Four in 10 gay or bisexual men with HIV infection in a 1500-man U.S. group had abnormal anal cells that may sometimes develop into anal cancer.1 In contrast, only one quarter of HIV-negative gay or bisexual men in the same study group had anal cell abnormalities.
Many anal cancers are caused by high-risk types of human papillomavirus (HPV), especially HPV-16. These high-risk HPVs often affect people who have anal intercourse, such as gays and other men who have sex with men. Research shows that anal cancer risk is 32 times higher in HIV-negative gay or bisexual men than in the general U.S. population and 52 times higher in HIV-positive gay or bisexual men.2 From 2001 through 2005, almost one third of anal cancers detected in U.S. men developed in HIV-positive men.2
Cervical cancer, an AIDS cancer also caused by HPV, can be prevented or detected early by examining cells collected in Pap tests. Examining cells collected from the anus can detect abnormalities that may develop into anal cancer. But health authorities have not yet proposed a screening-and-treatment plan to test anal cells and treat precancer abnormalities. One reason for this uncertainty is the tendency of some risky abnormal cells and even some precancer cells to return to normal without treatment.
To get a better understanding of abnormal anal cell rates in gay and bisexual men with and without HIV infection, U.S. researchers conducted this study.
How the Study Worked
The analysis involved men in the Multicenter AIDS Cohort Study (MACS), an ongoing study of HIV-positive gay or bisexual men and similar HIV-negative gay or bisexual men at risk of HIV infection. Men began entering the MACS group as early as 1984-1985 in four U.S. cities. They make study visits twice a year to get a physical exam, give samples for study, and answer questions about their health and health-related behaviors (see http://aidscohortstudy.org/).
MACS men began having anal cell tests -- called anal Pap tests -- in 2010. Researchers invited men who had a first anal cell test to have a second test 2 years later. Trained health professionals collected anal cell samples with a swab inserted into the anus. A single lab analyzed anal cell samples collected at all MACS study sites. Cell experts rated the anal cell samples according to a standard system that starts with normal cells and progresses to high-grade squamous intraepithelial neoplasia (HSIL), which can lead to anal cancer (Figure 1). Among people with HIV infection, about 2% with HSIL have anal cancer within 5 years.3
Men with abnormal anal cell results received information about high-resolution anoscopy, a procedure that allows a health professional to view the inside of the anus. The men were advised to see their primary provider to discuss whether they should have high-resolution anoscopy. During anoscopy an anal tissue sample (biopsy) can be snipped off, and that sample can be used to confirm HSIL.
The researchers also tested anal cells for HPV type 16 (HPV-16), which is the HPV type most often linked to anal cancer.
What the Study Found
The study involved 723 gay or bisexual men with HIV and 788 gay or bisexual men without HIV. Median (midpoint) age of the whole study group stood at 55 years. While 72% of study participants were white, 18% were black and 8% Hispanic. Most HIV-positive men in the study (91%) were taking antiretroviral therapy, 78% had an undetectable viral load, and median CD4 count was 583.
Among 1437 men with an adequate anal cell sample, 189 of 750 without HIV (25%) and 276 of 687 with HIV (40%) had abnormal anal cells (any cell type not normal in Figure 1). That large difference in abnormal anal cells between men with and without HIV is statistically significant, meaning the difference probably does not result from chance. Proportions of HIV-positive men with abnormal anal cells were higher in men with lower current CD4 counts: Among men with a CD4 count below 350, 47% had abnormal anal cells, compared with 41% of men whose CD4 count lay between 350 and 499 and 38% of men whose CD4 count lay above 499 (Figure 2).
The proportion of men with high-risk anal cell abnormalities detected in the anal Pap test (ASC-H or HSIL, see Figure 1) was low in men without HIV (3%) and only slightly higher in men with HIV (4%). The rate of lower-risk anal cell abnormalities (ASCUS or LSIL) was 22% in men without HIV and 28% in men with HIV. HPV-16 (the highest-risk human papillomavirus type) could be detected in anal cells of 16% of HIV-negative men and 20% of HIV-positive men.
Next the researchers analyzed anal cell samples from 447 men with HIV and 409 men without HIV who had two anal cell samples 18 to 30 months apart. None of these men received treatment for anal cell abnormalities between their two anal samples. Among all men who had normal anal cells in their first test, 29% with HIV versus 16% without HIV had abnormal anal cells in their second test. Most men with and without HIV who had abnormal anal cells on their first test had a lower-grade abnormality or normal cells on their second test. That probably means the abnormality was returning to normal on its own. Among men with HIV, 15% with a lower-grade abnormality (ASCUS or LSIL) on their first test had a higher-grade abnormality (for example, ASCUS → LSIL or LSIL → ASC-H or HSIL) on their second test. In contrast, only 5% of men without HIV went from a lower-grade abnormality to a higher-grade abnormality.
Among 1392 study participants who did not have HSIL confirmed by biopsy before the study, 220 (16%) had high-resolution anoscopy and biopsy during the study. Eighty-seven of these 220 men (40%) had HSIL confirmed by the biopsy. Among men with abnormal anal cells on their first test, 38 of 79 with HIV (48%) and 22 of 61 without HIV (36%) had HSIL confirmed by biopsy. One reason these proportions are so high is that men with more threatening Pap test results were the ones most likely to get follow-up testing. But some men with normal anal cells on their first test also had followup testing, and one of these men had HSIL confirmed by biopsy.
What the Results Mean for You
This large study of U.S. gay and bisexual men found a higher rate of abnormal anal cells in men with HIV than without HIV (40% versus 25%). Most men with HIV were taking antiretroviral therapy and three quarters of them had an undetectable viral load. Among men with HIV, abnormal anal cell rates were higher in men with lower CD4 counts (Figure 2).
This finding suggests that the better immune system health reflected by a higher CD4 count lowers chances of anal cell abnormalities. Starting antiretroviral therapy promptly after testing positive for HIV usually prevents the CD4 count from falling further.
About 1 in 50 HIV-positive people with HSIL -- the most serious anal-cell abnormality (see Figure 1) -- will go on to have anal cancer within 5 years.3 That may sound like a low proportion, but anal cancer rates are much higher in people with HIV than without HIV, especially among gay or bisexual men. Detecting abnormal anal cells could provide an early warning of developing anal cancer, just as abnormal cervical cells provide an early warning of cervical cancer. The researchers believe that the rate of biopsy-proved HSIL in gay men with or without HIV in this study "supports the need for effective screening methods in this population."
A large trial has begun to see whether detecting and treating high-grade anal cell abnormalities will lower the anal cancer rate in people with HIV. Until we have results of this trial, however, the value of anal-cell testing in preventing anal cancer remains uncertain. If you are an HIV-positive man or woman 35 or older, you might qualify for this trial. If you are interested in participating, read about the trial at the link at reference 4 below and discuss the trial with your HIV provider.
The authors believe their study "underscores the increased risk of anal disease among [gay or bisexual men] in general and especially among HIV-infected [men]."1 Men and women who have anal sex should be aware that anal sex boosts the risk of anal cell abnormalities. Men and women can lower their risk of anal cell abnormalities and anal cancer in several ways:
- Decrease contact with human papillomavirus (HPV) by using condoms during sex and by limiting the number of sex partners you have.
- Get the HPV vaccine, which is recommended for women up to age 26, for gay or bisexual men with or without HIV up to age 26, and for other men up to age 21.5
- Quit smoking or don't start smoking.
- D'Souza G, Wentz A, Wiley D, et al. Anal cancer screening in men who have sex with men in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr. 2016;71:570-576.
- Shiels MS, Pfeiffer RM, Chaturvedi AK, et al. Impact of the HIV epidemic on the incidence rates of anal cancer in the United States. J Natl Cancer Inst. 2012;104:1591-1598.
- Cachay E, Agmas W, Mathews C. Five-year cumulative incidence of invasive anal cancer among HIV-infected patients according to baseline anal cytology results: an inception cohort analysis. HIV Med. 2015;16:191-195.
- Topical or ablative treatment in preventing anal cancer in patients with HIV and anal high-grade squamous intraepithelial lesions. ClinicalTrials.gov identifier NCT02135419.
- Centers for Disease Control and Prevention. Human papillomavirus (HPV). Questions and answers. 2015.