Etiology

Viruses

A number of viruses have been implicated in the pathogenesis of salivary gland tumours. There is a strong association between Epstein Barr virus (EBV) and lymphoepithelial carcinomas {2253, 2636}, but this appears to be largely restricted to Asian patients {1173} and Greenlandic Inuits {986}. EBV has not been convincingly shown in other salivary gland carcinomas or neighbouring normal gland {2636}. A recent study did not support an etiological role for EBV or cytomegalovirus in benign parotid tumours {1407}. SV40 sequences have been demonstrated in human pleomor-phic adenomas {1643} but there is no convincing association between human salivary gland tumours and other viruses, including polyoma virus and papilloma virus.

Radiation

There is compelling evidence implicating exposure to ionizing radiation and the development of salivary gland tumours. Long-term follow-up studies of the survivors of the atomic bomb explosions in Hiroshima and Nagasaki show an increased relative risk of 3.5 for benign, and 11 for malignant salivary neoplasms {193,194,2543,2544}. The risk was directly related to the level of exposure to ionizing radiation. There was a high frequency of both mucoepidermoid carcinomas and Warthin tumours in these patients {2229}.

Therapeutic radiation, particularly of the head and neck region, has been linked with a significantly increased risk of developing salivary gland cancers {1725,1754,2197,2268}. There appears to be a risk from iodine131 used in the treatment of thyroid disease, as the isotope is also concentrated in the salivary glands {1111}.

There is evidence that exposure to routine dental radiographs is associated with an increased risk of salivary gland carcinoma {2088,2089}. Exposure to ultraviolet radiation has also been implicated {1832,2451,2452}. There appears to be no excess risk in those exposed to radon {1733}, or the microwaves of cellular telephones {92,1224}.

Occupation

It has been shown that workers in a variety of industries have an increased incidence of salivary gland carcinomas. These include rubber manufacturing {1127,1620}, exposure to metal in the plumbing industry {1730} and nickel compounds {1127}, woodworking in the automobile industry {2512} and employment in hairdressing and beauty shops {2513,2514}. An increased risk of salivary gland cancers was reported in people living in certain Quebec counties where asbestos was mined, and the risk was inversely proportional to the distance from the mines {935}.

Lifestyle and nutrition

No association was found between tobacco use and alcohol consumption and salivary gland cancers in a case/control study {1801}, confirming previous findings {1295,2792}. One study showed an elevated risk in men but not women {1127}. However, there is a strong association between smoking and Warthin tumour (Section on Warthin tumour). Exposure to silica dust and kerosene as a cooking fluid increased the risk of developing salivary malignancy in a Chinese population {2902}, and a higher level of risk of parotid carcinomas was associated with exposure to nickel, chromium, asbestos and cement dust in a European study {603}. An increased level of risk has been postulated in those with a high cholesterol intake {1128}.

Hormones

Endogenous hormones have been reported in normal and neoplastic salivary glands, but some of the results have been conflicting. Estrogen receptors were found in nearly 80% of normal glands in males and females and four out of eight salivary tumours in women had estrogen receptor levels similar to those of "hormonally dependent" breast carcinomas {606}. However, more recent studies have not confirmed this finding and questioned the methodology {616}. Estrogen receptors have been reported in a minority of cases of acinic cell carcinoma, mucoepidermoid carcinoma {1214} and salivary duct carcinoma {134}, but were not detected in adenoid cystic carcinoma {616,1214,1732,2335}. Estrogen or estrogen receptors have been reported in pleomorphic adenomas in some studies {1214,1764,1946}, but in others, estrogen receptors were absent {1851}.

Progesterone receptors have been reported in normal salivary glands {892,2335}. They have been detected in a minority of pleomorphic adenomas {892,1214} but high levels of expression were reported in recurrent pleomorphic adenomas and this was thought to be a prognostic factor {892}. However, a recent study failed to show progesterone receptors in all the benign salivary tumours examined {1851}. Progesterone receptors were seen in 2/10 acinic cell carcinomas and 3/10 mucoepidermoid carcinomas {1214} but were not detected in salivary duct carcinoma {134}. They have been reported in adenoid cystic carcinomas in some studies {1214,1965} but in others they were absent, or present in only a few tumours {616,1214}. Androgen receptors are present in over 90% of salivary duct carcinomas {711, 712,1265}. A recent study showed immunoreactivity for androgen receptors in all their cases of salivary duct carcinoma, carcinoma ex pleomorphic adenoma and basal cell adenocarcinoma {1851}. There was also staining for the receptors in a fifth of their cases of acinic cell carcinoma, mucoepidermoid carcinoma and adenoid cystic carcinoma.

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