Salivary gland cancer has no single known cause, but a combination of radiation exposure, genetic changes within cells, certain viral infections, occupational chemical exposure, and smoking all contribute to risk. It is rare, affecting roughly 0.7 per 100,000 men and 0.5 per 100,000 women worldwide each year. Because it’s uncommon, pinpointing exact causes has been harder than for more frequent cancers, but researchers have identified several clear risk factors and biological mechanisms.
Radiation Exposure Is the Strongest Known Risk Factor
Ionizing radiation to the head and neck region is the most well-documented external cause of salivary gland cancer. People who received radiation therapy for a previous cancer, particularly Hodgkin lymphoma, develop salivary gland malignancies at dramatically higher rates than the general population. Among more than 11,000 Hodgkin lymphoma patients treated with radiation, the rate of subsequent salivary gland cancer was nearly 17 times higher than expected. That risk climbed even further over time: by 15 or more years after treatment, it reached over 30 times the expected rate.
Age at exposure matters significantly. People who were irradiated before age 20 faced the highest risk, with rates over 45 times what would normally be expected. This pattern has been confirmed across multiple populations, including survivors of the atomic bombings in Japan, bone marrow transplant recipients, and children treated with radiation for brain tumors. The elevated risk persists for at least two decades after exposure and shows no sign of disappearing, with an estimated 44 excess cases per 100,000 person-years even after 20 years of follow-up.
Radiation doesn’t raise risk equally across all subtypes. Mucoepidermoid carcinomas, the most common form of salivary gland cancer, showed the strongest link to radiation at 44 times the expected rate. Adenocarcinomas also appeared at roughly 30 times the expected rate.
Genetic Mutations That Drive Tumor Growth
Salivary gland cancers arise from different cell types within the gland. Some start in acinar cells (the cells that produce saliva), others in the ductal cells that line the gland’s drainage channels, and still others in myoepithelial cells that surround the glands. The specific mutations driving each cancer vary by subtype, but several patterns are now well understood.
In salivary duct carcinoma, one of the more aggressive subtypes, the tumor-suppressing gene TP53 is altered in about 69% of cases. TP53 normally acts as a brake on abnormal cell growth, so when it stops working, cells can divide unchecked. Nearly 80% of these tumors also carry at least one change that could potentially be targeted with existing drugs, including amplification of HER2 (the same protein overexpressed in some breast cancers, found in 31% of cases) and mutations in growth-signaling pathways (28% of cases).
Adenoid cystic carcinoma, a slow-growing but persistent subtype, is driven by a different set of changes. A hallmark of this cancer is a chromosomal rearrangement that fuses the MYB gene with a partner gene called NFIB. This fusion creates an abnormal protein that pushes cells toward uncontrolled growth. Where the tumor arises within the salivary gland system also influences its molecular behavior: tumors in the parotid gland activate certain stress-response pathways at higher levels than those in the submandibular or minor salivary glands, and these pathway differences appear to affect survival outcomes.
Viral Infections Linked to Higher Risk
Several viral infections have been associated with salivary gland tumors. Epstein-Barr virus (EBV), the virus responsible for mononucleosis, has been detected in certain salivary gland cancer tissues. Human papillomavirus (HPV), better known for its role in cervical and throat cancers, and HIV have also been linked to increased risk. The connection with HIV may relate to the chronic immune suppression it causes, which can allow abnormal cells to survive and multiply rather than being cleared by the immune system.
Workplace Chemical Exposure
Certain occupational chemicals raise the risk of salivary gland malignancies, particularly for workers who inhale toxic particles regularly. Nickel compounds and alloys have long been flagged as potential risk factors. More recently, hexavalent chromium, a carcinogen already known to cause lung cancer, has been implicated. Workers exposed to chromium-containing coatings, such as military personnel who sand or scrape chromate-based paints from equipment, inhale fine particles that can reach the salivary glands.
Formaldehyde, encountered in soldering fumes and certain industrial processes, is another suspected contributor. A meta-analysis estimated that workers exposed to chromium and nickel compounds faced 18 times the normal risk of cancers in the nasal and sinus region, which shares anatomic proximity with the salivary glands. While large-scale studies specific to salivary gland cancer and occupational chemicals are limited due to the cancer’s rarity, the case evidence and biological plausibility are strong enough to warrant caution in these industries.
Smoking Raises Risk, but Less Than for Other Head and Neck Cancers
Cigarette smoking is a confirmed risk factor, though its effect on salivary gland tumors is more modest than its impact on other head and neck cancers. In a case-control study of 239 salivary gland tumor patients, smoking was associated with a 2.5-fold increase in risk. That’s notable, but far lower than the 123-fold increased risk that the combination of smoking, alcohol, and betel quid chewing creates for oral cancer.
The difference likely comes down to anatomy. Major salivary glands sit farther from the surfaces directly bathed by smoke and alcohol than the lining of the mouth and throat, so carcinogens reach them more indirectly. This explains why smoking had a stronger effect on minor salivary gland tumors (which sit closer to the mouth’s surface, with a 5.2-fold risk increase) than on major salivary gland tumors (2.4-fold increase). Alcohol alone did not show a statistically significant link to salivary gland tumors in the same study.
Possible Role of Hereditary Mutations
Salivary gland cancer is not typically considered a hereditary disease, but there are intriguing connections to inherited gene mutations. Researchers at Ohio State University examined families carrying BRCA mutations, the same gene variants linked to breast and ovarian cancer, and found salivary gland cancers appearing in these family trees. The rationale makes biological sense: salivary glands and breast tissue are both exocrine glands with similar cellular structures, and BRCA2 mutations impair the body’s ability to repair damaged DNA, which can allow cancers to develop across multiple organ systems.
This connection remains an area of active investigation rather than an established cause, but it suggests that people with known BRCA mutations may want to be aware of the association.
Diet and Other Protective Factors
A population-based case-control study found that certain dietary patterns may influence risk. People who ate the most dark-yellow vegetables (like carrots, sweet potatoes, and squash) or liver had roughly 70% lower risk of salivary gland cancer compared to those who ate the least. These foods are rich in vitamin A and its precursors, which play a role in maintaining healthy cell growth and differentiation in glandular tissues. While one study isn’t enough to make definitive dietary recommendations, it adds to broader evidence that diets high in colorful vegetables are associated with lower cancer risk across many organ sites.