Oropharyngeal Squamous Cell Carcinoma

Oropharyngeal squamous cell carcinoma is a type of cancer that develops in the middle part of the throat, affecting areas like the tonsils, base of the tongue, and soft palate. While cases are rising, especially in younger people, treatment options are improving and cure rates are increasing, particularly for cancers linked to human papillomavirus (HPV).

Table of contents

• What is oropharyngeal squamous cell carcinoma?
• Location and anatomy
• What causes this cancer?
• Who is at risk?
• How common is it?
• Signs and symptoms
• How is it diagnosed?
• Treatment options
• Outlook and survival
• Can it be prevented?
• Living with oropharyngeal cancer

What is oropharyngeal squamous cell carcinoma?

Oropharyngeal squamous cell carcinoma is a cancer that develops in the middle part of your throat, called the oropharynx (the area in your throat behind your mouth). It is commonly known as throat cancer or tonsil cancer^[1].

More than 90% of oropharyngeal cancers are squamous cell carcinomas, meaning they start in the thin, flat cells that line the inside of the oropharynx^[1][3]. These cells normally protect the throat, but sometimes they can change and grow out of control, forming tumors.

Location and anatomy

The pharynx is a hollow tube in the neck about 5 inches long that is part of both your digestive and respiratory systems^[4]. It is divided into three main parts. The nasopharynx is the upper part behind the nose. The oropharynx is the middle part. The hypopharynx is the lower part near the voice box.

The oropharynx includes several important structures^[1][4]:

• Base and back one-third of the tongue
• Tonsils
• Soft palate (the soft back part of the roof of the mouth)
• Side and back walls of the throat

When you breathe or swallow, the pharynx acts as a passageway for air to reach the lungs and for food to reach the stomach^[4]. The oropharynx makes saliva, keeps your mouth and throat moist, and helps you digest food^[2].

What causes this cancer?

There are two main types of oropharyngeal cancer based on their causes: HPV-associated and non-HPV-associated^[1][3].

HPV-associated oropharyngeal cancer occurs in people who have been infected with human papillomavirus. HPV is a common sexually transmitted virus. Among the many types of HPV, HPV type 16 is the most common type found in oropharyngeal cancers, accounting for about 90% of HPV-positive cases^[1][3]. In Europe and North America, HPV infection accounts for about 70 to 80% of oropharyngeal cancers^[3].

HPV makes proteins that interfere with genes that normally manage how cells in your mouth and throat grow. When these genes stop working properly, cells can grow uncontrollably and form tumors^[2]. Oral sex and open-mouthed kissing are the most common ways people get oral HPV infection^[1].

Non-HPV-associated oropharyngeal cancer is mainly caused by tobacco smoking and alcohol use^[1][3]. Tobacco use, including smoking cigarettes and cigars and using chewing tobacco, damages the cells that line your throat. When cells have to divide more often to replace damaged cells, they are more likely to make mistakes in copying their DNA, which increases the chance they will become cancerous^[2].

Drinking beverages containing alcohol may also damage cells in your throat, affecting their ability to repair DNA^[2].

Who is at risk?

The most significant risk factor for developing oropharyngeal cancer is being infected with HPV, particularly HPV type 16. The risk of developing oropharyngeal cancer is 16 times higher in HPV-positive patients^[3]. The number of sex partners and frequency of oral sex are important risk factors^[3].

Other major risk factors include^[1][2][3][4]:

• A history of smoking cigarettes for more than 10 pack years and other tobacco use
• Heavy consumption of beverages that contain alcohol
• A personal history of head and neck cancer
• History of radiation therapy to your head and neck
• Chewing betel quid, a stimulant commonly used in some cultures

People who smoke more than 1.5 packs per day have about a 3-fold increased risk of cancer, and those who drink 4 or more drinks per day have about a 7-fold increased risk. People who both drink and smoke heavily have 30 times the risk of developing oropharyngeal cancer^[3].

Other less common risk factors include a diet low in vegetables and fruits, poor nutrition, marijuana smoking, asbestos exposure, and certain genetic mutations such as P53 mutation and CDKN2A (p16) mutations^[1].

How common is it?

Oropharyngeal cancer is a relatively rare kind of cancer. According to the American Cancer Society, about 53,000 people in the U.S. develop oropharyngeal cancer each year^[2]. Oropharyngeal cancer is the sixth most common cancer worldwide^[1].

In the United States in 2024, there were an expected more than 21,000 new cases of oropharyngeal cancer^[3]. The male to female ratio is more than 2 to 1^[3]. Men are almost three times as likely as women to have oropharyngeal cancer^[11].

Although the incidence of oropharyngeal cancer is increasing, its cure rates are also improving^[3]. The increasing incidence is attributed to the rise in HPV-associated cases^[11]. As HPV infection has emerged as a more prevalent cause, patients have become younger^[3]. 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^[3].

Signs and symptoms

Oropharyngeal cancer symptoms may resemble symptoms of other less serious medical issues, such as common upper respiratory infections. Because symptoms often mimic those of common infections, it often takes many months before patients are referred to a specialist^[3].

Common oropharyngeal cancer symptoms include^[2][3][12]:

• A sore throat that doesn’t go away
• Pain or difficulty with swallowing (dysphagia, meaning trouble swallowing)
• Painful swallowing (odynophagia)
• Trouble opening up your mouth fully (trismus) or moving your tongue
• Unexplained weight loss
• Voice changes that don’t go away
• Ear pain that doesn’t go away
• A lump in the back of your throat or mouth
• A lump in your neck (often cystic)
• Coughing up blood
• A white patch on your tongue or lining of your mouth that doesn’t go away

A neck mass, often cystic, is a common presenting symptom of patients with oropharyngeal cancer^[3].

How is it diagnosed?

A healthcare provider will ask about your symptoms and your medical history, including whether you smoke, use tobacco products, drink alcohol, or have been exposed to HPV^[2].

Tests that examine the mouth and throat are used to diagnose and stage oropharyngeal cancer^[4]. All patients should undergo a direct laryngoscopy (a procedure to look inside the voice box) and biopsy before starting treatment to evaluate the primary lesion and to look for second primary lesions^[3].

A biopsy (removing a small sample of tissue for examination under a microscope) is the definitive way to diagnose oropharyngeal cancer. Diagnosis is made based on biopsy results of the affected tissue^[1].

For patients with confirmed cancer, imaging tests are used for staging to determine how far the cancer has spread. Patients with confirmed cancer typically have^[3]:

• Neck CT (computed tomography) scan with contrast
• PET (positron emission tomography) scan of the neck and chest

HPV DNA testing, determined by a laboratory technique called polymerase chain reaction, is used to confirm HPV infection. A test called immunohistochemical staining for p16 (an intracellular protein present in most HPV-positive cancers) is commonly used as an alternative way to determine HPV association^[3].

The staging of HPV-associated oropharyngeal cancer is different from non-HPV-associated cancer because HPV-positive tumors have different characteristics and a better outlook^[3].

Treatment options

Treatment for oropharyngeal cancer involves surgery, radiotherapy, chemotherapy, or a combination of these therapies^[1][3]. A team of doctors and other professionals, called a multidisciplinary team, will discuss the best treatment and care for you^[14].

Your treatment team may include^[14]:

• Specialist head and neck surgeons (including oral and maxillofacial surgeons, ear, nose and throat surgeons, and plastic surgeons)
• Cancer specialists in radiotherapy and drug treatment (oncologists)
• Restorative dental specialist
• Head and neck clinical nurse specialist
• Dietitian
• Speech and language therapist

Treatment is with radiation, chemotherapy, or both, but primary surgery has begun to be used more often^[3]. The treatment choice depends on the stage of the cancer, whether it is HPV-positive or HPV-negative, and the patient’s overall health.

For early stage cancers (Stage I and II), treatment options may include surgery alone or radiation therapy alone. For more advanced cancers (Stage III and IV), treatment typically involves a combination of radiation therapy and chemotherapy, known as chemoradiotherapy, or surgery followed by radiation therapy^[4].

Recent research has shown that proton beam therapy (a specialized type of radiation treatment) has emerged as a standard of care for oropharyngeal cancer, as it may cause fewer side effects compared to traditional radiation while maintaining high cure rates^[13].

Sometimes, a person may need a feeding tube during or after treatment to help maintain nutrition while recovering^[14].

Outlook and survival

The outlook for oropharyngeal cancer has improved significantly in recent years. Cure rates are high for HPV-driven oropharynx cancer, particularly when the tumors are small and occur in non-smokers^[12].

The survival rate is much higher in HPV-positive patients compared to HPV-negative patients^[3]. Several factors affect outlook and treatment options^[4]:

• Whether the cancer is HPV-associated or not
• The stage of the cancer
• Whether the patient smokes tobacco
• The patient’s overall health

The chance that oropharyngeal cancer will come back is greatest within 2 to 3 years after treatment, so close follow-up is needed during this time^[24]. Smoking and drinking alcohol heavily after treatment can increase the risk of the cancer coming back or of developing a second primary cancer^[24].

Can it be prevented?

Although you may not be able to avoid oropharyngeal cancer completely, you may reduce your risk of developing it by taking several steps^[2]:

• Protecting yourself against HPV through vaccination. Emerging evidence suggests that vaccination against HPV can help prevent oral cancers. Vaccination can be started at age 9, and is recommended through age 26 for those who were not vaccinated when they were younger^[25].
• Not smoking cigarettes or using other forms of tobacco
• Drinking beverages containing alcohol in moderation or not at all

Risk factors for oropharyngeal cancer do not directly cause cancer. Instead, they increase the chance of DNA damage in cells that may lead to oropharyngeal cancer. Learning about risk factors can help you make choices that might prevent or lower your risk of getting it^[4].

Living with oropharyngeal cancer

Treatment for oropharyngeal cancer can affect many aspects of daily life. Patients may experience difficulties with eating, drinking, speaking, and swallowing during and after treatment.

Eating and swallowing difficulties are common challenges. Mouth and oropharyngeal cancer and its treatment can affect your eating and drinking. You might have difficulties with swallowing, taste changes, weight loss, and a dry mouth^[21]. A dietitian can help if you are finding it difficult to eat and drink enough, and may suggest soft or pureed foods. A speech and language therapist can help if you are having problems with swallowing^[14][21].

Radiotherapy to your head or neck can make your throat very sore, making eating and drinking difficult or painful within the first few weeks of treatment. Your doctor will give you strong painkillers to help with this^[21].

Dry mouth (xerostomia) is a common side effect of radiation therapy to the head and neck. It can make eating and talking very uncomfortable and can last for several months, though some people find the dryness is permanent. Your doctor can prescribe artificial saliva or medications to stimulate your salivary glands. Carrying a bottle of water to take small sips can help^[21].

Taste changes are common during treatment. Radiotherapy and some cancer drugs can affect your taste buds. Some people say their food has a metallic, bitter, or salty taste, while others say that all foods taste the same. Taste changes are often temporary but can sometimes be permanent^[21].

Even if you are not eating, it is very important to keep your mouth and teeth clean. This helps to stop infection and could help you feel better^[21]. A restorative dentist may assess your teeth before treatment and recommend that you have some teeth removed if they are decaying or loose^[14].

Follow-up care is an important part of cancer care. Follow-up visits are usually scheduled every 1 to 3 months for the first year, every 2 to 4 months for the second year, every 4 to 6 months for the third to fifth years, and yearly after 5 years^[24]. During follow-up visits, your healthcare team will check for any signs that the cancer has come back and help manage any long-term side effects of treatment.