Cervical cancer vaccine: improving access for prevention and control

85% of deaths from cervical cancer occur in developing countries. Jane Parry looks at the challenges to access and the interventions seeking to reach the most vulnerable
Gardasil vaccine
Gardasil vaccine protects against the human papillomavirus (HPV) responsible for cervical cancer. Photograph: Voisin/Phanie/Rex Features

Cervical cancer is one of the most preventable of all cancers. Screening can detect cervical cell changes before they become cancerous lesions and treatment has excellent survival outcomes. The commercial launch of a vaccine against the human papillomavirus (HPV) in 2006 meant that future generations of women can go into their sexually active years protected from the viruses that cause 70% of cervical cancer cases.

Yet every year, cervical cancer causes approximately 275,000 deaths, with 85% of those deaths occurring in developing countries. The figure is estimated to rise to 430,000 by 2030 but the death toll could be reversed if young girls in low- and middle-income countries can be reached for HPV vaccination.

That breakthrough may now be possible as Gavi, which funds vaccines for children in the world's 73 poorest countries, has set a target of supporting the vaccination of 30 million girls against HPV by 2020.

Gavi-funded pilot projects are due to start in eight countries – Ghana, Kenya, Laos, Madagascar, Malawi, Niger, Sierra Leone and Tanzania. Seven will start this year but Tanzania is planning to start in 2014. A full rollout of funding will be available to those countries that can demonstrate their ability to deliver the vaccine.

The two HPV vaccines – Merck & Co's Gardasil, and GlaxoSmithKline's Cervarix – were licensed in 2006 and 2007, respectively and both became prequalified by the World Health Organisation in 2009.

"In terms of access, WHO pre-qualification is required for any UN agency funding to be used to purchase a vaccine and Gavi also requires it," says Dr Kimberley Fox of the Expanded Programme on Immunisation at WHO's Western Pacific regional office in Manila.

By 2011, HPV vaccination had been introduced in the national immunisation schedule of 38 countries (pdf), typically vaccinating girls aged 9 to 13 and young women up to the age of 25 either via school-based vaccination programmes or through family doctors, but few girls in low-income countries have had access to the vaccine.

"There is a triple whammy for women in the developing world: they have a higher incidence of HPV infection, there is usually no good screening programme in place, and if they do get cervical cancer they don't have good treatment options," says Seth Berkley, Gavi chief executive.

The WHO-recommended approach is comprehensive cervical cancer prevention and control, including prevention through education and vaccination, screening for early detection and early treatment of precancerous lesions and cervical cancer, as well as cancer treatment and palliative care.

Well-implemented and properly resourced cervical cancer screening programme work: in Finland, for example, the age standardised cervical cancer mortality rate (which minimises the effect of age composition in different populations) is 0.9 per 100,000, while the UK rate is 2.0. By contrast in Cambodia, where cervical cancer causes twice as many deaths as breast cancer, the rate is 16.2 per 100,000 and in Kenya it is even higher, at 17.3 per 100,000. In many low-income countries, cervical cancer incidence is either the highest or is neck-and-neck with breast cancer.

There are efforts afoot to make cervical cancer screening programmes more accessible and effective in developing countries, such as "see-and-treat" visual inspection with acetic acid followed by immediate cryotherapy.

However, the 70% level of protection offered by HPV vaccination "has lead to a lot of excitement, because countries can be confident of achieving a real impact from a fairly bounded intervention," says Fox.

WHO prequalification for HPV vaccines was a significant step towards making it accessible to low-income countries, but there are still substantial obstacles to reaching girls and to ensuring that they can be vaccinated the required three times within six months.

"The cost and complexity of implementation is a barrier because it is being delivered through new systems, such as through schools," says Fox. "That seems a very convenient way to reach girls aged nine to 13 but this is not a system that the national immunisation programmes already have in place."

This means immunisation programmes have to develop collaborations with education ministries as well as cancer control and reproductive health programmes. At the local level the other big challenge is communications.

"This vaccine has been a sensitive issue in many countries, because it relates to reproductive health," Fox says. "Communications with communities, schools, teachers, parents and girls are really crucial to ensure acceptance of vaccine. They have to understand what the vaccine is, that it's about preventing cancer."

Some countries have already run HPV vaccination pilot programmes with the help of international agencies such as Path, which is collaborating with partners in India, Peru, Uganda and Vietnam for its HPV vaccine: Evidence for Impact project (pdf); and charities such as the Australian Cervical Cancer Foundation, which is supporting vaccination programmes in six Asian and Pacific Island countries.

Merck's Gardasil Access Programme has also provided Gardasil to 20 countries for vaccination of over 360,000 girls in pilot projects to generate operational experience in vaccination programme implementation.

Professor Ian Frazer, the inventor of the HPV vaccine and research director of the Brisbane-based Translational Research Institute Pty Ltd, was able to follow the basic scientific discovery he made through to the end-user 20 years later.

Working through his family foundation together with the ministry of health in Vanuatu, where one in 100 women has cervical cancer, he was able to demonstrate that the vaccine could be effectively delivered. "We showed it could be done, that it was possible to vaccinate at least half of the eligible population, and they will roll out their full programme in March this year," he said.

Gavi's funding for HPV vaccination pilot projects has taken the additional cost of setting up new vaccination channels into account, using data from Path's pilot programmes to estimate the extra investment needed. The funding process requires countries to select a district covering both urban and rural communities, and if they plan to vaccinate through a school-based programme, they must show how they will reach the girls not in school. "These girls may be the ones most vulnerable to HPV infection," says Berkley. "We also asked countries to look at taking advantage of reaching adolescent girls, to look at what other health interventions they can be introduced, such as simple interventions like contraception information to more complex issues like HIV prevention."

Beyond cervical cancer, HPV vaccination points to a new role for vaccines, says Berkley. "We are in an era of cancer vaccines. The first anti-cancer vaccine was for hepatitis B, now we have HPV vaccination. When globally approximately 16% of cancers are caused by known infections, and more than 30% in Africa, the whole notion of non-communicable diseases is a misnomer."
