Cancers with epidemiologic signatures of viral oncogenicity among immunocompromised populations in the United States.

BACKGROUND: Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV (PWH) and solid organ transplant recipients (SOTRs), two immunosuppressed populations, may help identify novel etiologic relationships with infectious agents. METHODS: We utilized two linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified based on site and histology codes. Standardized incidence ratios (SIRs) were used to compare risk in PWH and SOTRs with the general population. For selected cancer entities, incidence rate ratios (IRRs) were calculated for indicators of immunosuppression within each population. FINDINGS: We identified 38,047 cancer cases in SOTRs and 53,592 in PWH, yielding overall SIRs of 1.66 (95%CI = 1.65-1.68) and 1.49 (95%CI = 1.47-1.50), respectively. Forty-three cancer entities met selection criteria, including conjunctival squamous cell carcinoma (SCC) (PWH SIR = 7.1, 95%CI = 5.5-9.2; SOTRs SIR = 9.4; 95%CI = 6.8-12.6). Sebaceous adenocarcinoma was elevated in SOTRs (SIR = 16.2; 95%CI = 14.0-18.6) and, among SOTRs, associated with greater risk in lung/heart transplant recipients compared to recipients of other organs (IRR = 2.3; 95%CI = 1.7-3.2). Salivary gland tumors, malignant fibrous histiocytoma (MFH), and intrahepatic cholangiocarcinoma showed elevated risk in SOTRs (SIR = 3.9; SIR = 4.7; and SIR = 3.2, respectively) but not in PWH. However, risks for these cancers were elevated following an AIDS diagnosis among PWH (IRR = 2.4; IRR = 4.3; and IRR = 2.0, respectively). INTERPRETATION: Elevated SIRs among SOTRs and PWH, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival SCC, sebaceous adenocarcinoma, salivary gland tumors, MFH, and intrahepatic cholangiocarcinoma.

Outcomes in solid organ transplant recipients with a pretransplant diagnosis of melanoma.

Melanoma causes significant morbidity in solid organ transplant recipients (SOTRs). Melanomas diagnosed before transplantation can recur with intensive immunosuppression, but outcomes have not been well studied. We evaluated 901 non-Hispanic White SOTRs with a pretransplant melanoma identified using linked transplant and cancer registry data in the United States. Most pretransplant melanomas were invasive (60.7%), and the median time from diagnosis to transplantation was 5.1 years. After transplantation, 41 SOTRs developed a new invasive melanoma, corresponding to 9-fold increased risk compared with the general population (standardized incidence ratio, 9.2; 95% confidence interval [CI], 6.6-12). Twenty-two SOTRs died from melanoma after transplantation, corresponding to 52-fold increased risk (standardized mortality ratio, 52; 95% CI, 33-79). Risk factors for posttransplant melanoma included age at transplantation (adjusted hazard ratio [HR], 2.86; 95% CI, 1.24-6.60; for age 55+ vs <55 years) and maintenance immunosuppression with cyclosporine/azathioprine (adjusted HR, 2.53; 95% CI, 1.08-5.90). Melanoma mortality was strongly elevated after a posttransplant melanoma diagnosis (HR, 35.6; 95% CI, 14.0-90.4; adjusted for cyclosporine/azathioprine maintenance therapy and calendar year of transplantation). In conclusion, SOTRs with a pretransplant melanoma are at risk of adverse melanoma-related outcomes after transplantation. These findings support thorough dermatologic evaluation prior to transplantation and frequent posttransplant surveillance.

Survival by sex and HIV status in patients with anal cancer in the USA between 2001 and 2019: a retrospective cohort study.

BACKGROUND: The risk of anal cancer is increased among people with HIV, particularly men who have sex with men. Estimating survival by HIV status and sex and identifying groups at high risk is crucial for documenting prognostic differences between populations. We aimed to compare all-cause and anal cancer-specific survival in patients with anal cancer with and without HIV, stratified by sex, and to identify predictors of survival, stratified by HIV status. METHODS: In this retrospective cohort study, we used data from the HIV/AIDS Cancer Match Study of 13 population-based HIV and cancer registries throughout the USA. We included individuals aged 20-79 years diagnosed with invasive anal cancer between 2001 and 2019. To estimate associations between HIV status and both all-cause and anal cancer-specific mortality overall, we used Cox proportional hazards models, adjusting for year of and age at diagnosis, sex, race and ethnicity, histology, cancer stage, region, and treatment. We also calculated sex-specific adjusted hazard ratios (HRs). By HIV status, we identified characteristics associated with mortality. Models among people with HIV were further adjusted for AIDS status and HIV transmission risk group. FINDINGS: Between Jan 1, 2001, and Dec 31, 2019, 1161 (43·6%) of 2662 patients with anal cancer and HIV and 7722 (35·4%) of 21 824 patients without HIV died. HIV was associated with a 1·35 times (95% CI 1·24-1·47) increase in all-cause mortality among male patients and a 2·47 times (2·10-2·90) increase among female patients. Among patients with HIV, all-cause mortality was increased among non-Hispanic Black individuals (adjusted HR 1·19, 95% CI 1·04-1·38), people with AIDS (1·36, 1·10-1·68), people who inject drugs (PWID; 1·49, 1·17-1·90), patients with adenocarcinoma (2·74, 1·82-4·13), and those with no or unknown surgery treatment (1·34, 1·18-1·53). HIV was associated with anal cancer-specific mortality among female patients only (1·52, 1·18-1·97). Among patients with HIV, anal cancer-specific mortality was increased among patients with adenocarcinoma (3·29, 1·89-5·72), those with no or unknown treatment (1·59, 1·17-2·17), and PWID (1·60, 1·05-2·44). INTERPRETATION: HIV was associated with all-cause mortality among patients with anal cancer, especially women. Anal cancer-specific mortality was elevated among female patients with HIV. As screening for anal cancer becomes more widespread, examining the effects of screening on survival by HIV status and sex is crucial. FUNDING: US National Cancer Institute Intramural Research Program.

Pancreatic cancer among solid organ transplant recipients in the United States.

INTRODUCTION: Pancreatic cancer (PC) in solid organ transplant (SOT) recipients is not well studied. Some PC cases may be incidentally detected during hepatobiliary imaging. METHODS: We evaluated PC among 374,106 SOT recipients during 1995-2017 in the United States using linked data from the national transplant registry and multiple state/regional cancer registries. Standardized incidence ratios (SIRs) were used to compare PC risk in recipients to the general population. We used multivariate Poisson regression to identify independent risk factors for PC. We assessed survival after PC diagnosis using Kaplan-Meier curves and log-rank tests. RESULTS: SOT recipients had elevated incidence for PC compared with the general population (SIR 1.40, 95% CI 1.29-1.52), and this increase was strongest in liver recipients (1.65, 1.41-1.92). Among all recipients, PC incidence was especially increased for cases arising in the head of the pancreas (SIR 1.50, 95% CI 1.34-1.68) and for cases diagnosed at localized stage (1.85, 1.37-2.44). Among SOT recipients, factors independently associated with increased incidence were consistent with those in general population including male sex, older age, non-O blood type, and history of diabetes. Additionally, compared to other organ recipients, liver transplant recipients had higher PC incidence (adjusted incidence rate ratio 1.28; 95% CI 1.06-1.54). Overall survival after PC diagnosis was poor (median 4 months) and similar between liver and other organ transplant recipients (p = 0.08). CONCLUSIONS: PC incidence is elevated among SOT recipients, and more commonly diagnosed in liver transplant recipients perhaps related to incidental detection. However, survival is poor even in liver recipients, arguing against routine PC screening.

Using LexisNexis to Improve Social Security Number Information in the New York State Cancer Registry.

Background: Social Security numbers (SSNs) collected by cancer surveillance registries in the United States are used for patient matching, deduplication, follow-up, and linkage studies. However, due to various reasons, a small proportion of patient records have missing or inaccurate SSNs. Recently, New York State Cancer Registry (NYSCR) data have been linked to LexisNexis data to obtain patient demographic information, including SSNs. The current study evaluated the feasibility of using LexisNexis to improve SSN information in the NYSCR. Materials and Methods: Patients diagnosed during the years 2005-2016, aged 21 or older, in the NYSCR were linked to LexisNexis data. For the matched patients, LexisNexis returned demographic information, including SSNs as available. Percentages of patients without LexisNexis matches or without LexisNexis SSNs were examined by demographic characteristics. We used multivariate logistic regression analyses to further evaluate how patient demographic characteristics affected the likelihood of no LexisNexis matches or of no SSNs returned. For patients with SSNs returned, LexisNexis SSNs were compared with registry SSNs. If patients had prior missing registry SSNs or if LexisNexis SSNs were inconsistent with registry SSNs, we used Match*Pro to review and verify match status. Registry SSNs were updated for those confirmed to be true matches. Improvement of SSNs was assessed based on percentage reduction of missingness. Results: Of 1,396,078 patient records submitted for LexisNexis linkage, 1.6% were not matched. Among those matched, 1.5% did not have SSNs returned. Multivariate logistic regression analyses indicated that patients who were female, Black, Asian Pacific Islander (API), Hispanic, born outside the United States, deceased, or living in poorer census tracts were more likely to not have LexisNexis matches, or to not have SSNs returned. Among 47,271 patients with missing registry SSNs (3.4%), 26,895 had SSNs returned from LexisNexis, and 24,919 were confirmed to be true matches. After registry SSNs updates, the percentage of SSN missingness was reduced to 1.7%, with a larger absolute reduction observed among those who were younger than 60 years, API, or alive. For 33,057 patients with inconsistent SSNs, 11,474 were due to incorrect consolidations of SSNs in the registry, and those SSNs were subsequently fixed. Conclusions: LexisNexis is a valuable resource for improving the quality of SSN information in registries. Our results showed that the overall percentage of patients with missing SSNs was reduced from 3.4% to 1.7% after LexisNexis link-age, and SSNs that were initially incorrectly consolidated for some patients were also identified and subsequently fixed. However, the magnitude of SSN improvement varied by patient demographic characteristics. Data quality improvements often require resources, and this evaluation can assist registries with decisions related to similar efforts.

Identifying Factors Associated with Loss to Follow-up Among Patients Reported to the New York State Cancer Registry.

Background: State cancer registries in the United States are data sources for estimating population-based cancer survival. However, the completeness of patient follow-up can affect the accuracy of survival estimates. Like many registries, the New York State Cancer Registry (NYSCR) conducts patient follow-up largely through linkages with other data sources. Even after expending great effort on linkages, a small proportion of patients remain lost to follow-up (LTFU). In this study, we identified factors that are associated with the likelihood of LTFU in the NYSCR. Methods: First primary cancers (sequence number, 00 or 01 and excluding death-certificate- and autopsy-only cases) diagnosed during 2000-2018 among New York State residents were selected for study. All patients were followed through December 31, 2018. Based on each patient's vital status and last contact date, follow-up status was categorized into 2 groups: patients LTFU and patients not LTFU. Patients LTFU were examined by demographic and tumor characteristics. Multivariate logistic regression analyses were performed to evaluate the association between demographic/tumor characteristics and likelihood of LTFU. For patients LTFU, the timing of LTFU (within 1 year, 1 to <5 years, 5 to <10 years, or >10 years) was further described. LTFU rates within 5 years after cancer diagnosis were also examined. Results: Among 1,797,228 patients, 74,722 were LTFU prior to December 31, 2018, representing 4.2% of all patients and 7.6% of alive patients. About 60% of LTFU occurred within 1 year after cancer diagnosis. Compared to the reference group, logistic regression analyses indicated that patients LTFU were more likely to be female, Black, Asian/Pacific Islander (API), Hispanic, foreign born, insured by Medicaid, uninsured, aged <20 years, and living in New York City or metropolitan counties. Cases reported by laboratories only and physician offices also had a higher likelihood of LTFU. Similar patterns and effects were identified when evaluating 5-year LTFU. Conclusion: Identifying factors associated with patient LTFU is important for cancer registries to improve follow-up data. We found that LTFU is not random; rather, certain patient groups have higher LTFU rates than others. For registries that conduct follow-up through linkages, it is critical to collect high-quality and complete demographic data, especially for females, children, the foreign born, and minority race/ethnicity groups.

Characteristics and survival of children with acute leukemia with Down syndrome or other birth defects in New York State.

BACKGROUND: Acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) among DS children have been studied extensively using data from clinical trials or institutional reports. The purpose of this study was to link population-based cancer and birth defects data to evaluate characteristics and survival of children with acute leukemia according to the presence of DS or other birth defects. METHODS: ALL and AML cases diagnosed between 1983 and 2012 among children aged 0-14 years were obtained from the New York State Cancer Registry. Birth defect status (DS, other birth defects, or no birth defects) was determined by linking with birth defects data. Associations between birth defect status and demographic characteristics were evaluated using contingency table analysis. Ten-year survival was calculated by birth defect status and other potential prognostic factors. Cox proportional hazards regression analysis was also performed. RESULTS: Among 2941 ALL children, 1.6% had DS, 3.8% had other birth defects, and 94.5% had no birth defects. Birth defect status was significantly associated with age at ALL diagnosis. Survivals were similar among three groups. Among 563 AML children, 11.0% had DS, 6.0% had other birth defects, and 83.0% had no birth defects. Children with DS were more likely to be diagnosed with AML at a younger age and showed the best survival. CONCLUSION: Age at leukemia diagnosis was significantly associated with the birth defect status. Comparable survival was observed for ALL children. However, AML children with DS demonstrated superior survival compared to children with other birth defects or no birth defects.

Cancer risk among lung transplant recipients with cystic fibrosis.

BACKGROUND: Previous studies demonstrated increased digestive tract cancers among individuals with cystic fibrosis (CF), particularly among lung transplant recipients. We describe cancer incidence among CF and non-CF lung recipients. METHODS: We used data from the US transplant registry and 16 cancer registries. Standardized incidence ratios (SIRs) compared cancer incidence to the general population, and competing risk methods were used for the cumulative incidence of colorectal cancer. RESULTS: We evaluated 10,179 lung recipients (1681 with CF). Risk was more strongly increased in CF recipients than non-CF recipients for overall cancer (SIR 9.9 vs. 2.7) and multiple cancers including colorectal cancer (24.2 vs. 1.7), esophageal cancer (56.3 vs. 1.3), and non-Hodgkin lymphoma (61.8 vs. 9.4). At five years post-transplant, colorectal cancer was diagnosed in 0.3% of CF recipients aged <50 at transplant and 6.4% aged ≥50. CONCLUSIONS: CF recipients have increased risk for colorectal cancer, suggesting a need for enhanced screening.

Comprehensive Evaluation of Medical Conditions Associated with Risk of Non-Hodgkin Lymphoma using Medicare Claims ("MedWAS").

BACKGROUND: Certain medical conditions affect risk of non-Hodgkin lymphoma (NHL), but the full range of associations is unknown. We implemented a novel method ("medical condition-wide association study," MedWAS) to comprehensively evaluate medical risk factors for NHL documented in administrative health claims. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we conducted a case-control study comparing NHL cases [N = 52,691, age 66+ years, with five subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, marginal zone lymphoma (MZL), T-cell lymphoma (TCL)] to controls (N = 200,000). We systematically screened for associations with 5,926 medical conditions documented in Medicare claims more than 1 year before selection. RESULTS: Fifty-five conditions were variously associated with NHL. Examples include well-established associations of human immunodeficiency virus, solid organ transplantation, and hepatitis C virus with increased DLBCL risk (ORs 3.83, 4.27, and 1.74, respectively), and autoimmune conditions with DLBCL and MZL (e.g., ORs of 2.10 and 4.74, respectively, for Sjögren syndrome). Risks for all NHL subtypes were increased after diagnoses of nonmelanoma skin cancer (ORs 1.19-1.55), actinic keratosis (1.12-1.25), or hemolytic anemia (1.64-4.07). Nine additional skin conditions increased only TCL risk (ORs 2.20-4.12). Diabetes mellitus was associated with increased DLBCL risk (OR 1.09). Associations varied significantly across NHL subtypes for 49 conditions (89%). CONCLUSION: Using an exploratory method, we found numerous medical conditions associated with NHL risk, and many associations varied across NHL subtypes. IMPACT: These results point to etiologic heterogeneity among NHL subtypes. MedWAS is a new method for assessing the etiology of cancer and other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1105-13. ©2016 AACR.

Reproductive outcomes among former Love Canal residents, Niagara Falls, New York.

Love Canal, located in Niagara Falls, NY, and among the earliest and most significant hazardous waste sites in the United States, first came to public attention in 1978. In this study, researchers evaluated 1,799 live births from 1960 through 1996 to 980 women who formerly lived in the Love Canal Emergency Declaration Area and were of reproductive age sometime during that time period. Using Upstate New York and Niagara County as external comparison populations, standardized incidence ratios with 95% confidence intervals were calculated for low birth weight, preterm birth, small for gestational age, and congenital malformations, and unadjusted proportions of male to female births were calculated. Internal comparisons among the infants were also performed according to several measures of potential exposure using generalized estimating equations. The results indicated a statistically significant elevated risk of preterm birth among children born on the Love Canal prior to the time of evacuation and relocation of residents from the Emergency Declaration Area, using Upstate New York as the standard population (standardized incidence ratio=1.40; 95% confidence interval: 1.01, 1.90). Additionally, the ratio of male to female births was lower for children conceived in the Emergency Declaration Area (sex ratio=0.94 versus sex ratio=1.05 in the standard population) and the frequency of congenital malformations was greater than expected among Love Canal boys born from 1983 to 1996 (standardized incidence ratio=1.50 when compared to Upstate New York), although in both cases the 95% confidence interval included the null value. Finally, increased risk for low birth weight infants among mothers who lived closest to the Canal as children was found (odds ratio=4.68; 95% confidence interval: 1.24, 17.66), but this estimate was limited due to small numbers (n=4). The study adds to the knowledge of the possible reproductive effects from exposure to chemicals arising from hazardous waste; however, given the small number of some events, the qualitative nature of the exposure assessment, and possibility of spurious associations due to multiple comparisons, the findings should be interpreted cautiously.

Primary care physician experience with children with oral clefts in three states.

BACKGROUND: The experience of primary care physicians in Arkansas, Iowa, and New York treating children with oral clefts (OCs) was investigated, along with their knowledge and comfort caring for or referring these children. METHODS: A mail survey was conducted with all primary care physicians in Iowa and Arkansas, and a random sample of 4000 physicians in New York, selected from the American Medical Association (AMA) Master File. The final dataset consisted of 1435 usable surveys. Outcome measures were experience and comfort providing care to or referring children with OC. Differences between states were tested using Pearson or Kruskal-Wallis chi-square tests, or F-tests for differences in means. RESULTS: Two-thirds of respondents had provided care to a child with an OC since completing residency. Physicians were most comfortable providing routine care and much less comfortable providing counseling on cleft-related issues. Eighty percent had an organized cleft team to which they could refer. About two-thirds were very comfortable with the expertise available for surgical care, speech, and hearing; half were for dental care; only 40% were for behavioral or emotional counseling. Two-thirds were interested in continuing medical education (CME) on cleft care. CONCLUSIONS: Primary care physicians in all three states had little experience with children with OCs. This limited experience poses significant barriers to care. Increased experience during training and CME opportunities could improve knowledge and comfort with providing OC-related care. Increasing knowledge of referral options for team care and other cleft-related services could also help physicians when caring for children with OCs.

Prenatal diagnosis of orofacial clefts: association with maternal satisfaction, team care, and treatment outcomes.

OBJECTIVE: Prenatal diagnosis of an orofacial cleft is thought to allow mothers greater opportunity to become prepared for the special needs of an infant with a cleft and plan for the care of their child. Using a population-based sample, we determined which children were more likely to be diagnosed prenatally, and whether early diagnosis was associated with maternal satisfaction and treatment outcomes. DESIGN: Interviews were completed with 235 (49% of eligible) mothers of children ages 2 to 7 with orofacial clefts initially enrolled in the National Birth Defects Prevention Study from the Arkansas, Iowa, and New York sites. Maternal satisfaction with information, support, and treatment outcomes was compared between women who received a prenatal diagnosis and those who did not. RESULTS: Of 235 infants with clefts, 46 (19.6%) were identified prenatally. One third of mothers were somewhat or not satisfied with information provided by medical staff. Satisfaction did not vary by timing of the diagnosis. Infants diagnosed prenatally were no more likely to have received care provided by a recognized multidisciplinary cleft team (76%) than were infants diagnosed at birth (78%). Speech problems and facial appearance as rated by the mother did not vary by timing of the diagnosis. CONCLUSIONS: Timing of the cleft diagnosis did not alter maternal satisfaction with information, whether care was provided by a designated cleft team, or maternal perception of facial appearance or speech. Further research should determine whether prenatal diagnoses alter maternal anxiety or influence postnatal morbidity.

Interdisciplinary craniofacial teams compared with individual providers: is orofacial cleft care more comprehensive and do parents perceive better outcomes?

OBJECTIVE: The primary objective was to examine whether children with orofacial clefts received more comprehensive care and whether their parents perceived better outcomes if the care was delivered by interdisciplinary teams compared with individual providers. DESIGN: Data about services received and outcomes were collected from mothers of children with orofacial clefts. PARTICIPANTS: Mothers of children born between 1998 and 2003 with orofacial clefts from Arkansas, Iowa, and New York who participated in the National Birth Defects Prevention Study were eligible. MAIN OUTCOME MEASURE(S): Services and treatments received and maternal perception of cleft care, health status, aesthetics, and speech were evaluated by team care status. RESULTS: Of 253 children, 24% were not receiving team care. Of those with cleft lip and palate, 86% were enrolled in team care. Compared with children with team care, those without had fewer surgeries and were less likely to have seen a dentist, received a hearing test, or had a genetic consultation. Mothers of children lacking team care were twice as likely to give lower ratings for overall cleft care; maternal perceptions of global health, facial appearance, and speech did not differ by team care status. CONCLUSIONS: Recommended care tended to be received more often among those with team care. A larger, longitudinal study might answer questions about whether team care provides the best care and the role that type and severity of the condition and racial/ethnic differences play in the services received and outcomes experienced.

Demographic characteristics, care, and outcomes for children with oral clefts in three states using participants from the National Birth Defects Prevention Study.

OBJECTIVE: The primary objective of this study was to evaluate whether there were differences in the characteristics and outcomes of care for children with oral clefts (OCs) among population-based samples in three states. DESIGN: Data on the health status and on speech and esthetic outcomes were collected using structured telephone interviews conducted during 2005-2006 with mothers of children with OCs aged 2 to 7 in Arkansas, Iowa, and New York. PARTICIPANTS: Mothers of children born with nonsyndromic OCs on or after January 1, 1998, and on or before December 31, 2003, in Arkansas, Iowa, or New York. Subjects were identified through their participation in the ongoing National Birth Defects Prevention Study. MAIN OUTCOME MEASURES: Demographic characteristics, rating of cleft care, severity of condition, health status, esthetic outcomes, and speech problems were evaluated by state of residence. RESULTS: Children with OCs from Arkansas were from lower income families, and their parents were less likely to be married. Children with OCs from Arkansas were more likely to have special health care needs and to require mental health care. Few differences were found across states in type of cleft, severity of cleft, or outcomes of cleft care. CONCLUSIONS: Combining results from population-based samples across multiple studies increases the variability of sample characteristics. Including multiple states can be an efficient way to learn more about the outcomes of medical care for less common conditions such as oral cleft.