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Cancer in HIV-infected populations: studies of incidence, prognosis and oncovirus seroprevalence

Applicant Wyss Natascha
Number 145489
Funding scheme Marie Heim-Voegtlin grants
Research institution Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Cancer
Start/End 01.09.2013 - 31.10.2015
Approved amount 179'950.00
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All Disciplines (2)

Discipline
Cancer
Methods of Epidemiology and Preventive Medicine

Keywords (15)

cancer epidemiology; AIDS-defining Malignancies; Anal Cancer; Anti-Retroviral Agents; Cervical Cancer; Highly active antiretroviral therapy; HIV; Human Herpesvirus Type 8; Humans; Incidence; AIDS-Related Lymphoma; Non-Hodgkin Lymphoma; Prevalence; Kaposi Sarcoma; Survival

Lay Summary (German)

Lead
Co-Infektionen mit Onkoviren, wie dem humanen Herpesvirus 8 (HHV-8) und den humanen Papillomaviren (HPV), erhöhen das Krebsrisiko in HIV-infizierten Menschen. So treten durch HHV-8 mitverursachte Kaposi Sarkome (KS) und HPV-assoziierte Analkarzinome bei HIV-Infizierten Patienten besonders häufig auf. Anders als beim Analkarzinom, wo bisher kein Rückgang durch antiretrovirale Kombinationstherapie (cART) bekannt ist, hat cART die Zahl der neuauftretenden Kaposi Sarkome deutlich reduziert.
Lay summary

Inhalt und Ziel des Forschungsprojekts

Unser Ziel ist es, das Krebsauftreten in HIV-infizierten Personen besser zu verstehen. Im Detail werden wir (i) die Krebsinzidenz, Prognose und Risikofaktoren für KS, Non-Hodgkin-Lymphome und Gebärmutterhalskrebs in HIV-infizierten Bevölkerungen von 5 Kontinenten analysieren,  (ii) das Vorkommen des  Analkarzinoms in HIV-Infizierten in Südafrika untersuchen und schliesslich (iii) eine systematische Übersichtsarbeit und Meta-Analyse zur HHV-8-Prävalenz in HIV-positiven und –negativen Personen durchführen.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Obwohl cART heute weit verbreitet ist, bleibt KS in vielen Gebieten noch immer die häufigste Krebserkrankung bei HIV-infizierten Personen. Das Wissen zur Prävalenz, Übertragung und Prävention von HHV-8 ist jedoch lückenhaft, und wichtige systematische Übersichtsarbeiten  fehlen. Andere Krebserkrankungen steigen weiter an in der HIV-infizierten Bevölkerung. Die im Rahmen dieses Projektes durchgeführten internationalen Vergleichsstudien werden Erkenntnisse zu Risikofaktoren und Präventionsmöglichkeiten dieser Krankheiten bei HIV-infizierten Menschen liefern.

 


 

Direct link to Lay Summary Last update: 22.10.2013

Responsible applicant and co-applicants

Name Institute

Employees

Name Institute

Publications

Publication
Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy: Collaborative Analysis of 21 European Cohort Studies.
Cancer Project Working Group for the Collaboration of Observational HIV Epidemiological Research Eur (2016), Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy: Collaborative Analysis of 21 European Cohort Studies., in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 63(10), 1373-1379.
HIV and human herpesvirus 8 co-infection across the globe: Systematic review and meta-analysis
Rohner Eliane, Wyss Natascha, Heg Zina, Faralli Zully, Mbulaiteye Sam M., Novak Urban, Zwahlen Marcel, Egger Matthias, Bohlius Julia (2016), HIV and human herpesvirus 8 co-infection across the globe: Systematic review and meta-analysis, in INTERNATIONAL JOURNAL OF CANCER, 138(1), 45-54.
HHV-8 seroprevalence: a global view.
Rohner Eliane, Wyss Natascha, Trelle Sven, Mbulaiteye Sam M, Egger Matthias, Novak Urban, Zwahlen Marcel, Bohlius Julia (2014), HHV-8 seroprevalence: a global view., in Systematic reviews, 3, 11-11.
Incidence Rate of Kaposi Sarcoma in HIV-Infected Patients on Antiretroviral Therapy in Southern Africa: A Prospective Multicohort Study.
Rohner Eliane, Valeri Fabio, Maskew Mhairi, Prozesky Hans, Rabie Helena, Garone Daniela, Dickinson Diana, Chimbetete Cleophas, Lumano-Mulenga Priscilla, Sikazwe Izukanji, Wyss Natascha, Clough-Gorr Kerri M, Egger Matthias, Chi Benjamin H, Bohlius Julia (2014), Incidence Rate of Kaposi Sarcoma in HIV-Infected Patients on Antiretroviral Therapy in Southern Africa: A Prospective Multicohort Study., in Journal of acquired immune deficiency syndromes (1999), 67(5), 547-54.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Conference on Retroviruses and Opportunistic Infections (CROI) Poster Kaposi Sarcoma in the Era of Combined Antiretroviral Therapy 02.03.2014 Boston, United States of America Wyss Natascha;
GHS Symposium Poster Kaposi Sarcoma in the Era of Combination Antiretroviral Therapy 28.11.2013 Münchenweiler, Switzerland Wyss Natascha;


Associated projects

Number Title Start Funding scheme
136620 AIDS-defining and non AIDS-defining cancers in patients starting ART in Southern Africa: cohort and linkage studies 01.12.2011 Ambizione

Abstract

Background: People living with HIV are at substantially increased risk of cancer, with oncoviruses playing an important role in this population. For example, Kaposi sarcoma is the most frequent cancer in the HIV-infected and is associated with the human herpesvirus 8 (HHV-8). Substantial inequalities in cancer survival exist between high income and low income countries. For example, the case fatality rate of Kaposi sarcoma is 90% in low-income countries compared to 77% in high-income countries and 68% versus 33% for invasive cervical cancer. With the scale-up of combination antiretroviral therapy (cART) the prognosis of individuals living with HIV/AIDS has improved substantially, however, the impact of cART on cancer incidence and survival in sub-Saharan Africa and other resource-limited settings, compared to industrialized countries, is not well defined at present.Objectives: I aim to examine the epidemiology of the AIDS-defining cancers and of anal cancer in HIV-infected persons in different regions of the world, and to examine the epidemiology of one important oncovirus in HIV-infected and HIV-negative individuals. This work will produce important data in a neglected field which will help define prevention measures and plan health services to reduce the incidence of cancer in the HIV-infected population and to improve the prognosis of patients with cancer. Specifically my objectives are:1) To examine the incidence and survival of AIDS-defining cancers in HIV-infected patients from five continents.2) To systematically review and meta-analyze the prevalence of HHV-8 infection in HIV-infected and HIV-negative persons.3) To examine the prevalence and incidence of anal cancer in HIV-infected people in South Africa.Methods: The International epidemiological Databases to Evaluate AIDS (IeDEA) are a global research consortium with seven regional networks established in 2005 to collect clinical and epidemiological data on HIV-infected people. Data on over 600,000 patients from North America, Caribbean, Central and South America, Asia-Pacific and Southern Africa will be analyzed together with data from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). I will conduct comprehensive literature searches to identify relevant studies on HIV-8 prevalence. Finally, I will link the data from the adult patients included in the HIV-cohorts from South Africa with a) the National Cancer Registry (NCR) in Johannesburg to identify anal cancer cases, b) with the National Health Laboratory Services (NHLS) to identify results from Papanicolaou tests (cytology) and biopsies (histology) and c) to the national death registry to ensure complete mortality follow-up. I calculate incidence and mortality rates and explore the importance of individual-level and region/country-level variables on the risk of cancer and the risk of cancer-related mortality in Weibull and Cox models with random effects to account for heterogeneity between sites. I will calculate pooled cumulative prevalence rates with 95% credibility intervals using Bayesian methods to account for the expected heterogeneity between studies. I will use random-effects meta-regression to analyses the association between region, risk group and the seroprevalence of HHV-8. Significance and relevance for my career: The planned work will make important contributions to an under-researched, neglected area: the epidemiology of HIV-associated cancers, with a focus on resource limited settings. The project will allow me to obtain a PhD in epidemiology and benefit from courses offered by the doctoral program of the Graduate School of Health Sciences (GSH) and the Swiss School of Public Health (SSPH+). I will gain hands on experience in the application of epidemiological methods, including the analysis of large multi-cohort datasets and record linkages. The project will be instrumental for my future career in an academic environment. At the end of the PhD I will be qualified to conduct research projects from development of the idea through to funding acquisition, conduct of the research and dissemination of the results at conferences and in high impact journals.
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