Epidemiological features, national burden of several HPV-related diseases and estimation of cost-effectiveness of HPV vaccines in Vietnam

Lead Research Organisation: London School of Hygiene & Tropical Medicine
Department Name: Epidemiology and Population Health

Abstract

This project is designed to collect the evidence that will be needed to support the introduction of the cancer-preventing vaccine HPV (Human Papillomavirus) into the national immunization program of Vietnam. HPV is the second vaccine that has been developed that can prevent cancer (the first being Hepatitis B vaccine which prevents liver cancer). HPV vaccine prevents HPV infection, which is responsible for almost all cases of cancer of the cervix in women. In Western countries cancer of the cervix is much less common than in developing countries, because the regular cervical screening (Pap smears) identifies and treats very early cases. HPV is very common in developing countries like Vietnam, and the cancers that it causes are usually detected late, leading to high mortality. HPV is also responsible for a variety of other cancers affecting both men and women, including penile cancer, anal cancer and throat cancer. The vaccine is used is most industrialized countries, and is given to girls, and in some countries to boys as well. It has been introduced into very few developing countries, because of its high price, and the lack of evidence about HPV infection and disease in those countries. Vietnam is a rapidly modernizing country, with a booming economy and a population that is becoming increasingly westernized. HPV is spread by unprotected sex, and rates of infection are very high among sex workers and men who have sex with men. This project will study the rate of HPV infection among young university students in north, south and central Vietnam to get a national perspective. We will also study two important high risk groups, sex workers and men who have sex with men in both the north and south. We will use the records of the cancer hospitals in Vietnam to estimate the proportion of the population who were affected by HPV associated cancer, and to understand better the ages affected and the outcome and treatment costs of cases. This will enable us to predict the effect of HPV vaccine introduction on the community and calculate the money that will be saved by the health system if those cancers are prevented. Finally we will develop, within Vietnam, the laboratory skills that are needed to study HPV disease, and especially to undertake a trial of HPV vaccines in Vietnam. The trial is not covered by this proposal, but we hope in future to do a trial that will help us to decide which is the simplest and therefore least expensive, way to introduce HPV vaccine into a developing country like Vietnam. The project will be undertaken jointly by five institutions. The three Vietnamese institutions (two in the north and one in the south) will be able to share their expertise in this area and also develop new skills with help from expert groups in London (London School of Hygiene and Tropical Medicine) and Australia (Murdoch Childrens Research Institute).

Technical Summary

This project will study the rate of HPV infection among young university students in north, south and central Vietnam to get a national perspective. We will also study two important high risk groups, sex workers and men who have sex with men in both the north and south. We will use the records of the cancer hospitals in Vietnam to estimate the proportion of the population who were affected by HPV associated cancer, and to understand better the ages affected and the outcome and treatment costs of cases. This will enable us to predict the effect of HPV vaccine introduction on the community and calculate the money that will be saved by the health system if those cancers are prevented. Finally we will develop, within Vietnam, the laboratory skills that are needed to study HPV disease, and especially to undertake a trial of HPV vaccines in Vietnam. The trial is not covered by this proposal, but we hope in future to do a trial that will help us to decide the simplest, and therefore least expensive, way to introduce HPV vaccine into a developing country like Vietnam. The project will be undertaken jointly by five institutions. The three Vietnamese institutions (two in the north and one in the south) will be able to share their expertise in this area and also develop new skills with help from expert groups in London (London School of Hygiene and Tropical Medicine) and Australia (Murdoch Childrens Research Institute).

Planned Impact

The proposed research will have benefits for the general Vietnamese community, the Vietnamese scientific and medical community, and the global health community.
For the Vietnamese community, we expect that the research will accelerate the introduction of effective HPV vaccination. At present the lack of clear epidemiological evidence for HPV and HPV-related cancers represents a major obstacle to the introduction of HPV vaccine in Vietnam. Prevalence of and types of HPV among young female adults and sex workers will help guide policy with regard to vaccine choice and schedule for the vaccination of girls. In particular the young, educated university students represent an important group whose level of sexual activity and HPV infection rate may prove decisive as the government considers the need for HPV vaccine introduction. MSM represent an important subgroup of young males, whose risk of HPV infection and HPV associated cancers is higher than the general population. As vaccination must take place before sexual orientation is clear, consideration of this group should help to guide the need for HPV vaccination of boys. Rates of cancer, ages of those affected, treatment costs and outcomes are all needed along with data on risk factors in order to make evidence based decisions regarding HPV vaccine introduction. A Japanese research group working with the Hai Phong University is in the process of collecting tumour specimens for HPV detection and genotyping, so we will not duplicate this work. Finally, our proposed new vaccine trial (not covered by this application) will guide the government of Vietnam to help them find a low cost but effect way of introducing HPV vaccine. Overall the information collected should accelerate the introduction of HPV vaccination.
This project will facilitate the introduction of a well-organized, national HPV research program, including both northern and southern institutions. While both NIHE and PIHCM have established HIV and sexual transmitted diseases (STD) programs that have collaborated in the past, this project provides the opportunity to strengthen their HPV epidemiology and diagnostics with a national collaborative project. While NIHE have made considerable progress in HPV virology, PIHCM have advantages in other areas, such as econometric modelling, while IBT brings strong skills in cellular immunology and molecular genetics. LSHTM brings health economics skill and vaccine trial design experience, and MCRI Melbourne bring strength in HPV immunology and vaccine evaluation. As the project is designed to enable the groups to work towards an HPV vaccine trial, this is envisioned as a collaborative north-south project.
Information gathered during this project will add to the global understanding of HPV epidemiology. Regionally it can be expected that data from Vietnam will influence HPV introduction in surrounding south-east Asian countries such as Cambodia and Thailand.

Publications

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Tuan LA (2021) Anal human papillomavirus prevalence and risk factors among men who have sex with men in Vietnam. in International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

 
Description After extracting data from two district hospitals, five provincial and regional hospitals, and the cancer registry in Can Tho, our preliminary analyses showed that about half of women diagnosed with cervical cancer in 2009-2012 from two districts (in Can Tho) were captured by the Can Tho cancer registry.
Exploitation Route The HPV prevalence study among young female university students was the first and largest in Vietnam across Hanoi, Hue, and Ho Chi Minh City. Our study demonstrated the feasibility of self-swab in HPV screening in Vietnam. This collection method would facilitate HPV screening nationwide, allowing for HPV screening with high precision assays, an important component of the HPV related cancer reduction programme.

From this project, we can understand the cost and quality of life for patients with HPV-related diseases, which will hopefully lead to better patient management.
Sectors Healthcare

 
Description The project has been delayed by many factors, not only the pandemic. In particular the field work in North Vietnam has seen very long delays due to issues with official approvals for projects based in the south. Nevertheless the work has attracted substantial interest from Government. As discussed with UKRI we have extended the duration of the project to enable a pilot study of vaccination of high risk, young sex workers in Hai Phong. This novel use of the vaccine has the potential to prevent many cases, in the ralatively near future. The pilot study is now complete and it shows substantial immunogenicity in the young women. This has now led to the development of a new program of research funded by a Vietnamese agency.
First Year Of Impact 2023
Sector Healthcare
Impact Types Policy & public services

 
Title Datasets and collections of samples that have been created as part of this project 
Description We conducted HPV prevalence studies among female sex workers, men-who-have-sex-with-men, and university students. A total of 700 FSW, 800 MSM, and 1500 first- and fourth-year university students were enrolled and surveyed. All the samples collected have been successfully genotyped. We have completed all data collection and harmonisation-sociological, epidemiological and virological data in Hanoi, Ho Chi Minh City, and Hue-and data analyses of the three study populations. We have also extracted data from cervical cancer and anal cancer patient records and surveyed 361 individuals with cervical cancers, anal cancers or anogenital warts. 
Type Of Material Data handling & control 
Year Produced 2021 
Provided To Others? Yes  
Impact The HPV prevalence study among young female university students was the first and largest in Vietnam across Hanoi, Hue, and Ho Chi Minh City. Our study demonstrated the feasibility of self-swab in HPV screening in Vietnam. More than 98% of samples from each site were valid for further HPV screening indicated by the presence of HLA internal control. This collection method would facilitate HPV screening nationwide, allowing for HPV screening with high precision assays, an important component of the HPV related cancer reduction programme. After extracting data from two district hospitals, five provincial and regional hospitals, and the cancer registry in Can Tho, our analyses showed that only 54% (57/105) of women diagnosed with cervical cancer in 2009-2012 from two districts (in Can Tho) were captured by the Can Tho cancer registry. Because of this study, we can understand the cost and quality of life for patients with HPV-related diseases, which will hopefully lead to better patient management. 
 
Description MCRI 
Organisation Murdoch Children's Research Institute
Country Australia 
Sector Academic/University 
PI Contribution Along with the MCRI researcher, Ryan Toh, the PI coordinated and managed the Vietnamese work. This involved the completion of recruitment for HPV prevalence studies among female sex workers, men-who-have-sex-with-men, and university students. A total of 700 FSW, 800 MSM, and 1500 first- and fourth-year university students were enrolled and surveyed. All the samples collected have been successfully genotyped. We have also completed all data collection and harmonisation-sociological, epidemiological and virological data in Hanoi, Ho Chi Minh City, and Hue-and data analyses of the three study populations. Currently, appropriate publications are being prepared and being reviewed internally. In the coming months, we expect to submit them to peer-reviewed journals. In addition, we have completed and run the mathematical model to the extent we are able to without full data sets, although we are unable to produce results until the remaining datasets have been completed. 3 manuscripts have been drafted o FSW manuscript submitted, but was rejected thrice- plans to resubmit in the coming months. o Manuscripts for MSM and university students are being reviewed internally after additional data were generated.
Collaborator Contribution The PI (staff of MCRI and LSHTM) a member of MCRI, two researchers of LSHTM, Mark Jit and Kiesha Prem, spent weeks in Vietnam working with both NIHE and PIHCM colleagues to help them write protocols, submit ethics applications, expedite field work, supported data analyses, and prepare publications. This approach improved the communication between all partners and allowed us to realise substantial progress in 2019. This was lessons learned when managing relationships within a country with highly complex ways of working from outside the country. Overall, MCRI has played a key role in this project involving: 1) purchasing reagents supplies to support field epidemiology studies in Vietnan; 2) providing coordination to the research team at National Institute of Hygiene and Epidemiology, Vietnam (performed the work (screening, typing and HPV immunological analysis capacity) at the cancer hospital in Hanoi); 3) managed VLP production and validation
Impact HPV prevalence studies We have completed the recruitment for HPV prevalence studies among female sex workers, men-who-have-sex-with-men, and university students. A total of 700 FSW, 800 MSM, and 1500 first- and fourth-year university students were enrolled and surveyed. All the samples collected have been successfully genotyped. We have also completed all data collection and harmonisation-sociological, epidemiological and virological data in Hanoi, Ho Chi Minh City, and Hue-and data analyses of the three study populations. Currently, appropriate publications are being prepared and being reviewed internally. In the coming months, we expect to submit them to peer-reviewed journals. In addition, we have completed and run the mathematical model to the extent we are able to without full data sets, although we are unable to produce results until the remaining datasets have been completed. 3 manuscripts have been drafted o FSW manuscript submitted, but was rejected thrice- plans to resubmit in the coming months. o Manuscripts for MSM and university students are being reviewed internally after additional data were generated. HPV-related disease burden studies (cancer epidemiology) With the approval to the ethics amendments in April 2019, we have obtained HPV-related cancer data in both Hanoi and Ho Chi Minh City. We have since begun preliminary analyses to describe historical trends in cervical and anal cancer by age and province in Vietnam since the 1980s. After extracting data from two district hospitals, five provincial and regional hospitals, and the cancer registry in Can Tho, preliminary analyses showed that only 54% (57/105) of women diagnosed with cervical cancer in 2009-2012 from two districts (in Can Tho) were captured by the Can Tho cancer registry. Fieldwork in Hai Phong, Hanoi and Ho Chi Minh city have also been completed for this aim. Data extraction from patient records and analyses are ongoing. More details can be found in Annex G. HPV vaccine modelling With our collaborators from Prof Marc Brisson's group at the University of Laval, we have parameterised the HPV-ADVISE transmission dynamic model of HPV vaccination to Vietnamese data in the literature. The only remaining step to producing results that are highly policy-relevant is to complete analysis of the data that are being collected from our field studies to input into the model. HPV vaccine demonstration project and immunology technology transfer PI and Vietnam collaborators have attended several site visits and have identified Hai Phong as the location for this demonstration project. Ethics approvals have been granted from the major institutions (NIHE, MCRI and London School Ethics Committee) and Department of Health in Hai Phong, Vietnam between Oct 2019-Feb 2020 for the conduct of demonstration project. Clinical trial insurance has also been obtained through MCRI.
Start Year 2016
 
Description National Institute of Hygiene and Epidemiology, Hanoi 
Organisation National Institute Of Hygiene And Epidemiology
Country Viet Nam 
Sector Hospitals 
PI Contribution We have worked with colleagues at NIHE on the following aspects: Cancer epidemiology and outcome, HPV carriage in female sex workers, men who have sex with men and female university students in Hanoi and Hue. We have worked with them on the diagnostic aspects of HPV testing. We have established a new project in Hai Phong to undertake pilot immunization of young female sex workers. This project has been delayed due to the pandemic but we expect it to take place this year.
Collaborator Contribution We have worked as research partners along with colleagues at the Pasteur Institute of HCMC on all aspects of this complex project.
Impact A number of publications under development. Information is shared directly with Government decision makers.
Start Year 2016
 
Description National Institute of Hygiene and Epidemiology, Hanoi 
Organisation Pasteur Institute of Ho Chi Minh City
Country Viet Nam 
Sector Academic/University 
PI Contribution We have worked with colleagues at NIHE on the following aspects: Cancer epidemiology and outcome, HPV carriage in female sex workers, men who have sex with men and female university students in Hanoi and Hue. We have worked with them on the diagnostic aspects of HPV testing. We have established a new project in Hai Phong to undertake pilot immunization of young female sex workers. This project has been delayed due to the pandemic but we expect it to take place this year.
Collaborator Contribution We have worked as research partners along with colleagues at the Pasteur Institute of HCMC on all aspects of this complex project.
Impact A number of publications under development. Information is shared directly with Government decision makers.
Start Year 2016
 
Description The Pasteur Institute (LSHTM) 
Organisation Pasteur Institute of Ho Chi Minh City
Country Viet Nam 
Sector Academic/University 
PI Contribution LSHTM core team, Mark Jit and Kiesha Prem coordinated analyses of the data collection and dissemination of final outputs of the cancer study with Pasteur Institute Vietnan, to support the demonstration study of the bivalent HPV vaccine
Collaborator Contribution The current no-cost extension was planned to allow for data collection from patients with HPV-related diseases, and data synthesis on disease burden across the cancer registries, hospitals and villages to be completed well within the new study deadline. Our Vietnamese colleagues at the Pasteur Institute Ho Chi Minh (PIHCM) have accelerated this work, and most of the work was completed by October 2020. Unfortunately, colleagues at the National Institute of Hygiene and Epidemiology (NIHE) who were responsible for the work in the north have not been able to find time to undertake the work there, so Pasteur colleagues have agreed to take over that component. Since then field work and data collection was completed, preliminary analyses of the HPV-related disease burden studies have started, and we expect to complete all analyses by early 2021.
Impact OBJECTIVES: 1. To assess the prevalence and characteristics of high-risk and low-risk HPV types, and sexual behaviour of three important population groups at risk of HPV infection - female university students, female sex workers (FSWs) and men who have sex with men (MSM) - in major cities of Vietnam. 2. To evaluate the burden of genital warts and HPV related cancers (e.g., cervical cancer, penile cancer, genital warts) and to estimate the benefits of proposed HPV vaccination in terms of health improvement, HPV prevalence, medical expenditure, and economical return to the country. 3. To enhance laboratory capacity on HPV diagnostics and immunology, providing basis for future vaccine research in Vietnam Objective 1: Prevalence and risk factors of HPV infection in three populations: FSW, MSM and university girls in Hanoi and Ho Chi Minh City (HCMC) Theme 1: FSW - Study completed o Recruited 699 FSW in total (N=350/city) from Hanoi and HCMC o Demographic and behaviour data collected o A cervical swab was collected and HPV testing performed to 33 HPV types - Major findings o 1 in 4 FSW were infected with HPV (around 1 in 5 were high risk HPV types) o Around 12% have abnormal pap smear o Married, divorce, widowed, living alone were associated with high-risk HPV type infection - Paper submitted and rejected by 3 journals. Currently in the process of resubmission to BMC sexual health? Theme 2: MSM - Study completed o Recruited 799 MSM in total (N=400/city) from Hanoi and HCMC o Demographic and behaviour data collected o A rectal swab was collected and HPV testing performed to 33 HPV types - Major findings o 1 in 3 MSM were infected with HPV (around 1 in 5 were high risk HPV types) o High risk HPV infection 2-fold higher in HCMC than Hanoi o inconsistent condom use, and sex under drugs were associated with 2-4-fold higher were associated with high-risk HPV type infection - Manuscript drafted -plan to submit by October 2020 Theme 3: University girls - Study completed o Recruited 1492 first- and fourth-year female students (Target, N=500/city) from Hanoi, Hue and HCMC o Demographic. knowledge and behaviour data collected o A vaginal swab was collected and HPV testing performed to 33 HPV types - Major findings o Low prevalence of HPV infection (4%) o Study stream, older students, sexually active and ever been pregnant were associated with were associated with any HPV infection o Around 60-70% of female students were aware of HPV and cervical cancer and HPV vaccines o Less than 30% were aware of HPV-related diseases other than cervical cancer - Manuscript drafted -plan to submit by December 2020 Three abstracts were presented at the 32nd and 33rd International Papillomavirus Conference (IPVC 2018 and IPVC2020)
Start Year 2016