SEATTLE - Infection with a common virus that causes genital warts is a serious risk factor for vaginal cancer, according a recent large-scale study of women in western Washington.
The study, led by researchers at the Fred Hutchinson Cancer Research Center, was the largest population-based analysis of risk factors for vaginal cancer, a rare disease that affects about one in 100,000 American women each year.
Like cervical and other anogenital cancers, vaginal cancer was found to be strongly associated with prior infection with human papillomavirus, or HPV. In addition, almost one- third of women with vaginal cancer had been treated for a prior anogenital tumor, most often of the cervix. Other risk factors common to many of these cancers include multiple sexual partners, early age of first intercourse and cigarette smoking.
The results, published in the February issue of Gynecologic Oncology, suggest that women with genital warts should be monitored for the development of multiple anogenital cancers.
Janet Daling, Ph.D., lead author of the paper, said that the infrequency of the disease has hampered research on vaginal cancer, which accounts for about 3 percent of all female reproductive cancers.
"Besides our work, there has been only one other population-based study on vaginal- cancer risk factors," said Daling, a member of Fred Hutchinson's Public Health Sciences Division. "Because of the rarity of the disease, it has been hard to accrue enough women to conduct a meaningful study," said Daling, also a professor of epidemiology at the UW School of Public Health and Community Medicine.
The new study included 156 western Washington women with squamous cell in situ (non-invasive) or invasive vaginal cancer diagnosed between 1981 and 1998 as well as 2,041 unaffected women who served as controls. Both groups of women were interviewed in person about prior health conditions, sexual and other behaviors, and they provided blood samples.
For women previously diagnosed with vaginal cancer, preserved tumor specimens were obtained when possible. Because the research team has extensively studied risk factors for other anogenital cancers, they were able to take advantage of previously developed study tools, including a questionnaire on health and lifestyle factors.
Women with vaginal cancer were more than four times more likely than controls to have antibodies to HPV-16 in their blood, an indication of prior infection with the virus. HPV-16 is a strain of the virus that is most commonly associated with anogenital tumors.
Researchers found that women with vaginal cancer were more likely than unaffected women to have had five or more sexual partners and to have had first intercourse prior to age 17. Women with vaginal cancer were also more apt to be smokers at the time of diagnosis.
About 30 percent of the women with vaginal cancer had been treated for an earlier anogenital tumor, most commonly of the cervix. HPV DNA was found in tumor specimens from more than 80 percent of the patients with the non-invasive form of the cancer and more than 60 percent of specimens from those with a more advanced form of the disease.
Although a woman's overall likelihood of developing vaginal cancer is small, Daling said that HPV infection, often characterized by a history of genital warts, is an important risk factor for several cancers and should be noted by doctors.
"Women with genital warts should absolutely be monitored for multiple cancers," she said. "It's clear that the majority of anogenital cancers - cervical, vulvar, vaginal and anal -are HPV-related."
While smoking is most commonly associated with lung cancer, Daling said that nicotine is a strong risk factor for virtually all forms of anogenital cancer.
"It's not clear what role smoking plays in these diseases, but it's a strong risk factor that is independent of sexual practice," she said. "One theory is based on the observation that nicotine inhibits apoptosis, the technical term for cell death. This is the pathway our body uses to eliminate abnormal cells, so it's possible these potentially cancerous cells accumulate in smokers."
Daling said the team's next project is to study women who get more than one anogenital cancer in their lifetime. "Vaginal cancer is frequently related to having had a prior anogenital tumor and is in fact a common second primary cancer," she said. "We'd like to know what factors determine who will get a second tumor."
The research was funded by the National Cancer Institute, a branch of the National Institutes of Health.
The Fred Hutchinson Cancer Research Center, home of two Nobel Prize laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 41 nationwide. For more information, visit the center's Web site at http://www.fhcrc.org.
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