Salivary gland cancer (SGC) is a rare malignancy, accounting for a small percentage of all head and neck cancers. These cancers develop in the tissues of the salivary glands, which produce saliva. The three major pairs of glands are the parotid glands, located in front of the ears, the submandibular glands beneath the jaw, and the sublingual glands under the tongue. Understanding the causes of this uncommon disease involves examining external exposures, inherited factors, and internal biological processes.
Established External Risk Factors
Exposure to ionizing radiation is the most significant external factor increasing the risk of developing salivary gland cancer. Prior therapeutic radiation treatment to the head and neck region for other malignancies, such as Hodgkin lymphoma or certain thyroid conditions, has a clear association with later SGC development. The risk can persist for many years, often appearing over two decades after the initial exposure. The risk is generally related to the total dose received.
Historical diagnostic procedures, such as repeated dental X-rays, also contributed to an elevated risk. Occupational exposure to radioactive substances in the workplace has similarly been shown to increase the chance of this cancer. This includes individuals whose jobs involved working with certain radioactive materials or high levels of radiation.
Workplace exposure to specific chemical and mineral compounds is also linked to an increased risk of SGC. Studies have identified an association for individuals who work in rubber manufacturing or who are exposed to nickel alloy dust and silica dust. Woodworking dusts and asbestos mining have also been implicated, suggesting that chronic inhalation of certain particulates may contribute to malignant changes.
Influence of Inherited Syndromes and Genetics
While most SGC cases arise from acquired damage to the DNA, a small number can be traced back to inherited genetic predispositions. Most DNA changes occur during a person’s lifetime as somatic mutations, triggered by external factors or random cell division. These mutations lead to uncontrolled cell growth.
Familial history alone is generally not a strong risk factor, but certain rare inherited conditions or gene mutations increase the likelihood of SGC. For example, individuals who inherit a mutation in the BRCA1 or BRCA2 genes, which are associated with breast and ovarian cancers, may also face a significantly higher risk of developing salivary gland cancer.
Genetic alterations also characterize the tumor type itself, such as the MECT1-MAML2 fusion oncogene found in most mucoepidermoid carcinomas. Similarly, more than half of adenoid cystic salivary gland cancers contain the MYB-NFIB oncogene fusion. These specific genetic rearrangements are typically acquired, not inherited, but they illustrate how a single, identifiable DNA change can drive the formation of a particular SGC subtype.
Biological Context: The Role of Pre-Cancerous Conditions and Viruses
A prominent internal cause of SGC involves the malignant transformation of a pre-existing, non-cancerous growth. Pleomorphic Adenoma (PA) is the most common benign salivary gland tumor, which can transition into Carcinoma Ex Pleomorphic Adenoma (CXPA). This change results from the accumulation of genetic alterations over time, with CXPA representing up to 20% of all malignant salivary tumors.
Molecular analysis of this transformation often reveals progressive genetic damage as the benign tumor evolves toward cancer. The sudden, rapid growth of a long-standing mass often signals this transformation, which can occur decades after the original benign tumor appeared. This process highlights an internal biological pathway for later malignant development.
Viral infections are another biological factor implicated in the development of certain SGC subtypes. The Epstein-Barr Virus (EBV) is strongly associated with lymphoepithelial carcinoma, a rare form of SGC. The Human Papillomavirus (HPV) has also been detected in some salivary gland tumors, including mucoepidermoid carcinomas and Warthin’s tumors, though its definite causative role in SGC is still being studied.
Chronic inflammatory conditions can also create an environment conducive to cancer development within the salivary glands. Sjögren’s syndrome, an autoimmune disorder, is associated with a significantly elevated risk of non-Hodgkin’s lymphoma, which can arise in the salivary glands. The sustained B-cell hyperactivity and chronic inflammation within the glands in Sjögren’s syndrome are thought to drive this increase in malignancy risk.