Generating epidemiological, economic and attitudinal evidence to inform policy-making about HPV vaccine introduction in India and Ethiopia

Human Papilloma Virus (HPV) is a virus found throughout the world. The virus is transmitted between humans, mainly by sexual contact. Cancer of the cervix is the second most common cause of cancer in most parts of the world. Almost all cases are caused by HPV. HPV also causes rarer genital and oral cancers in males and females. There are many types of HPV, but two types (16 and 18) are responsible for most (about 70%) of cancer cases throughout the world. Since 2006 two vaccines have been available that can prevent infection by types 16 and 18. In UK one of the vaccines was introduced into the national program in 2008, given to girls 12-13 years of age. Most industrialised countries now use the vaccine for girls, some also vaccinate boys. There are 3 types of vaccine available covering 2, 4 and 9 types of HPV. The burden of cervical cancer is highest in developing countries, partly for sociological reasons, and partly because few developing countries have cervical screening (Pap smear) programs that detect and treat early stages of cancer, reducing the number of cases that progress to clinical cancer. Vaccination could prevent most of these cases, but up to now HPV vaccine use in developing countries has been very limited because of the high price of the vaccine. In addition, because the vaccine is given to girls in early adolescence, fears have been expressed in some quarters about the safety and the effectiveness of the vaccines. Between India and Ethiopia it is estimated that 40% of all cervical cancers occur in these two countries. In India the vaccine has been used on a limited scale, based on decisions taken by local authorities. Some areas of India have high cervical cancer risk, while others have lower risk. By measuring the proportions of young women who are infected with high risk HPV types, and also measuring the patterns of sexual behaviour, we will develop a simple way by which Indian authorities can estimate the risk level in their communities, and therefore prioritise HPV vaccine introduction. We will also study the other types of HPV circulating to help the government decide on which vaccine to use. To help with vaccine decision making we will also measure the cost of cervical cancer, both in monetary and in human terms. We will investigate these issues by interviewing newly diagnosed cases, as well as conducting interviews with the families of deceased cases. To demonstrate that the vaccine actually works in India we will follow a group of young vaccinated women in the Punjab state where the HPV vaccine is being used. We expect that in future researchers will be able to show a greatly reduced number of infections in these girls. In Ethiopia, cervical cancer is common, but as there are no cancer registries it is not possible to say how common. The government has undertaken a pilot vaccination program in 2 areas of the country, Jimma in the south, and Mekelle in the north. We will measure how common HPV infection is in these areas. Then we will follow 2000 girls who have been vaccinated, and a similar number of unvaccinated girls, yearly to record sexual behaviour and to measure how many have been infected. This will provide the government and the community with proof of the effectiveness of the vaccine, enabling them to accelerate the introduction of the vaccine and to maintain vaccine coverage. To support this studies of the true cost of cervical cancer will be conducted along similar lines to the studies in India. During the course of this study we will evaluate the HPV laboratory in Vellore, India. That laboratory will be used for all Indian and many Ethiopian samples. During the study the laboratory techniques will also be taught to two Ethiopian scientists, after which they will establish a HPV laboratory in Ethiopia.

Cervical cancer is a major public health problem that is much worse in developing countries due to the lack of effective cervical screening. About 40% of the world's cervical cancer burden occurs in two countries, India and Ethiopia. Most cervical cancers, and a range of less common genital and oropharyngeal cancers, are preventable with the currently available Human Papilloma Virus (HPV) vaccines. Both India and Ethiopia have started small scale HPV vaccination, but major barriers to effective national roll-out of HPV vaccine exist, and in both countries there are other important health problems competing for the limited health budget, so a strengthened economic and epidemiological case for vaccine introduction is needed to support vaccine introduction. In India, where population based cancer registries exist in 32 areas, we will undertake studies of HPV infection prevalence in young women in two age strata in settings of high, intermediate and low cervical cancer risk. These data, along with concurrently collected sociological information covering sexual attitudes and practices and other risk factors, will enable the development of mathematical models to estimate cancer risk based on HPV epidemiology. These models will enable authorities in India to focus vaccine introduction on the highest risk communities, and to generate and maintain momentum for the program. In Ethiopia we will collect HPV prevalence and sociological data to better predict cancer risk and to strengthen the government's efforts to introduce HPV vaccine. In addition, we will also conduct studies of the cost of cervical cancer disease, both in financial and human terms to better understand the value of vaccination. We will also strengthen (in India) and establish (in Ethiopia) laboratory capacity for HPV detection, while at the same time establishing baseline data to enable future measurement of HPV vaccine effectiveness in the two countries.

The aim of this project is to provide evidence to accelerate the introduction of HPV vaccine into India and Ethiopia. The most direct beneficiaries of the research will be those women in the two countries who receive the HPV vaccine when they would not have, had it not been for the research. Those women are most likely to be living in one of the areas identified as higher risk, and so they themselves are likely to have been at higher risk of cancer. In addition, without this research it is possible that the HPV vaccination programs in Ethiopia or India may stall due to lack of funds. Vaccinated women are at much reduced risk of cervical cancer and many such women will be saved from cancer death. In addition, there is likely to be a herd immunity effect such that the partners of vaccinated women, and therefore other potential contacts of the partners will also be protected from HPV associated cancer. Some vaccinated women may become commercial sex workers with many partners, so vaccinating those women will have a magnified effect on the circulation of HPV in the community. It should also be recognised that for each of cancer prevented, there are far reaching benefits for family members and other dependants.

The overall aim of the research proposed is to provide a path by which developing countries can estimate the benefits of HPV vaccine introduction in their own setting. Thus the experience of HPV vaccine introduction and impact evaluation in India and Ethiopia is likely to accelerate the use of the vaccine in neighbouring countries in Asia and Africa. In each of these countries, introduction of HPV vaccine just one year earlier translates into the prevention of a large number of cancer cases and therefore a large number of lives saved. These effects are difficult to quantify, but may be very substantial given the importance of Ethiopia and India in their respective regions.

The introduction of HPV vaccine provides an opportunity for the development of an adolescent health platform at community level. Such a platform provides an opportunity for interventions on public health, substance abuse, contraception and other interventions suitable for adolescents. These in turn can provide lasting benefits for the communities concerned.

This project will also provide opportunities for scientific development within the two countries. In India the laboratory capacity will be strengthened, while epidemiological, social science and economic capacity will also be enhanced. In Ethiopia the same fields will benefit. In addition the field of cancer epidemiology will be strengthened, providing opportunities for young epidemiologists.