In Brief

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Cancer of the head and neck is the sixth most common cancer worldwide. The vast majority (approximately 90%) of these cases are squamous cell carcinomas that arise from the squamous epithelium of the upper aerodigestive tract (UADT).

The incidence of oropharyngeal cancer in the United States has had a marked rise relative to other mucosal malignancies of the head and neck, and whereas most cases in the past were attributed to tobacco and alcohol use, this recent trend is related to a rise in the prevalence of high-risk subtypes of the human papillomavirus (HPV). The oncogenic effects of HPV on the oropharyngeal mucosa have become apparent in the 15 years since HPV-16 DNA was identified in oropharyngeal tumors but not in adjacent normal mucosa or in normal mucosa from controls. More recently, case-control studies have linked HPV-16 exposure and oropharyngeal cancer to sexual behaviors. Interestingly, patients with HPV-associated tumors have a good response to treatment with radiotherapy and appear to have a better prognosis than stage-matched patients whose tumors are not HPV associated.

Squamous cell carcinomas of the oropharynx can have an insidious presentation, and the primary tumor itself may not be the cause of symptoms, as many patients present with a neck mass initially. In such cases, the clinician must have a high index of suspicion and evaluate the oropharynx for pathology.

With respect to treatment, our general philosophy is to use the minimum number of treatment modalities necessary to effect a cure, to reserve modalities in the case of a second primary tumor, and to decrease treatment-related morbidity. Because oropharyngeal cancers have a high propensity for lymphatic spread to the internal jugular lymph nodes and retropharyngeal nodes, the cervical nodal basins should be treated even if they are clinically and radiographically free of disease.

Recent advances in the fields of medical oncology and radiotherapy have contributed to the high rates of disease control and survival for oropharyngeal cancer patients. Although no prospective trials have definitely demonstrated the superiority of nonsurgical (versus surgical) therapies, many centers have advocated the use of nonsurgical therapies as the primary treatment choice, reserving surgery for salvage cases, in an effort to minimize treatment morbidity and improve patient quality of life. This has led to an evolution in the role of the head and neck surgeon, who often sees these patients first and in the past was the primary caregiver. Surgeons are now primarily involved in the diagnosis and staging of oropharyngeal cancers, symptom control and supportive care during nonsurgical therapy, and decisions regarding the management of residual disease in the neck or primary site after nonsurgical treatment has been completed.

With regard to nonsurgical therapy, external-beam radiotherapy has become the treatment of choice for patients with early stage oropharyngeal cancers (stage I and II), and there are compelling data that support the use of concurrent chemotherapy and radiation to treat patients with advanced tumors (stage III and IV). Emerging data also support the use of induction chemotherapy followed by irradiation or concurrent chemoradiation for these patients, and it is anticipated that ongoing phase III clinical trials will more clearly define the role of induction therapy.

Surgical management of the neck after nonsurgical treatment for oropharyngeal cancers that respond completely at the primary site is an active area of investigation. It was initially held by many investigators that patients with N2b or N3 disease should have a “planned neck dissection,” even if they had a complete response in the neck, but there are abundant data that support the practice of observation of the neck in this setting. What remains more controversial is the optimal way to manage a small amount of residual nodal tissue after radiation or chemoradiation that can be detected by computed tomography (CT) scanning and/or physical examination. Some authors think that any nodal tissue persisting after treatment should be removed via lymphadenectomy. Others believe that positron emission tomography (PET) can identify metabolically active tumor that needs to be resected, whereas metabolically inactive tissue can be observed. However, the timing of radiographic evaluation after treatment influences the chances of finding viable tumor, and some surgeons are concerned about delaying surgery. Nodal tissue that is persistently abnormal on radiographic evaluation 12 weeks after the completion of therapy is more likely to contain viable tumor than nodal tissue that has high uptake 6 weeks after irradiation. Therefore, some groups have recommended delaying nodal dissection until 10 to 12 weeks after the completion of treatment.

Although further study is clearly needed to determine the role of PET imaging in the post-treatment management of the neck in oropharyngeal cancer patients, the authors take a conservative approach, favoring operative intervention at 6 weeks after radiotherapy has been completed if CT scanning shows residual disease. The rationale for this is the extremely high failure rate of salvage treatment of the neck for patients who have undetected residual tumor in the undissected lymph nodes. It is also important to note that postradiotherapy neck dissection provides useful prognostic information, as patients with persistent viable tumor cells in the cervical nodes after treatment have worse oncologic outcomes and disease that often fails to respond to treatment locally and distantly as well as in the neck.

For patients with persistent disease at the primary site after radiotherapy or chemoradiotherapy, the rates of successful surgical salvage are discouragingly low. Therefore, surgery should be contemplated only for palliation or when salvage surgery can be combined with reirradiation via external-beam or brachytherapy approaches. Although salvage neck dissection for isolated nodal recurrence is sometimes successful, salvage surgery without additional radiotherapy is most often met with early local-regional failure due to the abundant microscopic residual disease that remains after surgery.

Primary surgical therapy is indicated for some less common cancers of the oropharynx, including tumors arising from the minor salivary glands (such as adenoid cystic carcinoma and mucoepidermoid carcinoma), sarcomas, melanoma, and squamous variants that are resistant to irradiation, such as verrucous carcinoma.

The major acute toxic effect and long-term morbidity associated with the treatment of oropharyngeal cancer is dysphagia, which often requires the placement of a feeding tube or, at minimum, oral nutritional supplementation during and possibly for a long time after treatment. Therefore, patients being treated for oropharyngeal cancer should undergo a comprehensive swallowing evaluation by an experienced speech pathologist before starting treatment.

Patients with recurrent disease who are not candidates for further curative therapy and those who present with incurable massive disease are best served by palliation. This can be accomplished with nonsurgical therapy such as radiotherapy in the radiation naïve or select previously irradiated patients or palliative chemotherapy to retard disease progression. The major goal of palliation is to alleviate the patient's pain and suffering, and efforts should be focused on pain control, nutritional support, and counseling on emotional and spiritual end-of-life issues. Often, a multidisciplinary approach led by a palliative care specialist is the best option for the patient and the family.

New developments in the field of targeted therapeutics are yielding promising results for patients with oropharyngeal cancers, and these novel therapeutics are already proving to be important adjuncts to currently available therapies.

In summary, oropharyngeal cancers have increased in incidence, but their curability seems to have increased as well, likely owing to the newly identified viral pathogenesis of the disease. This and advances in systemic and regional therapy approaches have led to shifting roles for oncologic specialists who care for patients with oropharyngeal cancers. Although surgeons play less of a role in the primary management of this type of cancer, they have become more important in the diagnosis, staging, and supportive care and rehabilitation of patients during nonsurgical treatment and play a critically important role in assessing treatment response and performing surgery for residual tumor in the neck. The best oncologic and functional treatment outcomes result from the prospective evaluation of the oropharyngeal cancer patient by a multidisciplinary team consisting of a head and neck surgeon, dentist, medical oncologist, radiation oncologist, and speech pathologist followed by multidisciplinary treatment decision making and planning.