NEJM： 降低宫颈癌疫苗成本

 

Considerations for policymakers debating the use of HPV vaccine in any particular country will include that country's disease burden, its health care infrastructure, and its capacity for initiating and sustaining an immunization program for adolescents. Other considerations include the affordability and cost-effectiveness of vaccination relative to other programs competing for resources and the likelihood of cultural acceptability, political will, and public support.

 

Ultimately, the field effectiveness of HPV vaccine will require improved systems for providing health care to adolescents. Sociocultural sensitivities in this area abound, although concern about vaccinating adolescents against a sexually transmitted infection have been tempered by an emphasis on the vaccine's role in cancer prevention. Yet in environments characterized by mistrust of governmental health care initiatives, vaccination programs targeted toward young women may be misunderstood as attempts to control fertility — misapprehensions that have held sway in some countries even with regard to immunization campaigns against poliovirus and tetanus. If such fears can be allayed, an adolescent immunization program, possibly school-based, could be designed to deliver other adolescent health services and immunizations against tetanus, measles, rubella, meningococcus, typhoid, or even, ultimately, the human immunodeficiency virus, as well as HPV. In areas where the rate of school enrollment among girls is low, community-based efforts to reach girls outside school must be evaluated.

 

The factors with the greatest influence on the cost-effectiveness of vaccination will be the price of the vaccine and the costs of a program to reach adolescents. An analysis of options for cervical-cancer control in Brazil found that at a cost of $5 per dose (excluding wastage, administration, and costs of programs), the cost-effectiveness ratio associated with adolescent vaccination would be less than $150 per year of life saved, and vaccination combined with screening women three times during their lifetime would meet the criteria for a very cost-effective intervention.3 At a price of $100 per dose, vaccination would not be cost-effective, as compared with screening three times per lifetime. For countries with a gross domestic product of less than $1,000 per capita, the per-dose cost may need to be as low as $1 to $2 to make vaccination both cost-effective and affordable.

 

Without a doubt, one of the greatest barriers to the introduction of this vaccine is price. The three-dose series of the Merck quadrivalent vaccine will cost an estimated $360 in the United States; dramatic price tiering will be required to facilitate its timely use in developing countries. The GAVI Alliance (formerly known as the Global Alliance for Vaccines and Immunization) — a partnership of national governments, the World Health Organization, the World Bank, the Bill and Melinda Gates Foundation, the vaccine industry, public health institutions, and nongovernmental organizations — provides technical assistance and financial support for vaccines in countries with a gross national income of less than $1,000 per capita, as well as in China, India, and Indonesia. With subsidies from GAVI, HPV vaccine can be brought to the poorest parts of the world. Over the course of the next year, GAVI will review its new-vaccine policies to determine whether HPV vaccine should be among the vaccines prioritized for support.

 

The high probability of acquiring HPV infection once one has become sexually active raises the question of whether the vaccine will be effective if given to girls who have already been infected with HPV type 16 or 18. According to data from the FUTURE II study, vaccination did not alter the course of existing HPV infection but did protect against infection by a strain to which subjects had not yet been exposed. This observation highlights the need for immunization before the onset of sexual activity. Though the question of immunization of older girls and women deserves attention, from a public health perspective, the first priority in resource-poor settings would be to vaccinate young adolescent girls.

 

Fortunately, for older women in developing countries there are new options for cervical-cancer screening that are likely to provide cost-effective strategies for reducing the risk of cancer.4,5 The resources, infrastructure, and technological expertise required, together with the need for repeated screening at frequent intervals, have made conventional cytology-based screening prohibitively difficult in most poor countries. Promising newer approaches include HPV DNA testing and visual-inspection methods, focusing screening efforts on women between 30 and 45 years of age, and minimizing loss to follow-up by delivering screening and treatment in as few visits as possible. Employing a single-visit "screen-and-treat" strategy is now possible if cryotherapy is used in women in whom lesions have been detected on visual inspection of the cervix with acetic acid; it will soon also be possible to pursue such a strategy with the use of low-cost, rapid HPV DNA testing. It is imperative that the momentum behind the past decade's efforts to develop feasible options for cervical-cancer screening in low-resource settings continue to build, since screening will still be required — not only for nonvaccinated women but also to prevent cancers caused by HPV types other than 16 or 18 that are not included in any HPV vaccine. Even in resource-poor settings, the ideal program for cervical-cancer prevention would include vaccination of adolescent girls and screening of women between 30 and 45 years of age.

Too many women living in poverty have died of invasive cervical cancer. With the availability of an effective, safe vaccine, there is real hope for reducing the global burden of cervical cancer. Although achieving broad coverage of young adolescents, negotiating tiered pricing, and securing financing will be challenging, it is sobering to realize that with every 5-year delay in bringing vaccination to developing countries, 1.5 million to 2 million more women will die. Vaccination has the potential to save many lives. Let us hope that a committed global effort makes fulfillment of the promise of the new vaccine possible.