HIV and Anal Cancer: Anal Pap Smears, Early Treatment, Recommended for High-Risk Men & Women

For several years San Francisco researcher Joel Palefsky,
M.D., and his staff at the University of California have been
monitoring an apparent increase in precancerous changes in
anal tissue among persons infected with the human papilloma
virus (HPV), the virus that causes genital and anal warts.
Dr. Palefsky presented data from his work at each of the last
International Conferences on AIDS, in Amsterdam and Berlin,
and he recently offered an update at an open forum in San
Francisco.

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.