KEY POINTS Oropharyngeal (OP) carcinoma comprises over ● half of all head and neck cancers in the United States. While the incidence of squamous cell carcinoma ● (SCC) in the other head and neck sites has been steadily declining in association with smoking cessation, the incidence of SCC in the OP is ris- ing, especially in younger patients and has been linked to the exposure of the human papilloma- virus (HPV). The treatment of OP carcinoma is complex be- ● cause of the intricate anatomy of the involved organs, their rich lymphatic networks, and their critical function in the activities of daily living. Such treatment therefore requires a multidisci- plinary approach. This chapter focuses on the epidemiology of ● OP squamous cell carcinoma, specifically look- ing at the emerging role of HPV virus in their development. It also describes the different treatment options ● for these tumors with a focus on those for organ preservation. Finally, it highlights recent advances in treat- ● ment using molecularly targeted therapies and modern radiation delivery using intensity- modulated approach with the goal to minimize treatment-related toxicity in these highly curable patients. CONTENTS 2.1 Introduction 16 2.2 Epidemiology 16 2.3 Staging 17 2.3.1 The Role of 18 Fluoro Deoxy-Glucose Positron Emission Topography in OPSCC Management 17 2.4 Treatment by Stages 18 2.4.1 Early Stage (Stages I–II) 18 2.4.2 Locally Advanced Stage (Stages III–IV) 19 2.4.2.1 Surgery and Adjuvant Radiotherapy vs. Radiotherapy or Chemoradiotherapy 19 2.4.2.2 Radiation Fractionation 19 2.4.2.3 Chemotherapy and Radiation Therapy 19 2.4.2.4 Targeted Therapy 20 2.4.2.5 Postoperative Treatment: Radiation and Chemoradiation 20 2.5 Radiation Therapy Technique: Three-Dimensional Conformal Radiation Therapy vs. Intensity-Modulated Radiotherapy 21 2.6 Treatment-Related Toxicities 22 2.6.1 Acute Toxicities 22 2.6.2 Late Toxicities 23 2.7 Conclusion 26 Abbreviations 26 References 26 Oropharynx: Epidemiology and Treatment Outcome 2 Edith Filion and Quynh-Thu Le Edith Filion, MD Department of Radiation Oncology, Stanford University Cancer Center, 875 Blake Wilbur Drive, Stanford, CA 94305-5847, USA Quynh-Thu Le, MD Department of Radiation Oncology, Stanford University Cancer Center, 875 Blake Wilbur Drive, Stanford, CA 94305-5847, USA