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Systemic Treatment in HPV-Induced Recurrent or Metastatic HNSCC

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Book cover HPV Infection in Head and Neck Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 206))

Abstract

Recurrent or metastatic head and neck cancer describes tumor deposits that arise locally, regionally, or at distant sites after treatment or distant metastases at the time of primary diagnosis. Prognosis for R/M squamous cell carcinomas of the head and neck (HNSCC) is poor and treatment options are limited in this situation. Human papillomavirus (HPV) is an important risk factor for HNSCC. About 40 % of all HNSCC have been attributed to HPV in Europe. HPV positivity at initial diagnosis is the single best prognostic factor for survival. However, data for the prognostic and predictive value of HPV in the R/M situation are still scarce. Due to the rising incidence of HPV-associated cancers, the number of R/M HPV+ carcinomas is also expected to rise. This chapter therefore aims to give an overview of the current knowledge concerning the role of HPV as a prognostic and predictive marker in recurrent or metastatic HNSCC.

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References

  • Abogunrin S, Di Tanna GL, Keeping S et al. (2014) Prevalence of human papillomavirus in head and neck cancers in European populations: a meta-analysis. BMC Cancer 14:968

    Google Scholar 

  • Ang KK, Harris J, Wheeler R et al. (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35

    Google Scholar 

  • Argiris A, Li S, Ghebremichael M et al. (2014) Prognostic significance of human papillomavirus in recurrent or metastatic head and neck cancer: an analysis of Eastern Cooperative Oncology Group trials. Ann Oncol 25:1410–1416

    Google Scholar 

  • Arteaga CL, Engelman JA (2014) ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 25:282–303

    Google Scholar 

  • Balermpas P, Rodel F, Rodel C et al. (2016) 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 138:171–181

    Google Scholar 

  • Bonner JA, Harari PM, Giralt J et al. (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578

    Google Scholar 

  • Bulut OC, Lindel K, Hauswald H et al. (2014) Clinical and molecular characteristics of HNSCC patients with brain metastases: a retrospective study. Eur Arch Otorhinolaryngol 271:1715–1722

    Google Scholar 

  • Cancer Genome Atlas N (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517:576–582

    Google Scholar 

  • Chaturvedi AK, Engels EA, Pfeiffer RM et al. (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29:4294–4301

    Google Scholar 

  • Deeken JF, Newkirk K, Harter KW et al. (2015) Effect of multimodality treatment on overall survival for patients with metastatic or recurrent HPV-positive head and neck squamous cell carcinoma. Head Neck 37:630–635

    Google Scholar 

  • Fakhry C, Zhang Q, Nguyen-Tan PF et al. (2014) Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol 32:3365–3373

    Google Scholar 

  • Gilbert J, Schell MJ, Zhao X et al. (2015) A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma. Oral Oncol 51:376–382

    Google Scholar 

  • Grünwald V, Keilholz U, Boehm A et al. (2015) TEMHEAD: a single-arm multicentre phase II study of temsirolimus in platin- and cetuximab refractory recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) of the German SCCHN Group (AIO). Ann Oncol 26:561-567

    Google Scholar 

  • Guigay J, Fayette J, Dillies AF et al. (2015) Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Ann Oncol 26:1941–1947

    Google Scholar 

  • Huang SH, Perez-Ordonez B, Liu FF et al. (2012) Atypical clinical behavior of p16-confirmed HPV-related oropharyngeal squamous cell carcinoma treated with radical radiotherapy. Int J Radiat Oncol Biol Phys 82:276–283

    Google Scholar 

  • Huang SH, Perez-Ordonez B, Weinreb I et al. (2013) Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer. Oral Oncol 49:79–85

    Google Scholar 

  • Jordan RC, Lingen MW, Perez-Ordonez B et al. (2012) Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol 36:945–954

    Google Scholar 

  • Keck MK, Zuo Z, Khattri A et al. (2015) Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res 21:870–881

    Google Scholar 

  • Kim HS, Lee JY, Lim SH et al. (2016) Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma. Cancer Res Treat 48:527-536

    Google Scholar 

  • Licitra L, Mesia R, Rivera F et al. (2011) Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Ann Oncol 22:1078–1087

    Google Scholar 

  • Licitra L, Storkel S, Kerr KM et al. (2013) Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer 49:1161–1168

    Google Scholar 

  • Machiels JP, Haddad RI, Fayette J et al. (2015) Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol 16:583–594

    Google Scholar 

  • Machiels JP, Specenier P, Krauss J et al. (2015) A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol 76:13–20

    Google Scholar 

  • Mehanna H, Beech T, Nicholson T et al. (2013) Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer--systematic review and meta-analysis of trends by time and region. Head Neck 35:747–755

    Google Scholar 

  • Misiukiewicz K, Camille N, Gupta V et al. (2014) The role of HPV status in recurrent/metastatic squamous cell carcinoma of the head and neck. Clin Adv Hematol Oncol 12:812–819

    Google Scholar 

  • Morris LG, Chandramohan R, West L et al. (2016) The Molecular Landscape of Recurrent and Metastatic Head and Neck Cancers: Insights From a Precision Oncology Sequencing Platform. JAMA Oncol

    Google Scholar 

  • Nichols AC, Finkelstein DM, Faquin WC et al. (2010) Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer. Clin Cancer Res 16:2138–2146

    Google Scholar 

  • Pogorzelski M, Ting S, Gauler TC et al. (2014) Impact of human papilloma virus infection on the response of head and neck cancers to anti-epidermal growth factor receptor antibody therapy. Cell Death Dis 5:e1091

    Google Scholar 

  • Posner MR, Lorch JH, Goloubeva O et al. (2011) Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann Oncol 22:1071–1077

    Google Scholar 

  • Rischin D, Spigel DR, Adkins D et al. (2016) PRISM: Phase 2 trial with panitumumab monotherapy as second-line treatment in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Head Neck 38 Suppl 1:E1756–1761

    Google Scholar 

  • Rischin D, Young RJ, Fisher R et al. (2010) Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol 28:4142–4148

    Google Scholar 

  • Rosenthal DI, Harari PM, Giralt J et al. (2016) 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 34:1300–1308

    Google Scholar 

  • Russell S, Angell T, Lechner M et al. (2013) Immune cell infiltration patterns and survival in head and neck squamous cell carcinoma. Head Neck Oncol 5:24

    Google Scholar 

  • Ruzevick J, Olivi A, Westra WH (2013) Metastatic squamous cell carcinoma to the brain: an unrecognized pattern of distant spread in patients with HPV-related head and neck cancer. J Neurooncol 112:449–454

    Google Scholar 

  • Seiwert TY, Burtness B, Mehra R et al. (2016) 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 17:956–965

    Google Scholar 

  • Seiwert TY, Fayette J, Cupissol D et al. (2014) A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck. Ann Oncol 25:1813–1820

    Google Scholar 

  • Seiwert TY, Zuo Z, Keck MK et al. (2015) Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res 21:632–641

    Google Scholar 

  • Tinhofer I, Budach V, Saki M et al. (2016) Targeted next-generation sequencing of locally advanced squamous cell carcinomas of the head and neck reveals druggable targets for improving adjuvant chemoradiation. Eur J Cancer 57:78–86

    Google Scholar 

  • Tinhofer I, Johrens K, Keilholz U et al. (2015) Contribution of human papilloma virus to the incidence of squamous cell carcinoma of the head and neck in a European population with high smoking prevalence. Eur J Cancer 51:514–521

    Google Scholar 

  • Tinhofer I, Konschak R, Stromberger C et al. (2014) Detection of circulating tumor cells for prediction of recurrence after adjuvant chemoradiation in locally advanced squamous cell carcinoma of the head and neck. Ann Oncol 25:2042–2047

    Google Scholar 

  • Vermorken JB, Mesia R, Rivera F et al. (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359:1116–1127

    Google Scholar 

  • Vermorken JB, Peyrade F, Krauss J et al. (2014) Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part). Ann Oncol 25:682–688

    Google Scholar 

  • Vermorken JB, Psyrri A, Mesia R et al. (2014) Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial. Ann Oncol 25:801–807

    Google Scholar 

  • Vermorken JB, Stohlmacher-Williams J, Davidenko I et al. (2013) Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol 14:697–710

    Google Scholar 

  • Wirth LJ, Dakhil SR, Kornek G et al. PARTNER: A randomized phase II study of docetaxel/cisplatin (doc/cis) chemotherapy with or without panitumumab (pmab) as first-line treatment (tx) for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). J Clin Oncol 31, 2013 (suppl; abstr 6029)

    Google Scholar 

Further Reading

  • Misiukiewicz K et al (2014) The role of HPV status in recurrent/metastatic squamous cell carcinoma of the head and neck. Clin Adv Hematol Oncol 12(12):812–819

    Google Scholar 

  • Psyrri A et al (2014) The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol

    Google Scholar 

  • Spreafico A et al (2014) Demystifying the role of tumor HPV status in recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol 25(4):760–762

    Google Scholar 

  • Vokes E et al (2015) HPV-associated head and neck cancer. J Natl Cancer Inst 107(12)

    Google Scholar 

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Authors and Affiliations

  1. Charité Comprehensive Cancer Center, Charité – Universitätsmedizin Berlin, Berlin, Germany

    Damian T. Rieke & Ulrich Keilholz

Authors
  1. Damian T. Rieke
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  2. Ulrich Keilholz
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Correspondence to Ulrich Keilholz .

Editor information

Editors and Affiliations

  1. Department of Head and Neck Surgery, Poznan University of Medical Sciences, The Greater Poland Cancer Centre, Poznań, Poland

    Wojciech Golusiński

  2. Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center/Cancer Center Amsterdam, Amsterdam, The Netherlands

    C. René Leemans

  3. Dept. of Head Medicine and Oral Health, University of Leipzig Clinic of Otolaryngology, Leipzig, Germany

    Andreas Dietz

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Rieke, D.T., Keilholz, U. (2017). Systemic Treatment in HPV-Induced Recurrent or Metastatic HNSCC. In: Golusiński, W., Leemans, C., Dietz, A. (eds) HPV Infection in Head and Neck Cancer. Recent Results in Cancer Research, vol 206. Springer, Cham. https://doi.org/10.1007/978-3-319-43580-0_11

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  • DOI: https://doi.org/10.1007/978-3-319-43580-0_11

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-43578-7

  • Online ISBN: 978-3-319-43580-0

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