www.hivandhepatitis.com

Anal Pap Screening of HIV+ Men Reveals Half Have Abnormal Cells

More than 80% of HIV positive men agreed to undergo Pap screening for anal cancer, demonstrating its feasibility, and 53% showed signs of potentially pre-cancerous abnormal cell growth.

Anal cancer remains a concern for people with HIV despite the advent of effective combination antiretroviral therapy (ART), which has reduced rates of AIDS-defining cancers.

Caused by high-risk types of human papillomavirus (HPV), anal cancer is not considered an AIDS-related cancer (as is cervical cancer caused by the same HPV types). However, it is more common among HIV positive compared with HIV negative people, and studies indicate that the risk rises with declining immune function.

Anal Pap smears -- a test that examines a small sample of cells for abnormal growth that could progress to cancer -- is not currently part of the standard of care for people with HIV, but a growing number of experts think it should be. By detecting cell abnormalities at an early, more treatable stage, expanded anal Pap screening could reduce anal cancer deaths, much as widespread cervical screening has done for cervical cancer deaths.

In the present study, published in the March 31, 2011, issue of AIDS Patient Care and STDs,
Isabella Rosa-Cunha from the University of Miami and colleagues assessed the acceptability and feasibility of screening for anal intraepithelial neoplasia (AIN), or abnormal tissue growth that can progress to cancer. They also looked at the relationship between presence of anal neoplasia and history of receptive anal intercourse, which is commonly considered a risk factor for anal cancer in both men and women.

Between February and July 2006, the researchers asked 160 HIV positive adults attending routine visits at a Veteran's Affairs HIV clinic in Miami if they would be willing to undergo anal Pap testing. Eligible participants had no prior history of anal cancer and had not received anal screening before. If Pap tests were positive, participants received follow-up high-resolution anoscopy (viewing the anus with a lighted magnifying instrument) and tissue biopsies; those with abnormal findings were offered treatment.

Results

• 131 patients (82%) agreed to participate in the study and undergo anal Pap smears.
• All were men, 52% were black, 33% were white, 14% were Hispanic, and the median age was 49 years (range 29 to 80 years).
• The men had well-controlled HIV disease overall, with more than 75% on ART and a median CD4 T-cell count of about 400 cells/mm3.
• With regard to sexual history, about 40% reported having had anal intercourse, nearly one-third reported 4 or more sexual partners during the past year, and about half had a history of other sexually transmitted diseases.
• 98 men (75%) had anal cytology samples adequate for analysis.
• Within this subset, 53% had abnormal Pap test results:
• 58% with atypical squamous cells of undetermined significance (abnormal cells);
• 37% with low-grade squamous intraepithelial lesion (mild dysplasia or potentially pre-cancerous abnormalities);
• 5% with high-grade squamous intraepithelial lesion (more serious neoplasia or possible malignancy).
• Among participants who subsequently underwent anoscopy with biopsy, 55% were found to have high-grade AIN, including 2 cases of anal carcinoma in situ (localized cancer).
• Lower CD4 cell count was the only significant predictor of abnormal Pap results.
• History of anal intercourse was not significantly associated with abnormal anal cytology results in this study.

"Anal cytology was well accepted and it was feasible to be incorporated into HIV primary care practice," the study authors concluded. "The high rate of abnormal results reinforces the need for further evaluation of the role of systematic anal Pap smear screening for HIV patients."

"In our study abnormal anal cytology was as frequent in patients who denied anal intercourse as in patients with history of anal intercourse," they elaborated in their discussion. "And among patients with abnormal cytology who underwent [high-resolution anoscopy], history of anal intercourse was not predictive of the degree of the dysplasia and the 2 cases of carcinoma in situ were in patients who denied anal intercourse."

It is possible that self-reports of sexual behavior were inaccurate, but these findings suggest that screening for anal cancer should not be limited to HIV positive men who self-identify as gay/bisexual or report having anal sex.

The researchers also noted that 25% of collected samples were unsatisfactory for cytology analysis, higher than the proportion seen in other recent anal Pap studies (4%-9%).

"[T]he results underscore the necessity of specialized training of clinicians in performing anal Pap smears and of routinely orienting the patients undergoing anal Pap smear screening to avoid anal intercourse, anal manipulation...anal enemas or anal douche within 24 hours prior to sample collection," they emphasized.

Abnormal Pap smear cytology predicted abnormal follow-up findings, but not the degree of tissue abnormality. The 2 men with carcinoma in situ, in fact, had ASCUS, the least serious abnormal Pap result. This finding, the researchers wrote, "support[s] the recommendation of further evaluation with [high-resolution anoscopy] with biopsy of visible lesions of patients with any abnormal anal cytology." They added that testing for high-risk HPV types -- as is now routinely done with cervical Pap tests -- might help improve accuracy.

"HIV-infected individuals benefiting from HAART are living longer and, therefore, anal cancer in this population will likely remain a significant medical challenge," they concluded. "Until there is a consensus regarding anal Pap smear screening, HIV-infected patients need to know they are at risk of anal cancer, and anal health should be an issue of priority for HIV care providers to discuss with their HIV-positive patients."

Investigator affiliations: Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL; Surgical Services, Veterans Affairs Medical Center, Miami, FL; Department of Pathology, University of Miami Miller School of Medicine, Miami, FL; Pathology and Laboratory Medicine Services, Veterans Affairs Medical Center, Miami, FL; Medical Services, Veterans Affairs Medical Center, Miami, FL; Departments of Epidemiology & Public Health and Pediatrics, University of Miami Miller School of Medicine, Miami, FL; Research Services, Veterans Affairs Medical Center, Miami, FL.

4/26/11

Reference

I Rosa-Cunha, VA DeGennaro, R Hartmann, et al. Description of a Pilot Anal Pap Smear Screening Program Among Individuals Attending a Veteran's Affairs HIV Clinic. AIDS Patient Care and STDs 25(4):213-219 (free full text). March 31, 2011.