Allan Hildesheim: Will the HPV Vaccine Reach Young Women in Developing Countries Who Can Benefit Most From Vaccination?

With licensure of the first prophylactic human papillomavirus (HPV) vaccines, a new era in cervical cancer prevention has begun. The new vaccines add to the existing arsenal of prevention tools that can be used in efforts to reduce the cervical cancer burden worldwide.

However, fulfilling its potential to significantly impact cervical cancer rates -- especially in the developing world, where the need is greatest -- will depend on the rational use of resources now available to us.

In addition to the virus-like particle-based HPV vaccines, which were designed to prevent HPV infections before they occur, other prevention tools include cytology-based screening programs (conventional Pap smear and more recently developed liquid-based cytology screening), HPV DNA diagnostic tests (used as an adjunct to cytology screening or as a primary screen), and visual screening methods (mainly in areas where alternative methods are not feasible) (1-4).

In countries where effective screening programs are in place, including the United States and parts of Europe, screening programs have led to important declines in the rate of cervical cancer incidence and mortality (5,6). In these countries, screening remains an essential method for the prevention of cervical cancer. Screening in these countries will remain important even after the introduction of HPV vaccination because, unlike the prophylactic HPV vaccines that target two carcinogenic HPV types (HPV types 16/18), screening programs are designed to detect all precancerous cervical lesions regardless of the HPV type involved, and therefore have broader coverage than vaccination programs could hope to achieve. Within high resource countries with established screening programs, one notable area where vaccination might contribute to further reductions in cervical cancer rates is through concerted efforts to vaccinate underserved populations who have historically failed to benefit from existing cervical cancer screening programs (7).

By far the largest promise for the new HPV vaccines is in countries without well established screening programs or where such programs are ineffective. Experts estimate that 80% of new cervical cancer cases occur in developing countries each year (8); over time, vaccination programs in these nations have the potential to make significant inroads in our efforts to reduce the worldwide burden of cervical cancer.

Given that effective screening programs are difficult to implement and maintain (9,10), and that vaccination campaigns have historically been highly effective in developing countries (mainly for childhood vaccines), there is hope that vaccination programs in these countries might achieve what screening programs have not.

However, it is disheartening that the countries most in need of HPV vaccination programs are also the least likely to avail themselves of the vaccine. Much of that is due to the vaccines' high initial cost and the complexities of delivering multiple doses over a 6-month period for a vaccine that requires refrigeration.

In many countries, the cost of purchasing HPV vaccines to cover young adolescent cohorts would exceed the current budget for all existing childhood vaccination programs.

In high resource countries, where most individuals already have access to cervical cancer prevention via screening, access to the HPV vaccine is expected to be higher than in resource poor regions of the world. Vaccination of girls and young women in richer countries will likely benefit society through the reduction of the social and economic costs associated with the detection and follow-up of abnormal Pap test findings, and through the reduction in the overall rate of Pap test abnormalities among vaccinated women. However, since these women would have been protected from cervical cancer though screening during their adult life, targeting these women for vaccination earlier in their lives might not contribute to further worldwide reductions in cervical cancer rates.

To avoid the likely scenario of high uptake of the new HPV vaccines in countries that least need the vaccines and low uptake of the vaccines in areas of the world that most need them, concerted efforts are needed to increase vaccine penetration in developing nations. Barriers to vaccination can be broadly divided into those associated with the vaccine itself; the maintenance of the vaccine once purchased in a temperature-controlled "cold chain" supply system; the maintenance of an effective health care delivery infrastructure (facilities and personnel); and population compliance for a multi-dose intervention.

Efforts in each of these areas are warranted to maximize the health impact of the new vaccines. As examples, efforts to reduce the cost of the vaccine should be pursued. Other vaccines have been made available at cents per dose; there is no reason why the HPV vaccines could not be offered at comparable prices.

Equally important will be the further development of the current vaccines or of second-generation vaccines to minimize the need for cold chain storage and/or to broaden coverage beyond the limited types included in the current vaccine formulations.

Also important will be continued active evaluation of existing vaccination trials and implementation programs, to better understand the durability of protection afforded by vaccination. One might envision how much simpler vaccine implementation would be if the vaccine were found to provide very long-term protection, making co-administration with other childhood vaccinations a possibility.

Finally, a careful examination of existing vaccinated groups to define the effectiveness of alternative delivery schedules would be of interest. Vaccine implementation would be considerably simplified if it were determined that fewer than 3 doses are needed for protection, for example, or that vaccination intervals that can more easily be incorporated into school vaccination programs are effective.

Many researchers worldwide have devoted years of their working lives to make HPV vaccines a reality. It is very satisfying to see the vaccines licensed and used. However, our work is not yet completed. Ultimately, success should be measured by real reductions in the number of deaths from cervical cancer worldwide.

References

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2. Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ. 2001 Consensus guidelines for the management of women with cervical cytological abnormalities. JAMA. 2002 Apr 24;287(16):2120-9.
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8. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001 Oct;37 Suppl 8:S4-66.
9. Kitchener HC, Castle PE, Cox JT. Chapter 7: Achievements and limitations of cervical cytology screening. Vaccine. 2006 Aug 21;24 Suppl 3:S63-70.
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