A Pap smear that many men should get, too
Positively Aware Erin Marcus, MD, MPD, FACP
By Erin Marcus, MD, MPH, FACP @ErinNMarcusMD

One recent morning, a group of men and women sat in a clinic reception room, waiting for their Pap smear appointments.

You read that correctly. The Pap smear—a screening test for cervical cancer and longtime fixture of the women’s health exam—is now used to detect and prevent cancer of the anus in both men and women. Experts believe that routine Pap testing could play an important role in curbing a doubling of new anal cancer cases that have occurred over the past three decades.

A Common Virus

While anal Paps are not indicated for most people, there is an increasing consensus that routine screening is important for people at high risk, specifically people whose immune systems are weakened due to HIV infection or medications taken after an organ transplant; men who have sex with men; and women who have cancerous or precancerous abnormalities on their cervical Pap smear.

Yet screening for anal cancer is unavailable in many parts of the U.S., and many people at high risk are unaware it exists.

“The awareness is remarkably low,” said Dr. Joel Palefsky, an infectious disease specialist and professor of medicine at the University of California, San Francisco. “Even in San Francisco it’s limited, though we have been doing [screening] a long time. The awareness is even lower elsewhere.”

Unlike colon and rectal cancer, most anal cancers are caused by a handful of strains of human papilloma virus, or HPV, a common virus (estimated to infect the majority of people in the U.S.) that has hundreds of different subtypes. Cervical cancer is caused by the same HPV strains. Most people clear HPV infections over time. But some are vulnerable to long-term infections that can eventually transform affected cells into invasive cancer.

More than 7,000 new cases of anal cancer are diagnosed in the U.S. each year, and about 1,000 individuals die of the disease annually. Even though a majority of those diagnosed—about two out of three—survive for five years or more, the disease and its treatment can be debilitating. Those who survive may have long-term problems with urination, defecation, and sexual relations. Contributing to the increase in anal cancer are the HIV epidemic and the longer lifespan of people with HIV due to highly active antiretroviral therapy, or HAART; an increase in the number of people with organ transplants may also have contributed.

One study of men with HIV found that anal cancer tended to be diagnosed about 13 years after they were found to be infected with HIV. Among men who have sex with men, anal cancer is now as common as cervical cancer was among women before the Pap smear was developed.

“All you’ve got to do is see one young guy with anal cancer” to realize the value of screening, said Dr. Elie Schochet, a colorectal surgeon in Fort Lauderdale. “I’ve had patients come to me with cancer and when I look back through the record, there was an opportunity to take care of this sooner.”

With or Without Anal Sex

Compared to screening for other cancers, screening for anal cancer is a relatively new phenomenon. Many primary care doctors are unaware of anal cancer screening, and don’t routinely ask patients about whether they engage in anal sex, have a history of sexually transmitted infections, or are experiencing anal discomfort. Many doctors don’t even feel comfortable performing rectal exams. (Even though a doctor’s rectal exam may miss very early disease, some experts believe it is better than nothing in people at risk). Patients may not feel comfortable telling their doctor about their sex practices. Women with a history of cervical Pap smear abnormalities may not realize that they are at risk even if they haven’t had anal intercourse, since the virus can spread between the genitals and the anus.

“A huge challenge for us is the stigma that surrounds (anal cancer) and that part of the body,” said Justine Almada, who co-founded the HPV and Anal Cancer Foundation with her brother and sister after her mother, who had been treated years earlier for precancerous cervical changes, died of anal cancer at age 53. “It’s something easily transmissible. You don’t need to have anal sex to have anal cancer.”

The Rub

Even if a primary care physician wants to perform an anal Pap on a patient, he or she is placed in a conundrum. If the screening Pap is abnormal, then the next step in the work-up for cancer or pre-cancer is a procedure called a high-resolution anoscopy. But in many parts of the U.S., specialists trained to perform this procedure are scarce or non-existent.

“It’s an ethical dilemma for doctors if they diagnose” an abnormality and can’t send a patient for anoscopy, said Jeff Taylor, 52, an HIV treatment educator and community member of the National Cancer Institute (NCI)’s AIDS Malignancy Consortium. “There’s a lot of frustration because access to [anoscopy] is so sporadic.”

Mark Hubbard, who was diagnosed with HIV 27 years ago, learned about anal Pap smears in the late 1990’s through his work as a health educator and advocate. He was concerned that he was at increased risk of anal cancer because of his HIV and because he had experienced outbreaks of anal warts, which are caused by different strains of HPV. Until recently, however, he was unable to find anyone in his home state of Tennessee who performed anal cancer screening, and had to travel to Pittsburgh—at a cost of about $500 per trip—to be tested.

“A lot of providers were completely clueless and would say crazy things,” he said. “Once I decided I really wanted to be screened, I couldn’t find anybody.”

As with the cervical Pap test, the anal Pap is simple and inexpensive. It involves swabbing the anus with a Dacron swab and then placing the swab in a liquid-filled jar that is the same type used for Pap smear samples. High resolution anoscopy—the next step if an anal Pap is abnormal—isn’t complex either, but it requires specialized training for the doctor or nurse. It uses a special microscope that is already widely available in many gynecologists’ offices, where it is used for colposcopy, the standard procedure to examine the cervix after an abnormal Pap smear.

The Exam

Early last year, I spent a morning watching Dr. J. Michael Berry, a cancer specialist at the University of California, San Francisco, coach a gynecologist and an HIV specialist on how to perform anal Paps and high-resolution anoscopy. The first patient was a middle-aged taxi driver who had recently had a normal colonoscopy. As the patient lay on his side on an exam table, the HIV specialist placed the tip of the scope in his anus and then looked through a connected set of magnifying binoculars, swabbing with an acetic acid-soaked cotton swab and searching for irregular areas. (The rest of us watched on a computer screen that showed what she was viewing.) The affected area turned pale. She took a small sample of the area and then rubbed it with a swab soaked in trichloracetic acid to destroy the abnormal tissue. After 20 minutes, she had finished her examination.

“To be good at this procedure, you have to do it a lot,” Berry said. “It’s very gentle—most people barely notice.”

The patient wondered why the abnormalities hadn’t been spotted on his colonoscopy. Berry explained that even though the colonoscope passes through the anus, the purpose of colonoscopy procedures is to examine the large intestine and rectum for cancer. Most colonoscopies don’t carefully examine the anus; for them to do so, the colonoscope would have to be turned backward in an unusual position. “Colonoscopy can be misleading,” Berry said. “People end up with a false sense of security—they say, ‘someone examined my butt and it was fine, so why do you want to look again?’”

Changing the Medical Field

Awareness of anal Pap screening has been growing among health workers. Palefsky estimates that he, Berry, and other HPV specialists have trained more than 500 health workers in high-resolution anoscopy. The International Anal Neoplasia Society, the world’s first professional group focused on preventing and treating anal cancer, held its inaugural meeting last year. The New York State Department of Health now recommends that HIV-infected men who have sex with men, as well as anyone with a history of anal or genital warts and women with a history of pre-cancerous Pap smear findings, undergo anal Pap testing each year.

“When we first started, it was like, ‘I’ve never seen anal cancer, what kind of nonsense are you talking about?’” Dr. Stephen Goldstone, a New York-based surgeon, said. “But we’re developing a critical mass. As the scientific body of evidence has grown, people have started to take notice.”

An 8-year, $89 million National Cancer Institute-funded study is now examining whether treating the precancerous anal abnormalities caused by HPV reduces anal cancer in people with HIV. The study plans to enroll more than 5,000 people in 15 sites around the U.S. Scientists hope the study will improve their understanding of the molecular changes that occur as anal cancer develops, help them ascertain whether some biomarkers,
or laboratory findings, predict who is at highest
risk of developing anal cancer, and find
new treatments.

Changing the HIV Field

Perhaps most important, the study will provide the “gold standard” clinical trial evidence that the U.S. Preventive Services Task Force and U.S. Centers for Disease Control require in order to decide whether to recommend cancer screening tests. These recommendations significantly sway whether doctors perform the test and influence insurance companies that are considering whether they will pay for the test (at present, many companies will pay for treatment of an anal abnormality but not for screening to look for that abnormality). While it may seem intuitive that early treatment of precancerous anal lesions reduces a person’s likelihood of developing cancer, proof is needed that the benefits of such therapy outweigh the harms, when performed on a massive scale.

The need for such a large study is frustrating for some advocates, who point out that the cervical Pap smear, which has been credited with saving millions of women’s lives, was introduced into routine practice without such rigorous, population-based evidence. But Hubbard said he hopes the study’s findings will lead to the widespread use of guideline-based, standardized treatments.

“Cervical dysplasia was treated for years without that evidence,” he said, but added, “people tend to overtreat when they don’t know what they’re doing. There are a lot of horror stories in the community about bad treatment. This is a really important study.”

Erin N. Marcus, MD, MPH, FACP, is a general internist at the University of Miami Miller School of Medicine and writes about public health. The reporting of this article was supported by a grant from the Ford Foundation.