HIV/AIDS-Associated Viral Oncogenesis

252 Pages·2019·4.1 MB·English

by  Craig Meyers

Cancer Treatment and Research
Series Editor: Steven T. Rosen
Craig Meyers Editor
HIV/AIDS-
Associated Viral
Oncogenesis
Second Edition
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PubMed/Medline
Cancer Treatment and Research
Volume 177
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Craig Meyers
Editor
HIV/AIDS-Associated Viral
Oncogenesis
Second Edition
123
Editor
CraigMeyers
PennState Cancer Institute
PennState University
Hershey,PA, USA
ISSN 0927-3042 ISSN 2509-8497 (electronic)
Cancer Treatment andResearch
ISBN978-3-030-03501-3 ISBN978-3-030-03502-0 (eBook)
https://doi.org/10.1007/978-3-030-03502-0
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2ndedition:©SpringerNatureSwitzerlandAG2019
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Contents
1 AIDS-Associated Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Ramya Vangipuram and Stephen K. Tyring
2 Molecular Biology of KSHV in Relation to HIV/AIDS-Associated
Oncogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Meilan He, Fan Cheng, Suzane Ramos da Silva, Brandon Tan,
Océane Sorel, Marion Gruffaz, Tingting Li and Shou-Jiang Gao
3 Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)-Associated
Disease in the AIDS Patient: An Update. . . . . . . . . . . . . . . . . . . . . . 63
Dirk P. Dittmer and Blossom Damania
4 Molecular Biology of EBV in Relationship
to HIV/AIDS-Associated Oncogenesis . . . . . . . . . . . . . . . . . . . . . . . . 81
Fengchao Lang, Yonggang Pei, Zachary L. Lamplugh
and Erle S. Robertson
5 Human Papillomavirus Infection and Cervical Cancer
in HIV+ Women. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Ping Du
6 HPV-Associated Oropharyngeal Cancer
in the HIV/AIDS Patient. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Jennifer E. Cameron and Michael Hagensee
7 HPV-Associated Anal Cancer in the HIV/AIDS Patient . . . . . . . . . . 183
Chia-Ching J. Wang and Joel M. Palefsky
8 Merkel Cell Carcinoma in the HIV-1/AIDS Patient . . . . . . . . . . . . . 211
Robert H. Goldstein and James A. DeCaprio
9 HIV–HBV and HIV–HCV Coinfection and Liver Cancer
Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
Jianming Hu, Kuancheng Liu and Jun Luo
v
Overview
AccordingtotheWHO,therearecurrentlyover36millionpeoplelivingwithHIV
globally, but with the successes of the antiretroviral therapy (ART), deaths due to
AIDS have continued to decline, and people living with HIV (PLWH) are now
living a longer and normal life span. However, non-AIDS-associated diseases are
nowincreasinginPLWH,andcancerhasnowbecomealeadingcauseofmorbidity
andmortality.Ithasbeenestimatedthatcancerisresponsibleforoverone-thirdof
alldeathsinHIV-infectedindividuals.ThemajorityofcancersinAIDSpatientsare
knowntoassociatewithco-infectionwithknownoncogenicvirusessuchashuman
papillomavirus(HPV),EpsteinBarrvirus(EBV),theKaposi’ssarcomaassociated
herpesvirus (KSHV) or human herpesvirus-8 (HHV-8), as well as hepatitis
B (HBV) and hepatitis (HCV), and more recently the Merkel cell polyoma virus
(MCPyV). With the successes of ART, a number of the AIDS-associated malig-
nanciessuchasKaposi’ssarcoma(KS)andsomelymphomashavedeclinedinthe
developed countries, but the KS disease burden remains high in Africa; the inci-
dence of KS has reported to be as high as prostate cancer in the US. In addition,
several additional non-AIDS defining malignancies (NADM) like anal cancers,
oropharyngeal cancers, Hodgkin lymphomas, hepatocarcinomas, and even lung
cancersareoccurringmoreoften inPLWH.Therefore,there isstillanurgentneed
tohaveabetterunderstandingoftheepidemiologyofthesecancers,theriskfactors
involved, the clinical presentations, the treatment, and their associate viral etio-
logical agents, including the viral gene functions, and their effects on the host in
leading to cellular transformation and oncogenesis.
ThisbookHIV/AIDS-AssociatedViralOncogenesiseditedbyMeyersrepresents
a must read material for clinicians, researchers, and students who are interested in
this area. It consists of review chapters authored by leading experts in the field,
covering all the known human oncogenic viruses and malignancies that are asso-
ciated with AIDS and NADM. There are a total of nine comprehensive chapters;
one chapter is on HIV/AIDS malignancies; two chapters on KSHV and KS; one
chapterisonEBVandassociatedlymphomas.TherearethreechaptersonHPVand
its associating cancers, head and neck squamous cell carcinomas and oral cancers,
theanal cancer,andcervical cancers. Thereisone chapteronMCPyV andMerkel
cell carcinomas, and one chapter on HBV/HCV and hepatocarcinomas.
vii
viii Overview
ThechapterbyPyringprovidedacomprehensivereviewonthecurrentstatusof
AIDS/HIV associated malignancies and their associating viral etiological agents.
There are two chapters on KSHV and KS. The first is by He et al. The authors
provided a comprehensive review on the molecular biology of KSHV, the regu-
lation of the viral gene expression, the host immune response against the virus
infection, and the mechanisms of cellular transformation and tumorigenesis. The
second KSHV chapter by Dittmer and Damania described the KSHV and its
associate diseases. It also described the prevalence of infection, the molecular
biology of the virus and the disease, and its treatment. The chapter on EBV and
lymphomasbyLangetalprovidedacomprehensivereview ofEBV,itsmolecular
biologyandtheregulationofviralandcellular geneexpression inEBV-associated
lymphomas.ItalsodescribedthevarioustypesoflymphomasassociatedwithEBV
anditsassociationwithHIVinfection.Therearethreechaptersonthethreecancers
associatewithHPV.ThefirstchapterisonHPVassociatecervicalcancerbyDu;it
described the biology of HPV and the global burden of cervical cancer, and
co-infectionbyHIVinwomen.Italsoreviewedtheriskfactorsinvolved,screening
forcervicalcancers,andpreventionofHPVinfection.ThesecondchapteronHPV
isbyHaganseeonoralcancer.Itdescribedtherisks,theprevalenceandprevention
of the cancer. It also described the molecular mechanisms that underlie
HPV-mediated oncogenesis to lead to cancer. The third chapter on HPV and anal
cancer is by Wang and Polefsky who reviewed the current literatures on anal
cancers, the virus, the epidemiology, the clinical characteristics, the prevention, as
wellasthetreatmentandoutcomeofthecancer.ThechapterbyCaprioonMerkel
cell carcinoma reviewed the clinical disease, its etiological agent and the gene
regulationofthevirusandchangesinthetumoratthemolecularlevels.Finally,the
chapter by Hu et al on HBV/HCV liver cancers reviewed the epidemiology of
HBV/HCV and HIV co-infections; also on the possible mechanisms of hepato-
carcinogenesisaswellasthemanagementofthecancer.Italsodiscussedtheother
hepatitis virus, the HGV.
AIDS-Associated Malignancies 1
Ramya Vangipuram and Stephen K. Tyring
Contents
1.1 Introduction...................................................................................................................... 2
1.2 Gammaherpesvirus-AssociatedMalignancies............................................................... 3
1.3 HumanPapillomavirus-AssociatedMalignancies........................................................ 12
1.4 Conclusion........................................................................................................................ 15
References................................................................................................................................. 16
Abstract
Malignancies were one of the earliest recognized manifestations that led to the
description of the acquired immune deficiency syndrome (AIDS). The majority
of cancers in AIDS patients are associated with coinfection with oncogenic
viruses, such as Epstein–Barr virus, human herpesvirus 8, and human
papillomavirus, with resulting malignancies occurring secondary to diminished
immunesurveillanceagainstvirusesandvirus-infectedtumorcells. Over50%of
AIDS lymphomas are associated with Epstein–Barr virus (EBV) and/or HHV8
infection. HHV8-associated diseases include Kaposi sarcoma (KS), primary
effusion lymphoma (PEL), and multicentric Castleman disease (MCD). EBV is
associated with several malignancies, including Hodgkin lymphoma (HL) and
non-Hodgkin lymphoma (NHL). Coinfection with HIV and HPV is associated
withanincreasedriskofvarioussquamouscellcarcinomasofepithelialtissues.
HAART has significantly impacted the incidence, management, and prognosis
ofAIDS-relatedmalignancies.InadditiontochangingthenaturalhistoryofHIV
infection in regard to incidence and survival, HAART has dramatically
R.Vangipuram(cid:1)S.K.Tyring(&)
DepartmentofDermatology,UniversityofTexasHealthSciencesCenteratHouston,
Houston,TX77030,USA
e-mail:[email protected]
©SpringerNatureSwitzerlandAG2019 1
C.Meyers(ed.),HIV/AIDS-AssociatedViralOncogenesis,CancerTreatment
andResearch177,https://doi.org/10.1007/978-3-030-03502-0_1
2 R.VangipuramandS.K.Tyring
decreasedtheincidenceofcertainvirallymediatedHIV-associatedmalignancies
such as KS and primary CNS lymphoma. The beneficial effects of HAART on
these tumors are attributed to drug-mediated HIV suppression and immune
reconstitution.However,HAARThashadalessfavorableimpactonEBV-and
HPV-relatedmalignancies.ThischapterpresentsanoverviewofHIV-associated
malignancies mediated by HHV-8, EBV, and HPV, and reviews the effect of
HAART on the epidemiology, presentation, treatment, and outcomes of these
cancers.
Keywords
(cid:1) (cid:1)
Human herpesvirus 8 Epstein–Barr virus Human papillomavirus
(cid:1) (cid:1)
Human immunodeficiency virus Kaposi sarcoma AIDS-associated
(cid:1)
lymphoma Anogenital cancer
1.1 Introduction
Malignancies were one of the earliest recognized manifestations that led to the
description of the acquired immune deficiency syndrome (AIDS). The rising inci-
dence of Kaposi sarcoma in young homosexual men, a rare skin cancer typically
seen in elderly men of Eastern European and Mediterranean descent, was a har-
binger of the AIDS epidemic in the early 1980s. This was followed by sporadic
reports of high-grade B-cell non-Hodgkin’s lymphoma (NHL), primary cerebral
lymphoma, and systemic NHL. By 1985, both Kaposi’s sarcoma and high-grade
B-cellNHLwereclassifiedas“AIDS-defining”illnessesbytheCentersforDisease
Control(CDC).Insubsequentyears, theCDClistedinvasivecervical cancerasan
AIDS-definingillness,givenitspoorerprognosisinHIV-positivewomen.Research
later showed that the majority of cancers in AIDS patients were associated with
coinfectionwithoncogenicviruses,suchasEpstein–Barrvirus,humanherpesvirus
8, and human papillomavirus, with resulting malignancies occurring secondary to
diminished immune surveillance against viruses and virus-infected tumor cells.
Over 50% of AIDS lymphomas are associated with Epstein–Barr virus
(EBV) and/orHHV8infection.HHV8-associateddiseases includeKaposisarcoma
(KS), primary effusion lymphoma (PEL), and multicentric Castleman disease
(MCD). EBV is associated with several malignancies, including Hodgkin
lymphoma (HL) and non-Hodgkin lymphoma (NHL). EBV is also implicated in
cases of leiomyosarcoma, cervical, and anal cancer in patients with AIDS.
HAART has significantly impacted the incidence, management, and prognosis
of AIDS-related malignancies. In addition to changing the natural history of HIV
infection in regard to incidence and survival, HAART has dramatically decreased
the incidence of certain virally mediated HIV-associated malignancies such as KS
andprimaryCNSlymphoma.ThebeneficialeffectsofHAARTonthesetumorsare