Socioeconomic disparities and comorbidities, not race, affect salivary gland malignancy survival outcomes.

OBJECTIVES/HYPOTHESIS: This study sought to determine whether comorbidities, race, and socioeconomic factors affect 5- and 10-year survival outcomes for patients with salivary gland malignancies treated at a single large academic institution with a large African American population. STUDY DESIGN: A retrospective cohort study was performed of all patients with salivary gland malignancies, from 1990 to 2015, at a large academic medical center. METHODS: Standard statistical analysis was performed using Kaplan-Meier survival curve analysis and Cox proportional hazard models. RESULTS: The overall 5- and 10-year survival rates decreased with age ≥ 60 years (P < .001), stage 3 or 4 (P < .001), clinical T stage 3 or 4 (P < .001), and clinical N stage 1, 2, or 3 (P < .001). Living in a ZIP code with an increasing proportion of residents with a high school degree or less (P < .05), being male (P < .05), increasing age at the time of diagnosis (P < .001), and increasing Charlson comorbidity index (P < .05) detrimentally impacted survival at 5 and 10 years. Race was associated with socioeconomic variables, but race was not a prognostic indicator of survival. CONCLUSIONS: Socioeconomic factors and comorbidities, not race, were negative prognostic indicators of survival of patients with salivary gland malignancies. Using race as a marker for socioeconomic status should be used with caution. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2545-2550, 2017.

Racial and Ethnic Disparities in Salivary Gland Cancer Survival.

IMPORTANCE: Several recent US studies have documented racial disparities in head and neck cancer outcomes, but few have investigated racial and ethnic differences in salivary gland cancer (SGCA) survival. OBJECTIVE: To determine whether patient race or ethnicity affects SGCA survival. DESIGN, SETTING, AND PARTICIPANTS: Retrospective survival analysis of all patients with SGCA from 1988 through 2010 in the Surveillance, Epidemiology, and End Results database. MAIN OUTCOMES AND MEASURES: Disease-specific survival according to race and ethnicity. End points assessed included age at diagnosis, sex, tumor grade, tumor size at diagnosis, extension at diagnosis, lymph node involvement at diagnosis, and treatment. Results were further analyzed by histologic subtype of SGCA. RESULTS: Of 11,007 patients with SGCA, 1073 (9.7%) were black, and 1068 (9.7%), Hispanic. Whites' mean age at diagnosis was 63 years vs 53 and 52 years for blacks and Hispanics, respectively (P < .001). Twenty-year disease-specific survival rates for all SGCA histologic subtypes combined for whites, blacks, and Hispanics were 78%, 79%, and 81%, respectively. Unadjusted survival curves showed no significant difference between blacks and whites and an apparent advantage for Hispanics. However, multivariable Cox regression models controlling for patient, tumor, and treatment characteristics showed poorer disease-specific survival vs whites for blacks (hazard ratio [HR], 1.22 [95% CI, 1.03-1.46]; P = .03) but not for Hispanics (HR, 0.97 [0.79-1.19]; P = .77). The overall disease-specific survival disparity was due to poorer disease-specific survival for blacks vs whites with mucoepidermoid (P = .03) and squamous cell carcinomas (P = .05). Less surgical treatment for blacks than whites (57.26% vs 76.94%; P < .001) was a source of the survival disparity for squamous cell but not mucoepidermoid SGCA. CONCLUSIONS AND RELEVANCE: Black race is a risk factor for poorer disease-specific survival for patients with mucoepidermoid or squamous cell carcinoma, whereas Hispanic ethnicity has no effect. Differing treatment between black and white patients affects survival in squamous cell but not mucoepidermoid SGCA. Differences in chemotherapy treatment, comorbidities, socioeconomic status, tumor genetic factors, and environmental exposures are potential but unproven additional sources of the racial survival disparities for mucoepidermoid and squamous cell SGCA.

Oral cavity, pharyngeal and salivary gland cancer: disparities in ethnicity-specific incidence among the London population.

OBJECTIVES: We examined the association between ethnicity and the incidence of oral and pharyngeal cancers in the London population. METHODS: Data on London residents diagnosed with oral and pharyngeal cancer (ICD-10 codes C00-C14) between 1998 and 2007 were retrieved from the Thames Cancer Registry. Age-standardised incidence rate ratios (IRR) for cancers of the nasopharynx (C11), oropharynx (C09-C10), hypopharynx (C12-C13), oral cavity (C00.3-C06), salivary glands (C07-C08) and Waldeyer's ring (C02.4, C09, C11.1, C14.2) were calculated for different ethnic groups using White males and females as the baseline groups. RESULTS: Records on 5833 individuals were examined, and ethnicity information was available for 4679 (80%) of these patients. The incidence rate of oral and pharyngeal cancer combined was 9.0 and 3.9 per 100,000 for males and females, respectively. Compared with their White counterparts, the highest incidence rate ratios of nasopharyngeal cancer were seen in Chinese males (IRR: 23, 95% confidence interval (CI): 7-73) and females (IRR: 16, 95% CI: 2-107). Waldeyer's ring cancers were most common in Bangladeshi and White groups. Analysis of the oropharynx and oral cavity cancers gave rise to variable but less obvious patterns among the different ethnic groups, whereas less variation was observed between ethnic groups for cancers of the hypopharynx and salivary glands. CONCLUSION: The incidence rates of individual oral and pharyngeal cancer types are low, but seem to vary by ethnic group. The variation in incidence appears to be unique to the different cancer subtypes and may therefore reflect specific ethnicity-related risk factors.

Cancer patterns in Inuit populations.

Inuit people inhabit the circumpolar region, with most living in Alaska, northwest Canada, and Greenland. Although malignant diseases were believed to be almost non-existent in Inuit populations during the beginning of the 20th century, the increasing life expectancy within these populations showed a distinct pattern, characterised by a high risk of Epstein-Barr virus-associated carcinomas of the nasopharynx and salivary glands, and a low risk of tumours common in white populations, including cancer of the prostate, testis, and haemopoietic system. Both genetic and environmental factors seem to be responsible for this pattern. During the second half of the 20th century, Inuit societies underwent major changes in lifestyle and living conditions, and the risk of lifestyle-associated tumours, especially cancers of the lung, colon, and breast, increased considerably after changes in smoking, diet, and reproductive factors. This Review will briefly summarise the current knowledge on cancer epidemiology in Inuit populations, with emphasis on the characteristic Inuit types of cancer.

Salivary gland tumors in Uganda: clinical pathological study.

BACKGROUND: The incidence of salivary gland tumors is claimed to be influenced by geographical and racial factors. The pathological classification and nomenclature of salivary gland tumors as defined by WHO classification (1991), is accepted world-wide but little is available in the literature regarding the spectrum of salivary gland tumors in Africa in the basis of this classification. Such efforts would allow comparison and justify any differences between the black African population and the rest of the world. OBJECTIVE: To outline the clinicopathological features of salivary gland tumors in Uganda. SETTING: Makerere University, Faculty of Medicine, Department of Pathology. METHODS: All epithelial tumors from major and minor salivary glands accessioned from 1979 to 1988 were analyzed in respect to sex and age of patients, anatomical location of the tumor and histological type. The histological diagnosis of each individual tumor was based on the 1991 WHO classification of salivary gland tumors. RESULTS: During the span of 10 years, 268 cases of salivary gland tumors were diagnosed. Of these, 113 (42.2%) were males, 148 (55.2%) females and in the remaining seven (2.6%) cases, the sex was not specified. The age range of the 247 patients with recorded ages was from 0.5 to 80 years. The mean age at diagnosis was 38.1 (SD =17.03) with the median of 38.0 years. Thirty four percent of tumors originated from the parotid, 33.2% from the submandibular and 32.8% from minor salivary glands. No tumor was implicated from the sublingual gland. There were a total of 125 (46.6%) malignant tumors and 143 (53.4%) benign tumors. The mean age of patients with malignant lesions (43.1 years; SD=16.75; median=44.00 years) was 9.6 years older than those with benign tumors (mean=33.5 years; SD=16.0; median=30.00 years). Pleomorphic adenoma was the most common benign tumor (74.8%), followed by myoepithelioma (9.8%). No Whartin's tumor was encountered. The malignant tumors were dominated by adenoid cystic carcinoma (28.8%) followed by mucoepidermoid carcinoma (21.6%). CONCLUSION: The pattern of distribution of salivary gland tumors in black African population seems to differ from that of Western series in that; i) females are more affected than males, ii) there is a low proportion of tumors from the parotid gland and high proportion of tumors from the submandibular and minor salivary glands, iii) the parotid and minor salivary gland tumors have more probability of being malignant than those tumors from the submandibular gland iv) the newly categorized pathological entities are common and v) Whartin's tumor is extremely rare in black African population.

Mutational events in LMP1 gene of Epstein-Barr virus in salivary gland lymphoepithelial carcinomas.

It is still unknown what kinds of roles Epstein-Barr virus (EBV) infection that are highly specific to salivary gland lymphoepithelial carcinomas (LECs) play in their tumorigenesis. To clarify the significance of EBV in LECs, we paid particular attention to the LMP1 gene, which is responsible for triggering several pathways for activating transcription factors. Sixty-one cases of EBV positive LECs confirmed by PCR and in-situ hybridization were collected from various areas of the world and studied immunohistochemically for latent membrane protein-1. Furthermore, PCR for the LMP1 carboxyl (C)-terminus region was performed, and the PCR products were sequenced for detection of other mutational events. LMP1 gene products were immunohistochemically demonstrated in 51% of the cases, while PCR amplification of the LMP1 gene was successful in 41 cases (67%). Among them, a 30 bp deletion in the C-terminus of the LMP1 gene, which had been shown to be characteristic to EBV in Chinese nasopharyngeal carcinomas, was found in 20 cases (32%). Most of them were from Guangzhou, Chengdu and Taiwan, while most of the cases from Shanghai and other areas exhibited no 30 bp deletion. In addition, several point mutations including codon 338 of LMP1 were commonly shared by the cases with or without the 30 bp deletion. These results indicate that there are 2 major genomic variations of EBV infecting salivary gland LECs. The frequent mutational events in the C-terminus in addition to the 30 bp deletion also seem to be critical for the pathogenesis because such mutational events may possibly promote cellular proliferation.

Racial/ethnic patterns of care for cancers of the oral cavity, pharynx, larynx, sinuses, and salivary glands.

BACKGROUND: Among Americans, both incidence and mortality from cancers of the larynx, oral cavity, and pharynx are higher for African Americans than whites and for men than women. In addition, the 5-year survival rates for these sites are significantly lower for African Americans than whites for each disease stage, particularly among African American males. We examine racial/ethnic variation in tumor characteristics, treatment practices, and their relationship to survival for cancers of the oral cavity, pharynx, larynx, nasal cavity and salivary glands. METHODS: Eligible individuals were age 20 or older and newly diagnosed with a primary invasive cancer of the oral cavity (excluding the lip), pharynx, larynx, sinuses or salivary glands in 1997 reported to one of nine National Cancer Institute's Surveillance Epidemiology and End Results Registries (SEER). Persons meeting the eligibility criteria for each registry were first stratified by race/ethnic group and stage then selected by random sampling within strata. RESULTS: We found racial/ethnic differences in diagnoses at specific anatomic sites, disease stage and treatment. African Americans less frequently received a cancer directed treatment than both whites and Hispanics and when treated were generally less likely to receive cancer-directed surgery. In multivariate analysis, the receipt of any cancer directed treatment was significantly associated with race and age group. African Americans and Hispanics had poorer, but not significantly so, overall, but not cancer-specific, survival. CONCLUSION: We found racial differences in the receipt of cancer treatment among patients diagnosed with selected head and neck cancers. We also found a less favorable distribution of stage for African Americans and Hispanics when compared with whites. The differences in stage we noted and the lower rates of oral cancer screening previously reported for these populations suggests that differential rates of early detection may contribute to racial differences in survival and mortality from cancers of the oral cavity and pharynx. Therefore, we conclude that more equitable receipt of cancer treatment along with preventive measures and earlier detection will help reduce racial/ethnic disparities in survival and mortality from cancers of the oral cavity, pharynx and larynx.

Salivary gland lesions: a Jamaican perspective.

A retrospective analysis of the spectrum and relative frequency of salivary gland lesions diagnosed in the Department of Pathology, University of the West Indies, Kingston, Jamaica, between 1965 and 1994, is reported. Four hundred and sixty-four salivary gland biopsies were received. Of these 99 (21.3%) were non-neoplastic and the remaining 365 (78.7%) were neoplasms: 261 (71.5%) were benign and 104 (28.5%) malignant. Benign mixed tumour (BMT)/pleomorphic adenoma (PA) was the most common neoplasm (63.3%) while mucoepidermoid carcinoma (MEC) was the most common malignant neoplasm (9.6%), followed by adenoid cystic carcinoma (ACC) (7.4%). The increased frequency of MEC over ACC is at variance with other reported series but the preponderance of pleomorphic adenoma is consistent. In the major salivary glands, benign neoplasms predominate at a ratio of 3:1, while a higher proportion of minor salivary gland neoplasms was malignant, ratio 1.2:1 (p = 0.003). These data represent the first attempt to document the spectrum of disease related to oral and maxillofacial pathology in Jamaica.

Salivery gland lesions: a Jamaican perspective

A retrospective analysis of the spectrum and relative frequency of salivary gland lesions diagnosed inthe Department of Pathology, University of the West Indies, Kingston, Jamaica between 1965 and 1994, is reported. Four hundred and sixty-four salivary gland biopsies were received. Of these 99 (21.3 percent) were non-neoplastic and the remaining 365 (78.7 percent) were neoplasm: 261 (71.5 percent) were benign and 104 (28.5 percent) malignant. Benign mixed tumour (BTM)/ pleomomorphic adenoma (PA) was the most common neoplasm (63.3 percent) while mucoepidermoid carcinoma (MEC) was the most common malignant neoplasm (9.6 percent), followed by adenoid cystic carcinoma (ACC) (7.4 percent). The increased frequency of MEC over ACC is at variance with other reported series but the preponderance of pleomorphic adenoma is consistent. In the major salivary glands, benign neoplasms predominate at a rotio of 3:1, while a higher proportion of minor salivary gland neoplasms was malignant, ratio 1.2:1 (p=0.003). These data represent the first attemp to document the spectrum of disease related to oral and maxillofacial pathology in jamaica. (AU)

Salivary gland lesions: a Jamaican perspective

A retrospective analysis of the spectrum and relative frequency of salivary gland lesions diagnosed in the Department of Pathology, University of the West Indies, Kingston, Jamaica, between 1965 and 1994, is reported. Four hundred and sixty-four salivary gland biopsies were received. Of these 99 (21.3) were non-neoplastic and the remaining 365 (78.7) were neoplasms: 261 (71.5) were benign and 104 (28.5) malignant. Benign mixed tumour (BMT)/pleomorphic adenoma (PA) was the most common neoplasm (63.3) while mucoepidermoid carcinoma (MEC) was the most common malignant neoplasm (9.6), followed by adenoid cystic carcinoma (ACC) (7.4). The increased frequency of MEC over ACC is at variance with other reported series but the preponderance of pleomorphic adenoma is consistent. In the major salivary glands, benign neoplasms predominate at a ratio of 3:1, while a higher proportion of minor salivary gland neoplasms was malignant, ratio 1.2:1 (p = 0.003). These data represent the first attempt to document the spectrum of disease related to oral and maxillofacial pathology in Jamaica.

Absence of Epstein-Barr virus encoded RNA and latent membrane protein (LMP1) in salivary gland neoplasms.

A series of 55 (42 benign and 13 malignant) salivary gland tumours were investigated by immunohistochemistry, to detect Epstein-Barr virus (EBV) latent membrane protein (LMP1) and by in situ hybridization for EBV-encoded RNA. Non-neoplastic gland from all the patients with tumours and 15 control glands were also examined. All cases, both neoplastic and non-neoplastic were negative for LMP1 and failed to show any positive signal by in situ hybridization for EBV RNA. One undifferentiated carcinoma from a European patient was included in the group. These results confirm previous reports of an ethnic association between EBV and undifferentiated carcinomas of the salivary gland. They do not support an aetiological role for EBV in other salivary gland tumours.

Increased risk of salivary gland tumors after low-dose irradiation.

OBJECTIVE: To assess the risk of neoplastic development among persons exposed to scalp irradiation. STUDY DESIGN: Historical cohort study initially; prospective follow-up subsequently. METHOD: Two control groups--population and siblings--matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. RESULTS: A 4.5-fold incidence of cancer (P < .01) and a 2.6-fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. CONCLUSIONS: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.

Lymphoepithelial carcinoma of the salivary gland: in situ detection of Epstein-Barr virus.

AIM: To examine the role of Epstein-Barr virus (EBV) in lymphoepithelial carcinoma of the salivary gland in Hong Kong Chinese. METHODS: Ten cases of lymphoepithelial carcinoma of the salivary gland (eight parotid and two submandibular) were examined. In situ hybridisation was used to localise EBER RNA, immunohistochemical methods to detect expression of latent membrane protein 1 (LMP-1) in EBV positive tumours, and Southern blot analysis to examine the clonality of EBV in the two cases where frozen tissue was available. RESULTS: None of the cases had a history of Sjögren's syndrome or histological evidence of a benign lymphoepithelial lesion. The IgA antibody titre against EBV viral capsid antigen was elevated in four cases. All cases were EBV positive by in situ hybridisation, with a strong uniform positive signal in the epithelial cells, and all cases expressed LMP-1. Southern blot analysis revealed that the clonal episomal form of the virus was present. Two of the three female patients in this series also developed carcinoma of cervix. One of these carcinomas had histological features of a lymphoepithelioma-like carcinoma but was EBV negative. CONCLUSIONS: A consistent association between EBV and lymphoepithelial carcinoma of the salivary gland was found. The presence of the virus in a clonal episomal form, and the expression of LMP-1 viral oncoprotein is further evidence of the role of EBV in the oncogenesis of this tumour.

Recent trends in the incidence of salivary gland cancer.

Beginning in 1985, a sudden and sustained doubling of salivary gland cancer incidence, among men only, is observed in the San Francisco-Oakland Metropolitan Statistical Area. Registry data are examined to determine the nature of this increase and its possible association with the AIDS epidemic. Changes in patient characteristics are assessed by comparing their distribution among recently diagnosed cases (1985-1988) to an expectation based on population growth and the age-specific incidence among patients diagnosed earlier (1973-1984). Based on the observed patterns, it is unlikely that the temporal increase in these tumours is a direct result of the AIDS epidemic or solely the result of a shift in the prevalence of established risk factors. The increase is predominantly seen in men over the age of 75 at diagnosis (O/E = 2.3, p = 0.02) and is observed among both those with and without a prior cancer (O/E = 2.7, p = 0.02 and O/E = 1.5, p = 0.06, respectively). Radiation for the prior cancer was not associated with increased occurrence. Military exposure is crudely approximated by examining birth cohorts. However, the cohort data do not support a hypothesis of military exposure.

Undifferentiated carcinoma of the salivary gland in Greenlandic Eskimos: demonstration of Epstein-Barr virus DNA by in situ nucleic acid hybridization.

Paraffin sections of 11 undifferentiated salivary gland carcinomas of lymphoepithelioma type (malignant lymphoepithelial lesion) arising in Greenlandic Eskimos (Inuit) were examined for the presence of Epstein-Barr virus (EBV) using in situ nucleic acid hybridization with a 35S-labeled EBV-specific probe. Epstein-Barr virus genomes were detected in each case in malignant epithelial cells, but were not found in lymphoid stroma or in residual benign salivary epithelium. Eight undifferentiated salivary gland carcinomas from non-Eskimo patients (including two with lymphoepithelioma-like features) were negative for EBV-DNA. Our results confirm the existence of a consistent and specific association between EBV and tumor cells of undifferentiated salivary gland carcinoma of lymphoepithelioma type arising in Greenlandic Eskimos.

Intraoral salivary gland neoplasms: a retrospective study of seventy cases in an African population.

Intraoral salivary gland neoplasms diagnosed in the Department of Oral Pathology, Medical University of Southern Africa, Medunsa, were reassessed and revised with regard to histologic diagnosis. New entities and subclassifications that have been described in recent years were taken into account. Seventy cases were diagnosed during an 8-year period, and the sample consisted of black patients only. Benign mixed tumor was the most common entity and accounted for 48% of all tumors. Polymorphous low-grade adenocarcinoma comprised 15.7% of the sample and was the most frequent malignant tumor. The mean age of patients with benign and malignant tumors were 36.5 and 49.8 years, respectively (p less than 0.05), and the palate was the most common site involved. Geographic differences do exist in the pattern and pathology of intraoral salivary gland neoplasms when compared with findings in other studies.

Undifferentiated carcinoma with lymphoid stroma of the major salivary glands.

Undifferentiated carcinoma with lymphoid stroma or lymphoepithelial carcinoma of the major salivary glands is a demographically and histopathologically unique malignancy. Although whites may have the disease, it is preponderantly a carcinoma of North American Eskimos and native Greenlanders. The carcinoma shares many features with undifferentiated nasopharyngeal carcinomas, from which it must be distinguished: histologic appearance, putative relationship with Epstein-Barr virus, predilection for mongoloid races, and response to therapy. In some cases, the carcinoma appears to have evolved from a lymphoepithelial lesion.

The malignant lymphoepithelial lesion of the salivary glands.

Malignant lymphoepithelial lesion (MLEL) is a rare neoplasm of the salivary gland which has an exceptionally high incidence in the Eskimo. Eighty-four cases have been previously reported. Seven additional cases in six Eskimos and one Filipino patient are reported in this paper. The etiology, treatment and prognosis of these lesions is then discussed.