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A review of combined treatment strategies for HPV(+), p16(+) oropharyngeal cancer – is de-escalated radiotherapy a convincing and promising paradigm?
Affiliations- Div. Research Programmes
- Radiotherapy and Chemotherapy Ward I, M. Skłodowska-Curie National Research Institute of Oncology, Branch Gliwice, Poland
open access
Abstract
Biological and clinical interest on HPV-associated oropharyngeal cancer (OPC) is rapidly increasing. The genetic and biological characteristics of HPV and p16 expression are presented. The significantly better prognosis (overall survival, locoregional control) of HPV p16(+) OPC patients has been well documented. The leading studies and clinical trials in this field are selected and discussed in details. There is a convincing suggestion that some, low-risk HPV(+) OPC patients might be overtreated. Different approaches with varying degrees of radiotherapy dose de-intensification are critically reviewed and the current de-escalated treatment paradigms are presented and discussed.
Abstract
Biological and clinical interest on HPV-associated oropharyngeal cancer (OPC) is rapidly increasing. The genetic and biological characteristics of HPV and p16 expression are presented. The significantly better prognosis (overall survival, locoregional control) of HPV p16(+) OPC patients has been well documented. The leading studies and clinical trials in this field are selected and discussed in details. There is a convincing suggestion that some, low-risk HPV(+) OPC patients might be overtreated. Different approaches with varying degrees of radiotherapy dose de-intensification are critically reviewed and the current de-escalated treatment paradigms are presented and discussed.
Keywords
HPV-associated OPC; treatment outcomes; de-escalated therapy paradigms
About this articleTitle
A review of combined treatment strategies for HPV(+), p16(+) oropharyngeal cancer – is de-escalated radiotherapy a convincing and promising paradigm?
Journal
Nowotwory. Journal of Oncology
Issue
Article type
Review paper
Pages
236-243
Published online
2020-12-04
Page views
488
Article views/downloads
500
DOI
Bibliographic record
Nowotwory. Journal of Oncology 2020;70(6):236-243.
Keywords
HPV-associated OPC
treatment outcomes
de-escalated therapy paradigms
Authors
Bogusław Maciejewski
Krzysztof Składowski
References (33)- Ang K, Harris J, Wheeler R, et al. Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer. N Eng J Med. 2010; 363(1): 24–35.
- O'Sullivan B, Huang SH, Siu LL, et al. Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol. 2013; 31(5): 543–550.
- Lassen P, Eriksen JG, Hamilton-Dutoit S, et al. Danish Head and Neck Cancer Group (DAHANCA). HPV-associated p16-expression and response to hypoxic modification of radiotherapy in head and neck cancer. Radiother Oncol. 2010; 94(1): 30–35.
- O'Sullivan B, Huang SH, Perez-Ordonez B, et al. Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiother Oncol. 2012; 103(1): 49–56.
- Chen AM, Felix C, Wang PC, et al. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study. Lancet Oncol. 2017; 18(6): 803–811.
- Marur S, Li S, Cmelak A, 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): 490–497.
- Rietbergen MM, Brakenhoff RH, Bloemena E, et al. Human papillomavirus detection and comorbidity: critical issues in selection of patients with oropharyngeal cancer for treatment De-escalation trials. Ann Oncol. 2013; 24(11): 2740–2745.
- Rietbergen MM, Martens-de Kemp SR, Bloemena E, et al. Cancer stem cell enrichment marker CD98: a prognostic factor for survival in patients with human papillomavirus-positive oropharyngeal cancer. Eur J Cancer. 2014; 50(4): 765–773.
- Rischin D, Young RJ, Fisher R, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010; 28(27): 4142–4148.
- Poseur MR, Lorch JH, Goloubeva O, et al. Survival and human papillomavirus in oropharynx cancer in TAX 324. A subset analysis from an international phase III trial. Ann Oncol. 2011; 22: 1071–1077.
- 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(4): 261–269.
- Billfalk-Kelly A, Yu E, Su J, et al. Radiologic Extranodal Extension Portends Worse Outcome in cN+ TNM-8 Stage I Human Papillomavirus-Mediated Oropharyngeal Cancer. Int J Radiat Oncol Biol Phys. 2019; 104(5): 1017–1027.
- Bhattasali O, Thompson LDR, Schumacher AJ, et al. Radiographic nodal prognostic factors in stage I HPV-related oropharyngeal squamous cell carcinoma. Head Neck. 2019; 41(2): 398–402.
- Huang SH, O'Sullivan B, Waldron J. The Current State of Biological and Clinical Implications of Human Papillomavirus-Related Oropharyngeal Cancer. Semin Radiat Oncol. 2018; 28(1): 17–26.
- Rietbergen M. The role of human papillomavirus in head and neck cancer. Vrije Univ. Amsterdam. Int J Cancer. 2013; 24: 2740–2745.
- Isayeva T, Li Y, Maswahu D, et al. Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review. Head Neck Pathol. 2012; 6 Suppl 1: S104–S120.
- Ang KK, Sturgis EM. Human papillomavirus as a marker of the natural history and response to therapy of head and neck squamous cell carcinoma. Semin Radiat Oncol. 2012; 22(2): 128–142.
- O’Sullivan B, Huang SA, Su J, et al. Development and validation of a staging system for HPV- related oropharyngeal cancer network for staging (icon-s). A multicenter cohort study. Lancet Oncol. 2016; 17: 440–451.
- Westra WH, Lewis JS. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx. Head Neck Pathol. 2017; 11(1): 41–47.
- O’Sullivan B, Lydiatt W, Haughey B. et al. HPV- mediated (p16+) oropharyngeal cancer. In: Amin M, Edge S, Greene F. et al. ed. AJCC Cancer Staging Manual. 8th ed. Switzerland Springer Nature 2017: 113–121.
- Klussmann J, Mooren J, Lehnen M, et al. Genetic Signatures of HPV-related and Unrelated Oropharyngeal Carcinoma and Their Prognostic Implications. Clin Cancer Res. 2009; 15(5): 1779–1786.
- Martinez I, Wang J, Hobson KF, et al. Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer. 2007; 43(2): 415–432.
- Leemans CR, Brakhuis BJ, Bratzenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011; 1: 9–22.
- Nakao Y, Yang X, Yokoyama M, et al. Induction of p16 during immortalization by HPV 16 and 18 and not during malignant transformation. Br J Cancer. 1997; 75(10): 1410–1416.
- Shi W, Kato H, Perez-Ordonez B, et al. Comparative prognostic value of HPV16 E6 mRNA compared with in situ hybridization for human oropharyngeal squamous carcinoma. J Clin Oncol. 2009; 27(36): 6213–6221.
- Hong A, Dobbing T, Lee CS, et al. Relationships between epidermal growth factor receptor expression and human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. Clin Oncol. 2006; 24: 5630–5636.
- Overgaard J, Eriksen J, Nordsmark M, et al. Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial. Lancet Oncol. 2005; 6(10): 757–764.
- Galloway TJ, Zhang QEd, Nguyen-Tan PF, et al. Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129. Int J Radiat Oncol Biol Phys. 2016; 96(2): 362–371.
- Chera BS, Amdur RJ. Current Status and Future Directions of Treatment Deintensification in Human Papilloma Virus-associated Oropharyngeal Squamous Cell Carcinoma. Semin Radiat Oncol. 2018; 28(1): 27–34.
- Chera BS, Amdur RJ, Tepper J, 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): 976–985.
- Lee N, Schoder H, Beattie B, et al. Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus-Related Oropharyngeal Carcinoma. Int J Radiat Oncol Biol Phys. 2016; 96(1): 9–17.
- Sørensen BS, Busk M, Horsman MR, et al. Effect of radiation on cell proliferation and tumor hypoxia in HPV-positive head and neck cancer in vivo models. Anticancer Res. 2014; 34(11): 6297–6304.
- Ma DJ, Price KA, Moore EJ, et al. Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma. J Clin Oncol. 2019; 37(22): 1909–1918.