Advanced Oropharyngeal Squamous Cell Carcinoma: Pathogenesis, Treatment, and Novel Therapeutic Approaches

Overview

Journal World J Clin Oncol

Publisher Baishideng Publishing Group

Specialty Oncology

Date 2016 Feb 11

PMID 26862488

Citations 9

Authors

Paul L Swiecicki

Kelly M Malloy

Francis P Worden

Affiliations

Soon will be listed here.

Abstract

Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus (HPV) and present with locally advanced tumors. HPV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HPV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. We also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease.

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References

Haddad R, ONeill A, Rabinowits G, Tishler R, Khuri F, Adkins D . 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. DOI: 10.1016/S1470-2045(13)70011-1. View

Lorch J, Goloubeva O, Haddad R, Cullen K, Sarlis N, Tishler R . Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol. 2011; 12(2):153-9. PMC: 4356902. DOI: 10.1016/S1470-2045(10)70279-5. View

Andre K, Schraub S, Mercier M, Bontemps P . Role of alcohol and tobacco in the aetiology of head and neck cancer: a case-control study in the Doubs region of France. Eur J Cancer B Oral Oncol. 1995; 31B(5):301-9. DOI: 10.1016/0964-1955(95)00041-0. View

Hui A, Lin A, Xu W, Waldron L, Perez-Ordonez B, Weinreb I . Potentially prognostic miRNAs in HPV-associated oropharyngeal carcinoma. Clin Cancer Res. 2013; 19(8):2154-62. DOI: 10.1158/1078-0432.CCR-12-3572. View

Dobrosotskaya I, Bellile E, Spector M, Kumar B, Feng F, Eisbruch A . Weekly chemotherapy with radiation versus high-dose cisplatin with radiation as organ preservation for patients with HPV-positive and HPV-negative locally advanced squamous cell carcinoma of the oropharynx. Head Neck. 2013; 36(5):617-23. PMC: 4205960. DOI: 10.1002/hed.23339. View

Daly M, Le Q, Maxim P, Loo Jr B, Kaplan M, Fischbein N . Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure. Int J Radiat Oncol Biol Phys. 2009; 76(5):1339-46. DOI: 10.1016/j.ijrobp.2009.04.006. View

MARCIAL V, Pajak T, Mohiuddin M, Cooper J, Al Sarraf M, Mowry P . Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Long-term results of the Radiation Therapy Oncology Group study 81-17. Cancer. 1990; 66(9):1861-8. DOI: 10.1002/1097-0142(19901101)66:9<1861::aid-cncr2820660902>3.0.co;2-i. View

Weinstein G, Quon H, OMalley Jr B, Kim G, Cohen M . Selective neck dissection and deintensified postoperative radiation and chemotherapy for oropharyngeal cancer: a subset analysis of the University of Pennsylvania transoral robotic surgery trial. Laryngoscope. 2010; 120(9):1749-55. DOI: 10.1002/lary.21021. View

Fakhry C, Zhang Q, Nguyen-Tan P, Rosenthal D, El-Naggar A, Garden A . Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol. 2014; 32(30):3365-73. PMC: 4195851. DOI: 10.1200/JCO.2014.55.1937. View

10.

Forastiere A, Metch B, Schuller D, Ensley J, Hutchins L, Triozzi P . Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol. 1992; 10(8):1245-51. DOI: 10.1200/JCO.1992.10.8.1245. View

11.

Rettig E, Wentz A, Posner M, Gross N, Haddad R, Gillison M . 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. PMC: 7286348. DOI: 10.1001/jamaoncol.2015.2524. View

12.

Jacobs C, Lyman G, Velez-Garcia E, Sridhar K, Knight W, Hochster H . A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol. 1992; 10(2):257-63. DOI: 10.1200/JCO.1992.10.2.257. View

13.

Kato I, Nomura A . Alcohol in the aetiology of upper aerodigestive tract cancer. Eur J Cancer B Oral Oncol. 1994; 30B(2):75-81. DOI: 10.1016/0964-1955(94)90056-6. View

14.

OSullivan B, Huang S, Siu L, Waldron J, Zhao H, Perez-Ordonez B . Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol. 2013; 31(5):543-50. DOI: 10.1200/JCO.2012.44.0164. View

15.

Calais G, Alfonsi M, Bardet E, Sire C, Germain T, Bergerot P . Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst. 1999; 91(24):2081-6. DOI: 10.1093/jnci/91.24.2081. View

16.

De Stefani E, Boffetta P, Oreggia F, Fierro L, Mendilaharsu M . Hard liquor drinking is associated with higher risk of cancer of the oral cavity and pharynx than wine drinking. A case-control study in Uruguay. Oral Oncol. 1998; 34(2):99-104. DOI: 10.1016/s1368-8375(97)00062-6. View

17.

. Tobacco habits other than smoking; betel-quid and areca-nut chewing; and some related nitrosamines. IARC Working Group. Lyon, 23-30 October 1984. IARC Monogr Eval Carcinog Risk Chem Hum. 1985; 37:1-268. View

18.

Lohaus F, Linge A, Tinhofer I, Budach V, Gkika E, Stuschke M . HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology.... Radiother Oncol. 2014; 113(3):317-23. DOI: 10.1016/j.radonc.2014.11.011. View

19.

Schwartz D, Harris J, Yao M, Rosenthal D, Opanowski A, Levering A . Metabolic tumor volume as a prognostic imaging-based biomarker for head-and-neck cancer: pilot results from Radiation Therapy Oncology Group protocol 0522. Int J Radiat Oncol Biol Phys. 2015; 91(4):721-9. PMC: 4672942. DOI: 10.1016/j.ijrobp.2014.12.023. View

20.

Lassen P, Eriksen J, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J . Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009; 27(12):1992-8. DOI: 10.1200/JCO.2008.20.2853. View