Purpose: Despite advances in the treatment of HIV, HIV-infected people remain at increased risk for many cancers, and the number of non–AIDS-defining cancers is increasing with the aging of the HIV-infected population. No prior study has comprehensively evaluated the effect of HIV on cancer-specific mortality.Patients and Methods: We identified cases of 14 common cancers occurring from 1996 to 2010 in six US states participating in a linkage of cancer and HIV/AIDS registries. We used Cox regression to examine the association between patient HIV status and death resulting from the presenting cancer (ascertained from death certificates), adjusting for age, sex, race/ethnicity, year of cancer diagnosis, and cancer stage. We included 1,816,461 patients with cancer, 6,459 (0.36%) of whom were HIV infected.Results: Cancer-specific mortality was significantly elevated in HIV-infected compared with HIV-uninfected patients for many cancers: colorectum (adjusted hazard ratio [HR], 1.49; 95% CI, 1.21 to 1.84), pancreas (HR, 1.71; 95% CI, 1.35 to 2.18), larynx (HR, 1.62; 95% CI, 1.06 to 2.47), lung (HR, 1.28; 95% CI, 1.17 to 1.39), melanoma (HR, 1.72; 95% CI, 1.09 to 2.70), breast (HR, 2.61; 95% CI, 2.06 to 3.31), and prostate (HR, 1.57; 95% CI, 1.02 to 2.41). HIV was not associated with increased cancer-specific mortality for anal cancer, Hodgkin lymphoma, or diffuse large B-cell lymphoma. After further adjustment for cancer treatment, HIV remained associated with elevated cancer-specific mortality for common non–AIDS-defining cancers: colorectum (HR, 1.40; 95% CI, 1.09 to 1.80), lung (HR, 1.28; 95% CI, 1.14 to 1.44), melanoma (HR, 1.93; 95% CI, 1.14 to 3.27), and breast (HR, 2.64; 95% CI, 1.86 to 3.73).Conclusion: HIV-infected patients with cancer experienced higher cancer-specific mortality than HIV-uninfected patients, independent of cancer stage or receipt of cancer treatment. The elevation in cancer-specific mortality among HIV-infected patients may be attributable to unmeasured stage or treatment differences as well as a direct relationship between immunosuppression and tumor progression.

Background: People living with HIV (PLWH) are at an increased risk of developing several cancers, but to the authors’ knowledge less is known regarding how HIV impacts the rate of progression to advanced cancer or death. Methods: The authors compared stage of disease at the time of presentation and mortality after diagnosis between 14,453 PLWH and 6,368,126 HIV‐uninfected patients diagnosed with cancers of the oral cavity, stomach, colorectum, anus, liver, pancreas, lung, female breast, cervix, prostate, bladder, kidney, and thyroid and melanoma using data from the National Cancer Data Base (2004‐2014). Polytomous logistic regression and Cox proportional hazards regression were used to evaluate the association between HIV, cancer stage, and stage‐adjusted mortality after diagnosis, respectively. Regression models accounted for the type of health facility at which cancer treatment was administered and the type of individual health insurance. Results: HIV‐infected patients with cancer were found to be more likely to be uninsured (HIV‐infected: 5.0% vs HIV‐uninfected: 3.3%; P < .0001) and were less likely to have private health insurance (25.4% vs 44.7%; P < .0001). Compared with those not infected with HIV, the odds of being diagnosed at an advanced stage of disease were significantly elevated in PLWH for melanoma and cancers of the oral cavity, liver, female breast, prostate, and thyroid (odds ratio for stage IV vs stage I range, 1.24‐2.06). PLWH who were diagnosed with stage I to stage III disease experienced elevated mortality after diagnosis across 13 of the 14 cancer sites evaluated, with hazard ratios ranging from 1.20 (95% CI, 1.14‐1.26) for lung cancer to 1.85 (95% CI, 1.68‐2.04), 1.85 (95% CI, 1.51‐2.27), and 2.93 (95% CI, 2.08‐4.13), respectively, for cancers of the female breast, cervix, and thyroid. Conclusions: PLWH were more likely to be diagnosed with advanced‐stage cancers and to experience elevated mortality after a cancer diagnosis, even after accounting for health care–related factors.

Organ transplant recipients (OTRs) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs in SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self‐report of skin biopsy (n = 170). Controls without SCSC (n = 324) were matched to cases on sex, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplantation and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the antimetabolite azathioprine were more than twice as likely to develop SCSC (odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.23–5.76). In contrast, the newer antimetabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR = 0.45, 95% CI 0.29–0.69). This inverse association between MPA and SCSC persisted among OTRs with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR = 0.52, 95% CI 0.32–0.84). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTRs prescribed newer regimens, including MPA and tacrolimus.

Background: Human immunodefieciency virus (HIV)-infected persons are living longer in the era of effective HIV treatment, resulting in an increasing cancer burden in this population. The combined effects of HIV and cancer on mortality are incompletely understood. Methods: We examined whether individuals with both HIV and cancer have excess mortality using data from the HIV/AIDS Cancer Match Study and the National Center for Health Statistics (1996–2010). We compared age, sex, and race-stratified mortality between people with and without HIV or one of the following cancers: lung, breast, prostate, colorectum, anus, Hodgkin lymphoma, or non-Hodgkin lymphoma. We utilized additive Poisson regression models that included terms for HIV, cancer, and an interaction for their combined effect on mortality. We report the number of excess deaths per 1,000 person-years for models with a significant interaction (P < 0.05). Results: For all cancers examined except prostate cancer, at least one demographic subgroup of HIV-infected cancer patients experienced significant excess mortality. Excess mortality was most pronounced at younger ages (30–49 years), with large excesses for males with lung cancer (white race: 573 per 1,000 person-years; non-white: 503) and non-Hodgkin lymphoma (white: 236; non-white: 261), and for females with Hodgkin lymphoma (white: 216; non-white: 136) and breast cancer (non-white: 107). Conclusions: In the era of effective HIV treatment, overall mortality in patients with both HIV and cancer was significantly higher than expected on the basis of mortality rates for each disease separately. Impact: These results suggest that HIV may contribute to cancer progression and highlight the importance of improved cancer prevention and care for the U.S. HIV population. Cancer Epidemiol Biomarkers Prev; 26(7); 1027–33. ©2017 AACR.

Epstein-Barr virus (EBV), a ubiquitous herpes virus that infects 90% of humans by adulthood, is linked to the development of various cancers, including nasopharyngeal carcinoma, gastric cancer, Burkitt lymphoma, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma. We reviewed the literature published since 1980 regarding an association between antibodies against EBV proteins and the risk of EBV-associated malignancies. Immunoglobulin A antibody levels that are elevated before diagnosis have consistently been associated with the risk of nasopharyngeal carcinoma, and patients with Hodgkin lymphoma have significantly higher immunoglobulin G antibody levels than disease-free controls. However, the link between the immune response to EBV and other EBV-associated malignancies was less clear. Although evidence of an association between the risk of Burkitt lymphoma and immunoglobulin G antibodies was consistent for available studies, the sample sizes were limited. Evidence for a link between antibodies against EBV and risk of either gastric cancer or NHL was inconsistent. Future investigations should account for tumor EBV status because only 7%–10% of gastric tumors and select NHL subtypes are related to EBV infection. Comparing differences in the associations between the humoral immune response to EBV and disease risk across cancers may help elucidate how this ubiquitous virus contributes to distinct tumors globally.

Although people living with HIV or AIDS (PLWHA) are at higher risk for many cancers, breast, prostate, and colorectal cancer rates are lower in this patient population. Because these tumors are often screen-detected, these inverse associations could be driven by HIV-related differences in utilization of cancer screening. We ascertained incident breast, prostate, and colorectal cancer in PLWHA using data from the HIV/AIDS Cancer Match Study (1996–2012). Comparisons with general population cancer rates were made using standardized incidence ratios (SIRs), overall and stratified by tumor stage/size, breast cancer estrogen receptor status, and colorectal site. We also examined the potential effect of study design and unmeasured confounding on inverse standardized incidence ratios. Compared with the general population, PLWHA had lower rates of invasive breast (SIR = 0.63, 95% confidence interval [CI] = 0.58 to 0.68), prostate (SIR = 0.48, 95% CI = 0.46 to 0.51), proximal colon (SIR = 0.67, 95% CI = 0.59 to 0.75), distal colon (SIR = 0.51, 95% CI = 0.43 to 0.59), and rectal cancers (SIR = 0.69, 95% CI = 0.61 to 0.77). Reduced risk persisted across tumor stage/size for prostate and colorectal cancers. Although distant-stage breast cancer rates were not reduced (SIR = 0.94, 95% CI = 0.73 to 1.20), HIV-infected women had lower rates of large (>5 cm) breast tumors (SIR = 0.65, 95% CI = 0.50 to 0.83). The magnitude of these inverse standardized incidence ratios could not plausibly be attributed to case underascertainment, out-migration, or unmeasured confounding. Breast, prostate, and colorectal cancer rates are markedly lower among PLWHA, including rates of distant-stage/large tumors that are not generally screen-detected. This set of inverse HIV-cancer associations is therefore unlikely to be due primarily to differential screening and may instead represent biological relationships requiring future investigation.