Universal HPV Vaccination Requires More Than Vaccine

BRISTOL, England, Aug. 24 -- For universal vaccination of pre-adolescent girls against human papillomavirus, the development of the vaccine was only the first step to wide-scale cancer prevention.

Implementation of an effective and cost-efficient HPV vaccination program requires more than making the vaccine widely available in countries that have a high incidence of cervical cancer, Angela E. Raffle, M.D., of the Bristol Primary Care Trust, wrote in the Aug. 25 issue of the British Medical Journal.

Universal HPV vaccination offers an effective new approach to cancer prevention in regions that devote resources to planning, education, and ongoing evaluation, Dr. Raffle said.

The association between cervical cancer and HPV came to light in the 1970s, and HPV type 16 was identified in cervical biopsies in the early 1980s. By 2003 seven HPV types that account for 87% of cervical cancers had been identified, noted Dr. Raffle. Two vaccines have been developed, and one has been approved.

Britain's cervical cancer screening program dates to the 1960s. Following an overhaul of the program's training and quality standards, cervical cancer incidence decreased from 15.4 per 100,000 in 1986 to 3.4 in 2004. Fewer than 1,000 women die of cervical annually in England.

The challenge of devising and implementing a new program based on HPV vaccination requires identification of the optimal combination of vaccination, testing, and treatment, said Dr. Raffle.

In the United States, the Advisory Council on Immunization Practices has recommended HPV vaccination for various subgroups, including women up to age 26. Thus far, Texas is the only state to adopt mandatory HPV vaccination, making it compulsory for all girls entering the sixth grade.

In Europe four countries have promulgated HPV vaccination recommendations: Austria, pre-adolescent girls; Germany, girls ages 12 to 17; France, girls 14 with catch up to 23; and Italy, 12-year-old girls. Only Italy has decided how to fund its program, according to Dr. Raffle.

Four phase II randomized controlled trials have evaluated the safety and efficacy of HPV vaccines in women, and several phase III trials are underway. The reports have been summarized in several publications, said Dr. Raffle. No serious adverse events have occurred, and vaccination has conferred protection rates of 88% to 100% for HPV infection and cervical intraepithelial neoplasia.

"Because studies have been followed up for five years only, we do not know how long immunity from vaccination lasts," wrote Dr. Raffle. "Further evidence will continue to emerge, so we may need to adjust our policies. For example, booster vaccinations may be needed."

A vaccination-based approach to cervical cancer prevention has several potential shortcomings. Current vaccines protect against HPV types 16 and 18, but a third of cervical cancers are caused by other HPV types. More than 80% of cervical lesions with borderline and mildly abnormal cytology are unrelated to HPV-16 or 18, along with more than 70% of low-grade abnormalities.

The quadrivalent vaccine provides immunity against HPV-6 and HPV-11, which cause genital warts. Though not life threatening, genital warts can cause substantial emotional distress. Preventing them would be an added benefit of vaccination, said Dr. Raffle.

If vaccination is merely an add-on to the existing screening program, few lives will be saved, said Dr. Raffle, because deaths from cervical cancer will continue to fall without vaccination as the impact of screening improvements in the 1980s take full effect. If vaccination is part of an overall plan to replace the existing screening program with one that involves fewer tests, then the program might cost only slightly more than the current one.

"The only way of determining the long-term impact of vaccination will be to follow vaccinated women for several decades," Dr. Raffle concluded.

Echoing Dr. Raffle's sentiments, Bernard Lo, M.D., of the University of California San Francisco, said that "a successful HPV vaccination program requires more than just a series of injections." In an editorial Dr. Lo cited a need for a broader perspective that encompasses controversial issues such as adolescent sexuality, parental control, and protection of children. Individuals who refuse to participate in a universal vaccination program must be addressed.

"Making HPV vaccine mandatory might advance the immediate goal of increasing uptake," Dr. Lo concluded. "However, public policies also need to consider a broader perspective. Such vaccination is not a goal in itself, but a means to achieve the goal of cancer prevention."

Universal HPV vaccination must be made available in poor countries that otherwise will face increasing health inequity, said Eduardo L. Franco, M.D., of McGill University in Montreal, in a commentary on the Raffle article.

"In the most impoverished nations in Africa and Latin America, where most of the disease burden lies, cervical screening is largely available only for the small proportion of women who can afford private or managed health care in urban centers," wrote Dr. Franco. "These countries may see great benefit from HPV vaccination because they qualify for financial help in implementing immunization programs."

Middle-income countries, such as Mexico and Brazil, face a different situation, he continued. These countries might not adopt universal HPV vaccination because they do not qualify for financial assistance and more pressing health issues take precedence.

"Inaction will have consequences," Dr. Franco concluded. "Deferring policy decisions because of the high costs of vaccination may further increase socioeconomic inequity with regard to cervical cancer in medium income countries."