Summary
Pharyngeal cancers include malignant tumors, most commonly squamous cell carcinomas, of the nasopharynx, oropharynx, hypopharynx, or tonsils. Alcohol and tobacco use are the two most important risk factors for pharyngeal cancer. Other risk factors include certain viral infections (e.g., HPV in the oropharynx), poor oral hygiene, and workplace-related exposures (e.g., radiation). Clinical presentation varies based on the location of the tumor. Symptoms may include a growing cervical lump, persistent sore throat, dysphagia, and/or a change in voice. Diagnosis is confirmed with tissue biopsy, and staging is determined via imaging modalities such as CT or MRI. Treatment usually requires surgery, radiation therapy, and/or chemotherapy. Posttreatment monitoring is indicated for all patients with advanced cancer because of high recurrence rates.
Epidemiology
- Oropharyngeal cancer [1]
-
Nasopharyngeal cancer [2]
- Nasopharyngeal cancer is rare in the United States (< 1:100,000)
- Most common in patients of Mediterranean and southern Chinese (including Hong Kong) descent
- About 85% of all new cases are diagnosed in Asia. [3]
-
Hypopharyngeal cancer: uncommon condition [4]
- Incidence: 2,500 new cases in the US annually
- Peak age: between 50–60 years of age
Epidemiological data refers to the US, unless otherwise specified.
Etiology
-
Risk factors
- HPV infection
- Tobacco product use (including smokeless products)
- Alcohol use
- Nitrosamine consumption from salted/preserved foods
- Obesity
- Chronic iron deficiency
- Long-term consumption of carcinogenic food (e.g., aflatoxin)
- Exposure to radiation
-
Associations
- Nasopharyngeal carcinoma: EBV infection
- Oropharyngeal carcinoma and tonsillar cancer: human papillomavirus infection
- Diseases causing atrophy of the mucosa (e.g., Plummer-Vinson syndrome)
The combined use of alcohol and tobacco products compounds the risk of either. [5]
Clinical features
Pharyngeal cancer is usually asymptomatic for a long time . Often, the first manifestations are swollen cervical lymph nodes.
Oropharyngeal cancer and hypopharyngeal cancer
- Common early symptom: local lymph node metastases causing enlarged cervical lymph nodes
- Foreign body sensation, dysphagia, sore throat
- Muffled voice
- Severe ear pain
Nasopharyngeal cancer [2]
- Painless lymphadenopathy
- Unilateral nasal discharge, nosebleeds, impaired nasal breathing (due to obstruction)
- Obstruction of the Eustachian tube: recurrent otitis media (may be accompanied by effusion); conductive hearing loss, tinnitus
- Infiltration of caudal cranial nerves → Garcin syndrome
- Sore throat
- Headache
Tonsillar cancer
- Persistent sore throat, globus sensation, dysphagia
- Unilateral otalgia
- Unilaterally indurated, ulcerated, and/or enlarged tonsil
- Enlarged cervical lymph nodes
- Halitosis
- Blood-tinged sputum
- Trismus (sign of local invasion)
Metastatic disease
- See “Clinical features of oral cavity cancer” for details.
References: [6]
Diagnosis
Initial workup [5]
-
Clinical evaluation
- Rule out features consistent with deep neck infection, e.g., rapid onset, features of tonsillopharyngitis.
- Initiate a prompt referral to otolaryngology for patients with suspected pharyngeal cancer.
- Endoscopy with biopsy (typically FNA): for direct visualization of the pharynx and larynx
-
Histopathologic evaluation
- Confirms the diagnosis and the type, grade, and extent of the tumor
- Pleomorphic cells and mitotic figures demonstrate a neoplastic change from dysplasia to SCC. [7]
Further workup [5]
-
HPV testing
- FNA samples from the oropharynx are tested for high-risk HPV mRNA.
- Overexpression of p16 suggests an HPV-associated malignancy. [5][8]
-
Imaging
- Staging imaging if malignancy is confirmed
- MRI and/or CT of the neck with IV contrast: to assess tumor anatomy
- FDG-PET/CT scan: to assess for distant metastasis
Treatment
General principles [5][9]
- Individualize treatment in consultation with a multidisciplinary tumor board.
- Treatment is based on patient factors such as TNM stage, comorbidities, performance status, and goals of care.
- Options include radiation therapy, chemotherapy, and/or surgical resection and reconstruction.
- Following treatment, monitor for recurrence at regular intervals.
Surgery or radiation therapy alone can be curative in patients with small nonmetastatic tumors.
A patient with pharyngeal carcinoma is at risk for airway obstruction. See “Airway management in head and neck cancer” before procedural sedation and/or airway manipulation.
Locoregional disease [1][2][4]
-
Oropharyngeal cancer [1]
- Radiation therapy or surgery for small tumors without nodal involvement
- Surgery and adjuvant radiotherapy, with or without concurrent chemotherapy for locally advanced disease [1]
-
Nasopharyngeal cancer [2]
- High-dose radiation therapy with chemotherapy
- Surgery (neck dissection) for persistent or recurrent lymph nodes in patients with controlled primary tumor
-
Hypopharyngeal cancer [4]
- Surgical resection (laryngopharyngectomy and neck dissection) with adjuvant radiation therapy
- Additional chemotherapy for locally advanced disease
Treatment aims to apply the most effective curative method while ensuring the best possible preservation of function, i.e., voice preservation, airway mechanics, and swallowing. [7]
Metastatic or recurrent disease [7][9]
- Resectable localized disease: surgical resection ± adjuvant therapy (chemotherapy and/or radiation therapy)
- Unresectable localized disease: radiation therapy or chemoradiotherapy
-
Metastatic disease
- Curative intent: platinum-based chemotherapy, and/or cetuximab or cancer immunotherapy (e.g., nivolumab, pembrolizumab) [7]
- Palliative intent: palliative chemotherapy and/or radiation therapy
Posttreatment monitoring [10]
- All patients should undergo regular history, physical, and endoscopy to assess for recurrence.
- Order posttreatment imaging for selected patients.
- T3/T4 or N2/N3 disease: baseline imaging of the primary site with FDG-PET/CT scan within 6 months of treatment [10][11]
- Any stage with signs of recurrent disease: repeat imaging
- Assess thyroid function (e.g., TSH levels) every 6–12 months after radiation therapy. [10]
For patients who received radiation therapy, measure TSH every 6–12 months to assess for thyroid complications. [10]
Prognosis
-
5-year survival rates after initial diagnosis vary by disease stage. [12]
- Overall (all stages): ∼ 69%
- Localized disease (no spread): ∼ 88%
- Regional disease (spread to lymph nodes): ∼ 70%
- Distant disease (metastatic): ∼ 38%
- 50–60% of patients with stage III or stage IV experience recurrence despite treatment. [5]
Prognosis of HPV-associated pharyngeal cancer is better than that of HPV-negative cancer. [10]