Review
Global implementation of human papillomavirus (HPV) vaccine: Lessons from hepatitis B vaccine

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Abstract

Development of safe and effective vaccines against human papillomavirus (HPV)–the second vaccine against a major human cancer–is one of the most important medical and public health achievements of this century. As with all new vaccines, HPV is currently expensive and this cost precludes its use in the developing world, which has the greatest burden of disease from HPV-related cancers. Hepatitis B (HB) virus vaccine, which prevents chronic HB infection and related cirrhosis and liver cancer, has been successfully introduced as a routine vaccine for children in 89% of countries, including the poorest. The success of this vaccine provides a model for the introduction of HPV vaccine and control of cervical and other HPV-related cancers and genital warts. Lessons learned from HB vaccine introduction are relevant to our efforts to introduce HPV vaccine globally. As with HB vaccine, introduction of HPV vaccine into national immunization programs and routine use of this vaccine, funded by governments, will be needed to control HPV-related disease on a global basis. Global funding support will be needed to make control a reality for the poorest countries, and the program to accomplish this, the Global Alliance for Vaccines and Immunization (GAVI), has already expressed great interest in including HPV vaccine. For this to occur, the manufacturers will need to dramatically reduce the vaccine price for the poorest developing countries, and tier prices for wealthier developing countries not eligible for GAVI support. Countries will need to decide on the priority of HPV control in the context of other important new vaccines against pneumococcal pneumonia and rotavirus diarrhea.

Introduction

Human papillomavirus (HPV) vaccines (bivalent and quadrivalent) have been shown to be immunogenic, safe, and highly effective in preventing chronic infection and precancerous lesions in women [1], [2], and the quadrivalent vaccine has been shown to prevent genital warts and chronic infection in men and women as well [3]. It is the second vaccine able to prevent a major human cancer (cervical cancer), as well as other less common cancers (vulvar, vaginal, anal, penile, and head and neck) in women and men. Currently, as with all modern vaccines, the price of the vaccine is high and precludes its introduction into public sector programs in most developing countries where the benefit of the vaccine will be maximal. However, the price of the vaccine will fall with time, and vaccine manufacturers have stated that they are willing to tier prices for developing countries and dramatically reduce prices for the poorest developing countries that get their newer vaccines through the Global Alliance for Vaccines and Immunization (GAVI) and the Pan American Health Organization (PAHO) Revolving Fund for Latin America.

Hepatitis B (HB) vaccine, the first vaccine to prevent a major human cancer (primary liver cancer), can serve as a model for the introduction of HPV vaccine on a number of levels. First, the answer to the question “How can we deliver HPV vaccine to young people in the developing world?” is to integrate the vaccine into the World Health Organization (WHO) Expanded Program on Immunization (EPI) and all national immunization programs. Second, the HB model suggests that it may be possible to do more than protect immunized individuals: we may be able to reduce viral transmission and induce heard immunity to protect non-immunized individuals as well. Third, the HB model suggests that we may wish to investigate the immunization of children younger than is currently proposed in order to increase immunization coverage, and we may wish to re-examine the premise that this is a cost-effective vaccine primarily for adolescent females.

Section snippets

Vaccines as a major tool in the prevention of cancer

Cancer prevention activities have been dominated by issues such as smoking reduction, screening for breast, cervical, colon, and prostate cancer prevention or early detection, occupational exposures, and dietary factors. However, the cancer prevention community has been largely unaware that vaccines have emerged as a primary tool for cancer prevention, with HB and HPV vaccines as the first examples. Educating the cancer control community to get their powerful advocacy and funding support will

How are vaccines delivered to children in the developing world?

Every country has a national immunization program that routinely delivers vaccines to children. While many countries have a private market for vaccines where expensive new vaccines are first introduced, in most countries in both the developing and industrial world the public sector programs deliver vaccines to the great majority of children and adolescents. Even in the US, more than half of children and adolescents get their vaccines through the federally funded Vaccines for Children program [5]

How are vaccines funded in the developing world?

The poorest 72 countries in the developing world receive most of their newer vaccines through GAVI, which has an international fund that helps to pay for the vaccines. GAVI receives major support from the International Finance Facility for Immunisation, the Bill and Melinda Gates Foundation, and support from many governments [14]. Countries in Latin America receive their vaccines through the PAHO Revolving Fund, under which countries pay for vaccines obtained at very low prices negotiated by

Information about HB vaccine

HB vaccine was introduced in 1982 in industrial countries and primarily used at that time to immunize members of “high-risk” groups such as healthcare workers, hemophiliacs, certain ethnic groups from highly endemic areas, intravenous drug users, men who had sex with men, and heterosexuals with multiple partners [19]. The vaccine cost about $100 for three doses and at that price it was not possible to introduce the vaccine into public sector programs in the developing world. The strategy to

HB vaccine in the developing world

As mentioned, the vaccine was initially too expensive for public sector programs in the developing world. Production of the vaccine in South Korea and later China, India, and Brazil, and the expiration of key patents reduced the price dramatically to about $1.00 per pediatric dose by the early 1990s [22]. The price of the vaccine for developing countries is now about $0.20 per dose. In 1992, the WHO called for all countries to add HB vaccine to their routine immunization schedule [23]. However,

HB vaccine impact

Similar to HPV vaccine, HB vaccine is a “subunit” vaccine composed of spherical particles of HB surface antigen formerly called the Australia antigen. The alum-adjuvanted vaccine is highly immunogenic and highly effective in preventing HB infection. More than 90% of children will be protected from acquiring chronic HB infection, the precursor to liver cancer and cirrhosis. The duration of protection induced by HB vaccine is unknown but is at least 20 years [25]. Very importantly, the duration

Impact on cancer

As with HPV, HB carriers usually develop cancer following decades of chronic infection. Therefore, we do not expect dramatic falls in cancer rates for decades following immunization. Cancer epidemiologists and public health officials differ on how they conceptualize the situation: while cancer epidemiologists count impact when cancer rates fall, immunization experts measure impact when successful immunization is given preventing the chronic infection that causes the disease. Cases of liver

Conclusion

HB immunization provides a useful model for introduction and possible impact of HPV vaccine implementation and gives us good reason to believe that global implementation of HPV immunization is possible and will probably have a major impact on cervical and other HPV-related cancers. Global funding of HPV vaccine through GAVI and inclusion of HPV vaccine into the EPI and national immunization programs are necessary steps for global introduction. With this introduction, the second major

Key points

  • The success of hepatitis B (HB) vaccine introduction provides a useful model for global human papillomavirus (HPV) vaccine introduction.

  • Inclusion of HPV vaccine into national immunization programs and the WHO Expanded Program on Immunization will be necessary to achieve global control.

  • The international community must agree to fund HPV vaccine for the poorest countries. The mechanism to do this is through the Global Alliance for Vaccines and Immunization (GAVI), which funds new vaccines for the

Conflict of interest statement

Dr. Kane is a member of the Merck Global Advisory Board for HPV and has given talks sponsored by Merck and GSK.

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