Worldwide, cervical cancer is the fourth most common cancer among women. Human papillomavirus (HPV) vaccination, if broadly implemented, has the potential to significantly reduce global rates of morbidity and mortality associated with cervical and other HPV-related cancers. More than 100 countries around the world have licensed HPV vaccines. As of February, 2015, there were an estimated 80 national HPV immunization programs and 37 pilot programs. This article discusses global implementation of HPV vaccination programs and issues such as vaccine financing and different approaches to HPV vaccine delivery.
Key points
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As of 2012, more than 100 countries had licensed human papillomavirus (HPV) vaccines. As of February, 2015, there were an estimated 80 national HPV vaccination programs and 37 pilot programs.
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Financing mechanisms through GAVI, the Vaccine Alliance, and the Pan American Health Organization have helped many low-income and middle-income countries (LMICs) implement HPV vaccination programs, though funding challenges continue to represent a significant barrier in many countries.
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School-based approaches to HPV vaccine delivery have generally been very successful in both LMICs and high-income countries.
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Clinic-based or office-based delivery strategies have been evaluated, with some countries showing limited success (eg, the United States) and others having greater success (eg, Denmark).
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Community outreach approaches have shown some success in HPV vaccine uptake, particularly in reaching children who are not in school.
Introduction
Worldwide, genital human papillomavirus (HPV) is very common. In most cases, HPV infections are symptomless and do not progress to disease; however, persistent HPV infection can progress to cause genital warts (via nononcogenic or low-risk types), as well as cancers of the anogenital area and head and neck (via oncogenic or high-risk types). Worldwide, HPV types 16 and 18 are causally implicated in the development of approximately 70% of cervical cancers, whereas HPV types 6 and 11 cause about 90% of genital warts. Globally, cervical cancer is the fourth most common cancer among women. In 2012, an estimated 527,624 women were diagnosed with cervical cancer and more than 85% of the 265,653 deaths occurred in developing countries ( Fig. 1 ). In the United States it is estimated that more than 17,000 women and more than 9000 men are diagnosed with HPV-related cancers each year ( Table 1 ).
| Type of Cancer | Average Annual Number of Cases | Cases Probably Caused by HPV |
|---|---|---|
| Cervix | 11,422 | 10,400 |
| Vagina | 735 | 600 |
| Vulva | 3168 | 2200 |
| Anus (W) | 2821 | 2600 |
| Oropharynx (W) | 2443 | 1800 |
| Total Women | 20,589 | 17,600 |
| Penis | 1048 | 700 |
| Anus (M) | 1549 | 1400 |
| Oropharynx (M) | 9974 | 7200 |
| Total Men | 12,571 | 9300 |
There are currently 3 vaccines that prevent HPV infections and diseases: a bivalent vaccine (HPV2) that protects against types 16 and 18 ; a quadrivalent vaccine (HPV4) that protects against types 16, 18, as well as 6 and 11 ; and a 9-valent vaccine (HPV9) that protects against the 4 types covered in HPV4, plus 5 additional oncogenic types (31, 33, 45, 52, and 58). HPV vaccine efficacy, effectiveness, and safety are well-established.
Key points on HPV vaccines include
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As of 2012, more than 100 countries had licensed HPV vaccines
- •
As of February, 2015, there were an estimated 80 national HPV vaccination programs and 37 pilot programs, with many of these implemented in low-income and middle-income countries (LMICs; Fig. 2 )
Fig. 2
Global progress in HPV vaccine introduction (February, 2015).
( From Cervical Cancer Action. Global maps: global progress in HPV vaccination. 2015. Available at: http://www.cervicalcanceraction.org/comments/comments3.php . Accessed May 27, 2015.)
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The HPV9 vaccine was licensed by the US Food and Drug Administration in December, 2014
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The World Health Organization (WHO) recommends a 2-dose vaccination schedule for patients younger than 15 years of age
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The United States continues, for now, to recommend a 3-dose schedule, regardless of age.
In the United States, the national goal for HPV vaccination 3-dose series completion is 80% of all children by age 13 to 15 years. However, the 2013 National Immunization Survey-Teen found that only 37.6% of females and 13.9% of males, ages 13 to 17 years, had received 3 or more doses of the vaccine. In contrast, other high-income countries (HICs), such as Canada, the United Kingdom, Denmark, and Australia, have achieved very high HPV vaccination rates, as have several LMICs (see Fig. 2 ). The relative success or failure of HPV vaccination programs is likely due to many factors, including vaccine funding, implementation approaches, logistical and resource barriers, and cultural and political issues related to vaccination. See later sections for discussion of these factors.
Introduction
Worldwide, genital human papillomavirus (HPV) is very common. In most cases, HPV infections are symptomless and do not progress to disease; however, persistent HPV infection can progress to cause genital warts (via nononcogenic or low-risk types), as well as cancers of the anogenital area and head and neck (via oncogenic or high-risk types). Worldwide, HPV types 16 and 18 are causally implicated in the development of approximately 70% of cervical cancers, whereas HPV types 6 and 11 cause about 90% of genital warts. Globally, cervical cancer is the fourth most common cancer among women. In 2012, an estimated 527,624 women were diagnosed with cervical cancer and more than 85% of the 265,653 deaths occurred in developing countries ( Fig. 1 ). In the United States it is estimated that more than 17,000 women and more than 9000 men are diagnosed with HPV-related cancers each year ( Table 1 ).
| Type of Cancer | Average Annual Number of Cases | Cases Probably Caused by HPV |
|---|---|---|
| Cervix | 11,422 | 10,400 |
| Vagina | 735 | 600 |
| Vulva | 3168 | 2200 |
| Anus (W) | 2821 | 2600 |
| Oropharynx (W) | 2443 | 1800 |
| Total Women | 20,589 | 17,600 |
| Penis | 1048 | 700 |
| Anus (M) | 1549 | 1400 |
| Oropharynx (M) | 9974 | 7200 |
| Total Men | 12,571 | 9300 |
There are currently 3 vaccines that prevent HPV infections and diseases: a bivalent vaccine (HPV2) that protects against types 16 and 18 ; a quadrivalent vaccine (HPV4) that protects against types 16, 18, as well as 6 and 11 ; and a 9-valent vaccine (HPV9) that protects against the 4 types covered in HPV4, plus 5 additional oncogenic types (31, 33, 45, 52, and 58). HPV vaccine efficacy, effectiveness, and safety are well-established.
Key points on HPV vaccines include
- •
As of 2012, more than 100 countries had licensed HPV vaccines
- •
As of February, 2015, there were an estimated 80 national HPV vaccination programs and 37 pilot programs, with many of these implemented in low-income and middle-income countries (LMICs; Fig. 2 )
Fig. 2
Global progress in HPV vaccine introduction (February, 2015).
( From Cervical Cancer Action. Global maps: global progress in HPV vaccination. 2015. Available at: http://www.cervicalcanceraction.org/comments/comments3.php . Accessed May 27, 2015.)
- •
The HPV9 vaccine was licensed by the US Food and Drug Administration in December, 2014
- •
The World Health Organization (WHO) recommends a 2-dose vaccination schedule for patients younger than 15 years of age
- •
The United States continues, for now, to recommend a 3-dose schedule, regardless of age.
In the United States, the national goal for HPV vaccination 3-dose series completion is 80% of all children by age 13 to 15 years. However, the 2013 National Immunization Survey-Teen found that only 37.6% of females and 13.9% of males, ages 13 to 17 years, had received 3 or more doses of the vaccine. In contrast, other high-income countries (HICs), such as Canada, the United Kingdom, Denmark, and Australia, have achieved very high HPV vaccination rates, as have several LMICs (see Fig. 2 ). The relative success or failure of HPV vaccination programs is likely due to many factors, including vaccine funding, implementation approaches, logistical and resource barriers, and cultural and political issues related to vaccination. See later sections for discussion of these factors.
Human papillomavirus vaccine funding
HPV vaccine cost is a central factor in successful implementation of vaccination programs. High out-of-pocket costs for individuals decrease HPV vaccine acceptability and high costs for LMICs may limit the ability to provide vaccine for citizens. The cost for the vaccine in the public sector ranges by country and region, from US $4.50 to more than $100 per dose, representing a potential barrier to its implementation in many countries worldwide.
Significant progress has been made to improve the affordability of HPV vaccine to LMICs through financing mechanisms, including GAVI, the Vaccine Alliance, and the Pan American Health Organization (PAHO) Revolving Fund. In June, 2011, Merck & Co (West Point, PA, USA), announced that HPV4 would be offered to GAVI for $5 per dose for GAVI-eligible countries. In 2013, a further record-low price of $4.50 per dose was announced. Many GAVI-eligible countries are able to procure the vaccine for a small copayment of $0.20 per dose, increasing affordability. However, this low cost is only available to the 49 LMICs that are currently eligible for GAVI support, which have a gross national income per capita in 2015 less than $1580. Countries that have successful experiences delivering HPV vaccines to adolescents are eligible to apply to GAVI for financial support for national implementation or, if additional experience is required, can apply for support to implement demonstration projects. The cost to procure the HPV vaccine for LMICs in Latin America and the Caribbean through the PAHO Revolving Fund is approximately $10 to $15. The PAHO Revolving Fund was established in 1978 as a mechanism for procurement of supplies and equipment necessary for sustained delivery of vaccines.
The cost for the vaccine and delivery approach of HPV vaccine programs has been found to vary by country and program. Reasons for variation in cost between pilot projects included scope and scale, delivery strategy, national income levels and public health cost, infrastructure and the compensation structure for health staff, and health system policies. A recent study comparing the costs of HPV pilot, demonstration, or national programs in Peru, Uganda, Vietnam, India, Bhutan, and Tanzania found that introduction costs per fully immunized girl ranged from $1.49 to $18.94, with recurring costs from $1.00 to $15.69. Despite subsidization of the HPV vaccine for many LMICs, costs to deliver and sustain HPV vaccination programs remain a significant ongoing investment and potential financial barrier. In addition, although significant progress has been made to achieve lower prices for the vaccine, many middle-income countries are ineligible for the low prices and copayment systems offered through GAVI, or may have graduated from GAVI-eligibility. These countries may continue to experience barriers to fund and sustain HPV vaccination programs and opportunities to support these countries should be investigated.
In HICs, vaccine financing varies greatly from a patchwork combination of private and public funding in the United States to publically funded programs in, for example, Canada, Australia, the United Kingdom, and several European countries. Not all European countries provide public financing for HPV vaccine, however, and several require self-pay.
Human papillomavirus vaccination implementation approaches
School-Based Approaches
School-based delivery methods have been an effective approach to achieve high coverage in several LMICs through demonstration projects, donation programs, and national vaccination programs. Demonstration programs through the international nongovernmental organization PATH have achieved high coverage through school-based delivery in Peru (82.6%), Uganda (88.9%), and Vietnam (96.1%). High coverage has also been seen in school-based demonstration projects in South Africa, Brazil, and Nepal. The Gardasil Access Program (GAP) was implemented by Axios Healthcare Development, and received small donations of vaccine by Merck & Co, to support countries to gain experience in the design and implementation of HPV vaccination programs. Between 2009 and 2012, 21 vaccination programs were implemented in 14 LMICs around the world. The GAPs achieved an average vaccine uptake rate of 88.7% through 3 delivery strategies, including school-based, facility-based, and mixed approaches. The school-based strategy was specifically identified as a factor that positively influenced vaccine uptake rates. In 2011, national implementation of the HPV vaccine in Rwanda achieved 93.2% coverage for girls in grade 6 through school-based vaccination and community sensitization and involvement.
School-based HPV vaccination programs have also been implemented successfully in several HICs, including the United Kingdom, Australia, and Canada. Of the European countries that report an organized HPV vaccination program, more than 50% use a school-based delivery approach. In the United States, there has been very limited implementation of school-based HPV vaccination, though this approach has been identified as an ideal way to reach the largest number of adolescents. A pilot school-based adolescent vaccination initiative evaluated in Chicago, IL, was only modestly successful in delivering HPV vaccination. Obstacles included difficulty getting informed consent forms returned from parents and inconsistent participation by schools over time. In some areas of the United States, vaccines, including HPV vaccine, can be delivered via school-based health centers (SBHCs). However, while this approach eliminates some barriers to vaccination, vaccines are delivered on an individual patient basis and, therefore, SBHC-delivery is not as efficient as an approach that involves administration of vaccines on a single day to groups of youth. Attitudes of key stakeholders in the United States (eg, parents, school nurses, school administrators) about the feasibility of school-based HPV vaccination implementation are mixed, with some research showing relatively little concern among parents and administrators and other research indicating uncertain support and doubts about program implementation.
Clinic-Based or Office-Based Approaches
The principal approach to HPV vaccine delivery in the United States and several European countries is via medical clinics and doctors’ offices. Office-based vaccination is standard practice for most childhood vaccines in the United States. For vaccines required for school-entry, this approach has generally been quite successful, with high levels of vaccination coverage achieved. However, with the exception of the state of Virginia and the District of Columbia, HPV vaccination is not required for school entry. Moreover, Virginia has a relatively weak HPV vaccine school entry law, which has not proven particularly effective. Without a clear public health policy supporting HPV vaccination, the burden of decision-making and recommendations largely falls to health care providers (HCPs) and parents. As a result, despite the licensure of HPV4 in 2006 and public and private financing for vaccination, HPV vaccination rates in the United States remain at lower than desired levels.
Reasons for nonvaccination seem to be related to unwarranted parental concerns about safety; failure of HCPs to make strong, routine recommendations for vaccination at the targeted ages of 11 to 12 years; lack of knowledge; and access issues (particularly for follow-up doses). Box 1 contains a list of factors that have been identified as barriers to HCPs making a strong recommendation for HPV vaccination.
