What You Need to Know About Salivary Gland Cancers

Salivary glands produce saliva to keep the mouth moist and aid digestion. Salivary gland cancer, which begins in the tissue of one of these glands, is among rare cancers. According to 2020 Türkiye Cancer Statistics, salivary gland cancers rank 28th in frequency, with 552 new cases annually. In the US, this cancer affects 1 person per 100,000 each year and accounts for less than 1% of all cancers.

What is Salivary Gland Cancer?

The mouth contains major and minor salivary glands. Salivary gland cancer occurs when a cancerous tumor begins to develop in one of them.

There are 3 pairs of major salivary glands:

1. Parotid (or parotis) glands: salivary glands in front of the ears
2. Sublingual glands: salivary glands under the tongue
3. Submandibular glands: salivary glands under the jaw

The parotid glands are the largest salivary glands and lie directly in front of each ear. Tumors most often occur here. Although tumors growing here are usually benign, this may also be the starting point for most malignant tumors.

The sublingual glands are the smallest of the major tumors and lie under the tongue. Tumors very rarely start in these glands.

The submandibular glands lie just below the jaw. According to the American Cancer Society (AKD), approximately 10-20% of salivary gland tumors start here, and almost 50% are malignant.

There are also hundreds of microscopic minor salivary glands throughout the mouth:

• Sinuses
• Tongue
• Inside the cheeks
• Nose
• Throat
• Larynx

Tumors are less likely to develop in these minor glands, but if they do, they are most likely malignant.

Cancers of the blood and lymphatic system, such as non-Hodgkin lymphoma, may also involve the salivary glands.

Benign tumors do not spread locally or to distant parts of the body. However, a benign tumor may become malignant if untreated or not properly removed surgically. Malignant tumors are aggressive and have a higher risk of metastasis or local spread. Surgery in the early stages of salivary gland tumors usually provides a complete cure.

How is Salivary Gland Cancer Recognized? Symptoms

A person with salivary gland cancer may experience:

• Difficulty opening the mouth fully
• Weak facial muscles on one side of the face
• Swelling or a lump around the jaw, mouth or neck
• Noticeable changes in the shape of one side of the neck or face
• Numbness or loss of sensation in part of the face
• Persistent pain in a salivary gland

People with painless lumps not directly caused by a known infection should see a specialist.

What is the Life Expectancy for Salivary Gland Cancer?

The prognosis of salivary gland cancer depends on how far it has spread from where it began.

The following figures come from US Cancer Statistics:

• Localized salivary gland cancer: If the cancer is treated before spreading from its starting point, the 5-year survival rate after diagnosis is above 95%.
• Regionally advanced cancer: If the cancer has spread to nearby tissues, the rate falls to 69%.
• Cancer spread to distant sites: In this situation, the 5-year survival rate is 44%.

These rates may vary with age, general health and treatment success. Early diagnosis and treatment are the best way to improve a person's outcome with salivary gland cancer.

Who Gets Salivary Gland Cancer? Causes and Risk Factors

The causes of salivary cancer have not yet been fully clarified. However, some of the following factors may increase the risk of developing salivary gland cancer.

• Radiation exposure: People previously treated with radiation for head and neck cancer have a higher risk of developing salivary gland cancer later in life.
• Age: The risk of developing salivary gland cancer increases with age.
• Sex: Men are more likely than women to develop salivary gland cancer.
• Pollution: Workplaces with exposure to substances such as nickel alloys and silica dust may also be a factor.
• Family history: Genetic factors may also increase risk, although confirmed examples are rare.

Because the cause has not yet been established, ways of preventing this cancer have not been clarified either. Trying to avoid the factors above, taking care to protect oneself at work and avoiding tobacco and alcohol products may reduce the risk of salivary gland cancer.

What Types of Salivary Gland Cancer Are There?

Many types of cancer can develop in the salivary glands. Some are adenocarcinomas, arising in cells that secrete substances:

• Mucoepidermoid carcinomas: The most common form of salivary gland cancer. They usually begin in the parotid glands and grow slowly.
• Adenoid cystic carcinomas: These tumors grow slowly but are difficult to treat because they grow along nerves.
• Acinic cell carcinomas: These carcinomas tend to occur at younger ages and grow slowly.
• Polymorphous low-grade adenocarcinomas: This cancer type develops in the minor salivary glands and is usually treatable.
• Other epithelial lesions: This classification of different cancer types includes intercalated duct hyperplasia and nodular oncocytic lesions.

In some cases, adenocarcinoma is identified but its type cannot be determined. This is known as adenocarcinoma NOS (not otherwise specified), most commonly found in the parotid and minor salivary glands. Other cancers may also develop, including sarcomas, cancers of connective tissue cells, and non-Hodgkin lymphoma in the salivary glands of people with Sjögren Syndrome.

How is Salivary Gland Cancer Diagnosed?

Ear, nose and throat specialists ask about a person's medical history and examine their cheeks, inside the mouth and around the jaw to diagnose salivary gland cancer. Swelling in the lymph nodes may be a sign of cancer, but swollen lymph nodes are usually not cancer-related. They may result from infection or viral inflammation.

Facial muscle weakness, numbness or loss of sensation may indicate that cancer has spread to nerves. Specialists may request imaging to locate the disease and determine its extent, such as X-ray, CT and MRI. They may also recommend a biopsy to collect and analyze salivary gland tissue. An incisional biopsy takes a tumor sample through a small cut for examination.

How Are Salivary Gland Cancers Treated?

Treatment options usually include surgery, radiation therapy, chemotherapy or a combination. A small proportion of patients may also benefit from targeted drugs directed at genetic targets or from immunotherapies.

Treatment Approach: Summary

• Surgery is the main treatment for localized (very early-stage) salivary gland cancers. Surgery is also considered first for resectable regionally advanced cancer. 
• For patients with regionally recurrent disease, surgery is the optimal treatment if the disease is resectable (this is called salvage surgery).
• For patients undergoing salvage surgery who have not previously received radiation therapy (RT), adjuvant (protective treatment after the main treatment) radiotherapy is considered instead of observation alone.
• Treatment options for patients with metastatic (stage 4) disease are:
  • For clinically stable patients with oligometastatic disease (a single or small number of metastases), regional treatment (such as surgery or radiotherapy), alone or with systemic treatment, is considered instead of systemic treatment alone. Patients with single lung or liver metastases and adenoid cystic carcinoma (AKK) histology may particularly benefit from this approach.
  • Systemic treatment is offered to patients with systemic disease progression on imaging, systemic symptoms, threatened end-organ dysfunction and/or poor performance status due to progressive disease. Active surveillance may instead be considered for slow-growing, asymptomatic or minimally symptomatic disease, regardless of histological subtype.
  • The approach to systemic treatment for metastatic or recurrent salivary gland tumors is summarized below:
    • For most patients with adenoid cystic carcinoma (AKK) without a molecular driver mutation or non-AKK histology, a combination chemotherapy regimen (for example, cisplatin, doxorubicin and cyclophosphamide [CAP]) is considered as initial treatment rather than a single agent. A single agent may nevertheless be a suitable alternative for some patients unable to tolerate combination chemotherapy. Vinorelbine or mitoxantrone is appropriate if single-agent treatment is used. Taxanes are avoided in the chemotherapy regimen for AKK histology because of a lack of efficacy.
    • For patients with AKK tumors that progress on initial treatment who remain treatment candidates, treatment may continue with the vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) lenvatinib. Because this drug is currently unavailable in Türkiye, other VEGF inhibitors such as sorafenib or axitinib may also be considered.
    • For patients with non-AKK histology and indications for treatment, genomic testing for histology-based specific molecular targets (for example, NTRK gene mutations) is recommended to help select systemic treatment.
    • Non-AKK, nonsecretory tumors (for example, mucoepidermoid carcinoma, salivary duct carcinoma and adenocarcinoma) should be tested for androgen receptor and human epidermal growth factor receptor 2 (HER2) expression.
    • For patients with HER2 overexpression, adding HER2-targeted trastuzumab to taxane-based chemotherapy should be considered.
    • For patients expressing androgen receptors without HER2 overexpression, chemotherapy should be considered as initial treatment instead of androgen deprivation therapy (ADT). Upon disease progression, androgen suppression with leuprolide plus bicalutamide may be considered.

Surgery

Surgery is usually the first treatment for salivary gland cancer. The surgical team may need to remove the entire gland along with any nerves or ducts to which the cancer may have spread. If the tumor is small and accessible, the team may remove only the tumor and a small amount of surrounding tissue.

Complications after surgery are generally rare but may include:

• Adverse reactions to anesthetics
• Slow wound healing
• Infection
• Excessive bleeding

Nerve damage may also occur, causing one side of the face to droop. A person may have difficulty swallowing and speaking after surgery. In some cases, reconstructive surgery may be needed, and a speech therapist can help recover some lost eating and speaking functions.

Gustatory sweating, or Frey Syndrome, occurs when nerves grow abnormally. This growth may cause sweating in parts of the face while chewing. Specialists may recommend further surgery to treat it.

Radiation Therapy

Radiotherapy directs high-powered energy particles or beams at the tumor to slow or destroy cancer cell growth. The most common type for salivary gland cancer is external beam radiation therapy, which delivers an intense level of radiation. Patients usually receive treatment 5 days a week, and this may last up to 7 weeks.

A newer type that may be more successful is accelerated hyperfractionated radiation, which gives several small doses each day.

Radiosensitizing drugs may also be given. They make the tumor more sensitive to radiation therapy, meaning more cancer cells are killed.

Common possible side effects of radiation therapy include:

• Skin burns
• Nausea
• Vomiting
• Fatigue

These symptoms usually disappear after treatment, but radiotherapy may also affect other parts of the head and neck:

• Dry mouth due to reduced saliva production
• Sores in the throat and mouth
• Dry throat
• Difficulty swallowing
• Complete or partial loss of taste
• Bone pain and damage
• Worsening dental problems
• Damage to the thyroid gland
• Ringing or a feeling of fullness in the ears.

Chemotherapy

Chemotherapy kills cancer cells but may also affect healthy cells such as hair follicles and cells inside the mouth. The most common side effects of chemotherapy are:

• Loss of appetite, nausea and vomiting
• Reduced white and red blood cell counts, increasing the risk of infection and fatigue
• Reduced platelet levels, leading to easy bruising
• Hair loss
• Mouth sores

After treatment is completed, the patient continues to be closely monitored. Follow-up is important for minimizing treatment-related side effects and detecting signs of possible cancer recurrence early.

Summary

Salivary gland cancer can occur in any salivary gland around the mouth. Researchers have not yet identified a clear cause, but factors such as radiation exposure, age and sex increase the risk. Treatment may include surgery, radiation therapy, chemotherapy and immunotherapy. Early diagnosis is generally better for the patient's overall condition.