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) 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.
(See also Overview of Head and Neck Tumors.)
In the United States in 2024, there were an expected > 21,000 new cases of oropharyngeal cancer (1). Although the incidence of oropharyngeal cancer is increasing, its cure rates are also improving. The male:female ratio is > 2:1 (2).
HPV type 16 accounts for the majority of HPV-positive oropharyngeal cancers (3), and patients have become younger as HPV infection has emerged as a more prevalent etiology (4). 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 males, with a median age of 61 years. 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 references
1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024 [published correction appears in CA Cancer J Clin. 2024 Mar-Apr;74(2):203. doi: 10.3322/caac.21830]. CA Cancer J Clin 2024;74(1):12-49. doi:10.3322/caac.21820
2. American Cancer Society medical and editorial content team. Oral Cavity (Mouth) and Oropharyngeal (Throat) Cancer: Survival rates for oral cavity and oropharyngeal cancer. Updated March 1, 2023. Accessed July 30, 2024.
3. Lu Y, Clifford GM, Fairley CK, et al. Human papillomavirus and p16INK4a in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis. Int J Cancer 154(5):830–841, 2024. doi:10.1002/ijc.34763
4. Gayar OH, Ruterbusch JJ, Elshaikh M, et al. Oropharyngeal carcinoma in young adults: an alarming national trend. Otolaryngol Head Neck Surg 2014;150(4):594-601. doi:10.1177/0194599813519738
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 Pathologic Staging of HPV-Associated Oropharyngeal Cancer and Pathologic Staging of Non-HPV-Associated Oropharyngeal Cancer.)
Pathologic Staging of HPV-Associated Oropharyngeal Cancer*
Stage | Tumor (Maximum Penetration)† | Regional Lymph Node Metastasis‡ | Distant Metastasis§ |
|---|---|---|---|
I | T0-2 | pN0-1 | M0 |
II | T0-2 | pN2 | M0 |
T3-4 | pN0-1 | M0 | |
III | T0-4 | pN2 | M0 |
IV | Any T | Any pN | M1 |
* HPV association as indicated by p16 positivity | |||
Head and neck cancers are staged according to size and site of the primary tumor (T), number and size of metastases to the cervical lymph nodes (N), and evidence of distant metastases (M). † T0 = no primary tumor identified; T1 = tumor ≤ 2 cm in greatest dimension; T2 = tumor > 2 cm but ≤ 4 cm; T3 = tumor > 4 cm or invading the lingual surface of the epiglottis; T4 = tumor invading the larynx, extrinsic tongue muscles, medial pterygoid, the hard palate, mandible, or beyond | |||
‡ pN = Pathologic N; pN0 = none; pN1 = metastasis in ≤ 4 lymph nodes; pN2 = metastasis to > 4 lymph nodes. | |||
§ M0 = none; M1 = present | |||
Data from Amin MB, Edge S, Greene F, Byrd DR, et al: American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition. New York, Springer, 2017; AJCC Cancer Staging Form Supplement, 2018. | |||
Pathologic Staging of Non-HPV–Associated Oropharyngeal Cancer*
Stage | Tumor (Maximum Penetration)† | Regional Lymph Node Metastasis‡ | Distant Metastasis§ |
|---|---|---|---|
I | T1 | pN0 | M0 |
II | T2 | pN0 | M0 |
III | T3 | pN0 | M0 |
T1-3 | pN1 | M0 | |
IVA | T4a | pN0-1 | M0 |
T1-4a | pN2 | M0 | |
IVB | T4b | Any pN | M0 |
Any T | pN3 | M0 | |
IVC | Any T | Any pN | M1 |
* HPV association as indicated by p16 positivity. | |||
† Definition of Primary Tumor (T) in Oropharynx (p16-) | |||
Tis | Carcinoma in situ | ||
T1 | Tumor ≤ 2 cm in greatest dimension | ||
T2 | Tumor > 2 cm but ≤ 4 cm | ||
T3 | Tumor > 4 cm OR extension to lingual surface of epiglottis | ||
T4a | Moderately advanced local disease; tumor invades the larynx, extrinsic tongue muscles, medial pterygoid, hard palate, or mandible (Note: mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx) | ||
T4b | Very advanced local disease; tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery | ||
† Definition of Primary Tumor (T) in Hypopharynx | |||
Tis | Carcinoma in situ | ||
T1 | Tumor limited to one subsite of hypopharynx and/or ≤ 2 cm | ||
T2 | Tumor invades more than one subsite of hypopharynx or an adjacent site, OR is > 2 cm but ≤ 4 cm without fixation of hemilarynx | ||
T3 | Tumor > 4 cm OR with fixation of hemilarynx or extension to esophagus | ||
T4a | Moderately advanced local disease; tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue (including prelaryngeal strap muscles and subcutaneous fat) | ||
T4b | Very advanced local disease; tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures | ||
‡ Definition of Pathologic N (pN) — Oropharynx (p16-) and Hypopharynx | |||
N0 | No regional lymph node metastasis | ||
N1 | Metastasis to one ipsilateral lymph node, ≤ 3 cm, no extranodal extension | ||
N2 | Metastasis in one ipsilateral node ≤ 3 cm with extranodal extension OR > 3 cm but ≤ 6 cm and no extranodal extension; OR in multiple ipsilateral nodes, < 6 cm and no extranodal extension; OR in bilateral or contralateral lymph nodes ≤ 6 cm and no extranodal extension | ||
N3 | Metastasis in a lymph node > 6 cm and no extranodal extension; OR in one ipsilateral node > 3 cm with extranodal extension; OR in multiple ipsilateral, contralateral, or bilateral nodes, any with extranodal extension | ||
§ Definition of Distant Metastasis (M) — Oropharynx (p16-) and Hypopharynx | |||
M0 | No distant metastasis | ||
M1 | Distant metastasis | ||
Data from Amin MB, Edge S, Greene F, Byrd DR, et al: American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition. New York, Springer, 2017; AJCC Cancer Staging Form Supplement, 2018. | |||
Treatment of Oropharyngeal Squamous Cell Carcinoma
Surgery, often transoral laser microsurgery
Radiation therapy, with or without chemotherapy
Surgery is used as the primary treatment of oropharyngeal cancer (1) 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 a 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. When TORS is used on patients with more advanced tumors, postoperative radiation or chemotherapy combined with radiation (chemoradiation) is often done.
Radiation therapy, sometimes combined with chemotherapy, 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.
Treatment reference
1. National Cancer Institute: Oropharyngeal Cancer Treatment (PDQ®)–Health Professional Version. Updated March 2024.
Prognosis for Oropharyngeal Squamous Cell Carcinoma
The overall 5-year survival rate in patients with oropharyngeal cancer is about 52% (1). However, prognosis varies with the cause. Patients who are HPV-positive have a 5-year disease free survival of > 80, whereas HPV-negative patients have a 5-year disease free survival of < 50% (2). 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.
Prognosis references
1. American Cancer Society medical and editorial content team: Oral Cavity (Mouth) and Oropharyngeal (Throat) Cancer: Survival rates for oral cavity and oropharyngeal cancer. Updated March 1, 2023. Accessed July 30, 2024.
2. De Felice F, Humbert-Vidan L, Lei M, King A, Guerrero Urbano T: Analyzing oropharyngeal cancer survival outcomes: a decision tree approach. Br J Radiol 2020;93(1111):20190464. doi:10.1259/bjr.20190464
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.
