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INTRODUCTION

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Approximately 41,000 cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed annually in the United States, of which approximately one-third arises within the oropharynx.1 Located posterior to the oral cavity and between the nasopharynx and larynx, the oropharynx is critical in maintaining normal speech and swallowing. Its main components include the soft palate, posterior and lateral pharyngeal walls, faucial arches, tonsillar fossa, as well as the base of tongue (which anchors to the hyoid bone at the inferior border of the oropharynx). Its nonrestraining soft tissue boundaries as well as its rich lymphatic supply allow the escape of malignant cells, resulting in the majority of patients presenting with advanced disease (stage III or IV).1 Treatment often consists of surgical resection followed by adjuvant radiotherapy (RT) with or without chemotherapy; however, successful nonsurgical strategies have been developed over recent years through the refinement of RT techniques and/or the use of combination chemoradiotherapy (CRT).2 Recently, however, the introduction of minimally invasive techniques has rekindled interest in surgical therapy.

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While the incidence of the majority of head and neck malignancies has decreased in parallel with the reduction in smoking, this trend has not been observed in cancers of the oropharynx. This coincides with an increased understanding of the contribution of the human papillomavirus (HPV), especially that of HPV16, to the oncogenic process. It is estimated that over the last two decades, HPV-related oropharyngeal malignancies have increased from 50% to now approximately 80% of all oropharyngeal cancers.3,4 While the biology is not fully elucidated, there are defining clinicopathologic features that are exemplified in this patient population. For instance, HPV-associated tumors predominately arise in the base of tongue or tonsils and are often associated with an early-stage (T1/T2) primary tumor yet advanced (N2/3) and cystic neck disease. In contrast to patients with HPV-negative oropharynx squamous cell carcinoma (SCC), those with virus-mediated disease are often younger by 10 years.5,6 While outcomes are improved compared to those anticipated in treating smoking-related oropharyngeal cancers, the changing nature of the disease creates challenges in terms of maximizing tumor control while reducing late-occurring side effects.3,7

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This chapter focuses on how an increased understanding of the pathogenesis of oropharyngeal malignancies has informed therapeutic approaches as well as the technological advancements that aim to not only improve oncologic outcomes but also maintain functional integrity of the oropharynx and patient-reported quality of life (QoL).

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PATHOGENESIS AND RISK FACTORS

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Current evidence suggests that improvement in oncologic outcomes for HNSCC has not only coincided with refinement of treatment techniques but also reflected a shift in the etiology and pathogenesis of oropharyngeal malignancies.8 Converging clinical, molecular, and epidemiologic evidence now confirm that HPV status is the single most important determinant of prognosis in OPSCC. HPV is an epitheliotropic, double-stranded DNA virus with >100 characterized genotypes; HPV16 with its predilection for ...

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