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.

An Evaluation of Dose-Related HPV Vaccine Effectiveness Using Central Registries in Michigan.

BACKGROUND: Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+). METHODS: We linked females in Michigan's immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case-cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination. RESULTS: Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI, 60%-71%) for UTD, 33% (95% CI, 18%-46%) for 2 doses-not UTD, and 40% (95% CI, 27%-50%) for 1 dose. The case-cohort analysis yielded VE estimates of 72% (95% CI, 64%-79%) for UTD, 39% (95% CI, 10%-58%) for 2 doses-not UTD, and 48% (95% CI, 25%-63%) for 1 dose. VE was higher for vaccination at age <20 than ≥20 years. CONCLUSIONS: The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination. IMPACT: Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness.

Anaplastic large cell lymphoma in human immunodeficiency virus-infected people and solid organ transplant recipients.

Human immunodeficiency virus (HIV)-infected people and solid organ transplant recipients have elevated risk of anaplastic large cell lymphoma (ALCL). Little is known regarding ALCL risk factors in immunosuppressed populations. We used data from US cancer registries linked to HIV registries (1996-2016) and to the national transplant registry (1992-2017). ALCL risk in HIV-infected people and transplant recipients relative to the general population was calculated as a standardized incidence ratio (SIR). ALCL risk factors were evaluated using Poisson regression. We identified 121 incident ALCL cases in the HIV (n = 86) and transplant (n = 35) populations. We reviewed pathology reports for 45 cases and most (86·7%) were confirmed as ALCL. Epstein-Barr virus tested positive in 1/8 (12·5%) cases. Compared to the general population, ALCL risk was strongly elevated among HIV-infected people [SIR 5·43; 95% confidence interval (CI) 4·27-6·81] and transplant recipients (5·96; 4·03-8·49). Among HIV-infected people, ALCL incidence was strongly related to CD4 count [adjusted incidence rate ratio (aIRR) 0·15 for ≥500 vs. <200 cells/µl; P trend < 0·001]. Among transplant recipients, risk was highest within the first year (aIRR 6·82) and 10+ years post-transplant (5·99). In conclusion, ALCL risk is strongly increased in these immunosuppressed populations but may be unrelated to EBV infection based on limited reports.

The Impact of Liver Transplantation on Hepatocellular Carcinoma Mortality in the United States.

BACKGROUND: Hepatocellular carcinoma (HCC) carries a poor prognosis. Liver transplantation (LT) is potentially curative for localized HCC. We evaluated the impact of LT on U.S. general population HCC-specific mortality rates. METHODS: The Transplant Cancer Match Study links the U.S. transplant registry with 17 cancer registries. We calculated age-standardized incidence (1987-2017) and incidence-based mortality (IBM) rates (1991-2017) for adult HCCs. We partitioned population-level IBM rates by cancer stage and calculated counterfactual IBM rates assuming transplanted cases had not received a transplant. RESULTS: Among 129,487 HCC cases, 45.9% had localized cancer. HCC incidence increased on average 4.0% annually [95% confidence interval (CI) = 3.6-4.5]. IBM also increased for HCC overall (2.9% annually; 95% CI = 1.7-4.2) and specifically for localized stage HCC (4.8% annually; 95% CI = 4.0-5.5). The proportion of HCC-related transplants jumped sharply from 6.7% (2001) to 18.0% (2002), and further increased to 40.0% (2017). HCC-specific mortality declined among both nontransplanted and transplanted cases over time. In the absence of transplants, IBM for localized HCC would have increased at 5.3% instead of 4.8% annually. CONCLUSIONS: LT has provided survival benefit to patients with localized HCC. However, diagnosis of many cases at advanced stages, limited availability of donor livers, and improved mortality for patients without transplants have limited the impact of transplantation on general population HCC-specific mortality rates. IMPACT: Although LT rates continue to rise, better screening and treatment modalities are needed to halt the rising HCC mortality rates in the United States.See related commentary by Zhang and Thrift, p. 435.

Overview of Centers for Disease Control and Prevention's Case Investigation of Cervical Cancer Study.

Background: Despite advances in cervical cancer screening, a significant number of women in the United States have not received adequate screening. Studies have suggested that approximately half of the women who developed cervical cancer were not adequately screened. The Centers for Disease Control and Prevention (CDC) Case Investigation of Cervical Cancer (CICC) Study took a unique approach to reconstruct the time before a woman's cervical cancer diagnosis and understand the facilitators and barriers to screening and care. This article provides an overview of the study. Methods: This study included all cervical cancer survivors diagnosed with invasive cervical cancer aged 21 years and older in three U.S. states from 2014-2016. The study design consisted of three different data collection methods, including comprehensive registry data, a mailed survey, and medical chart abstraction. This overview compares the characteristics of cervical cancer survivors in the three states by study participation and eligibility status. Results: Registries identified 2,748 women diagnosed with invasive cervical cancer. Of these, 1,730 participants were eligible for participation, 28% (n = 481) enrolled in the study and 23% (n = 400) consented to the medical chart abstraction. Conclusion: The CICC Study is unique in that it addresses, with medical record verification, the medical history of woman 5 years before their cervical cancer diagnosis as well as provides information from the woman on her health care behaviors. This study provides data on a general population of cervical cancer survivors in three states that could be used to guide interventions to increase cervical cancer screening.