Jack L. Finch

CONTEXT: Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology. OBJECTIVE: To describe the overall pattern of cancer following solid organ transplantation. DESIGN, SETTING, AND PARTICIPANTS: Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries. MAIN OUTCOME MEASURES: Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population. RESULTS: The registry linkages yielded data on 175,732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10,656 cases and an incidence of 1375 per 100,000 person-years (SIR, 2.10 [95% CI, 2.06-2.14]; EAR, 719.3 [95% CI, 693.3-745.6] per 100,000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100,000 person-years; SIR, 7.54 [95% CI, 7.17-7.93]; EAR, 168.3 [95% CI, 158.6-178.4] per 100,000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100,000 person-years; SIR, 1.97 [95% CI, 1.86-2.08]; EAR, 85.3 [95% CI, 76.2-94.8] per 100,000 person-years), liver (n = 930; incidence: 120.0 per 100,000 person-years; SIR, 11.56 [95% CI, 10.83-12.33]; EAR, 109.6 [95% CI, 102.0-117.6] per 100,000 person-years), and kidney (n = 752; incidence: 97.0 per 100,000 person-years; SIR, 4.65 [95% CI, 4.32-4.99]; EAR, 76.1 [95% CI, 69.3-83.3] per 100,000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 [95% CI, 5.18-7.21]) but also increased among other recipients (kidney: SIR, 1.46 [95% CI, 1.34-1.59]; liver: SIR, 1.95 [95% CI, 1.74-2.19]; and heart: SIR, 2.67 [95% CI, 2.40-2.95]). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 [95% CI, 40.90-46.91]), who manifested exceptional risk in the first 6 months (SIR, 508.97 [95% CI, 474.16-545.66]) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 [95% CI, 1.57-3.04]). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 [95% CI, 6.12-7.23]) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 [95% CI, 1.40-2.29]) and heart recipients (SIR, 2.90 [95% CI, 2.32-3.59]). CONCLUSION: Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers.

Data are limited regarding cancer risk in human immunodeficiency virus (HIV)-infected persons with modest immunosuppression, before the onset of acquired immunodeficiency syndrome (AIDS). For some cancers, risk may be affected by highly active antiretroviral therapy (HAART) widely available since 1996. We linked HIV/AIDS and cancer registries in Colorado, Florida and New Jersey. Standardized incidence ratios (SIRs) compared cancer risk in HIV-infected persons (initially AIDS-free) during the 5-year period after registration with the general population. Poisson regression was used to compare incidence across subgroups, adjusting for demographic factors. Among 57,350 HIV-infected persons registered during 1991-2002 (median CD4 count 491 cells/mm(3)), 871 cancers occurred during follow-up. Risk was elevated for Kaposi sarcoma (KS, SIR 1,300 [n = 173 cases]), non-Hodgkin lymphoma (NHL, 7.3 [n = 203]), cervical cancer (2.9 [n = 28]) and several non-AIDS-defining malignancies, including Hodgkin lymphoma (5.6 [n = 36]) and cancers of the lung (2.6 [n = 109]) and liver (2.7 [n = 14]). KS and NHL incidence declined over time but nonetheless remained elevated in 1996-2002. Incidence increased in 1996-2002 compared to 1991-1995 for Hodgkin lymphoma (relative risk 2.7, 95%CI 1.0-7.1) and liver cancer (relative risk infinite, one-sided 95%CI 1.1-infinity). Non-AIDS-defining cancers comprised 31.4% of cancers in 1991-1995, versus 58.0% in 1996-2002. For KS and NHL, risk was inversely related to CD4 count, but these associations attenuated after 1996. We conclude that KS and NHL incidence declined markedly in recent years, likely reflecting HAART-related improvements in immunity, while incidence of some non-AIDS-defining cancers increased. These trends have led to a shift in the spectrum of cancer among HIV-infected persons.

BACKGROUND: Understanding the ways in which socioeconomic status (SES) affects mortality is important for defining strategies to eliminate the unequal burden of cancer by race and ethnicity in the United States. METHODS: Disease stage, treatment, and 5-year mortality rates were ascertained by reviewing medical records, and SES was determined by analyzing income and education at the census tract level for 4844 women with breast cancer, 4332 men with prostate cancer, and 4422 men and women with colorectal cancer who were diagnosed in 7 U.S. states in 1997. RESULTS: Low SES was associated with more advanced disease stage and with less aggressive treatment for all 3 cancers. The hazard ratio (HR) for 5-year all-cause mortality associated with low SES was elevated after a diagnosis of breast cancer when the analysis was adjusted for age (HR, 1.59; 95% confidence interval [CI], 1.35-1.87). Adjustment for mediating factors of race/ethnicity, comorbid conditions, cancer stage, and treatment reduced the association. The age-adjusted mortality risk associated with low SES was elevated after a diagnosis of prostate cancer (HR, 1.33; 95% CI, 1.13-1.57), and multivariate adjustments for mediating factors also reduced that association. There was less association between SES and mortality after a diagnosis of colorectal cancer. For all 3 cancer sites, low SES was a much stronger predictor of mortality among individuals aged <65 years and among individuals from racial/ethnic minority groups. CONCLUSIONS: The current results indicated that low SES is a risk factor for all-cause mortality after a diagnosis of cancer, largely because of a later stage at diagnosis and less aggressive treatment. These findings support the need to focus on SES as an underlying factor in cancer disparities by race and ethnicity.

OBJECTIVES/HYPOTHESIS: To document the increasing incidence of oropharyngeal (OP) cancer and to provide evidence that this increase is caused by oncogenic human papilloma virus (HPV). STUDY DESIGN: Epidemiologic review and retrospective case series analysis. METHODS: We collected data from Colorado and the United States comparing the average annual age-adjusted incidence rates of OP and non-OP head and neck cancer between the periods 1980 to 1990 and 1991 to 2001. We obtained data on 72 patients with OP cancer from a single county in Colorado, from 1980 through 2004. HPV status was determined by DNA-polymerase chain reaction. We assessed disease-specific survival. RESULTS: The average annual age-adjusted incidence of OP cancer in males in Colorado increased from 2.54 per 100,000 to 3.47 (P < .05) or 36.6%, whereas the U.S. rate increased from 4.34 to 4.81 (P < .05) or 10.8%. The rates in females and the rates of non-OP head and neck cancer decreased. Of the 72 cases, 50 (69%) were positive for HPV subtype 16. The ratio of HPV-positive to HPV-negative cases prior to 1995 was 0.72 (8:11) but was 3.81 (42:11) afterward. Survival was positively affected by HPV status (hazard ratio of 0.15, confidence intervals 0.07-0.36, P < .001). Disease-specific survival was 83% in the HPV-positive patients and 15% in the HPV-negative group. CONCLUSIONS: OP cancer incidence is increasing in Colorado males and to a lesser extent in U.S. males. The HPV-positive OP cancer cases were more frequent in the later years of the study. Disease-specific survival was much better in the HPV-positive patients, confirming that HPV testing defines a unique subset of patients. These findings suggest that HPV oncogenesis accounts for the increase in average annual age-adjusted incidence of OP cancer.

BACKGROUND: Solid organ transplant recipients have elevated risks of virus-related cancers, in part because of long-term immunosuppression. Merkel cell carcinoma (MCC) is an aggressive skin cancer recently found to have a viral origin, but little is known regarding the occurrence of MCC after transplant. METHODS: We linked the US Scientific Registry of Transplant Recipients with data from 15 population-based cancer registries to ascertain MCC occurrence among 189498 solid organ transplant recipients from 1987 to 2009. Risks for MCC following transplantation were compared with the general population using standardized incidence ratios, and Poisson regression was used to compare incidence rates according to key patient and transplant characteristics. All statistical tests were two-sided. RESULTS: After solid organ transplantation, overall risk of MCC was increased 23.8-fold (95% confidence interval = 19.6 to 28.7, n = 110). Adjusted risks were highest among older recipients, increased with time since transplantation, and varied by organ type (all P ≤ .007). Azathioprine, cyclosporine, and mTOR inhibitors given for maintenance immunosuppression increased risk, and non-Hispanic white recipients on cyclosporine and azathioprine experienced increasing MCC risk with lower latitude of residence (ie, higher ultraviolet radiation exposure, P = .012). CONCLUSIONS: MCC risk is sharply elevated after solid organ transplant, likely resulting from long-term immunosuppression. Immunosuppressive medications may act synergistically with ultraviolet radiation to increase risk.