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De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma

  1. Liam Masterson1,*,
  2. Daniel Moualed2,
  3. Ajmal Masood3,
  4. Raghav C Dwivedi1,
  5. Richard Benson4,
  6. Jane C Sterling5,
  7. Kirsty M Rhodes6,
  8. Holger Sudhoff7,
  9. Piyush Jani1,
  10. Peter Goon8

Editorial Group: Cochrane ENT Group

Published Online: 15 FEB 2014

DOI: 10.1002/14651858.CD010271.pub2

How to Cite

Masterson L, Moualed D, Masood A, Dwivedi RC, Benson R, Sterling JC, Rhodes KM, Sudhoff H, Jani P, Goon P. De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD010271. DOI: 10.1002/14651858.CD010271.pub2.

Author Information

  1. 1

    Cambridge University Hospitals NHS Foundation Trust, ENT Department, Cambridge, UK

  2. 2

    Great Western Hospitals NHS Foundation Trust, ENT Department, Swindon, UK

  3. 3

    Norfolk and Norwich University Hospital, ENT Department, Norwich, UK

  4. 4

    Addenbrooke's Hospital, Oncology Centre, Cambridge, UK

  5. 5

    Addenbrooke's Hospital, Department of Dermatology, Cambridge, UK

  6. 6

    University of Cambridge, MRC Biostatistics Unit, Cambridge, Cambridgeshire, UK

  7. 7

    Bielefeld Academic Teaching Hospital, Department of Otolaryngology, Head and Neck Surgery, Bielefeld, Germany

  8. 8

    University of Cambridge, Department of Pathology, Cambridge, UK

*Liam Masterson, ENT Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK.

Publication History

  1. Publication Status: New
  2. Published Online: 15 FEB 2014



References to studies excluded from this review

  1. References to studies excluded from this review
  2. References to ongoing studies
  3. Additional references
Argiris 2011 {published data only}
Chen 2013 {published data only}
Chera 2012 {published data only}
  • Chera B, Green R. De-intensification of radiation and chemotherapy for low-risk human papillomavirus-related oropharyngeal squamous cell carcinoma. 2012. [NCT01530997]
DAHANCA 5 {published data only}
  • Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J, Danish Head and Neck Cancer Group (DAHANCA). HPV-associated p16-expression and response to hypoxic modification of radiotherapy in head and neck cancer. Radiotherapy and Oncology 2010;94:30-5.
DAHANCA 6 & 7 {published data only}
  • Lassen P, Eriksen JG, Krogdahl A, Therkildsen MH, Overgaard M, Specht L, et al. Danish Head and Neck Cancer Group (DAHANCA). The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: evaluation of the randomised DAHANCA 6&7 trial. Radiotherapy and Oncology 2011;100:49-55.
Eisbruch 2012 {published data only}
  • Eisbruch A. Reduced-intensity therapy for advanced oropharyngeal cancer in non-smoking human papilloma virus (HPV)-16 positive patients. 2012. [NCT01649414]
Fakhry 2008 {published data only}
  • Fakhry C, Westra WH. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. Journal of the National Cancer Institute 2008;100(4):261-9.
Gilbert 2012 {published data only}
Huang 2012 {published data only}
  • Huang S, O'Sullivan B. Temporal regression of cervical lymph node in N2-N3 head-and-neck cancer treated with primary radiation therapy +/- chemotherapy: stratified by HPV status. International Journal of Radiation Oncology, Biology, Physics 2012;1:S205.
Kies 2010 {published data only}
  • Kies MS, Holsinger FC. Induction chemotherapy and cetuximab for locally advanced squamous cell carcinoma of the head and neck: results from a phase II prospective trial. Journal of Clinical Oncology 2010;28(1):8-14.
Le 2012 {published data only}
Mehrotra 2012 {published data only}
  • Mehrotra B, Schwartz DL, Frank D, Saltman B, Roy R, Lebowicz YZ, et al. Phase II trial of neoadjuvant chemotherapy for HPV-associated squamous cell carcinoma of the oropharynx followed by reduced-dose radiotherapy/chemoradiotherapy for responders or standard dose chemoradiotherapy for non-responders. Journal of Clinical Oncology 2012;30:Abstract TPS5601.
Merlano 2013 {published and unpublished data}
  • Merlano M, Denaro N. The phase III study interceptor in HNC: preliminary report on toxicity. Oral Oncology. 2013; Vol. 49:S21-2.
O'Sullivan 2012 {published and unpublished data}
  • O'Sullivan B, Huang SH. Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiotherapy and Oncology 2012;103(1):49-56.
Psyrri 2011 {published data only}
  • Psyrri A, Ghebremichael MS. P16 protein status and response to treatment in a prospective clinical trial (ECOG 2303) of patients with head and neck squamous cell carcinoma (HNSCC). Journal of Clinical Oncology 2011;29(15 Suppl):Abstract e16032.
Quon 2012 {published data only}
  • Quon H, Blackford A. Phase II study of radiation therapy dose de-intensification for HPV-associated oropharyngeal carcinoma. International Journal of Radiation Oncology, Biology, Physics 2012;84(3):S208. [NCT01088802]
REALISTIC 2012 {published and unpublished data}
  • Jones T. A phase I, dose escalation trial of recombinant listeria monocytogenes (Lm)- based vaccine encoding human papilloma virus serotype 16 target antigens (ADXS11-001) in patients with HPV-16 +ve oropharyngeal carcinoma. Liverpool Cancer Trials Unit ( 2012 (accessed 3 February 2014). [ ISRCTN47069182]
RTOG 0129 {published data only}
RTOG 0522 {published data only}
  • Ang KK, Zhang QE. A randomized phase III trial (RTOG 0522) of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III-IV head and neck squamous cell carcinomas. Journal of Clinical Oncology 2011;29(15 Suppl):Abstract 5500.
RTOG 9003 {published data only}
  • Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, et al. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. Journal of Clinical Oncology 2012;10:2102-11.
Seiwert 2011 {published data only}
  • Seiwert TY, Haraf DJ. A randomized phase II trial of cetuximab-based induction chemotherapy followed by concurrent cetuximab, 5-FU, hydroxyurea, and hyperfractionated radiation (CetuxFHX), or cetuximab, cisplatin, and accelerated radiation with concomitant boost (CetuxPX) in patients with locoregionally advanced head and neck cancer (HNC). Journal of Clinical Oncology 2011;29(15 Suppl):Abstract 5519.
Semrau 2012 {published data only}
  • Semrau R, Duerbaum H, Temming S, Huebbers C, Stenner M, Drebber U, et al. Prognostic impact of human papillomavirus status, survivin, and epidermal growth-factor receptor expression on survival in patients treated with radiochemotherapy for very advanced nonresectable oropharyngeal cancer. Head and Neck 2012 Oct 5 [Epub ahead of print]. [DOI: 10.1002/hed.23126]
Siu 2009 {published data only}
  • Siu L, Waldron J. Radiation therapy and cisplatin or panitumumab in treating patients with locally advanced stage III or stage IV head and neck cancer. 2009. [NCT00820248]
Snietura 2011 {published data only}
  • Snietura M, Piglowski W. Impact of HPV infection on the clinical outcome of p-CAIR trial in head and neck cancer. European Archives of Oto-Rhino-Laryngology 2011;268(5):721-6.
Takenaka 2013 {published data only}
  • Takenaka Y. Phase II study of de-intensified treatment (radiation alone) for human papilloma virus-associated oropharyngeal cancer. 2013.
TAX 324 {published data only}
Teknos 2010 {published data only}
  • Teknos T. Vorinostat in the treatment of advanced staged oropharyngeal squamous cell carcinoma. 2010. [NCT01064921]
Thibaudeau 2011 {published data only}
  • Thibaudeau E, Fortin B, Coutlée F. HPV prevalence and prognostic value in a prospective cohort of 255 patients with locally advanced HNSCC: a single-centre experience. International Journal of Otolaryngology 2013 Apr 24 [Epub ahead of print]. [DOI: 10.1155/2013/437815]
TROG 02.02 {published data only}
  • Rischin D, Young RJ. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. Journal of Clinical Oncology 2010;28(27):4142-8.
Yao 2013 {published data only}
  • Yao M. Erlotinib, docetaxel, and radiation therapy in stage III or stage IV squamous cell carcinoma of the head and neck. 2008. [NCT00720304]

References to ongoing studies

  1. References to studies excluded from this review
  2. References to ongoing studies
  3. Additional references
Cohen 2010 {published and unpublished data}
  • Cohen E. Selection of chemoradiotherapy based on response to induction chemotherapy - a randomized phase II study in locally advanced squamous cell carcinoma of head and neck. 2010. [NCT01133678]
De-ESCALaTE 2012 {published and unpublished data}
  • Mehanna H. De-ESCALaTE: Determination of epidermal growth factor receptor-inhibitor (cetuximab) versus standard chemotherapy (cisplatin) early and late toxicity events in human papillomavirus-positive oropharyngeal squamous cell carcinoma: a randomised controlled trial. http://www.cancerresearchuk 2011.
DFCI 2010 {published and unpublished data}
  • Papadimitrakopoulou V. Paclitaxel, carboplatin and cetuximab (PCC) versus cetuximab, docetaxel, cisplatin and fluorouracil (C-TPF) in previously untreated patients with locally advanced head and neck squamous cell carcinoma (HNSCC). 2010. [NCT01154920]
ECOG 1308 {published and unpublished data}
  • Marur S, Comis RL. A phase II trial of induction chemotherapy followed by cetuximab (Erbitux) with low dose vs. standard dose IMRT in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx. 2010. [NCT01084083]
Quarterback 2012 {published data only}
  • Posner M. The Quarterback Trial: a randomized phase III clinical trial comparing reduced and standard radiation therapy doses for locally advanced HPV16 positive oropharynx cancer. New York:, 2012. [NCT01706939]
RTOG 1016 {published data only (unpublished sought but not used)}
  • Trotti A. Phase III trial of radiotherapy plus cetuximab versus chemoradiotherapy in HPV-associated oropharynx cancer. 2011. [NCT01302834]
TROG-12.01 {published and unpublished data}
  • Rischin D, Sivasuthan J. A randomised trial of weekly cetuximab and radiation versus weekly cisplatin and radiation in good prognosis locoregionally advanced HPV-associated oropharyngeal squamous cell carcinoma. 2013. [NCT01855451]

Additional references

  1. References to studies excluded from this review
  2. References to ongoing studies
  3. Additional references
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  • 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 Oncology 2010;11(1):21-8.
Bourhis 2006
  • Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J, et al. Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck (MARCH) Collaborative Group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 2006;368(9538):843-54.
Bourhis 2010
  • Bourhis J, Lefebvre JL, Vermorken JB. Cetuximab in the management of locoregionally advanced head and neck cancer: expanding the treatment options?. European Journal of Cancer 2010;46(11):1979-89.
Chaturvedi 2011
  • 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. Journal of Clinical Oncology 2011;29(32):4294-301.
Choi 2009
  • Choi WH, Hu KS, Culliney B. Cancer of the oropharynx. In: Harrison LB, Sessions RB, Hong WK editor(s). Head and Neck Cancer: A Multidisciplinary Approach. 3rd Edition. Philadelphia: Lippincott, William & Wilkins, 2009:285-335.
Chung 2011
  • Chung CH, Zhang Q, Hammond EM, Trotti AM, Wang H, Spencer S, et al. Integrating epidermal growth factor receptor assay with clinical parameters improves risk classification for relapse and survival in head-and-neck squamous cell carcinoma. International Journal of Radiation Oncology, Biology, Physics 2011;81(2):331-8. [DOI: 10.1016/j.ijrobp.2010.05.024]
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de Martel 2012
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Dirix 2010
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Haddad 2008
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Hoffman 2010
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