9% and 2.1% per year, respectively.3,7 These trends have been associated with a shift in demographics to a younger population that is typically high-functioning with lower rates of co-morbid illness, with minimal or no history of tobacco use, and longer
overall life expectancies.8–12 Infection with oncogenic HPV types per se is considered an independent Inhibitors,research,lifescience,medical risk factor, with an increased likelihood of over 200-fold for the development of oropharyngeal cancer.13–16 This etiologic agent may play a synergistic role in the development of oropharyngeal cancer with tobacco and alcohol use.17,18 Moreover, HPV tumor status was shown to be a strong prognostic factor for OPSCC.19 HPV-positive tumor status significantly improves survival, regardless of the treatment modality, compared to HPV-negative tumor status, in patients with smoking- and alcohol-related head and neck cancers.1,14,20 The mechanisms that underlie the improved prognosis conferred by HPV-positive disease are unknown, but are thought to be partly because of better therapeutic Inhibitors,research,lifescience,medical response to induction chemotherapy and to chemoradiation treatment.21–26 These studies focused our attention on the need to reduce treatment-related toxicity in order to improve short- and long-term quality of life (QOL) of patients. Traditional treatments for OPSCC include surgical therapy, intensity-modulated
radiation therapy (IMRT), combined chemotherapy and radiation Inhibitors,research,lifescience,medical therapy (CRT), and combinations of these modalities.27–31 Surgical approaches to the oropharynx traditionally involved skin incisions and mandibulotomy.32 Although this approach was effective at obtaining tumor control, the speech, swallowing, and cosmetic LDN193189 outcomes were poor, with a high rate of complications. In 2002, Inhibitors,research,lifescience,medical Parsons et al.32 analyzed the largest series reporting on the traditional approaches of Inhibitors,research,lifescience,medical treating OPSCC from 1970 to 2000. They compared outcomes of surgery versus radiation for oropharyngeal cancer and found that
the 5-year cause-specific survival with surgery averaged 57%, whereas the severe complication rate was 23%. They concluded that given the higher complication rate with surgery, most oropharyngeal cancers should be treated with radiation. In the last few decades, organ preservation Linifanib (ABT-869) modalities have become the mainstay of treatment. Thus, despite excellent local control rates with primary surgery, the trend shifted towards CRT as the primary treatment for oropharyngeal carcinomas, with surgery reserved for salvage.27,28,32–36 Indeed, between 1985 and 2001, the use of definitive chemoradiotherapy for advanced oropharyngeal cancer doubled.28 Nonetheless, chemoradiotherapy bears considerable acute and late toxicities, such as dysphagia, mucositis, xerostomia, fibrosis, osteoradionecrosis, trismus, neutropenia, neurotoxicity, nephrotoxicity, and ototoxicity.34,37,38 The addition of chemotherapy to radiation therapy (RT) increases the risk of long-term gastrostomy tube dependence from 1% to 13%.