Advancing Cervical Cancer Prevention, Diagnosis and Treatment

At the Podium – October 2006

By Janet Rader, MD

With the Food and Drug Administration’s speedy approval of Gardasil, the vaccine developed to prevent cervical cancer, comes new hope for many girls and young women not yet exposed to HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause approximately 70 percent of cervical cancers; HPV types 6 and 11 cause approximately 90 percent of genital warts.

Results of clinical trials testing the vaccine were impressive in short-term follow-up of two to four years. In women between the ages of 16 and 26, Gardasil was nearly 100 percent effective in preventing precancerous cervical lesions, precancerous vaginal and vulvar lesions, and genital warts caused by HPV types 6, 11, 16 and 18. In addition, studies performed to measure the immune response to the vaccine in those ages 9 to 15 showed their response was as good as that found in 16- to 26-year-olds. As a result, the vaccine is now available for use in females 9 to 26 years of age.

No one knows how the vaccine’s availability will affect the incidence of cervical cancer. Each year in the United States, there are more than 9,710 new cases of cervical cancer and about 3,700 deaths attributed to the disease. Although the number of cases in the United States declined significantly following the introduction of the Pap test in the mid-1950s, in recent years the number of women diagnosed has remained about the same.

Worldwide, cervical cancer is the second most common cancer in women, and it is associated with more than 470,000 new cases and 233,000 deaths each year. It’s predicted the rate of cervical cancer will double by 2050 because of population increases in Third-World countries, where Pap testing often is unavailable. And it is in Third-World countries where administering the new lifesaving vaccine will be most difficult. Issues regarding the vaccine administration protocol – three injections must be given over a six-month period – and refrigeration are just two problems yet to be addressed.

Looking beyond the vaccine’s potential for saving lives, for researchers like me and my colleagues at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital, there remains an elemental question: Why do some women develop cervical cancer and others don’t? We’ve known about the link between HPV and cervical cancer for more than 20 years – whenever a woman develops cervical cancer, HPV is present. But from 40 percent to 70 percent of the country’s sexually active population has at some time contracted a self-limiting HPV infection, and relatively few women actually go on to develop cervical cancer.

From these facts, it is clear some women have a genetic predisposition for developing cervical cancer. We are working to identify that genetic susceptibility, which appears to exist in gene markers dealing with immune response. We currently are recruiting for an association study in which we are obtaining a DNA sample from 800 women with either high-grade cervical dysplasia or cancer and their parents. Within genes that appear critical for the development of cancer, we are focusing on small variations and evaluating their influence on interactions between HPV and cervical cells. Each variation is then tested by comparing the frequency distribution of markers on patients’ genes with markers that weren’t transmitted from the parents’ genes, our control sample. We hope our findings will eventually lead to the development of superior screening and diagnostic testing tools and treatments tailored to cervical cancer genotypes.

For women diagnosed with cervical cancer, their best treatment options exist at a tertiary care center that sees a large number of patients with gynecologic cancers. A cancer program that sees one or two patients with cervical cancer a year cannot offer the advanced technology and complex therapies needed to treat the disease best, including the latest in imaging modalities, chemotherapy regimens and radiation oncology techniques.

An example of advanced diagnostic methods at Siteman is the use of PET in determining whether cervical cancer has spread beyond the cervix. In a study comparing CT scans with PET scans in 101 women with cervical tumors detected during a physical exam, Siteman radiation oncologist Perry Grigsby, MD, and his colleagues found the PET scans showed the patients had more traces of tumor in their lymph nodes than previously suspected. In fact, PET findings altered treatment for about half of the women in the study. Another PET scan study showed that cervical tumors with greater glucose uptake are associated with lower survival rates and lower disease-free survival rates, and we are working to develop specialized therapies for these types of tumors.

Siteman also offers the latest surgical techniques and chemotherapy agents available as well as treatment with implanted or injected radiation sources. In addition, we participate in more clinical studies than any other gynecologic oncology group in the Midwest. At any given time, we have 15 to 20 clinical studies in progress. Some are developed by our own researchers and physicians, while others result from our membership in the Gynecologic Oncology Group, a National Cancer Institute-sponsored cooperative group.

Unlike some gynecologic cancers, cervical cancer can occur in teenagers as well as in middle-age and older adults. Hopefully, the new vaccine will help ensure that many young women can avoid this cancer. And we anticipate that in the near future, our research will result in a genetic test that identifies women at risk for developing the disease so that proper preventive measures may be taken.

Janet Rader

Janet Rader, MD, is professor of obstetrics and gynecology and associate professor of genetics at Washington University School of Medicine and Barnes-Jewish Hospital.

Cervical cancer treatment at Siteman.