SEATTLE — Jul. 6, 2004 — Anal cancer is on the rise in both sexes, particularly among American men, and changing trends in sexual behavior — combined with current tobacco use and infection by a specific strain of the human papillomavirus — may help explain the increase. These findings, from two separate studies by researchers at Fred Hutchinson Cancer Research Center, will be reported in a pair of papers in the July 15 issue of Cancer.
The first study, by lead author Lisa G. Johnson, Ph.D., a statistical-research associate in Fred Hutchinson's Public Health Sciences Division, found that incidence rates of anal cancer have increased significantly in the past 30 years, jumping 160 percent in men and 78 percent in women.
The sharpest increase was among African-American men, whose incidence of anal cancer has more than doubled in the past three decades. Black men also had a lower survival rate from the disease. The five-year survival rate for black men with early stage disease was 62 percent as compared to 79 percent for white men with localized cancer.
The study, funded by the National Cancer Institute, was based on the records of 6,093 anal-cancer patients (2,888 men and 4,015 women) diagnosed between 1973 and 2000. The data came from tumor registries in five states (Connecticut, Hawaii, Iowa, New Mexico and Utah) and four metropolitan areas (Atlanta, Detroit, San Francisco and Seattle), all of which are part of the NCI Surveillance, Epidemiology and End Results, or SEER, program.
The second study, led by epidemiologist Janet Daling, Ph.D., a member of Fred Hutchinson's Public Health Sciences Division, set out to better understand the underlying biological and lifestyle causes behind the rising incidence of anal cancer.
The study tested for the presence of human papillomavirus, or HPV — a well-known sexually transmitted viral marker of anal cancer — in both blood and tumor tissue. It also assessed the impact of various lifestyle factors associated with the disease, such as smoking, sexual orientation, number of sexual partners and history of anal intercourse.
"We found that infection with HPV is necessary in most if not all cases of anal cancer, as close to 90 percent of the tumors studied were positive for the virus," said Daling, a pioneer in studying the link between HPV and anogenital-cancer risk.
Overall, regardless of the patient's sexual orientation or gender, the researchers found that 88 percent of the tumors were positive for HPV DNA. Of these, 73 percent tested positive for a strain called HPV-16, and 7 percent contained a strain called HPV-18. Both strains of HPV are implicated in cervical-cancer development as well.
The researchers also found significantly higher amounts of circulating HPV antibodies in the blood of anal-cancer patients as compared to healthy controls. Approximately 40 percent of the women and 50 percent of the men with anal cancer tested positive for HPV antibodies as compared to about 15 percent of the men and women in the control group.
Since the blood test can only detect HPV antibodies in a subset of those who are exposed to the virus, the overall HPV exposure among the control group was probably much higher, Daling cautions.
One of the most surprising findings, Daling said, was that smoking appears to play a significant role in anal-cancer development that's independent of other behavioral risk factors, such as sexual activity. More than half of the anal-cancer patients studied were current smokers at the time of diagnosis, as compared to a smoking rate of about 23 percent among the controls.
"Current smoking is a very important promoter of the disease," said Daling, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine. "There's a fourfold increase in risk if you're a current smoker, regardless of whether you're male or female."
"Even in controlling for other risk factors, like the number of sexual partners, anal intercourse, and HPV status, smoking was a strong risk factor for squamous-cell anal cancer," Daling said, referring to the most common type of anal cancer, which accounts for about half of all cases. "Therefore, quitting smoking is the best thing a person can do to prevent anal cancer, particularly if they've been exposed to HPV or other risk factors, because it certainly has a promotional effect on these tumors."
The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous. Another possibility is that smoking suppresses the immune system, which can decrease the body's ability to clear persistent infection or abnormal cells.
Other risk factors associated with increased anal-cancer risk included gay or bisexual orientation among men, a high number of lifetime sexual partners and a history of receptive anal sex.
Among the male cases studied, nearly half reported that they were not exclusively heterosexual. Among these men, a history of receptive anal intercourse and a history of 15 or more sexual partners each increased the risk of anal cancer sevenfold.
The study also suggested that the overall increase in anal cancer rates might be partially attributable to an increase in the average number of lifetime sexual partners and an increase in the number of people engaging in anal sex, particularly among women.
For example, among the female control group studied, 21.5 percent had reported practicing anal sex, a significant increase from a previous case-control study by Daling and colleagues, published in 1987, in which 11 percent of female controls had reported ever having anal sex.
Similarly, 40 percent of the women in the control group of the current study reported having five or more lifetime sexual partners as compared to 9 percent of the female control group in the 1987 study.
This and other studies indicate that gay or bisexual sex among men is on the rise, which may account for the increase in anal cancer. A national survey study called the General Social Survey found that the number of men who reported having intercourse with another man increased from 1.8 percent in 1988 to 3.5 percent in 2000. The survey also reported that black men, the group with the highest anal-cancer incidence in the current study, were more likely than white men to report having had intercourse with another male in the last year.
"It could be that sexual practices have changed, but it also could be that people are just more likely to discuss their sexual behavior these days," Daling said. "However, I suspect that increased incidence of anal intercourse among both men and women is most likely to be the primary cause behind the rise in anal cancer."
The study involved 306 Seattle-area residents (119 men and 187 women) who were diagnosed with anal cancer between 1986 and 1998, as well as 1,700 healthy controls, who served as a comparison group. All participants were interviewed about sexual history and other lifestyle factors and provided blood samples that were analyzed for the presence of HPV antibodies. In addition, tumor samples from the patients were analyzed for the presence of HPV DNA.
The National Cancer Institute funded the study, with additional support from Fred Hutchinson Cancer Research Center and the State of Washington Department of Health.
Human papillomaviruses include more than 100 different strains, or types. More than 30 of these types, such as HPV-16, are sexually transmitted. Approximately 20 million Americans are infected with HPV and most are unaware of it, because the majority of HPV infections have no symptoms.
The most common clinical manifestations of HPV are genital warts, which are most often caused by non-cancerous HPV types. Pre-cancerous changes in the cervix, vulva, anus or penis, caused by cancer-related HPV types, can lead to cancer if left untreated.
Although anal cancer is relatively rare, accounting for about 1 percent of gastrointestinal malignancies, about 4,000 new cases will be diagnosed this year in the United States, according to the American Cancer Society.
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Fred Hutchinson Cancer Research Center
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 independent 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, in collaboration with its clinical and research partners, the University of Washington Academic Medical Center and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 38 nationwide. For more information, visit the center's Web site at www.fhcrc.org.