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Aids-related malignancies

Key Points

  • Several different types of cancer are observed at an increased frequency in acquired immune deficiency syndrome (AIDS) patients and in other immunosuppressed individuals. Most of these are virus-associated cancers.

  • Kaposi's sarcoma (KS) is the most common neoplasm that occurs in patients with AIDS (AIDS-KS). KS is believed to be caused by Kaposi's-sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8), but the tumour microenvironment is an important aspect of KS progression.

  • AIDS-lymphoma is another significant cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. Over 50% of AIDS lymphomas are associated with Epstein–Barr virus (EBV) and/or KSHV infection. EBV activates B-cell precursors, leading to a transformed phenotype.

  • Human papillomavirus (HPV)-related cancers are another type of AIDS-related malignancy. There are likely to be two mechanisms by which papillomaviruses induce neoplasia — by altering the tumour microenvironment, and by directly disrupting cell differentiation, to induce cell proliferation.

  • Antiviral strategies might be used to prevent cancer in AIDS patients. For example, highly active antiretroviral therapy has been shown to prevent or stop the progression of KS in AIDS patients.

Abstract

Cancer remains a significant burden for human immunodeficiency virus (HIV)-infected individuals. Most cancers that are associated with HIV infection are driven by oncogenic viruses, such as Epstein–Barr virus, Kaposi's sarcoma-associated herpesvirus and human papillomavirus. Gaining insight into the epidemiology and mechanisms that underlie AIDS-related cancers has provided us with a better understanding of cancer immunity and viral oncogenesis.

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Figure 1: Putative pathways of endothelial-cell and Kaposi's sarcoma spindle-cell differentiation.

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Acknowledgements

We apologize to colleagues whose primary research papers are not cited, due to the restricted number of references. We would like to thank T. Sharp, H. Laman, A. Godfrey and S. Direkze for advice on the text and figures. The authors studies are supported by Cancer Research UK, the Medical Research Council UK, The Wellcome Trust, the Leukaemia Research Fund and GlaxoSmithKline.

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DATABASES

Cancer.gov

AIDS-related lymphoma

anal cancer

breast cancer

cervical cancer

colon cancer

Hodgkin's disease

Kaposi's sarcoma

laryngeal carcinoma

multiple myeloma

oesophageal carcinoma

oral carcinoma

penile cancer

primary central nervous system lymphoma

prostate cancer

skin cancer

vulval cancer

vaginal cancer

GenBank

v-cyclin

E2

E6

E7

EBV

herpes simplex virus

HIV-1

HIV-2

HPV16

HPV18

KSHV

LANA1

LMP1

Tat

LocusLink

BCL6

bFGF

CD20

CD31

CD34

CDC6

CDK2

CDK6

CIP/KIP family

cyclin A

cyclin E

E2F

E2F1

E-selectin

IFN-γ

IL-6

INK4 family

MUM1

MYC

oncostatin-M

ORC1

p107

p130

p21

plasminogen-activator inhibitor-1

RB

syndecan-1

TNF-α

VEGFC

VEGFD

VEGFR2

VEGFR3

Medscape DrugInfo

cidofovir

rituximab

zidovudine

OMIM

epidermodysplasia verruciformis

FURTHER INFORMATION

Centers for Disease Control

Chris Boshoff's lab

National Cancer Institute AIDS-malignancy Branch

Los Alamos National Laboratory, KSHV Database

Glossary

SEPSIS

(SEPTICAEMIA). A systemic infection that is caused by microbial organisms and their toxins in the blood (blood poisoning). Bacteraemia denotes the detecTable presence of bacteria in the bloodstream.

PODOCYTES

('Cells with feet'). Specialized epithelial cells that line the kidney glomerular capillaries. Their foot processes make an incomplete barrier for filtration of substances from the capillary.

EPISOME

A circular piece of DNA (such as a virus) that can replicate independently of the host chromosome (extrachromosomal), or integrate and replicate as part of the chromosome. The term was first used by Jacob and Wollman in 1958 in relation to genetic elements that can either exist independently in a cell or become integrated into the host chromosome.

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Boshoff, C., Weiss, R. Aids-related malignancies. Nat Rev Cancer 2, 373–382 (2002). https://doi.org/10.1038/nrc797

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