90:1–636.

    Google Scholar 

  2. Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014;32(27):2940–50.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Pignon JP, le Maître A, Maillard E, Bourhis J, Group M-NC. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92(1):4–14.

    Article  PubMed  Google Scholar 

  4. Brizel DM, Albers ME, Fisher SR, Scher RL, Richtsmeier WJ, Hars V, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med. 1998;338(25):1798–804.

    Article  PubMed  CAS  Google Scholar 

  5. Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357(17):1705–15.

    Article  PubMed  CAS  Google Scholar 

  6. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–78.

    Article  CAS  PubMed  Google Scholar 

  7. Reddy VM, Cundall-Curry D, Bridger MW. Trends in the incidence rates of tonsil and base of tongue cancer in England, 1985-2006. Ann R Coll Surg Engl. 2010;92(8):655–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Hammarstedt L, Lindquist D, Dahlstrand H, Romanitan M, Dahlgren LO, Joneberg J, et al. Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer. Int J Cancer. 2006;119(11):2620–3.

    Article  PubMed  CAS  Google Scholar 

  9. Jemal A, Simard EP, Dorell C, Noone AM, Markowitz LE, Kohler B, et al. Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus(HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst. 2013;105(3):175–201.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 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  PubMed  CAS  Google Scholar 

  11. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157–60.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Stein AP, Saha S, Kraninger JL, Swick AD, Yu M, Lambert PF, et al. Prevalence of human papillomavirus in oropharyngeal cancer: a systematic review. Cancer J. 2015;21(3):138–46.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA. 2012;307(7):693–703.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Giuliano AR, Nyitray AG, Kreimer AR, Pierce Campbell CM, Goodman MT, Sudenga SL, et al. EUROGIN 2014 roadmap: differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection. Int J Cancer. 2015;136(12):2752–60.

    Article  CAS  PubMed  Google Scholar 

  17. Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008;26(4):612–9.

    Article  PubMed  Google Scholar 

  18. Gillison ML, D'Souza G, Westra W, Sugar E, Xiao W, Begum S, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008;100(6):407–20.

    Article  PubMed  Google Scholar 

  19. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990;63(6):1129–36.

    Article  PubMed  CAS  Google Scholar 

  20. Heck DV, Yee CL, Howley PM, Münger K. Efficiency of binding the retinoblastoma protein correlates with the transforming capacity of the E7 oncoproteins of the human papillomaviruses. Proc Natl Acad Sci U S A. 1992;89(10):4442–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Saraiya M, Unger ER, Thompson TD, Lynch CF, Hernandez BY, Lyu CW, et al. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. J Natl Cancer Inst. 2015;107(6):djv086.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Münger 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. 1989;63(10):4417–21.

    PubMed Central  PubMed  Google Scholar 

  23. Nguyen N, Bellile E, Thomas D, McHugh J, Rozek L, Virani S, et al. Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma. Head Neck. 2016;38(7):1074–84.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Fakhry C, Zhang Q, Nguyen-Tan PF, Rosenthal D, El-Naggar A, Garden AS, et al. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol. 2014;32(30):3365–73.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Stenmark MH, Shumway D, Guo C, Vainshtein J, Mierzwa M, Jagsi R, et al. Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States. Laryngoscope. 2017;127(10):2270–8.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11(1):21–8.

    Article  CAS  PubMed  Google Scholar 

  28. Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, et al. Association of human papillomavirus and p16 status with outcomes in the IMCL-9815 phase III registration trial for patients with locoregionally advanced oropharyngeal squamous cell carcinoma of the head and neck treated with radiotherapy with or without cetuximab. J Clin Oncol. 2016;34(12):1300–8.

    Article  CAS  PubMed  Google Scholar 

  29. Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, et al. Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity. J Clin Oncol. 2014;32(34):3858–66.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. O'Sullivan B, Huang SH, Siu LL, Waldron J, Zhao H, Perez-Ordonez B, et al. Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol. 2013;31(5):543–50.

    Article  PubMed  CAS  Google Scholar 

  31. Lydiatt WM, Patel SG, O'Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, et al. Head and neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):122–37.

    Article  PubMed  Google Scholar 

  32. AJCC Cancer Staging Manual. 8 ed. Springer International Publishing; 2017.

    Google Scholar 

  33. Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomark Prev. 2005;14(2):467–75.

    Article  CAS  Google Scholar 

  34. Jordan RC, Lingen MW, Perez-Ordonez B, He X, Pickard R, Koluder M, et al. Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol. 2012;36(7):945–54.

    Article  PubMed  PubMed Central  Google Scholar 

  35. El-Naggar AK, Westra WH. p16 expression as a surrogate marker for HPV-related oropharyngeal carcinoma: a guide for interpretative relevance and consistency. Head Neck. 2012;34(4):459–61.

    Article  PubMed  Google Scholar 

  36. Schlecht NF, Brandwein-Gensler M, Nuovo GJ, Li M, Dunne A, Kawachi N, et al. A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer. Mod Pathol. 2011;24(10):1295–305.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Löning T, Ikenberg H, Becker J, Gissmann L, Hoepfer I, zur Hausen H. Analysis of oral papillomas, leukoplakias, and invasive carcinomas for human papillomavirus type related DNA. J Invest Dermatol. 1985;84(5):417–20.

    Article  PubMed  Google Scholar 

  38. Boscolo-Rizzo P, Pawlita M, Holzinger D. From HPV-positive towards HPV-driven oropharyngeal squamous cell carcinomas. Cancer Treat Rev. 2016;42:24–9.

    Article  PubMed  Google Scholar 

  39. Klussmann JP, Gültekin E, Weissenborn SJ, Wieland U, Dries V, Dienes HP, et al. Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus. Am J Pathol. 2003;162(3):747–53.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Maxwell JH, Kumar B, Feng FY, Worden FP, Lee JS, Eisbruch A, et al. Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res. 2010;16(4):1226–35.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  41. Dahlstrom KR, Garden AS, William WN, Lim MY, Sturgis EM. Proposed staging system for patients with HPV-related oropharyngeal cancer based on nasopharyngeal cancer N categories. J Clin Oncol. 2016;34(16):1848–54.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Klozar J, Koslabova E, Kratochvil V, Salakova M, Tachezy R. Nodal status is not a prognostic factor in patients with HPV-positive oral/oropharyngeal tumors. J Surg Oncol. 2013;107(6):625–33.

    Article  PubMed  Google Scholar 

  43. Huang SH, Xu W, Waldron J, Siu L, Shen X, Tong L, et al. Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas. J Clin Oncol. 2015;33(8):836–45.

    Article  PubMed  Google Scholar 

  44. Ward MJ, Mellows T, Harris S, Webb A, Patel NN, Cox HJ, et al. Staging and treatment of oropharyngeal cancer in the human papillomavirus era. Head Neck. 2015;37(7):1002–13.

    Article  PubMed  Google Scholar 

  45. Budach W, Bölke E, Kammers K, Gerber PA, Orth K, Gripp S, et al. Induction chemotherapy followed by concurrent radio-chemotherapy versus concurrent radio-chemotherapy alone as treatment of locally advanced squamous cell carcinoma of the head and neck (HNSCC): a meta-analysis of randomized trials. Radiother Oncol. 2016;118(2):238–43.

    Article  PubMed  Google Scholar 

  46. Reid SR, Losek JD. Imaging before appendectomy. Pediatrics. 2003;112(6 Pt 1):1461–2. author reply −2

    Article  PubMed  Google Scholar 

  47. Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, 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(4):261–9.

    Article  PubMed  CAS  Google Scholar 

  48. Cooperstein E, Gilbert J, Epstein JB, Dietrich MS, Bond SM, Ridner SH, et al. Vanderbilt Head and Neck Symptom Survey version 2.0: report of the development and initial testing of a subscale for assessment of oral health. Head Neck. 2012;34(6):797–804.

    Article  PubMed  Google Scholar 

  49. Marur S, Li S, Cmelak AJ, Gillison ML, Zhao WJ, Ferris RL, et al. E1308: phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx- ECOG-ACRIN Cancer Research Group. J Clin Oncol. 2017;35(5):490–7.

    Article  PubMed  CAS  Google Scholar 

  50. Garden AS, Blanchard P. ECOG-ACRIN 1308: commentary on a negative phase II trial. J Clin Oncol. 2017;35(17):1969–70.

    Article  PubMed  Google Scholar 

  51. Yom SS. Is induction chemotherapy needed to select patients for deintensified treatment of human papillomavirus-associated oropharyngeal Cancer? J Clin Oncol. 2017;35(5):479–81.

    Article  CAS  PubMed  Google Scholar 

  52. Marur S, Li S, Cmelak A, Burtness B. Reply to A. Garden et al. J Clin Oncol. 2017;35(17):1970–1.

    Article  PubMed  Google Scholar 

  53. Marur S, Cmelak AJ, Burtness B. Purpose of induction chemotherapy in E1308 and importance of patient-reported outcomes in deintensification trials. J Clin Oncol. 2017;35(17):1968–9.

    Article  PubMed  Google Scholar 

  54. NRG-HN002: A randomized phase II trial for patients with p16 positive, non-smoking associated, locoregionally advanced oropharyngeal cancer: NRG Oncology; Available from: www.nrgoncology.org/CLinical-Trials/NRG-HN002.

  55. Chera BS, Amdur RJ, Tepper J, Qaqish B, Green R, Aumer SL, et al. Phase 2 trial of de-intensified chemoradiation therapy for favorable-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2015;93(5):976–85.

    Article  PubMed  Google Scholar 

  56. Haddad R, O'Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013;14(3):257–64.

    Article  CAS  PubMed  Google Scholar 

  57. Yom SS, Gillison ML, Trotti AM. Dose de-escalation in human papillomavirus-associated oropharyngeal cancer: first tracks on powder. Int J Radiat Oncol Biol Phys. 2015;93(5):986–8.

    Article  PubMed  Google Scholar 

  58. Villaflor VM, Melotek JM, Karrison TG, Brisson RJ, Blair EA, Portugal L, et al. Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer. Ann Oncol. 2016;27(5):908–13.

    Article  CAS  PubMed  Google Scholar 

  59. Riaz N, Sherman EJ, Katabi N, Leeman JE, Higginson DS, Boyle J, et al. A personalized approach using hypoxia resolution to guide curative-intent radiation dose-reduction to 30 Gy: A novel de-escalation paradigm for HPV-associated oropharynx cancers (OPC). J Clin Oncol. 2017;35(15_suppl):6076.

    Article  Google Scholar 

  60. Melotek J, Seiwert TY, Blair EA, Karrison TG, Agrawal N, Portugal L, et al. Optima: A phase II dose and volume de-escalation trial for high- and low-risk HPV+ oropharynx cancers. J Clin Oncol. 2017;35(15_suppl):6066.

    Article  Google Scholar 

  61. Blanchard P, Baujat B, Holostenco V, Bourredjem A, Baey C, Bourhis J, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol. 2011;100(1):33–40.

    Article  PubMed  Google Scholar 

  62. Guan J, Zhang Y, Li Q, Li L, Chen M, Xiao N, et al. A meta-analysis of weekly cisplatin versus three weekly cisplatin chemotherapy plus concurrent radiotherapy (CRT) for advanced head and neck cancer (HNC). Oncotarget. 2016;7(43):70185–93.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Robert F, Ezekiel MP, Spencer SA, Meredith RF, Bonner JA, Khazaeli MB, et al. Phase I study of anti-epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. J Clin Oncol. 2001;19(13):3234–43.

    Article  CAS  PubMed  Google Scholar 

  64. Koutcher L, Sherman E, Fury M, Wolden S, Zhang Z, Mo Q, et al. Concurrent cisplatin and radiation versus cetuximab and radiation for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2011;81(4):915–22.

    Article  CAS  PubMed  Google Scholar 

  65. Nolan N, Diavolitsis VM, Blakaj D, Pan X, Grecula JC, Savvides P, et al. Intensity modulated radiation therapy with cetuximab versus platinum chemotherapy in p16-positive oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 93(3):E333–E4.

    Google Scholar 

  66. Magrini SM, Buglione M, Corvò R, Pirtoli L, Paiar F, Ponticelli P, et al. Cetuximab and radiotherapy versus cisplatin and radiotherapy for locally advanced head and neck Cancer: a randomized phase II trial. J Clin Oncol. 2016;34(5):427–35.

    Article  PubMed  CAS  Google Scholar 

  67. Ringash J, Waldron JN, Siu LL, Martino R, Winquist E, Wright JR, et al. Quality of life and swallowing with standard chemoradiotherapy versus accelerated radiotherapy and panitumumab in locoregionally advanced carcinoma of the head and neck: a phase III randomised trial from the Canadian Cancer Trials Group (HN.6). Eur J Cancer. 2017;72:192–9.

    Article  CAS  PubMed  Google Scholar 

  68. Szturz P, Wouters K, Kiyota N, Tahara M, Prabhash K, Noronha V, et al. Weekly low-dose versus three-weekly high-dose cisplatin for concurrent chemoradiation in locoregionally advanced non-nasopharyngeal head and neck cancer: a systematic review and meta-analysis of aggregate data. Oncologist. 2017;22(9):1056–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sher DJ, Adelstein DJ, Bajaj GK, Brizel DM, Cohen EEW, Halthore A, et al. Radiation therapy for oropharyngeal squamous cell carcinoma: executive summary of an ASTRO Evidence-Based Clinical Practice Guideline. Pract Radiat Oncol. 2017;7(4):246–53.

    Article  PubMed  Google Scholar 

  70. Weinstein GS, Quon H, Newman HJ, Chalian JA, Malloy K, Lin A, et al. Transoral robotic surgery alone for oropharyngeal cancer: an analysis of local control. Arch Otolaryngol Head Neck Surg. 2012;138(7):628–34.

    Article  PubMed  Google Scholar 

  71. de Almeida JR, Byrd JK, Wu R, Stucken CL, Duvvuri U, Goldstein DP, et al. A systematic review of transoral robotic surgery and radiotherapy for early oropharynx cancer: a systematic review. Laryngoscope. 2014;124(9):2096–102.

    Article  PubMed  Google Scholar 

  72. Seiwert TY, Melotek JM, Blair EA, Stenson KM, Salama JK, Witt ME, et al. Final results of a randomized phase 2 trial investigating the addition of cetuximab to induction chemotherapy and accelerated or hyperfractionated chemoradiation for locoregionally advanced head and neck cancer. Int J Radiat Oncol Biol Phys. 2016;96(1):21–9.

    Article  PubMed  CAS  Google Scholar 

  73. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  74. Thomas ED, Lochte HL, Lu WC, Ferrebee JW. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med. 1957;257(11):491–6.

    Article  PubMed  CAS  Google Scholar 

  75. 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.

    Article  CAS  PubMed  Google Scholar 

  76. Jie HB, Schuler PJ, Lee SC, Srivastava RM, Argiris A, Ferrone S, et al. CTLA-4+ regulatory T cells increased in cetuximab-treated head and neck cancer patients suppress NK cell cytotoxicity and correlate with poor prognosis. Cancer Res. 2015;75(11):2200–10.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  77. Balermpas P, Rödel F, Rödel C, Krause M, Linge A, Lohaus F, et al. CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: a multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer. 2016;138(1):171–81.

    Article  PubMed  CAS  Google Scholar 

  78. Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17(7):956–65.

    Article  PubMed  CAS  Google Scholar 

  79. Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  80. Trosman SJ, Koyfman SA, Ward MC, Al-Khudari S, Nwizu T, Greskovich JF, et al. Effect of human papillomavirus on patterns of distant metastatic failure in oropharyngeal squamous cell carcinoma treated with chemoradiotherapy. JAMA Otolaryngol Head Neck Surg. 2015;141(5):457–62.

    Article  PubMed  Google Scholar 

  81. Argiris A, Li S, Ghebremichael M, Egloff AM, Wang L, Forastiere AA, et al. Prognostic significance of human papillomavirus in recurrent or metastatic head and neck cancer: an analysis of Eastern Cooperative Oncology Group trials. Ann Oncol. 2014;25(7):1410–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  82. Frakes JM, Naghavi AO, Demetriou SK, Strom TJ, Russell JS, Kish JA, et al. Determining optimal follow-up in the management of human papillomavirus-positive oropharyngeal cancer. Cancer. 2016;122(4):634–41.

    Article  PubMed  Google Scholar 

  83. Mehanna H, Wong WL, McConkey CC, Rahman JK, Robinson M, Hartley AG, et al. PET-CT surveillance versus neck dissection in advanced head and neck cancer. N Engl J Med. 2016;374(15):1444–54.

    Article  PubMed  CAS  Google Scholar 

  84. Rettig EM, Wentz A, Posner MR, Gross ND, Haddad RI, Gillison ML, et al. Prognostic implication of persistent human papillomavirus type 16 DNA detection in oral rinses for human papillomavirus-related oropharyngeal carcinoma. JAMA Oncol. 2015;1(7):907–15.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Argiris A, Li Y, Forastiere A. Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck. Cancer. 2004;101(10):2222–9.

    Article  PubMed  Google Scholar 

  86. Amin MB, Edge SB, Greene FL, et al., editors. AJCC cancer staging manual. 8th ed. New York: Springer; 2017.

    Google Scholar 

  87. Stein AP, et al. Prevalence of human papillomavirus in oropharyngeal squamous cell carcinoma in the United States across time. Chem Res Toxicol. 2014;27(4):462–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Kluwe, C.A., Cmelak, A.J. (2018). Treatment Paradigms in HPV-Associated SCCHN. In: Burtness, B., Golemis, E. (eds) Molecular Determinants of Head and Neck Cancer. Current Cancer Research. Humana Press, Cham. https://doi.org/10.1007/978-3-319-78762-6_21

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