Oropharyngeal Cancer

What oropharyngeal cancer is

The pharynx (throat) has three parts. The oropharynx is the middle part, which you can partly see when you open your mouth wide and say "ah". Nearly all oropharyngeal cancers are squamous cell carcinomas, which start in the flat cells lining the throat.

Doctors now treat oropharyngeal cancer as two different diseases:

Symptoms

• A lump in the neck that does not go away, often painless and sometimes cystic. In HPV-related cancer this is frequently the only symptom, because the cancer has spread to a lymph node while the primary tumor in the tonsil or tongue base is small.
• A sore throat that lasts more than 3 weeks
• Pain in one ear (referred pain from the throat) with a normal-looking ear
• One tonsil larger than the other
• Difficulty swallowing or pain on swallowing
• A feeling of something stuck in the throat
• Voice changes, such as a muffled "hot potato" voice
• Coughing up blood
• Unexplained weight loss
• Trouble opening the mouth fully (trismus) in advanced cases

Many of these symptoms are common with infections. What matters is that they persist beyond 2 to 3 weeks, are on one side, or come with a neck lump.

Causes and risk factors

HPV

HPV is a very common sexually transmitted virus. Most oral HPV infections clear by themselves within 1 to 2 years. In a small number of people, high-risk HPV persists in the deep folds (crypts) of the tonsils and tongue base and, over many years, can cause cancer. Risk rises with more oral sex partners and earlier age at first sexual activity. HPV-related oropharyngeal cancer is now the most common HPV-associated cancer in the US, more common than cervical cancer, and it occurs mostly in men.

Studies of long-term partners of people with HPV-positive throat cancer have not found raised rates of oral HPV, so partners do not usually need testing or treatment. There is no approved oral HPV test for screening.

Tobacco and alcohol

Smoking cigarettes, cigars or pipes, and chewing tobacco, raise the risk substantially. Heavy drinking adds to this, and the combination multiplies the risk.

Other factors

• Older age and male sex
• A weakened immune system, including HIV
• Betel quid or areca nut chewing
• Diets low in fruit and vegetables

Diagnosis

1. Examination of the mouth, throat and neck.
2. Flexible nasopharyngolaryngoscopy: a thin camera passed through the nose to view the tongue base and throat.
3. Fine-needle aspiration of a neck lump, often under ultrasound.
4. Biopsy of the tumor, sometimes under general anesthesia, which may include removing a tonsil.
5. HPV testing of the tumor, usually with a p16 stain, often confirmed with HPV DNA or RNA testing.
6. Imaging: CT or MRI of the neck and a CT of the chest, or a PET-CT scan, to see how far the cancer has spread.

Staging uses the tumor size, lymph node involvement and spread elsewhere (TNM). HPV-positive and HPV-negative cancers are staged differently, because HPV-positive cancers with large neck nodes still have a good outlook.

Treatment

A head and neck cancer team, including surgeons, radiation and medical oncologists, speech-language pathologists and dietitians, plans treatment.

Early-stage cancer

• Transoral surgery: surgeons remove the tumor through the mouth, often with robotic tools (TORS) or a laser, plus removal of neck lymph nodes (neck dissection). Radiation may follow.
• Radiation therapy alone is an alternative, especially for small tumors.

Locally advanced cancer

• Chemoradiation: radiation therapy over about 6 to 7 weeks combined with chemotherapy, usually cisplatin.
• Surgery followed by radiation, with or without chemotherapy, depending on what is found.

Clinical trials are testing lower doses of treatment for HPV-positive cancer to reduce long-term side effects while keeping high cure rates.

Recurrent or metastatic cancer

Immunotherapy with checkpoint inhibitors such as pembrolizumab or nivolumab, alone or with chemotherapy, is standard. Targeted drugs such as cetuximab are another option.

Side effects and recovery

Treatment can affect swallowing, speech, saliva and taste. Common effects include:

• dry mouth from damage to salivary glands
• painful mouth and throat during radiation, and difficulty swallowing; some people need a temporary feeding tube
• changes in taste
• neck stiffness and swelling (lymphedema)
• an underactive thyroid years later
• tooth decay and, rarely, jaw bone damage after radiation (osteoradionecrosis), which is why a dental checkup is done before treatment

Swallowing exercises with a speech-language pathologist before and during treatment help preserve function.

Outlook

Survival is high for HPV-positive oropharyngeal cancer: most people with early or locally advanced disease are cured, with 5-year survival rates commonly reported above 80%. HPV-negative cancers, especially in people who continue to smoke, have lower survival rates. Stopping smoking improves treatment results and lowers the risk of a second cancer. Follow-up visits continue for at least 5 years.

Prevention

• HPV vaccination prevents infection with the HPV types that cause most oropharyngeal cancers. It is routinely recommended at ages 11 to 12, with catch-up through age 26, and may be offered up to age 45 after discussion with a doctor.
• Do not smoke or chew tobacco, and limit alcohol.
• See a doctor or dentist about throat symptoms or neck lumps that last more than 2 to 3 weeks.

Related cancers are covered under head and neck cancer, tonsil cancer and oral cancer.

Frequently asked questions

What is the first sign of oropharyngeal cancer?

Often a painless lump in the side of the neck, which is a lymph node containing cancer, especially in HPV-related cases. Other early signs include a sore throat, ear pain or swallowing pain on one side lasting more than 3 weeks, or one tonsil that is larger than the other.

How do you get HPV-related throat cancer?

Oral HPV is spread mainly through oral sex and deep kissing. Most infections clear on their own. In a small minority, high-risk HPV, usually type 16, persists in the tonsils or tongue base and causes cancer many years later, often 10 to 30 years after infection.

What is the survival rate for oropharyngeal cancer?

It depends on HPV status and stage. HPV-positive oropharyngeal cancer has a high cure rate, with 5-year survival commonly above 80% even when lymph nodes are involved. HPV-negative cancer, usually linked to smoking, has lower survival. Your oncologist can give figures specific to your stage.

Is oropharyngeal cancer the same as throat cancer?

It is one type of throat cancer. "Throat cancer" can mean cancer of the nasopharynx, oropharynx, hypopharynx or larynx (voice box). Oropharyngeal cancer specifically affects the tonsils, back of the tongue, soft palate and middle throat walls.

Does the HPV vaccine prevent throat cancer?

The HPV vaccine prevents infection with HPV 16 and 18 and other high-risk types, which cause most HPV-related oropharyngeal cancers. Studies show it greatly reduces oral HPV infections, so it is expected to prevent many of these cancers. It works best when given before any exposure to HPV.