Cervical cancer screening by co testing method for vietnamese women from 25 to 55 years old a cost effectiveness analysis

MINISTRY OF EDUCATION AND TRAINING - MINISTRY OF HEALTH HANOI UNIVERSITY OF PUBLIC HEALTH BUI THU HIEN CERVICAL CANCER SCREENING BY CO-TESTING METHOD FOR VIETNAMESE WOMEN FROM 25 TO 55 YEARS OLD: A COST – EFFECTIVENESS ANALYSIS H P U MASTER OF PUBLIC HEALTH SPECIALIZED CODE: 8720701 H HANOI, 2022 MINISTRY OF EDUCATION AND TRAINING - MINISTRY OF HEALTH HANOI UNIVERSITY OF PUBLIC HEALTH BUI THU HIEN CERVICAL CANCER SCREENING BY CO-TESTING METHOD FOR VIETNAMESE WOMEN FROM 25 TO 55 YEARS OLD: A COST – EFFECTIVENESS ANALYSIS H P U MASTER OF PUBLIC HEALTH SPECIALIZED CODE: 8720701 H SUPERVISOR PhD PHAM NU HANH VAN ASSOC PROF VU HONG THANG HANOI, 2022 Acknowledgement In successfully completing my master thesis, many people have supported me I would like to thank all those who are related to this project Primarily, I would like to express my sincere thanks and gratitude from the bottom of my heart to my supervisors Professor Vu Hong Thang of the Department of Oncology, Hanoi Medical University and Pham Nu Hanh Van Ph D, of the Department of Pharmaceutical Administration & PharmacoEconomics, Hanoi University of Pharmacy They were very welcoming and kept me in the right direction through their advice They enabled me to draw on my knowledge, skills, and experience by raising questions and guidance to rectify my mistakes H P Secondly, I would also like to thank Professor Hoang Van Minh who motivates me to enhance my knowledge of health technology assessment and Ms Do Thanh Huyen for support administration process and helping me to adapt in a new learning environment A special thanks to all the teachers at the Hanoi University of Public health for teaching and helping me to obtain knowledge to be able to conduct this study U Nobody has been more important to me in the pursuit of this project than the members of my family I would like to thank my parents, whose love and guidance are with me in whatever I pursue They are the ultimate role models Most importantly, I wish H to thank my loving and supportive husband who provides unending inspiration i LIST OF ABBREVIATIONS AND ACRONYMS AGC Atypical glandular cells ASC Atypical squamous cells ASC-H Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion ASC-US Atypical squamous cells of undetermined significance CC Cervical cancer CEA Cost effectiveness analysis CIN Cervical intraepithelial neoplasia DSA Deterministic sensitivity analysis HPV Human papillomavirus HPV hr+ High-risk HPV infection HSIL High-grade squamous intraepithelial lesion K Hospital Viet Nam National Cancer Hospital LBC Liquid-based cytology LSIL Low-grade squamous intraepithelial lesion LMIC Lower- and middle-income countries MOH Vietnam Ministry of Health PSA Probabilistic sensitivity analysis QADAS Quality assessment tool for diagnostic accuracy studies QALYs Quality adjusted life years RCTs Randomized controlled trials SDI Social-demographic Index VIA Visual inspection with Acetic acid VILI Visual inspection with Lugol's Iodine WHO World Health Organization H P U H ii Table of content Abstract v Introduction Research objectives .5 Chapter : Literature review .6 1.1 Epidemiology of cervical cancer: 1.2 Burden of cervical cancer in the world and Southeast Asia region: 1.3 Burden of cervical cancer in Viet Nam: 1.4 Strategy to eliminate cervical cancer in the world and Viet Nam: 10 1.5 Cervical screening methods: 13 1.6 Target age group and screening interval: .15 1.7 Cost-effectiveness analysis of co-testing for cervical cancer screening: 16 1.8 Research conceptual framework: 17 Chapter : Research methodology 19 2.1 Research methodology for the objective 1: 19 2.1.1 Research timeline 19 2.1.2 Research object: 20 2.2 Research methodology for the objective 2: 20 2.2.1 Research timeline: .20 2.2.2 Target population: .21 2.2.3 Intervention and comparator: 21 2.2.4 Decision model and assumption: 21 2.2.5 Time horizon, cycle length and analytical perspective: 24 2.2.6 Discount and inflation adjustment: 24 2.2.7 Input parameter and data sources: .24 2.2.8 Sensitivity analysis: 28 2.3 Ethical issues: .29 Chapter : Results .30 3.1 The literature review of cost-effectiveness studies of cervical cancer screening for women by the co-testing method 30 3.1.1 Target population 33 3.1.2 Interventions and comparators 34 3.1.3 Input parameters 41 3.1.4 Summary results 42 3.2 Parameter inputs for CEA of the co-testing method: .43 3.2.1 Transition probabilities .43 3.2.2 Effectiveness of co-testing and cytology method .44 3.2.3 QALY weights 46 H P H U iii 3.2.4 Cost for co-testing method, cytology method and cervical cancer treatment from provider perspective 47 3.3 CEA results – co-testing times v.s cytology times 50 3.3.1 Incremental cost-effectiveness ratio (ICER) .50 3.3.2 Sensitivity analysis 51 Chapter : Discussion .56 4.1 Main findings from the literature review 56 4.1.1 Target population 56 4.1.2 Interventions and comparators 56 4.1.3 Input parameter 58 4.1.4 CEA results .58 4.2 Main findings from the CEA of the co-testing method 61 Strength and limitations .62 Chapter : Conclusion and recommendation 65 Conclusion .65 Recommendation 66 Annex 1: Consent form for expert consultation 67 Annex 2: Interview guide for consulting with cancer experts 68 Annex 3: Interview guide for consulting with reproductive health expert 70 Annex 4: Interview guide for consulting with financial staff 72 Annex 5: List of selected CEA studies for literature review .74 Annex 6: Application of transition probabilities in the Markov modelling 83 Annex 7: One-way DSA results in age groups .85 Annex 8: Letter approval of the Ethical Committee 88 Reference 89 H P H U iv List of figures Figure 1.1: Estimated number of new cases in 2020, females, all ages Figure 1.2: Estimated number of new cases in 2020, High income (left) and Low middle income (right), females, all ages Figure 1.3: Estimate number of prevalent cases Figure 1.4: Age-specific incidence rates (per 100,000 women) for cervical cancer, Vietnam, between 1999 and 2017 10 Figure 1.5: the proportion of nonvaccinated women willing to receive the HPV vaccine before and after knowing its price .13 Figure 1.6: The conceptual framework of the study 18 H P Figure 2.1: Markov model of Felix, J C et al (2016) .23 Figure 3.1 PRISMA diagram for literature reviews 31 Figure 3.2: PRISMA diagram for test effectiveness 44 Figure 3.3: PSA analysis results 53 Figure 3.4: PSA analysis results 54 Figure 3.5 PSA analysis results 55 U H List of tables Table 3.1: List of selected studies .32 Table 3.2: Cervical cancer screening age interval .33 Table 3.3: Interventions and comparators 35 Table 3.4: List of systematic review studies about co-testing and cytology effectiveness 46 Table 3.5: Test effectiveness .47 Table 3.6: QALY weights 48 Table 3.7: Unit cost 48 Table 3.8: Transition probabilities 49 Table 3.9: Cost, QALY weights and ICER between alternatives (3% discount) 50 v Abstract Background: Cervical cancer (CC) poses a great disease burden for low- and middleincome countries In Viet Nam, this disease is a common cancer among Vietnamese women cancer patients Although cervical cancer can be controlled effectively by coverage HPV vaccination and cervical cancer screening for women regularly, LMIC countries meet challenges of financial constrain and scarcity of infrastructures For early detection of cervical cancer, cytology and HPV testing are popular methods for cervical cancer screening and are selected as primary method for national screening program in many countries HPV test has a significant low specificity while sensitivity of cytology notably depends on quality control and quality assurance Drawbacks of HPV testing can be backup H P by cytology and vice versa The combination of these test (co-testing) can prolong the interval between screening times from years to years; hence, the screening frequency in women’s lifetime can be reduced The HPV test with 5-year interval is suitable for HPV vaccinated population while in country with low coverage of HPV vaccination as Viet Nam, the interval for HPV test is years Therefore, the co-testing will be a potential method for a population with low prevalence of HPV vaccination Viet Nam is a lower- U middle income country with low coverage of HPV vaccination; hence, it is a demand to looking for a primary cervical screening method that proves cost-effectiveness H Research methodology: A Markov model with health states was used to investigate cost-effectiveness of times consecutive CC screening by the co-testing method (intervention) and times consecutive CC screening by the cytology method (comparator) The proposed intervention and comparator followed the WHO recommendation that women with adequate screening history and no abnormal smear could stop screening due to low risk of HPV infection Based on literature review, parameter inputs for the model including transition probabilities, effectiveness of interventions, cost from provider perspectives and QALYs were computed Experts from cancer field, reproductive health and finance reviewed results from literature review for adaptation of parameter inputs to the Viet Nam situation Deterministic analysis and probabilistic analysis were performed to handle uncertainties vi Results: Three times consecutive CC screening by the co-testing is dominated The intervention is less effective and more costly than five times consecutive CC screening by the cytology method in all age groups Therefore, it can thus consider times co-testing with the 5-year interval to be inferior to times cytology with the 2-year interval Conclusions: The strategy using times consecutive CC screening by co-testing cannot be recommended for Vietnamese women aged 25 to 55 years old due to less benefits and higher cost H P H U Introduction According to global statistic on cancer, cervical cancer (CC) poses a great disease burden for low and middle income countries (LMIC) and can be controlled effectively by coverage of HPV vaccine and cervical screening programs (1,2) Cervical cancer is the second most frequent cancer among women in low-income and LMIC In 2018, 290,000 (51%) of the 570,000 new cervical cancer cases worldwide occurred in women living in LMICs (500,000 [88%] when including upper-middleincome countries) (1) Without further intervention, these inequalities in the burden of cervical cancer are expected to grow, because recent increases in the uptake of human papillomavirus (HPV) vaccination and cervical cancer screening have mainly H P occurred in high-income countries Less than 30% of LMICs have introduced HPV vaccination compared with more than 85% of high-income countries (3,4) Additionally, less than 20% of women in LMICs have ever been screened for cervical cancer compared with more than 60% in high-income countries (5) In Viet Nam, this disease is a common cancer among women cancer patients (6,7) U From 2016, Vietnam Ministry of Health (MOH) approved a national action plan on prevention and control of cervical cancer for the period 2016 – 2025 H However, the budget for the screening program has not been included in the national health insurance and relies on resources called from the local budgets and official development aid sources Unstable budget allocation for the action plan constitutes a significant challenge of objectives achievement According to the guidelines for control and prevention of cervical cancer from MOH, cervical cancer screening methods can be applied for women aged 21 – 65 years They include: (i) cervical cytology, (ii) cervical observation with axis acetic (VIA - visual inspection with Acetic acid) or examination of the cervix with Lugol's solution (VILI - visual inspection with Lugol's Iodine) and (iii) test to detect human papillomavirus (HPV) types These tests can be used separately or in combination with the screening for which the intervals vary from two to five years With the combination of HPV test H P H U H P H U H P H 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