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Oropharyngeal Squamous Cell Carcinoma


Bradley A. Schiff

, MD, Montefiore Medical Center, The University Hospital of Albert Einstein College of Medicine

Reviewed/Revised Dec 2022
Topic Resources

Oropharyngeal cancer refers to cancer of the tonsil, base and posterior one third of the tongue, soft palate, and posterior and lateral pharyngeal walls. Squamous cell carcinoma comprises over 95% of oropharyngeal cancers. Tobacco and alcohol are major risk factors, but human papillomavirus (HPV) now causes most of these tumors. Symptoms include sore throat and painful and/or difficult swallowing. Treatment is with radiation, chemotherapy, or both, but primary surgery has begun to be used more often. Survival rate is much higher in HPV-positive patients.

In the US in 2020, there were an expected > 18,000 new cases of oropharyngeal cancer (1 General reference Oropharyngeal cancer refers to cancer of the tonsil, base and posterior one third of the tongue, soft palate, and posterior and lateral pharyngeal walls. Squamous cell carcinoma comprises over... read more ). Although the incidence of oropharyngeal cancer is increasing, its cure rates are also improving. The male:female ratio is > 2.7:1.

HPV type 16 causes 60% of oropharyngeal cancers, and patients have become younger (median age 57 years, and bimodal peaks at 30 years and 55 years) as HPV infection Human Papillomavirus (HPV) Infection Human papillomavirus (HPV) infects epithelial cells. Most of the > 100 subtypes infect cutaneous epithelium and cause skin warts; some types infect mucosal epithelium and cause anogenital warts... read more Human Papillomavirus (HPV) Infection has emerged as an etiology. The number of sex partners and frequency of oral sex are important risk factors. The risk of developing oropharyngeal cancer is 16 times higher in HPV-positive patients. In Europe and North America, HPV infection accounts for about 70 to 80% of oropharyngeal cancers.

As with most head and neck cancers, non-HPV related oropharyngeal cancer is more common among older men, with a median age of 61. Tobacco and alcohol remain important risk factors for oropharyngeal cancer. Patients who smoke more than 1.5 packs/day have about a 3-fold increased risk of cancer, and patients who drink 4 or more drinks/day have about a 7-fold increased risk. People who both drink and smoke heavily have 30 times the risk of developing oropharyngeal cancer.

General reference

Symptoms and Signs of Oropharyngeal Squamous Cell Carcinoma

Oropharyngeal cancer symptoms vary slightly depending on the subsite, but typically patients present with sore throat, dysphagia, odynophagia, dysarthria, and otalgia. A neck mass, often cystic, is a common presenting symptom of patients with oropharyngeal cancer. Because the symptoms of oropharyngeal cancer mimic those of common upper respiratory infections, it often takes many months before patients are referred to a specialist.

Diagnosis of Oropharyngeal Squamous Cell Carcinoma

  • Laryngoscopy

  • Operative endoscopy and biopsy

  • Imaging tests for staging

All patients should undergo a direct laryngoscopy and biopsy before starting treatment to evaluate the primary lesion and to look for second primary lesions. Patients with confirmed carcinoma typically have neck CT with contrast, and most clinicians also do PET of the neck and chest.

HPV DNA positivity, determined by polymerase chain reaction, is diagnostic of HPV. Immunohistochemical staining for p16 (an intracellular protein present in most HPV-positive cancers but also in few HPV-negative cancers) is a commonly used surrogate to determine HPV association.

The staging criteria of HPV-associated oropharyngeal cancer correspond to the frequent lymph node involvement and better prognosis of these tumors versus HPV-negative tumors. (See tables and .)


Prognosis for Oropharyngeal Squamous Cell Carcinoma

The overall 5-year survival rate in patients with oropharyngeal cancer is about 60%. However, prognosis varies with the cause. Patients who are HPV-positive have a 5-year survival of > 75% (and a 3-year survival of almost 90%), whereas HPV-negative patients have a 5-year survival of < 50%. The higher survival with HPV-positive cancer is due to a favorable tumor biology and a younger, healthier patient population. High expression of p16 appears to improve prognosis for both HPV-positive and HPV-negative oropharyngeal tumors.

Treatment of Oropharyngeal Squamous Cell Carcinoma

  • Surgery, increasingly, transoral laser microsurgery

  • Radiation therapy, with or without chemotherapy

Surgery is used as the primary treatment of oropharyngeal cancer, more than it was in the past. Transoral laser microsurgery (TLM) is increasingly being used to resect tumors of the tonsil and base of tongue endoscopically, avoiding the morbidity of open surgery. Transoral robotic surgery (TORS) is an increasingly popular means of treating select oropharyngeal lesions. In TORS, a surgical robot with multiple adaptable arms is controlled by a surgeon at a console. The articulating arms of the robot and an endoscopic camera are inserted through the patient's mouth (which is held open by a retractor). The robotic procedure provides better visualization of structures and causes less surgical morbidity compared to open surgery. However, the indications for using TORS are not yet well defined. When TORS is used on patients with more advanced tumors, postoperative radiation or chemoradiation is often done.

Radiation therapy, sometimes combined with chemotherapy (chemoradiation), can be used as primary therapy or postoperatively. Traditionally, radiation has been used for early-stage cancers and chemoradiation has been used for advanced cancers. Intensity-modulated radiation therapy (IMRT) has increasingly been used as a way to spare surrounding tissue and decrease long-term adverse effects.

Because the oropharynx is rich in lymphatics, cervical lymph node metastasis is common and must be considered in all patients with oropharyngeal cancer. If a cervical lymph node metastasis does not resolve after radiation to the neck or chemoradiation, post-treatment neck dissection is warranted.

Treatment of oropharyngeal carcinoma is the same regardless of the HPV status of the tumor. Deintensified treatment of HPV-associated tumors is being studied to see if less harmful treatments can achieve successful disease management.

Key Points

  • Most cases of oropharyngeal cancer are caused by human papillomavirus (HPV) infection.

  • Symptoms of oropharyngeal cancer depend on the location of the tumor; a neck mass is a common finding.

  • Diagnose oropharyngeal cancer with laryngoscopy, operative endoscopy, and imaging studies for staging.

  • Treat oropharyngeal cancer with transoral laser microsurgery or transoral robotic surgery when possible as alternatives to open surgery.

  • Use radiation therapy, sometimes combined with chemotherapy for advanced cancers, as primary treatment or postoperatively.

More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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