Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada

doi:10.1093/cid/ciz329

. 2020 Mar 3;70(6):1176-1185.

doi: 10.1093/cid/ciz329.

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada

Raúl U Hernández-Ramírez¹, Li Qin², Haiqun Lin³, Wendy Leyden⁴, Romain S Neugebauer⁴, Keri N Althoff⁵, Nancy A Hessol⁶, Chad J Achenbach⁷, John T Brooks⁸, M John Gill⁹, Surbhi Grover¹⁰, Michael A Horberg¹¹, Jun Li¹², W Christopher Mathews¹³, Angel M Mayor¹⁴, Pragna Patel⁸, Charles S Rabkin¹⁵, Anita Rachlis¹⁶, Amy C Justice^{2

17

18}, Richard D Moore¹⁹, Eric A Engels¹⁵, Michael J Silverberg⁴, Robert Dubrow²⁰; North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS

Collaborators, Affiliations

Collaborators

North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS:
Constance A Benson, Ronald J Bosch, Gregory D Kirk, Kenneth H Mayer, Chris Grasso, Robert S Hogg, P Richard Harrigan, Julio S G Montaner, Benita Yip, Julia Zhu, Kate Salters, Karyn Gabler, Kate Buchacz, Jun Li, Kelly A Gebo, Richard D Moore, Richard D Moore, Benigno Rodriguez, Michael A Horberg, Michael J Silverberg, Jennifer E Thorne, Charles Rabkin, Joseph B Margolick, Lisa P Jacobson, Gypsyamber D'Souza, Marina B Klein, Abigail Kroch, Ann Burchell, Adrian Betts, Joanne Lindsay, Robert F Hunter-Mellado, Angel M Mayor, M John Gill, Steven G Deeks, Jeffrey N Martin, Jun Li, John T Brooks, Michael S Saag, Michael J Mugavero, James Willig, William C Mathews, Joseph J Eron, Sonia Napravnik, Mari M Kitahata, Heidi M Crane, Daniel R Drozd, Timothy R Sterling, David Haas, Peter Rebeiro, Megan Turner, Amy C Justice, Robert Dubrow, David Fiellin, Stephen J Gange, Kathryn Anastos, Richard D Moore, Michael S Saag, Stephen J Gange, Mari M Kitahata, Keri N Althoff, Michael A Horberg, Marina B Klein, Rosemary G McKaig, Aimee M Freeman, Richard D Moore, Aimee M Freeman, Mari M Kitahata, Stephen E Van Rompaey, Heidi M Crane, Daniel R Drozd, Liz Morton, Justin McReynolds, William B Lober, Stephen J Gange, Keri N Althoff, Jennifer S Lee, Bin You, Brenna Hogan, Jinbing Zhang, Jerry Jing, Elizabeth Humes, Sally Coburn

Affiliations

¹ Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut.
² Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
³ Department of Biostatistics, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut.
⁴ Division of Research, Kaiser Permanente Northern California, Oakland.
⁵ Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
⁶ Department of Clinical Pharmacy, University of California, San Francisco.
⁷ Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
⁸ Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
⁹ Department of Medicine, University of Calgary, Alberta, Canada.
¹⁰ Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia.
¹¹ Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, Maryland.
¹² Epidemiology Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
¹³ Department of Medicine, University of California, San Diego.
¹⁴ Retrovirus Research Center, Department of Medicine, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico.
¹⁵ Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
¹⁶ Sunnybrook Health Sciences Centre and Department of Medicine, University of Toronto, Ontario, Canada.
¹⁷ Department of Health Policy and Management, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut.
¹⁸ Research Service, Veterans Affairs Connecticut Healthcare System, West Haven.
¹⁹ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
²⁰ Department of Environmental Health Sciences, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut.

PMID: 31044245
PMCID: PMC7319056
DOI: 10.1093/cid/ciz329

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada

Raúl U Hernández-Ramírez et al. Clin Infect Dis. 2020.

. 2020 Mar 3;70(6):1176-1185.

doi: 10.1093/cid/ciz329.

Authors

Collaborators

North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS:
Constance A Benson, Ronald J Bosch, Gregory D Kirk, Kenneth H Mayer, Chris Grasso, Robert S Hogg, P Richard Harrigan, Julio S G Montaner, Benita Yip, Julia Zhu, Kate Salters, Karyn Gabler, Kate Buchacz, Jun Li, Kelly A Gebo, Richard D Moore, Richard D Moore, Benigno Rodriguez, Michael A Horberg, Michael J Silverberg, Jennifer E Thorne, Charles Rabkin, Joseph B Margolick, Lisa P Jacobson, Gypsyamber D'Souza, Marina B Klein, Abigail Kroch, Ann Burchell, Adrian Betts, Joanne Lindsay, Robert F Hunter-Mellado, Angel M Mayor, M John Gill, Steven G Deeks, Jeffrey N Martin, Jun Li, John T Brooks, Michael S Saag, Michael J Mugavero, James Willig, William C Mathews, Joseph J Eron, Sonia Napravnik, Mari M Kitahata, Heidi M Crane, Daniel R Drozd, Timothy R Sterling, David Haas, Peter Rebeiro, Megan Turner, Amy C Justice, Robert Dubrow, David Fiellin, Stephen J Gange, Kathryn Anastos, Richard D Moore, Michael S Saag, Stephen J Gange, Mari M Kitahata, Keri N Althoff, Michael A Horberg, Marina B Klein, Rosemary G McKaig, Aimee M Freeman, Richard D Moore, Aimee M Freeman, Mari M Kitahata, Stephen E Van Rompaey, Heidi M Crane, Daniel R Drozd, Liz Morton, Justin McReynolds, William B Lober, Stephen J Gange, Keri N Althoff, Jennifer S Lee, Bin You, Brenna Hogan, Jinbing Zhang, Jerry Jing, Elizabeth Humes, Sally Coburn

Affiliations

¹ Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut.
² Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
³ Department of Biostatistics, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut.
⁴ Division of Research, Kaiser Permanente Northern California, Oakland.
⁵ Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
⁶ Department of Clinical Pharmacy, University of California, San Francisco.
⁷ Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
⁸ Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
⁹ Department of Medicine, University of Calgary, Alberta, Canada.
¹⁰ Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia.
¹¹ Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, Maryland.
¹² Epidemiology Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
¹³ Department of Medicine, University of California, San Diego.
¹⁴ Retrovirus Research Center, Department of Medicine, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico.
¹⁵ Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
¹⁶ Sunnybrook Health Sciences Centre and Department of Medicine, University of Toronto, Ontario, Canada.
¹⁷ Department of Health Policy and Management, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut.
¹⁸ Research Service, Veterans Affairs Connecticut Healthcare System, West Haven.
¹⁹ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
²⁰ Department of Environmental Health Sciences, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut.

PMID: 31044245
PMCID: PMC7319056
DOI: 10.1093/cid/ciz329

Abstract

Background: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk.

Methods: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion.

Results: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/µL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/µL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6).

Conclusions: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

Keywords: CD4+ T-cell count; HIV infection; HIV-1 RNA viral load; anal cancer; risk.

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References

1. Hernández-Ramírez RU, Shiels MS, Dubrow R, Engels EA. Cancer risk in HIV-infected people in the USA from 1996 to 2012: a population-based, registry-linkage study. Lancet HIV 2017; 4:e495–504. - PMC - PubMed
1. Colón-López V, Shiels MS, Machin M, et al. . Anal cancer risk among people with HIV infection in the United States. J Clin Oncol 2018; 36:68–75. - PMC - PubMed
1. Palefsky JM, Holly EA. Chapter 6: immunosuppression and co-infection with HIV. J Natl Cancer Inst Monogr 2003;2003:41–6. - PubMed
1. Palefsky J. Biology of HPV in HIV infection. Adv Dent Res 2006; 19:99–105. - PubMed
1. Brickman C, Palefsky JM. Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era. Curr HIV/AIDS Rep 2015; 12:6–15. - PubMed

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[1] Hernández-Ramírez RU, Shiels MS, Dubrow R, Engels EA. Cancer risk in HIV-infected people in the USA from 1996 to 2012: a population-based, registry-linkage study. Lancet HIV 2017; 4:e495–504. - PMC - PubMed

[2] Hernández-Ramírez RU, Shiels MS, Dubrow R, Engels EA. Cancer risk in HIV-infected people in the USA from 1996 to 2012: a population-based, registry-linkage study. Lancet HIV 2017; 4:e495–504. - PMC - PubMed

[3] Colón-López V, Shiels MS, Machin M, et al. . Anal cancer risk among people with HIV infection in the United States. J Clin Oncol 2018; 36:68–75. - PMC - PubMed

[4] Colón-López V, Shiels MS, Machin M, et al. . Anal cancer risk among people with HIV infection in the United States. J Clin Oncol 2018; 36:68–75. - PMC - PubMed

[5] Palefsky JM, Holly EA. Chapter 6: immunosuppression and co-infection with HIV. J Natl Cancer Inst Monogr 2003;2003:41–6. - PubMed

[6] Palefsky JM, Holly EA. Chapter 6: immunosuppression and co-infection with HIV. J Natl Cancer Inst Monogr 2003;2003:41–6. - PubMed

[7] Palefsky J. Biology of HPV in HIV infection. Adv Dent Res 2006; 19:99–105. - PubMed

[8] Palefsky J. Biology of HPV in HIV infection. Adv Dent Res 2006; 19:99–105. - PubMed

[9] Brickman C, Palefsky JM. Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era. Curr HIV/AIDS Rep 2015; 12:6–15. - PubMed

[10] Brickman C, Palefsky JM. Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era. Curr HIV/AIDS Rep 2015; 12:6–15. - PubMed

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Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada

Collaborators

Affiliations

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada

Authors

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Abstract

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