Cancer risk among women living with HIV

136 Pages·2017·1.81 MB·English

Cancer risk among women living with HIV:
Implications for care in the modern cART era
by
Kate A. Salters
Master of Public Health, Simon Fraser University, 2012
Bachelor of Arts, Brock University, 2008
Thesis Submitted in Partial Fulfillment of the
Requirements for the Degree of
Doctor of Philosophy
in the
Doctor of Philosophy Program
Faculty of Health Sciences

© Kate A. Salters
SIMON FRASER UNIVERSITY
Summer 2017

Copyright in this work rests with the author. Please ensure that any reproduction
or re-use is done in accordance with the relevant national copyright legislation.
Approval
Name: Kate A. Salters
Degree: Doctor of Philosophy
Title: Cancer risk among women living with HIV:
Implications for care in the modern cART era
Examining Committee: Chair: Charlotte Waddell
Professor
Robert S. Hogg
Senior Supervisor
Professor
Angela Kaida
Supervisor
Associate Professor
Neora Pick
Supervisor
Associate Professor
Department of Medicine
University of British Columbia
Mark Brockman
Internal Examiner
Associate Professor
Helen Trottier
External Examiner
Associate Professor
Preventive and Social Medicine
University of Montreal

Date Defended/Approved: June 28 2017

ii
Ethics Statement

iii
Abstract
Following the advent of modern combination antiretroviral therapy (cART) in 1996, a
temporal decline was widely observed in AIDS-related morbidity and mortality. In the
province of British Columbia (BC), universal provision of cART free-of-charge for people
living with HIV (PLHW) has contributed in part to a significant demographic shift, with
individuals over 50 years of age comprising over half of all PLHW. In this context there is
a need to understand how comorbidities, such as cancer, impact this aging cohort.
Within this line of inquiry, it is imperative to look at cancer risk specifically amongst
women living with HIV (WLWH). The majority of studies looking at cancer as a co-morbid
condition among PLWH fail to conduct sex-stratified analyses, which may obscure the
burden of cancer risk specific to WLWH. Using a Life Course Epidemiology framework,
the objectives of this PhD dissertation were to: 1) measure cancer incidence among
WLWH in BC compared to a general population sample of women; 2) identify the role of
early cART initiation in mitigating excess risk of cancer observed among WLWH; and 3)
estimate the burden of cancer-related mortality among PLWH. This research utilized
administrative health data from Population Data BC (which included data from the BC
Cancer Agency and Vital Statistics) and clinical HIV data from the BC Centre for
Excellence in HIV/AIDS. Findings suggest WLWH experience an increased risk of
certain cancers, notably for certain viral-related malignancies, in comparison to HIV-
negative women in the modern cART era. A protective effect of early initiation of cART
therapy was found for some types of cancer, suggesting oncological health benefits
might be associated with timely initiation of cART after HIV diagnosis for WLWH. Finally,
sex stratified age-adjusted cancer-related mortality rates promisingly suggest there may
not be significantly different cancer-related mortality outcomes between PLWH and the
general population. This dissertation demonstrates that cancer-related morbidity is a
healthcare priority for the growing aging demographic of WLWH and subsequently
highlights the importance of appropriate and effective routine cancer screening
measures as well as comprehensive HIV care inclusive of timely diagnosis and cART
initiation.
Keywords: Women living with HIV; combination antiretroviral therapy; HIV; cancer;
co-morbidity; mortality
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Dedication
“[I think] being smart is cooler than anything in the world”
–Michelle Obama
For women and those fighting for women. Those who came before me are the reason I
have the opportunity to write this dissertation. I hope to always act in service of this.
v
Acknowledgements
I would like to extend my thanks to my PhD committee. Dr. Bob Hogg has been a
constant source of support and encouragement. He has instilled in me the desire to “do
good research and work with good people” and has truly led by example. Dr. Angela
Kaida has been a mentor in the truest sense of the word and has helped guide and
shape me as a researcher far beyond what lies within these pages. Dr. Neora Pick has
provided enthusiastic support and has granted me the opportunity to learn from her
passionate clinical experience. Drs. Brockman and Trottier were extremely thoughtful
and fair examiners who significantly helped to refine this work. I also thank Dr. Waddell
for Chairing my defence and providing structure and guidance in that process.
The COAST team, under the guidance of Dr. Hogg, has provided me with a
wealth of data as well as ongoing support. I could not have finished this dissertation
without the help of colleagues and friends at the BC Centre for Excellence in HIV/AIDS.
Special thanks to Dr. Jeannie Shoveller, Paul Sereda, Michelle Lu, Monica Ye,
Alexandra Collins, Allison Carter, Oghenowede Eyawo, Shahab Jabbari, Dr. Aranka
Anema, and Wendy Zhang. I would like to state that I am forever indebted to Angela
Cescon, Dr. Surita Parashar and Dr. Alexis Palmer for their guidance and friendship. I
am the Ringo Starr in this rock star band of women. I am so appreciative that they have
let me hang around them for so many years and learn from them.
I would like to acknowledge my doctoral funding support from the Canadian
Institutes of Health Research (CIHR) and the Canadian Association for HIV Research
(CAHR) as well as support from the BC Centre for Excellence in HIV/AIDS and the
Soroptimist Foundation of Canada. I would also like to thank Population Data BC
including Monique Gagne, who greatly supported this student work as well as the
COAST study overall. Finally, graduate student awards from Simon Fraser University as
well as the incredible support from all those in the Faculty of Health Sciences including
Margaret Van Soest, Jen Van Rassel and many others.
I want to thank my dear friends – those in Vancouver and those far away. Your
faith in me means everything. Special thanks to Greg, Alison, Meghan, Jill, Kim, Tristan,
and Jillian for being there for me throughout this entire process and keeping me sane. I
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also have to give a shout-out to the CFBC family who have put up with me complaining
about graduate student life every morning for the past 4 years and cheered for me
regardless. Matthew, thank you for caring for me, encouraging me to be proud of myself
and for reminding me, when need be, that I “haven’t cried that much” during this
process. Most of all, thanks for making me happy. Finally, I want to thank my family for
instilling in me the drive and dedication needed to complete this PhD. Anything good in
me comes from you. Thanks for your unwavering support Mom, Dad, Leigh and Oma. I
sincerely mean it when I say I could not have done it without you.
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Table of Contents
Approval ............................................................................................................................. ii
Ethics Statement ............................................................................................................... iii
Abstract ............................................................................................................................. iv
Dedication ......................................................................................................................... v
Acknowledgements ........................................................................................................... vi
Table of Contents ............................................................................................................ viii
List of Tables ..................................................................................................................... xi
List of Figures .................................................................................................................. xii
List of Acronyms ............................................................................................................. xiii
Preface ............................................................................................................................ xiv
Chapter 1. Introduction ............................................................................................... 1
1.1. Abstract ................................................................................................................... 1
1.2. Background ............................................................................................................. 1
1.2.1. Cancer comorbidity in the modern cART era ................................................... 1
1.2.2. Relationship between HIV and cancer ............................................................. 2
1.2.3. Cancer-related mortality ................................................................................... 5
1.2.4. Cancer among Women living with HIV ............................................................. 6
1.3. Guiding framework .................................................................................................. 8
1.3.1. Life Course Epidemiology ................................................................................. 8
1.4. Gaps in the Literature ............................................................................................. 9
1.5. Relevance ............................................................................................................. 10
1.6. Study Setting and Design ..................................................................................... 11
1.6.1. BC Cancer Agency (objective 1) .................................................................... 11
1.6.2. BC Centre for Excellence in HIV/AIDS Drug Treatment Program (objectives 1,
2 and 3) ....................................................................................................................... 12
1.6.3. COAST study (objectives 2 and 3) ................................................................. 12
1.7. Ethical Approval .................................................................................................... 14
1.7.1. Potential Risks and Benefits ........................................................................... 15
1.8. Study Objectives, Hypotheses, and Summaries ................................................... 15
1.9. Summary ............................................................................................................... 17
Chapter 2. All-type, AIDS-defining and non-AIDS-defining malignancy risk
among women living with HIV: A scoping review ........................................... 18
2.1. Abstract ................................................................................................................. 18
2.2. Background ........................................................................................................... 19
2.3. Methods ................................................................................................................ 21
2.3.1. Definition of cancer ......................................................................................... 21
2.3.2. Search terms .................................................................................................. 22
2.3.3. Inclusion and exclusion criteria ....................................................................... 22
2.4. Results .................................................................................................................. 23
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2.4.1. Literature review results ................................................................................. 23
2.4.2. All-type cancer incidence among WLWH ....................................................... 24
2.4.3. AIDS-defining malignancies among WLWH ................................................... 25
2.4.4. Non-AIDS-defining malignancies among WLWH ........................................... 26
Lung cancer ............................................................................................................. 28
Breast Cancer .......................................................................................................... 28
Virus-related non-AIDS-defining malignancies among WLWH ............................... 29
HPV-related cervical cancer .................................................................................... 30
HPV-related anal cancer ......................................................................................... 30
EBV-related Hodgkin’s lymphoma ........................................................................... 31
Hepatitis-related liver cancer ................................................................................... 31
H pylori-related stomach cancer .............................................................................. 31
2.5. Discussion ............................................................................................................. 32
2.6. Summary ............................................................................................................... 33
Chapter 3. Cancer incidence among women living with HIV in British Columbia,
Canada: A heightened risk of virus-related malignancies .............................. 35
3.1. Abstract ................................................................................................................. 35
3.2. Background ........................................................................................................... 36
3.3. Methods ................................................................................................................ 37
3.3.1. Study Population ............................................................................................ 37
3.3.2. Inclusion and Exclusion Criteria ..................................................................... 38
3.3.3. Outcome Variable ........................................................................................... 38
3.3.4. Explanatory Variables ..................................................................................... 39
3.3.5. General Population Comparison .................................................................... 39
3.3.6. Statistical Analyses ......................................................................................... 39
3.4. Results .................................................................................................................. 40
3.5. Discussion ............................................................................................................. 44
3.6. Summary ............................................................................................................... 47
Chapter 4. Timing of cART initiation influences cancer risk among women living
with HIV ................................................................................................................ 48
4.1. Abstract ................................................................................................................. 48
4.2. Background ........................................................................................................... 49
4.3. Methods ................................................................................................................ 51
4.3.1. Study population ............................................................................................. 51
4.3.2. Inclusion and exclusion criteria ....................................................................... 52
4.3.3. Outcome variable ........................................................................................... 53
4.3.4. Primary explanatory variable .......................................................................... 53
4.3.5. Covariates ...................................................................................................... 53
4.3.6. Statistical methods ......................................................................................... 54
4.4. Results .................................................................................................................. 54
4.4.1. Sample characteristics ................................................................................... 54
4.4.2. Bivariate comparison of WLWH with and without cancer diagnosis ............... 55
4.4.3. Immune suppression at cART initiation among WLWH ................................. 57
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4.4.4. Cancer incidence by CD4 cell count at cART initiation .................................. 58
4.4.5. Predictors of cancer risk among women living with HIV ................................. 60
4.5. Discussion ............................................................................................................. 61
4.6. Summary ............................................................................................................... 64
Chapter 5. Cancer-related mortality among women and men living with HIV in the
modern cART era ................................................................................................ 65
5.1. Abstract ................................................................................................................. 65
5.2. Introduction ........................................................................................................... 66
5.3. Methods ................................................................................................................ 69
5.3.1. Study population ............................................................................................. 69
5.3.2. Inclusion criteria .............................................................................................. 70
5.3.3. Outcome variable ........................................................................................... 70
5.3.4. Covariates ...................................................................................................... 71
5.3.5. Statistical methods ......................................................................................... 71
5.4. Results .................................................................................................................. 72
5.4.1. Sample characteristics ................................................................................... 72
5.4.2. Cancer mortality among PLWH and the general population with cancer ....... 75
5.4.3. Cancer mortality rates .................................................................................... 76
5.4.4. Temporal trends in cancer mortality among PLWH ........................................ 78
5.4.5. Predictors of cancer-related mortality ............................................................. 79
5.5. Discussion ............................................................................................................. 80
5.6. Summary ............................................................................................................... 83
Chapter 6. Summary and Recommendations ......................................................... 84
6.1. Abstract ................................................................................................................. 84
6.2. Summary of findings ............................................................................................. 84
6.3. Significance and contribution ................................................................................ 87
6.4. Consideration of limitations ................................................................................... 88
6.5. Implications for clinical care .................................................................................. 90
6.6. Recommendations ................................................................................................ 92
6.7. Future research directions .................................................................................... 94
6.8. Conclusions .......................................................................................................... 96
References ..................................................................................................................... 98

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