AIDS TREATMENT NEWS Issue #203, July 22, 1994
Denny Smith

His observations, bolstered by several similar studies, are based on the notion that HPV may provoke the growth of abnormal anal cells, called dysplasia. These can then become tumor cells, or neoplasia. Researchers have also suspected that co-infection with HPV and HIV, not an unusual situation, may further increase the risk of dysplasia. When Dr. Palefsky's staff scanned the cancer registry statistics for the city of San Francisco, they found that indeed, the incidence of reported anal cancer was higher in communities where HIV infection was prevalent.

Cancer and infectious disease might ordinarily be considered very separate realms of medicine, but there are precedents for a connection. Long-term infection with hepatitis B, for example, has been associated world-wide with cancer of the liver. And Epstein-Barr virus has been connected to the development of certain lymphomas.

Even before Dr. Palefsky's study began, HPV was already thought to foster cervical dysplasia in women. The cells of the anus are very similar to the epithelial cells of the cervix. Moreover, the incidence of anal cancer in the general population of Europe and the U.S. has been on the rise, particularly in women, as well as in men who practice receptive intercourse.

The combination of HPV and HIV infections is now strongly connected to cellular changes called cervical intraepithelial neoplasia (CIN) in women, and to anal intraepithelial neoplasia (AIN) in both men and women.

One of Dr. Palefsky's AIN studies enrolled over 600 men; more than half of them have HIV, with the others participating as an HIV-negative control group. Of those men with HIV, about a third had CD4 counts below 200. True to his hypothesis, Dr. Palefsky has found that 11% of the HIV-positive participants developed AIN at some point in the study, compared to only 2% of the negative controls.

Another study tested 114 women who were considered at risk for HPV infection. HPV was found in 77% of anal swab samples from HIV-positive women, compared to 56% of the HIV-negative controls. Anal cell abnormalities were seen in 14% of the women, mostly in those who also had HIV. That is higher than the incidence of cervical dysplasia in women with both HPV and HIV.

The goal of these studies is not simply to watch for the development of anal cancer, but to watch for signs of dysplasia that precede it, in order to intervene with treatment. The researchers do this by performing periodic exams already well-known to women as Pap smears. (Many physicians apparently do not realize that Pap smears can be productive diagnostic techniques on anal tissue as well as cervical tissue.)

External anal tissue does not usually reveal dysplasia, so the studies used a technique called anoscopy, with a vinegar preparation that highlights any warts, to collect the specimens. The procedure is not painful. The smears can reveal most instances of AIN. When this tissue is viewed under a microscope, the HPV-infected cells have halos and their nuclei are bloated.

If a lesion is seen during the anoscopy, a biopsy is taken. The biopsy can cause some discomfort, but that is easily managed with non-prescription analgesics.

The dysplasia are graded according to the appearance of the cells: low-grade dysplasia are simply monitored every six months, while higher-grade dysplasia are referred for treatment. AIN is effectively and easily treated on an out- patient basis with cauterization or excision.

Unfortunately, most HIV care providers probably do not now include anal Pap smears in their daily practice. The data from studies such as Dr. Palefsky's may change that. He suggests that the following individuals should be screened annually for AIN: all HIV-infected people with CD4 counts below 500, all women with a history of high-grade CIN, and all men with a history of receptive anal intercourse. Many people with these profiles may not even realize they are infected with HPV, so the monitoring should not be limited to those with a known history of anal warts.

An excellent review by Dr. Palefsky addressing AIN epidemiology, diagnosis and treatment can be found in the medical journal AIDS, volume 8, number 3, pages 283-295, 1994.

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