Etiology and Biology

Dr Mia Hashibe of Huntsman Cancer Institute and the University of Utah School of Medicine opens our discussion with a review of the changing epidemiology of these 2 diseases. She reviews the evolution of the tobacco epidemic and advances in tobacco control in the United States since the Surgeon General’s Warning of 1964. Although this public health success has resulted in a drop in the incidence rates for most types of head and neck cancer, oropharyngeal cancer incidence rates have been on the rise because of an epidemic of HPV-associated oropharyngeal cancer. These HPV-associated malignancies have unique demographic and clinical behaviors distinct from those of classical tobacco-associated and alcohol-associated head and neck cancers. Dr Jim Rocco and colleagues of the Massachusetts Eye and Ear Infirmary and Harvard Medical School provide an in-depth discussion of HPV biology and the HPV-related carcinogenesis. The classic presentation of HPV-associated oropharyngeal cancer appears to be a small base of tongue or tonsil cancer, typically with multiple metastatic lymph nodes, in a middle-aged white man with significant sexual exposures. As reviewed by Dr Rocco and colleagues, these HPV-associated cancers have better response rates to traditional treatment and are associated with much improved survival compared to HPV-negative cancers. However, both controversies and opportunities have arisen. Accurate determination of HPV status and accurate prognostic stratification are areas of intense discussion and investigation, and clinical trials of de-escalated treatment for improved functional outcomes and of novel therapies are under way.

Dr Nishant Agrawal of Johns Hopkins University, together with Dr Myers, presents a review of the genomics of head and neck malignancies and how the current understanding of the somatic genetic changes in these cancers reflect the emerging epidemiologic and clinical picture of 2 diseases, one driven by tobacco carcinogens and the other by the oncogenic effects of HPV. The number and spectrum of somatic mutations differ significantly between HPV-associated and non-HPV-associated tumors, reflecting the differences in pathogenesis and partially explaining the distinct response rates to chemotherapy and radiotherapy. To complete our discussion of the etiology and biology of oral cavity and oropharyngeal cancer, Dr David Kutler of the Weill Cornell Medical Center introduces us to Fanconi anemia, an inherited syndrome that puts individuals at extreme risk for the development of oral cavity cancers. Clinicians should at least consider this diagnosis and referral to a clinical geneticist for patients presenting with squamous carcinoma (particularly of the oral cavity) at oddly young ages and should be aware of the other clinical signs of Fanconi anemia, as patients with this syndrome are at very high risk for severe toxic effects from radiotherapy or chemotherapy.

Evaluation and Therapy

An identifiable lesion that is premalignant but with a high potential for becoming an invasive cancer provides an opportunity for screening, early diagnosis, and less invasive treatments to prevent cancers and reduce cancer mortality. These principles are the basis of public health efforts that led to routine Pap testing in the United States, which has resulted in a dramatic reduction in the incidence of and mortality associated with another HPV-associated tumor type, cervical cancer. Unfortunately, an analogous premalignant lesion for HPV-associated oropharyngeal cancer has yet to be identified, and thus hope for a screening program for oropharyngeal cancer remains elusive. However, oral cavity premalignant lesions are easily identifiable and are treatable by one of several methods. Dr Pierre Saintigny of The University of Texas MD Anderson Cancer Center reviews recent progress in screening, risk assessment, chemoprevention, and treatment of oral premalignancy.

The emergence and recognition of HPV as the causative agent in most cases of squamous cell carcinoma of the oropharynx over the past 2 decades necessitates separate discussions of evaluation/staging of squamous cell carcinoma of the oral cavity and evaluation/staging of squamous cell carcinoma of the oropharynx. Dr Mark Zafereo of MD Anderson Cancer Center addresses both topics and also discusses novel diagnostic and staging approaches, including sentinel lymph node biopsy and FDG-PET/CT imaging. Because HPV status has such a profound influence on oropharyngeal cancer outcomes, the current staging system for oropharyngeal cancer, which does not include this critical biological determinate, appears inadequate.

Drs Daniel Clayburgh and Neil Gross of the Knight Cancer Institute at the Oregon Health and Science University provide an overview of both the traditional and the cutting-edge surgical approaches for oral cavity and oropharyngeal cancers. Sentinel lymph node biopsy has emerged as an alternative to staging neck dissection for a selection of patients with small oral cavity cancers for more aggressive treatment (neck dissection and/or radiotherapy). Transoral surgery with robotic and laser assistance is being touted as a less morbid alternative to radiotherapy for early-stage oropharyngeal cancer or as a means of allowing de-intensified radiotherapy for intermediate-stage oropharyngeal cancer; clinical trials are being initiated to substantiate these claims. The past decade has also seen exciting advances in the field of radiotherapy for oral cavity and oropharyngeal cancer, including new delivery strategies, such as intensity modulated radiotherapy; new types of particles, including protons; and newer fractionation schemes and sensitizing strategies. Drs Brandon Gunn and Steven Frank of MD Anderson Cancer Center review these advances and the opportunities for better treatment of these 2 diseases. Dr William William of MD Anderson Cancer Center discusses systemic therapy for oral cavity and oropharyngeal cancer and the impact of conventional chemotherapy or molecularly targeted agents delivered as induction treatment or concurrently with radiotherapy on the outcomes of patients with these types of tumors.

Quality of Life and Quality of Care

A comprehensive discussion of functional assessment and rehabilitation of patients with oral cavity and oropharyngeal cancer is provided by Drs Kate Hutcheson and Jan Lewin of MD Anderson Cancer Center. Understanding how current and emerging treatments influence speech and swallowing outcomes is critical to treatment selection for individual patients as well as for assessing results of clinical trials. Supportive and rehabilitative care during and after treatment yield measurable long-term functional benefits, and patients should be evaluated before initiation of cancer treatment to ensure maximum rehabilitation and function. Efforts to improve functional and oncologic outcomes will have to fit within health care system reforms that aim to control costs, reduce waste, improve quality, and increase access. Both treatment standardization based on evidence and regionalization of complex care at specialized institutions are central to improved efficiency; Drs Carol Lewis and Randal Weber of MD Anderson Cancer Center review these important issues. Although overall and disease-free survival have improved for patients successfully treated for oral cavity and oropharyngeal cancers, these cancers and their treatment predispose patients to an increased risk of mortality. In addition, cancer survivors are exposed to the same risk factors for other causes of morbidity and mortality as the general population. Dr Ian Ganly of Memorial Sloan-Kettering Cancer Center addresses these and other survivorship issues for patients with oral cavity and oropharyngeal cancers.