Cancer risk associated with cytomegalovirus infection among solid organ transplant recipients in the United States

Jennifer M. Geris, Logan G. Spector, Ruth M. Pfeiffer, Ajit P. Limaye, Kelly J. Yu, Eric A. Engels

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Cytomegalovirus (CMV) is among the most common viral infections after solid organ transplantation (SOT). Associations of CMV with cancer risk among SOT recipients have been incompletely evaluated. Methods: The authors used linked data from the US SOT registry and 32 cancer registries. Poisson regression was used to compare cancer incidence across CMV risk groups based on donor (D) and recipient (R) immunoglobulin G (IgG) serostatus: high risk (R-negative/D-positive), moderate risk (R-positive), and low risk (R-negative/D-negative). Results: In total, 247,318 SOT recipients were evaluated during 2000–2017 (R-negative/D-positive, 20.3%; R-positive, 62.9%; R-negative/D-negative, 16.8%). CMV-seropositive recipients were older, more racially/ethnically diverse, and had lower socioeconomic status than CMV-seronegative recipients. Compared with R-negative/D-negative recipients, recipients in the R-negative/D-positive and R-positive groups had a lower incidence of diffuse large B-cell lymphoma (DLBCL; R-negative/D-positive: adjusted incidence rate ratio [aIRR], 0.74; 95% confidence interval [CI], 0.59–0.91; R-positive: aIRR, 0.83; 95% CI, 0.69–1.00). CMV serostatus modified the association between Epstein–Barr virus (EBV) status and DLBCL (p =.0006): DLBCL incidence was increased for EBV R-negative/D-positive recipients (aIRR, 3.46; 95% CI, 1.50–7.95) among CMV R-negative/D-negative recipients but not among the other CMV risk groups. Compared with recipients who were CMV R-negative/D-negative, those who were R-negative/D-positive had a lower incidence of small intestine cancer (aIRR, 0.23; 95% CI, 0.09–0.63), and R-positive recipients had a higher incidence of lung cancer (aIRR, 1.24; 95% CI, 1.05–1.46). CMV status was not associated with risk for other cancers. Conclusions: CMV status was not associated with risk for most cancers among SOT recipients. The inverse association with DLBCL may reflect the protective effects of CMV prophylaxis or treatment with off-target efficacy against EBV infection (the major cause of lymphoma in SOT recipients).

Original languageEnglish (US)
Pages (from-to)3985-3994
Number of pages10
JournalCancer
Volume128
Issue number22
DOIs
StatePublished - Nov 15 2022
Externally publishedYes

Bibliographical note

Funding Information:
The authors gratefully acknowledge the support and assistance provided by individuals at the Health Resources and Services Administration, the Scientific Registry of Transplant Recipients (SRTR; Ajay Israni, Bertram Kasiske, Paul Newkirk, and Jon Snyder), and the following cancer registries: the states of Alabama (Justin George), Alaska (David O'Brien), Arkansas (Lunda Lehing), California (Cyllene Morris), Colorado (Jack Finch), Connecticut (Lou Gonsalves), Florida (Brad Wohler), Georgia (Rana Bayakly), Hawaii (Brenda Hernandez), Idaho (Bozena Morawski), Illinois (Lori Koch), Iowa (Charles Lynch), Kentucky (Jaclyn McDowell), Louisiana (Meichin Hsieh), Michigan (Georgetta Alverson), Montana (Heather Zimmerman), Nebraska (Lifeng Li), Nevada (Ben Claassen), New Jersey (Xiaoling Niu), New Mexico (Angela Meisner), New York (Maria Schymura), North Carolina (Chandrika Rao), North Dakota (Yun Zeng), Ohio (Roberta Slocumb), Oklahoma (Espinoza Raffaella), Oregon (Jeff Soule), Pennsylvania (Jim Rubertone), Puerto Rico (Carlos Cintron), Rhode Island (Junhie Oh), South Carolina (Deborah Hurley), Texas (Leticia Nogueria), Utah (Jen Doherty), Virginia (Shuhui Wang), and the Seattle–Puget Sound area of Washington (Margaret Madeleine). The authors also thank analysts at Information Management Services for programming support (David Castenson, Matthew Chaloux, Michael Curry, and Ruth Parsons). The views expressed in this article are those of the authors and should not be interpreted to reflect the views or policies of the National Cancer Institute, the Health Resources and Services Administration, the SRTR, the cancer registries, or their contractors. The SRTR is currently operated under contract number 75R60220C00011 by the Hennepin Healthcare Research Institute (Minneapolis, Minnesota). Previously, the SRTR was managed under contracts HHSH250201000018C and HHSH234200537009C. The following cancer registries were supported by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute: California (contracts HHSN261201000036C, HHSN261201000035C, and HHSN261201000034C), Connecticut (HHSN261201800002I), Hawaii (HHSN261201000037C, N01-PC-35137, and N01-PC-35139), Idaho (HHSN261201800006I), Illinois (75N91021D00006), Iowa (HSN261201000032C, N01-PC-35143, and HHSN261201800012I), Kentucky (HHSN261201800013I), New Jersey (75N91021D00009), New York (75N91018D00005 [Task Order 75N91018F00001]), Seattle-Puget Sound (N01-PC-35142), and Utah (HHSN261201800016I). The following cancer registries were supported by the National Program of Cancer Registries of the Centers for Disease Control and Prevention: California (agreement 1 U58 DP000807-01), Colorado (U58 DP000848-04), Georgia (5U58DP003875-01), Idaho (1NU58DP006270), Illinois (5U58DP003883-03), Michigan (5U58DP003921-03), New Jersey (5NU58DP006279-02-00), New Mexico (HHSN261201800014I, Task Order HHSN26100001), New York (6NU58DP006309), North Carolina (U58DP003933), North Dakota (NU58DP006317-05-01), Ohio (NU58DP006284), Oregon (NU58DP006288), Texas (5U58DP000824-04), and Utah (NU58DP006320). Additional support was provided by the states of California, Colorado, Connecticut, Illinois, Iowa, Montana (5 NU58DP006339-05-00), New Jersey, New York (including the Cancer Surveillance Improvement Initiative), and Texas, and the Fred Hutchinson Cancer Research Center in Seattle, Washington. Jennifer M. Geris was supported by a fellowship from the Institute for Molecular Virology Training Program at the University of Minnesota by the National Institutes of Health (Grant/Award Number T32 AI083196). Ajit P. Limaye was supported by a grant by the National Institute of Allergy and Infectious Diseases (Grant/Award Number U0AI163090). This research was supported in part by the Intramural Research Program of the National Cancer Institute.

Funding Information:
Jennifer M. Geris was supported by a fellowship from the Institute for Molecular Virology Training Program at the University of Minnesota by the National Institutes of Health (Grant/Award Number T32 AI083196). Ajit P. Limaye was supported by a grant by the National Institute of Allergy and Infectious Diseases (Grant/Award Number U0AI163090). This research was supported in part by the Intramural Research Program of the National Cancer Institute.

Funding Information:
The SRTR is currently operated under contract number 75R60220C00011 by the Hennepin Healthcare Research Institute (Minneapolis, Minnesota). Previously, the SRTR was managed under contracts HHSH250201000018C and HHSH234200537009C. The following cancer registries were supported by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute: California (contracts HHSN261201000036C, HHSN261201000035C, and HHSN261201000034C), Connecticut (HHSN261201800002I), Hawaii (HHSN261201000037C, N01‐PC‐35137, and N01‐PC‐35139), Idaho (HHSN261201800006I), Illinois (75N91021D00006), Iowa (HSN261201000032C, N01‐PC‐35143, and HHSN261201800012I), Kentucky (HHSN261201800013I), New Jersey (75N91021D00009), New York (75N91018D00005 [Task Order 75N91018F00001]), Seattle‐Puget Sound (N01‐PC‐35142), and Utah (HHSN261201800016I). The following cancer registries were supported by the National Program of Cancer Registries of the Centers for Disease Control and Prevention: California (agreement 1 U58 DP000807‐01), Colorado (U58 DP000848‐04), Georgia (5U58DP003875‐01), Idaho (1NU58DP006270), Illinois (5U58DP003883‐03), Michigan (5U58DP003921‐03), New Jersey (5NU58DP006279‐02‐00), New Mexico (HHSN261201800014I, Task Order HHSN26100001), New York (6NU58DP006309), North Carolina (U58DP003933), North Dakota (NU58DP006317‐05‐01), Ohio (NU58DP006284), Oregon (NU58DP006288), Texas (5U58DP000824‐04), and Utah (NU58DP006320). Additional support was provided by the states of California, Colorado, Connecticut, Illinois, Iowa, Montana (5 NU58DP006339‐05‐00), New Jersey, New York (including the Cancer Surveillance Improvement Initiative), and Texas, and the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Publisher Copyright:
© 2022 American Cancer Society.

Keywords

  • cytomegalovirus (CMV)
  • leukemia
  • lymphoma
  • solid organ transplantation
  • solid tumors

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

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