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Forty-Fold Elevated Risk for Lymphoepithelial Carcinoma of Salivary Gland Among People with AIDS in the United States
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Kishor Bhatia*, F Shebl, and E Engels
NCI, NIH, Bethesda, MD, US
Infections and Immunoepidemiology Branch DCEG, NCI;.
Contact bhatiak@mail.nih.gov
Background: HIV infection is associated with elevated risk of malignancies caused by viruses, such as Epstein-Barr virus (EBV). EBV is linked to lymphoepithelial carcinoma (LEC) of the nasopharynx and salivary gland, but these malignancies are rare, and an elevated risk for these cancers in HIV-infected persons has not been previously described. Of note, HIV-infected people also have an increased risk for lymphoepithelial sialadenitis (LES), an inflammatory condition of the salivary gland that might predispose to LEC. We hypothesized therefore, that HIV-infected people might be at increased risk of LEC, particularly of the salivary gland.
Methods: We utilized linked AIDS and cancer registry data from the HIV/AIDS Cancer Match Study to evaluate cancer risk among 503,560 people with AIDS in the US (1980 to 2004). We categorized carcinomas arising in the salivary gland and nasopharynx into LEC and other subtypes. Standardized incidence ratios (SIR) compared risk of these cancers among people with AIDS, for the period from 60 months before until 60 months after AIDS onset, with risk in the general population.
Results: Overall, people with AIDS had an elevated risk for cancers of the salivary gland (42 cases, SIR 1.8, 95%CI 1.3 to 2.4) and nasopharynx (36 cases, SIR 2.1, 95%CI 1.4 to 2.8). Importantly, the increased risk was observed selectively for 2 histologic subtypes of salivary gland cancer (LEC and squamous cell carcinoma). Specifically, LEC risk was elevated 40-fold (7 cases, SIR 40, 95%CI 16 to 83), and squamous cell carcinoma risk was increased 5-fold (12 cases, SIR 5.1, 95%CI 2.6 to 8.9). In comparison, for nasopharyngeal cancer, the elevation in risk was smaller for LEC (4 cases, SIR 1.9, 95%CI 0.5 to 4.8) and a related subtype, non-keratinizing squamous cell carcinoma (5 cases, SIR 3.3, 95%CI 1.1 to 7.7); risk was also elevated for keratinizing squamous cell carcinoma (21 cases, SIR 2.5, 95%CI 1.5 to3.8).
Conclusions: Persons with HIV/AIDS have more than a 40-fold increased risk of LEC of the salivary gland. An increased risk for squamous cell carcinomas of both salivary gland and nasopharynx is also apparent. The magnitude of elevated risk for LEC of the salivary gland suggests an underlying viral etiology. The marked increase in risk for LEC of the salivary gland is in striking contrast to the modest increase in the risk for LEC of the nasopharynx. Our data are consistent with the hypothesis that LES promotes salivary gland cancers in the HIV-infected population.
AUTHOR DISCUSSION
The remarkable increase in risk for LEC and squamous cell carcinoma of the salivary gland in individuals with AIDS in the USA strongly suggests an underlying viral etiology (example EBV).
The differential impact of HIV in the magnitude of LEC of the salivary versus nasopharynx raises the possibility that AIDS related salivary gland conditions (example sialadenitis) might be a factor in predisposing to salivary gland cancer.
The increased risk of squamous cell carcinoma of both salivary gland and nasopharynx might be attributed to both a viral etiology (example HPV) and/to tobacco and alcohol use.
This study is the first to quantify the magnitude of risk in defined sutypes of salivary gland and nasopharyngeal cancer. The lage sample size allows the derivation of SIR estimates that are stable. The small number of specific histologic subtypes however make it difficult to adjust for other co-factors such as smoking, alcohol use.
AUTHOR CONCLUSIONS
These observations support the possibility that LEC and squamous cell carcinoma of salivary gland arise, at least in part, from loss of immune control -- potentially directed at oncogenic viruses.
The modestly elevated risk of the LEC subtype of nasopharyngeal cancer and the greatly elevated risk of this subtype in nasopharynx suggest HIV infection associated changes specific to the salivary gland milieu play a role in promoting salivary gland cancer.
Background
Immunosuppression resulting from HIV infection increases the risk for viral associated cancers.
Cancers associated with HHV-8 (Kaposi's sarcoma), EBV (NHL) and HPV (Cervical cancer) form the spectrum of AIDS defining Cancers
EBV is also associated with non-lymphoid cancers, primarily nasopharyngeal cancer (NPC) and subset of salivary gland cancers- particularly Lymphoepithelial carcinoma of the salivary gland.
In the US both NPC and LEC of salivary gland are considered generally rare cancers.
Worldwide frequency of NPC and LEC of salivary gland shows striking ethno/geographic correlations.
HIV infected people in the US have an increased risk for lymphoepithelial sialadenitis (LES).
LES has been reported to predispose to LEC.
The frequency and patterns of Salivary cancers and NPC arising in HIV-infected persons have not been well documented
Hypothesis
HIV infected people might be at increased risk for cancers of the salivary gland and nasopharynx, particularly LEC.
Methods
HIV/AIDS Cancer Match Study
--Linkage of HIV/AIDS and cancer registry databases in 9 U.S. states and 5 metropolitan areas
--We evaluated cancer risk in 503,560 persons with AIDS (1980-2008).
Cancer outcomes in the period -60 to +60 months relative to AIDS diagnosisCategorized carcinomas arising in the salivary gland and nasopharynx into LEC and other subtypes.
Statistical analysis
--Standardized incidence ratios (SIRs) compared risk in individuals with AIDS to general population.
--Logistic regression to compare risk according to demographic factors, mode of exposure
--Poisson regression to examine change in SIRs with time relative to AIDS onset.
Demographic characteristics of people with AIDS (N=503,560)
β80% were male
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