Figure courtesy of Dr. Denise Galloway
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, conducted by researchers in the Public Health Sciences and Human Biology divisions as well as collaborators at the University of Washington, is the largest-ever population-based analysis of risk factors for vaginal cancer, a rare disease that affects about 1 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 papilloma virus (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 suggest that women with genital warts should be monitored for the development of multiple anogenital cancers.
Dr. Janet Daling, 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," she said. "Because of the rarity of the disease, it has been hard to accrue enough women to conduct a meaningful study."
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 provided blood samples. For women previously diagnosed with vaginal cancer, preserved tumor specimens were obtained when possible.
Because the research team had studied extensively risk factors for other anogenital cancers, they took advantage of previously developed study tools, including questionnaires 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 lifetime sexual partners and to have had first intercourse prior to age 17. Women with vaginal cancer were also more apt to be current 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 in situ form of the cancer and more than 60 percent of specimens from invasive-cancer patients.
Although a woman's overall likelihood of developing vaginal cancer is small, Daling said that HPV infection 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."
Nicotine risk factor
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."
Ongoing studies of anogenital cancers are supported by a program project grant from the National Institutes of Health that is directed by Dr. Jim McDougall in the Human Biology Division and PHS Divisions. Collaborators on the vaginal cancer study and other projects include Drs. Margaret Madeleine and Stephen Schwartz of PHS and Dr. Denise Galloway in Human Biology and PHS.
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."