STEP recently interviewed researcher Paul Nelson, certified Physician Assistant, about his role as the Healthcare Specialist for the Men's Anal Health Study (MAHS). Some 365 gay or bisexual, HIV-positive men have volunteered to participate in this attempt to examine the links between HIV, the human papilloma virus (HPV), and anal cancer. Funded by a grant from the National Institutes of Health (NIH) and administered by the University of Washington (UW), the study began in July 1996 and closed March 31, 2001. Previously, the research group involved with MAHS conducted a study called "Be A Hero." That study compared the rates of anal disease in HIV-positive versus HIV-negative gay and bisexual men, to determine if HIV increases the risk of anal cancer. For more information on MAHS and upcoming studies, call (206) 731-8663.
STEP: Why are you studying anal cancer in HIV-positive men-who-have-sex-with-men (MSM)?
Paul Nelson: Research for the past 20 years on anal cancer has shown that homosexual or bisexual men are at higher risk for anal disease. This is especially true if a person has had more than 10 sexual partners, practiced receptive anal intercourse, or has a history of genital warts or gonorrhea. In the "Be a Hero" study we compared HIV-positive men to HIV-negative men, and found that out of 781 men enrolled, 56 HIV-positive and 13 HIV-negative men had high-grade dysplasia [abnormal cell growth] on cytology [examination of the cells] and biopsy [small tissue sample]. We found that those patients with CD4 cells less than 500 were 7.5 times more likely to develop anal dysplasia than those who were HIV-negative. Gay and bisexual men who are HIV-negative still have the increased risk of anal cancer, but the progression rate from abnormal cells to cancer is very slow.
STEP: Can you explain briefly what dysplasia is, and how it relates to cancer?
PN: The word dysplasia means abnormal cell growth. The anal dysplasia we study is most commonly caused by HPV. This virus, with approximately 70 known types, is an extremely common communicable disease. These viruses cause genital warts or tissue changes, also known as dysplasia, that can cause normal tissue to become cancerous. Several of the types are known to cause warts that can target the hands and feet, while other types affect the face, and still others the genital tract. HPV is known to cause cervical cancer and can increase the risk of anal cancer. As a sexually transmitted disease (STD), it is thought to be transmitted by direct contact between infected skin on the penis, scrotum, vagina, vulva, or anus and uninfected skin in the same areas of the partner's body.
STEP: How does a person know if they have dysplasia?
PN: An anal pap smear is used to check for dysplasia in the anus. An anal pap smear is very similar to a cervical pap smear. A pap smear is a few cells collected using a swab from the anus and placed on a slide. The slides are placed in a preservative and sent to a lab where they are stained and then read by a pathologist. The pathologist will look at the slide and can determine if abnormal cells are present, representing dysplasia. The amount of abnormal cells seen determines the rating of dysplasia. Low-grade dysplasia generally means that the current risk of cancer at this time is low but should be monitored in the future. High-grade dysplasia indicates the presence of severe abnormalities and the need for further evaluation. Specialists in this area have set no formal recommendations for how often anal pap smears should be done. We believe that any gay or bisexual male who has had sex with another male, is HIV-positive, and has a history of anal warts should have a pap smear and possibly a biopsy of tissue from the anal canal.
STEP: Without an anal pap smear, is there any way to detect anal cancer?
PN: Rectal bleeding is the most common initial symptom of anal cancer, but it only occurs in 45% of patients. Bleeding from the anus may have other causes, as well, such as hemorrhoids, tears, or infection. Thirty percent of patients have either pain or the sensation of a rectal mass. In 20% of cases of anal cancer there are no symptoms. Symptoms only occur when the cancer has begun to grow. People with anal cancer usually find out about it late in the disease when treatments are limited to surgery, chemotherapy, or radiation therapy, which do not have good recovery rates. In our study we are using anal pap smears to detect the early signs of anal cancer, namely the cell changes called dysplasia. We found that anal dysplasia can slow or revert to normal. Among HIV-negative people and those who had good control of their HIV infection, the percentage of people who will progress to cancer is as low as 1-3%.
STEP: What is the treatment for a person who has HPV, anal warts, dysplasia, or cancer?
PN: None of the men in our study have developed invasive anal cancer. Some had severe dysplasia with pre-cancerous cells on biopsy, which can lead to cancer if not treated. None of the treatments for anal dysplasia are totally effective for treating HPV. Surgery is one option -- removing only tissue that is abnormal, but it is only 50% effective in permanently preventing reoccurrence. The use of acids to burn warts or liquid nitrogen to freeze them has been used, but effectiveness has not been evaluated. Several drugs are being developed, and vaccines for HPV are starting to be evaluated in limited studies in the U.S. New chemotherapy treatments are being developed to treat anal cancer. The goal is to develop a better screening test than the pap smear, and begin screening programs to find those at risk for anal cancer.
STEP: How important is screening?
PN: Early detection is important. The earlier you find a cancer like prostate, testicular, or anal cancer, the less likely it is to invade other parts of the body. Men over the age of 40 should have their prostate examined annually, and men over the age of 20 should be doing testicular self-exams monthly. As with anal cancer, a person with any signs of problems or history of warts, STDs, or abnormal internal or external bumps should be screened by their provider. I tell my patients that it is their responsibility to get a complete physical exam with their healthcare provider, and they should not wait for problems to begin.
STEP: How can someone obtain this type of exam, regardless of HIV status?
PN: Most primary care providers can do an anal exam. We are trying to educate doctors on how to perform anal pap smears to provide the screening exam. We are also working with the Seattle-King County STD Clinic and Madison Clinic (at Harborview) to perform this type of screening exam. By the end of 2001, this program may be up and running. If you have concerns, simply talk with your doctor or ask for a referral to a colorectal specialist to perform this exam. There is little discomfort to having an anal pap smear and internal examination performed. It is also important to talk freely with your doctor about risk factors such as having receptive anal sex, using toys, fisting, drug use and HIV status.
STEP: Is there anything a person can do to reduce his or her risk of developing anal cancer?
PN: Certainly, one way is to reduce the risk of contracting the HPV virus by using condoms when having anal intercourse, reducing the number of sexual partners, and not sharing sex toys. We don't know how contagious the HPV viruses are, so the more you prevent exposure, the less your risk of contracting HPV. It may also help to eat healthily, more fruits and vegetables, to increase the fiber in your diet. It is also important to avoid irritants to the anal canal, such as lubricants with nonoxynol-9 spermicide.
STEP: Now that you are concluding your four-year study on anal dysplasia, what are some of the tentative findings?
PN: Although the study should be completed this year, the total conclusion will take several months to complete. Some interesting initial findings are that the rate of high-grade anal dysplasia is directly related to your overall health. HIV-positive patients who have gone on anti-HIV medications and keep their CD4 counts above 500 are less likely to progress to anal cancer any faster than if they were HIV-negative. We have also found that two types of HPV are more likely to cause anal cancer. There are more than 70 different strains/types of HPV, and the two types (#16 and 18) that are known to cause cervical cancer are also suspected as the cause of anal cancer. We have noted differences between anal and cervical cancer in our latest research. The signs of cervical cancer in abnormal pap smears usually start at an early age and then progress with time. But with anal dysplasia, pap smear abnormalities can become high grade at an early age and then regress to low grade at middle age, and then possibly progress to high-grade abnormalities after the age of 40. HIV-positive patients, however, may not have this period of regression, and may progress to anal cancer more quickly. So staying in good health is proving to be very important. We won't have all the answers until all the data is evaluated.
STEP: I understand that a new study is in the works that compares the incidence of anal cancer in gay and bisexual men, and includes both HIV-positive and HIV-negative participants.
PN: Yes, this year we are writing a grant to look at better ways of detecting anal cancer. Since anal pap smears may be only 70% effective, we would like to develop new tests, and possibly look for new ways of treating anal dysplasia. This study may not begin until late in 2001 or early 2002. When we get the study going, we will begin a major advertising campaign and start recruiting patients for anal cancer screening. So watch your local newspaper or keep in touch with your doctor, because we will be sending information to local doctors when it becomes available.