A TEST OF AN INTERVENTION TO PROMOTE PAP TESTING IN A GROUP OF WOMEN LIVING WITH HIV By Jeanne Murphy A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland May 2014 © 2014 Jeanne Murphy All Rights Reserved ABSTRACT Background: Cervical cancer is the second most common type of cancer among women worldwide. Women with human immunodeficiency virus (HIV) bear a disproportionate burden of cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN), that result from persistent high-risk Human Papillomavirus (HPV) infection. HIV clinical practice guidelines recommend two Pap tests in the year following diagnosis, and if both are normal, yearly thereafter. Nationally, only 25% of women meet this recommendation. The mean annual Pap testing rate for federally-funded HIV centers is only 55.7%. In 2009, quality improvement statistics from the Johns Hopkins Hospital Adult HIV Clinic, a large urban HIV center, revealed an annual Pap testing rate of 59%. This occurred despite interventions to address adherence issues were implemented, including nurse case management, co-location of HIV and gynecology services, flexible scheduling, and continuity of care. Women keep their appointments for HIV primary care more often than for gynecology care in the adult HIV Clinic, so an intervention that takes place during a primary care visit could improve cervical cancer screening rates. The availability of HPV testing provides a unique opportunity to increase perceived susceptibility to and severity of cervical cancer among women with HIV, and to encourage follow-up Pap testing. Detection of high-risk strains of the virus indicates a higher risk for high grade CIN and cancer, while a negative HPV test predicts a less than 2% risk of developing CIN. Women can perform HPV testing easily through vaginal self-collection in a primary care visit. Studies of women without HIV who do not have regular Pap testing have demonstrated that self-collected HPV testing and results counseling increases the overall screening rate, and women who test positive for HPV have a high rate of follow-up Pap testing. Self-collected HPV testing and results counseling could be utilized in the HIV primary care setting to promote Pap testing among ii women with HIV. Objectives: This dissertation study was a randomized trial to test whether receiving self-collected HPV testing and results counseling in HIV primary care would increase completion of Pap testing in a group of women a hospital-based outpatient Adult Clinic for HIV Care. The study was informed by the Health Belief Model (HBM), which posits that screening behavior will increase if persons at risk for disease have a cue to action that increases their perception of susceptibility to and severity of the disease. In this study, the HPV test and results counseling were cues to action that also correctly identify women at increased for disease. Sampling, design and methods: To achieve these aims, 97 women who were late for Pap testing were recruited for participation while they were at an HIV care appointment. They were randomized to HPV self-collection and results counseling, or to a control group receiving usual care. Six months after enrollment, medical records were reviewed for completion of Pap testing in the intervening months. Findings: Self-collected HPV testing and results counseling did not improve Pap test attendance when compared with usual care as experienced by the control group. Overall, 35% of the entire sample completed their Pap tests within 6 months of the baseline visit. Perceived threat of cervical cancer did not change for the intervention group, even when the HPV test was positive. The follow-up interview rate for the Perceived Threat scale was 91%. Conclusions: Self-collection of cervico-vaginal cells for HPV testing was feasible in this population. Overall the study served as an effective intervention to promote Pap testing. High follow up rates overall demonstrated that intensive interventions to improve cervical cancer screening are effective. Advisor: Hayley Mark, PhD, RN iii DEDICATION This dissertation study is dedicated to my children: Sonia and Bridget Murphy Anger, and Daniel and Katya Anger. Thank you for your love and for believing in me. iv Funding for this dissertation was provided by: Health Disparities Predoctoral Fellowship, National Institute of Nursing Research T32-NR007968, 2009-2012 National Research Service Award, National Institute of Nursing Research, F31-NR013633, 2012-2014 Council for the Advancement of Nursing Science/Southern Nursing Research Society 2013 Dissertation Grant Award The content of this study is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health or other funding agencies. v ACKNOWLEDGEMENTS This dissertation is the culmination of years of hard work and fruitful collaboration with many faculty and staff at Johns Hopkins University Schools of Nursing, Medicine and Public Health. I am extremely grateful to my advisors and committee members, Dr. Hayley Mark and Dr. Jeri Allen, for their encouragement and for providing inspiration during hard times. Dr. Jean Anderson, another committee member and co-sponsor of my study, provided clinical expertise and thoughtful commentary throughout the research process. My other committee members were Dr. Sarah Szanton and Dr. Haera Han, with whom I had scholarly discussions that helped shape the scope and direction of my research and final dissertation. Dr. Jason Farley, who served on my preliminary oral examination committee, has been a steadfast supporter of this research and deserves much credit for its completion. I would also like to thank my alternate committee members Dr. Jenell Coleman and Dr. Nicole Warren, who are both enthusiastic and helpful. I feel truly blessed to have been surrounded at the School of Nursing by so many wonderful people who have generously shared their expertise and good energy with me through the years. I particularly thank Dr. Chakra Budhathokan for his patience and assistance in the statistical analyses herein. I also acknowledge Dr. Ibby Tanner, Dr. Gayle Page, Dr. Deborah Gross, Dr. Jacquelyn Campbell, Dr. Jennifer Wenzel, Dr. Benita Walton-Moss and Dr. Marie Nolan for each, in her own way, providing course correction along my journey and helping me arrive safely on the other side. Dr. Patti Gravitt, formerly at Bloomberg School of Public Health and now at the University of New Mexico, was very generous with her time discussing HPV- related research. Last but not least, the PhD students at the School of Nursing are special; the vi norm is to help each other, and to “pay it forward” as much as one can. They are truly the village that raised this dissertation. It was challenging to do a randomized controlled trial of a clinical intervention in a real- world setting, but the Moore Clinic for HIV Care made that possible. I am grateful to Jeanne Keruly, CRNP, Lois Eldred, DrPH, PAC, and Richard Moore, MD for making it possible. Anitha Devadason, the research coordinator for the Center for AIDS Research, was an invaluable asset in the day-to-day conduct of my study. The support of nurse-manager Kisten Nolan, RN, MPH, was vital to the study and our conversations about clinic flow and patient needs helped inform how the study was conducted. The front desk staff was gracious and patient, and provided me with both company and entertainment (like breaking into song occasionally) during the long hours of recruitment. Of course, this study would be impossible without the women themselves. I learned so much from each and every patient I spoke to in the Moore Clinic. These women live with HIV with grace and fortitude. I am profoundly grateful to them, and look forward to years of research dedicated to helping them improve their health. Lastly, I thank my family who survived these years with me. First my children, who loved and believed in me: Sonia, Bridget, Katya and Daniel. My sister Susan was always ready to answer the phone or fly down from Boston to be with me. And I end with a final thanks to my mother Anna Murphy, who escaped Wind Mill Lane in Limerick, Ireland to become a dedicated reading teacher, and produced (now) three daughters with doctorates: go raibh maith agat. vii DISSERTATION TABLE OF CONTENTS ABSTRACT ………………………………………………………………………..ii DEDICATIONS ……………………………………………………………………iv ACKNOWLEDGEMENTS ………………………………………………………..vi TABLE OF CONTENTS ………………………………………………………….viii LIST OF TABLES ………………………………………………………………….xi LIST OF FIGURES ………………………………………………………………..xii CHAPTER ONE: INTRODUCTION ………………………………………………1 SIGNIFICANCE ……………………………………………………………1 SPECIFIC AIMS ……………………………………………………………3 REVIEW OF LITERATURE ……………………………………………….4 BACKGROUND ……………………………………………………………6 DISSERTATION ORGANIZATION ………………………………………………7 REFERENCES ……………………………………………………………………...8 CHAPTER TWO. …………………………………………………………...……..18 MANUSCRIPT ONE: Murphy, J. and Mark, H.: Cervical Cancer Screening in the Era of Human Papillomavirus Testing and Vaccination. J Midwifery Womens Health 2012;00:1–8. doi: 10.1111/j.1542-2011.2012.00207 ABSTRACT ………………………………………………………………………..18 INTRODUCTION ………………………………………………………………….18 METHODS …………………………………………………………………………19 Design ………………………………………………………………………19 viii RESULTS …………………………………………………………………………..20 DISCUSSION ………………………………………………………………………31 REFERENCES ……………………………………………………………………..33 ADDITIONAL LITERATURE REVIEW………………………………………….44 HPV AND CERVICAL CANCER IN WOMEN WITH HIV ……………..44 SENSITIVITY/SPECIFICITY OF SELF-COLLECTED HPV TESTS…....46 CHAPTER THREE: MANUSCRIPT TWO ……………………………………….55 Self-collected HPV testing and results counseling as an intervention to improve Pap testing among women with HIV: A randomized controlled trial. ABSTRACT…………………………………………………………….…………..57 INTRODUCTION ……………………………………………………….…………57 METHODS ……………………………………………………………….………...60 Study design.……….…………………………….………...……….……….60 Study procedures……………………………….……..…………………….62 Statistical methods………………………….……………………………….63 RESULTS ……………………………………………………………….………….64 DISCUSSION …………………………………………..…………………….…….65 REFERENCES ……………………………………………………………………..70 CHAPTER FOUR: MANUSCRIPT THREE…………………………..……….…..81 Effect of testing HPV positive on perceived threat of cervical cancer among women with HIV. ABSTRACT………………………………………………………………..……….82 INTRODUCTION ……………………………………………………. …………...84 METHODS ……………………………………………………………..…………..87 ix Study design………………………………………………….……..……….88 Statistical methods…………………………………………………...……...89 RESULTS …………………………………………………………………………..90 DISCUSSION ……………………………………………………………....……....92 REFERENCES ……………………………………………………………..……....96 CHAPTER FIVE: DISCUSSION …………………………………………....……104 INTRODUCTION………………………….…………………………........104 SUMMARY OF FINDINGS BY AIMS …….…………………….……....104 Aim 1……………………………………….……………….………104 Aim 2………………………………………………………..….104-105 STRENGTHS AND LIMITATIONS………………………………..……..105 IMPLICATIONS/DISSEMINATION OF FINDINGS…………….………105 RECOMMENDATIONS FOR FUTURE RESEARCH……...….………...105 CONCLUSION ……………………………………………………………107 APPENDICES………………………………………………………………….…..108 APPENDIX 1: INTERVIEW FORMS………………………………………….….108 APPENDIX 2: ETHICAL APPROVALS…...………….……………………….….117 APPENDIX 3: LABORATORY PERMITS/APPROVALS…....…………….…….119 APPENDIX 4: CURRICULUM VITAE………………...……….………….……...122 x