Head and Neck Cancer
Epidemiology and Etiology
Head and neck squamous cell cancer (HNSCC) includes carcinoma of the lip, oral cavity, oropharynx, nasopharynx, and larynx. It is estimated that approximately 53,260 patients in the US will be diagnosed with HNSCC in the year 2020.1 Tobacco use and alcohol consumption are associated with increased risk of developing HNSCC.
HPV infection is implicated in oropharyngeal squamous cell carcinomas, and the incidence of HPV-associated HNSCC is increasing. EBV infection is associated with nasopharyngeal cancers. Given the diffuse nature of mucosal exposure to tobacco smoke or smokeless tobacco, the primary cancer site is often surrounded by areas of premalignant lesions such as carcinoma in situ and dysplasia. For this reason, patients with tobacco-associated HNSCC are at increased risk for secondary HNSCCs.Clinical Presentation
Patients with HNSCC can present with a variety of symptoms depending on the primary tumor site including an oral mass, nonhealing ulcers, trismus from invasion of pterygoid muscles, dysphagia, odynophagia, otitis media from eustachian tube blockage, hoarseness, a neck mass, weight loss, and cranial nerve palsies. Nasopharyngeal tumors can invade the cavernous sinus and frequently affect the abducens and trigeminal nerves. Salivary gland tumors may invade the facial nerve.
Diagnostic Testing
• Comprehensive ear, nose, and throat evaluation with fiberoptic endoscopy or mirror examination is required. Particular attention should be paid to dentition. Functional evaluation that includes assessment of swallowing, biting, chewing, and speech should be performed.
• Examination under anesthesia is a critical component of staging. Imaging should include a panoramic dental radiograph to evaluate dentition and mandibular involvement. A CT of the neck and chest should be obtained to evaluate lymph node involvement and rule out pulmonary metastases, respectively.
Whole-body PET can be considered in select patients.• Positivity of p16 on IHC is used as a surrogate for HPV infection and is an independent favorable prognostic factor for survival. PD-L1 status may help guide therapy in the recurrent, unresectable, and metastatic settings.
Staging
The TNM classification and staging is specific to each site of disease and HPV status. However, in general, stage I to II disease indicates the absence of lymph node involvement. Stage III tumors are larger (defined as gt;4 cm for most sites) or have isolated or regional lymph node involvement. Unlike most other malignancies, stage IVA and IVB HNSCC are locally advanced tumors and only stage IVC tumors are defined by distant metastases.
TREATMENT
• Stage I-II (local): Patients may be treated with either surgery or definitive radiation with a 70%-90% long-term survival.8
• Stage III-IVB (locally advanced): Treatment options include surgical resection followed by adjuvant radiation with or without chemotherapy; concurrent chemoradiotherapy; induction chemotherapy followed by concurrent chemotherapy and radiation; or radiation alone. Chemoradiation or induction chemotherapy followed by radiation can potentially spare patients from undergoing a total laryngectomy and improve quality of life. Surgery is most commonly used for tumors of the oral cavity. Nodal neck dissection is an important part of surgical management. Radical neck dissection refers to surgical removal of lymph nodes from all five neck stations unilaterally, along with excision of the internal jugular vein, spinal accessory nerve, and sternocleidomastoid. Modified neck dissections spare some of these structures. Cisplatin is the chemotherapy agent most commonly used in combination with radiation for definitive treatment.
• Stage IVC (metastatic): Treatment options include chemotherapy, ICIs, or combination chemoimmunotherapy. Cisplatin is often combined with 5-fluorouracil (5-FU) or a taxane (paclitaxel or docetaxel). The role of pembrolizumab depends on the clinical setting and composite or combined PD- L1 score (CPS). Patients with CPS gt;20 and without rapidly progressing tumors may be treated with pembrolizumab alone, whereas those with CPS between 1 and 20 may be treated with pembrolizumab alone or in combination with platinum-based chemotherapy. Patients with CPS lt;1 may be treated with chemotherapy alone or in combination with cetuximab, an EGFR mAb.9