The risk of salivary gland cancer (SGC) is increased in atomic bomb survivors and after radiotherapy, but other risk factors are not well established. Some studies have suggested an association of SGC with breast cancer and with exposure to various viruses or UVB radiation. Corroborating evidence of these associations was sought by using population-based registries to examine the demographic distribution of SGC, patterns of secondary primary cancers after SGC, and risk of SGC with AIDS. SGC incidence per 100,000 persons did not change between 1973 and 1992, averaging 1.2 in males and 0.8 in females, with a steep age gradient. To examine the relationship between UVB exposure and SGC, population-based, age-adjusted incidence rates of SGC were plotted against the UVB insolation of each registry site. Regression analysis suggested no correlation between SGC incidence and increasing UVB insolation (ß = 0.10, R² = 0.08). SGC also did not appear to be associated with second cancers that have been linked to herpes or papilloma viruses or with AIDS [observed/expected (O/E) ratio, <2.8], but all of these conditions are so uncommon that only very large relative risks would have been statistically significant. Women with SGC before age 35 had a statistically nonsignificant elevation in breast cancer risk [O/E, 3.30; 95% confidence interval (CI), 0.66–9.65], and older women had no increased risk of breast cancer. SGC patients were at increased risk for nonsalivary, second-primary oropharyngeal cancers (O/E, 3.27; 95% CI, 2.00–5.05), thyroid cancer (O/E, 3.31; 95% CI, 1.07–7.73), and lung cancer (O/E, 1.86; 95% CI, 1.45–2.35), particularly in patients whose SGC was treated with radiotherapy (O/E, 2.83; 95% CI, 2.06–3.80). In summary, SGC remains rare and does not appear to be associated with AIDS, virally related malignancies, or UVB. Patients who have had SGC, however, should be monitored for subsequent oropharyngeal, thyroid, and lung cancers.

SGC² is a rare disease, with an incidence rate of approximately 0.9 per 100,000 in the United States (1) . In contrast to other malignancies, there is relatively little international variation in the incidence of SGC (2) . The etiology of SGC is not well known, although correlations of varying strengths between SGC and possible risk factors have been found. One of the most well-established risk factors of SGC is exposure to radiation. High-dose radiation has been conclusively linked to excess SGC in studies of atomic bomb survivors, with a strong dose-response seen for mucoepidermoid carcinomas (3) .

Therapeutic radiation has been linked to an increased risk of SGC. Schneider et al. (4) found an increased incidence of SGC among patients who had been exposed to head, face, or neck radiation that was used as a treatment for benign tumors, and Preston-Martin et al. (5, 6, 7) determined that exposure to radiation during dental radiography led to an increased risk of SGC. Hall et al. (8) found an increased risk of SGC among patients who had been treated with ¹³¹I for hyperthyroidism, as did Hoffman et al. (9) , although the latter association was not statistically significant. Using 1973–1981 data from the SEER program, Spitz et al. (10) noted an increased incidence of SGC in the southern registries, suggesting an association between SGC and UVB exposure.

Several viruses have been implicated in the etiology of SGC. EBV has been found in lymphoepithelioma-like carcinomas of the salivary gland (11) , although only among Asian patients (12) . Human papillomavirus types 16 and 18 have been found in SGCs (1) , in addition to their known or potential roles in anal (13) , cervical (14) , vulvar (15 , 16) , esophageal (17 , 18) , and oral (19 , 20) squamous cell cancers. Polyomavirus can induce SGC if it is injected into mice on the first day of life (1 , 21) . If injected after the first day of life, the incidence of SGC drops dramatically, suggesting that polyomavirus may play a role in SGC only when the immune system is immature. Cytomegalovirus can induce salivary gland tumors in mice (22) , and human immunodeficiency virus type 1 has been found in cystic lymphoepithelial lesions of the salivary gland (23) .

Workers in various occupations experience an increased incidence of SGC, including rubber manufacturing (1) , plumbing (1) , and woodworking in the automobile industry (24) . Graham et al. (25) found an increased risk of SGC among people living in asbestos-mining counties in Quebec, with the risk inversely related to the distance from the asbestos mines.

The present study was designed to examine the demographic distribution of SGC in the United States, including potential associations with the AIDS or with second primary malignancies after SGC. Berg et al. (26) originally found an 8-fold increase of breast cancer among patients with SGC. However, Moertel and Elveback (27) found no increase in breast cancers. Three studies found an increase of breast cancers after SGC, but these were not statistically significant (28, 29, 30) . Prior and Waterhouse (31) did find a statistically significant excess of SGC after breast cancer, although this excess was 2-fold, compared with the 8-fold excess originally found by Berg et al. (26) . In a much larger study using the Danish Cancer registry, Schou et al. (32) did not find a statistically significant excess of SGCs after breast cancer. Aside from breast cancers, excesses of skin, prostate, lung, larynx, and colon cancers after SGC have been found. Reversing the temporal sequence, excesses of SGC have been found after lung cancer (33) , squamous cell skin cancer (34) , and squamous cell conjunctival cancer (35) . Unfortunately, each of the previous studies of second primaries after SGC had limited power. Furthermore, none of these studies included cases of SGC occurring after 1982, and no investigation of a possible association between SGC and AIDS has been undertaken.

Since 1973, the National Cancer Institute has monitored cancer incidence in 10% of the United States population through the SEER program (36) , which includes data from nine population-based cancer registries covering the states of Connecticut, Hawaii, Iowa, New Mexico, and Utah, as well as the metropolitan areas of Atlanta, Seattle, San Francisco and Oakland, and Detroit. SEER files also contain information on the initial type of treatment given for each tumor, within broad categories. Subsequent treatments and the details of radiation and chemotherapy dose are not recorded.

We searched the SEER incidence files for invasive malignant neoplasms occurring at least 2 months after diagnosis of an invasive SGC (ICD-O, 142) between 1973 and 1992. Tumors of all histologies were included, but tumors of the minor salivary gland were not included in this study because of limitations imposed by the ICD-O system. The person-years at risk were calculated according to 5-year age groups and 5-year calendar periods from 2 months after the date of SGC diagnosis to the date of diagnosis of the second primary, of death, or until December 31, 1992, whichever came first. At the end of the study, the number of expected cases for each secondary site was calculated by multiplying the person-years at risk by age-, sex-, and calendar year-specific incidence rates from the SEER database. The ratios of O/E cases were calculated, with 95% CI that assumed a Poisson distribution. Differences in ORs were evaluated with a ² homogeneity test.

To evaluate a possible association between SGC and AIDS, population-based AIDS and cancer registries were linked in California, Florida, metropolitan Atlanta, and New Jersey as described elsewhere (37) . The analysis was restricted to people of ages <70 years and to time periods in which both registries were functioning. The linkage analysis included 859,398 cancer cases and 50,050 AIDS cases. We calculated the expected incidence of SGC after AIDS diagnosis by multiplying SEER age-specific incidence rates by the corresponding person-years at risk after AIDS diagnosis. A person was at risk until the occurrence of cancer, death, or until 2.25 years after the AIDS diagnosis, or the end of cancer surveillance, whichever came first. To estimate the expected number of cancers that occurred up to 5 years before AIDS, we used modifications of cancer prevalence techniques described in detail previously (38) . The pre-AIDS and post-AIDS observed and expected number of cases, respectively, were summed, giving an O/E ratio and Poisson-distributed 95% CI (39) .

Finally, to examine a possible association between exposure to UVB radiation and the incidence of SGC, we used SEER data on the incidence of SGC from 1973 through 1992 and mean UVB insolation indices as previously published and described (40) . Briefly, photosensitive meters (Robertson-Berger meters) were installed at various National Weather Service stations (usually airports) in 1974. These meters provide a direct measure of UVB flux reaching the earth’s surface with a magnesium tungstate sensor. The insolation index (also known as Robertson-Berger counts) are weighted according to an action spectrum that parallels that for skin erythema. The current analysis used mean insolation indices for calendar years 1974–1985 that were recorded in the following SEER sites: San Francisco, Atlanta, Detroit, Seattle, Albuquerque (for New Mexico), Mauna Loa (for Hawaii), Des Moines (for Iowa), and Salt Lake City (for Utah). The age-adjusted SGC incidence rate at each site was plotted on a log-log scale against the UVB insolation index of that site. Only white cases were included for this analysis, because of their presumed higher susceptibility to UVB radiation. Using the Statistical Analysis System (SAS, Cary, NC), the linear regression was weighted by the number of cases at each site, giving more influence to the age-adjusted rates at sites where more cases were found. The association between UVB and SGC incidence was estimated by the slope of the regression (ß), and the fit of the model was estimated by the correlation coefficient (R²).

From 1973 through 1992, the SEER system received reports of 4250 cases of SGC, including 2304 among males and 1946 among females. Mucoepidermoid was the most common histology (24%), followed by adenoid cystic carcinoma (16%), squamous cell carcinoma (13%), adenocarcinoma (12%), and acinar cell carcinoma (10%), with mixed and undetermined histologies for the remainder. There were 19 cases (0.4%) of lymphoepithelioma. Of the SEER cases, 3690 SGC patients (1972 males and 1718 females) could be evaluated for risk of second primary cancers (Table 1) . In general, the females tended to develop SGC at an earlier age, and they had longer follow-up periods. These SGC cases included 3117 (84.5%) whites, 262 (7.1%) blacks, and 311 (8.4%) persons of other races.

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