What’s in the Future for HPV and Cervical Cancer

Vaccines

Vaccines that target high-risk HPV types could be available in three years, experts say. Both prophylactic vaccines that prevent HPV infection and therapeutic vaccines that prevent the development of precancerous cells are in progress. Other vaccines in development are combination —both prophylactic and therapeutic.⁴⁷ An oral vaccine also is being tested, which would be easily delivered in developing countries because it could be administered without the need for sterile injection equipment or highly skilled medical personnel.⁴⁸

Two years ago, researchers at the University of Washington found that a vaccine should be effective in preventing cervical cancer by making young women immune to HPV type 16.⁴⁹

Now a vaccine that would cover four strains— 6, 11, which are associated with genital warts, and 16, and 18, which are linked to the highest risk for cervical cancer—is being tested in about 25,000 women in more than 34 countries in the third and final phase of clinical studies required for FDA approval. If 100 percent effective, such a quadrivalent (four HPV types) vaccine has the potential to reduce the incidence of cervical cancer by 75 percent and that of genital warts by 90 percent. However, because the vaccine will be given to young girls and the highest risk of cervical cancer does not occur until several decades later, after age 40,⁵⁰ the impact on cervical cancer rates will not be seen for some time.

The vaccine would need to be administered before people become sexually active, so children as young as 12 would be inoculated. If all 12-year-old girls currently living in the United States received it, an effective vaccine could prevent 1,300 deaths during their lifetimes, and the cost of administering such a vaccine would be far less than the medical costs incurred by HPV, according to a Stanford study completed in January 2003.⁵¹ Another economic study found that HPV vaccination in combination with continued cervical cancer screening would be cost-effective.⁵²

A European-manufactured vaccine has been shown to be 100 percent effective in preventing the two highest-risk HPV types (HPV-16 and HPV-18) in clinical trials. HPV-18 is more closely associated with cervical adenocarcinoma, which is more difficult to detect by Pap test alone. The manufacturer plans to file for regulatory approval of the vaccine in Europe in 2006—two years ahead of schedule.⁵³ This vaccine also would be given to women before they become sexually active, maybe as young as age 10. Experts believe that a course of three injections over a six-month period might provide life-long immunity.⁵⁴

For both vaccines, convincing society of the need to vaccinate young girls against what is essentially a sexually transmitted infection will surely be a hurdle.

“If they live up to their potential, the vaccines in development will have a significant impact,” Solomon said. “They will not eliminate the need for screening, nor will they eliminate cervical cancer entirely, but there is huge potential there to significantly reduce morbidity and mortality.”

This would be especially true in the many developing countries that do not have the resources to establish comprehensive screening programs.

Harper, who is leading the HPV-16/HPV-18 clinical trial at Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, said the vaccine has been shown to be highly safe and effective and has the potential to greatly reduce the number of deaths from cervical cancer.

“Over the last 20 years, there has been nothing else developed that will make such a huge impact on women’s health,” she said.

New Screening Methods

New modes of screening for cervical cancer also are in development. A paper-based HPV DNA screening test is being studied in India. Coupled with a single-step DNA extraction procedure, the test allows for dry collection of cervical cells, along with transportation and storage at room temperature.⁵⁵

A recent study involving 143 women from Senegal, West Africa, showed that a simple urine test might provide an alternative to Pap screening for cervical cancer. In the study, urine-based detection of abnormal methylation—chemical modification—of three genes was used to identify women at risk of cervical cancer. Sensitivity of the test was promisingly high. Ongoing studies are examining the increase in sensitivity provided by the addition of other genes to the test.⁵⁶

“More studies involving a much larger group of women need to be done, but we are hopeful about the potential of urine testing as a costeffective and less-invasive way to screen for cervical cancer,” says Nancy Kiviat, PhD, director of pathology at Harborview Medical Center, a University of Washington professor of pathology, and principal investigator of the study.

A new automated screening test for HPV, called the Automated Cellular Imaging System (ACIS^®), is being evaluated. Two tests to identify HPV genetic subtypes are being developed for use in conjunction with the liquid-based Pap.⁵⁷ These tests may improve the ability to distinguish high-risk from low-risk HPV. Investigators also are developing tests to detect certain biologic factors that will be used as markers. Such markers would indicate a higher risk for cancer if HPV is also present.⁵⁸

With research and development of powerful new ways to combat HPV and screen women for cervical cancer, could it eventually become a disease of the past? Harper has said she believes cervical cancer could “go the way of smallpox,” given the necessary investment.⁵⁹

“I’m really hoping that there will be other advances,” Harper said. “That there will be enough research and development, enough capital, and enough scientific interest available to look at HPV from multiple aspects—that we can bring to HPV research what we know from engineering, chemistry, social science, and all the other fields to improve our ability to find what is important to find and to keep people from getting cancer.”