Anal Pap Smears to Detect Pre-cancerous Cell Changes Are as Effective as Cervical Screening, especially at Low CD4 Counts

		SUMMARY: Anal cytology testing works about as well as cervical cytology tests -- better known as Pap smears -- for detecting pre-cancerous cell changes (neoplasia) in HIV positive and HIV negative individuals, according to a study published in the January 28, 2010 issue of AIDS. The test was more accurate for higher grades of neoplasia, for HIV positive participants, and for those with lower CD4 cell counts.

By Liz Highleyman

Several studies have shown that people with HIV are more likely to develop anal cancer compared with the HIV negative general population, and that the risk rises as CD4 count falls. Invasive cervical cancer is classified as an AIDS-defining condition in HIV positive women. However, anal cancer is not similarly designated, even though it is caused by the same high-risk types of human papillomavirus (HPV).

Pap smear cytology testing involves collecting a sample of cells and examining them under a microscope for unusual changes. Among women in the general population, the widespread adoption of regular Pap screening starting in the 1950s dramatically reduced the rate of death due to cervical cancer.

HIV positive women are more likely than negative women to be infected with high-risk HPV types and to have pre-cancerous cell changes. However, in industrialized countries, they do not have a higher rate of cervical cancer death, which is attributed to regular Pap screening to detect changes at an early, treatable stage. Anal cytology screening is not currently considered part of the standard of care for at-risk HIV positive people, but some experts believe it should be.

In the present study, Mayura Nathan from Homerton University Hospital in London and colleagues assessed the performance of anal cytology as a screening tool, comparing cytology testing versus histology testing (using tissue biopsy specimens) and high-resolution anoscopy (examination of the anal canal and rectum using a lighted magnifying instrument).

The study included a total of 395 participants (367 men and 28 women) referred for follow-up examination due to suspected anal abnormalities. Just over half (54%) were HIV positive and 39% were HIV negative. About three-quarters were men who have sex with men (MSM), a group at increased risk for anal cancer.

The researchers obtained an anal Pap test specimen prior to anoscopy examination and tissue biopsy in the same individual, and evaluated agreement between the methods. In total, they analyzed 584 cytology specimens and 288 histology specimens.

They reported diagnostic accuracy in terms of sensitivity (number of cases correctly identified), specificity (absence of pathology correctly ruled out), and negative predictive value (proportion of patients without pathology correctly diagnosed).

Results

	Measured against histology results, the sensitivity of anal cytology to detect any degree of disease was 70% and specificity was 67%.
	For high-grade disease including anal intraepithelial neoplasia, the sensitivity of anal cytology was 81% and the negative predictive value was 85%.
	Sensitivity depended on the extent of disease, and was more accurate if there were cell changes in 2 or more quadrants (86%) compared with 1 or more quadrants (69%).
	Sensitivity was higher for MSM (71%) compared with heterosexual participants (59%).
	Sensitivity was higher for HIV positive participants (76%) than for HIV negative people (59%).
	Among HIV positive individuals, the sensitivity was 90% when CD4 count was 400 cells/mm3 versus 67% when it was > 400 cells/mm3.

Based on these results, the study authors concluded, "Anal cytology performs similar to cervical cytology in a clinical setting."

"Sensitivity of anal smear is dependent on the area (quadrants) of disease present," they continued. "Sensitivity of anal cytology is enhanced when CD4 cell count is less than 400 cells/[mm3] in HIV positive men."

They added that their findings might help explain the variable sensitivity results observed in prior studies.

"Given the inaccuracies that exist with any method of evaluation, we need to have a number of assessment methods for the diagnosis of anal neoplasia, as is the case with cervical neoplasia," they recommended in their discussion. "This study supports the introduction of earlier screening in HIV positive patients, given their higher burden of anal disease and increased sensitivity with lower CD4 cell count levels."

Department of Sexual Health, Homerton University Hospital NHS Foundation Trust, London, UK.

1/26/10

References
M Nathan, N Singh, N Garrett, and others. Performance of anal cytology in a clinical setting when measured against histology and high-resolution anoscopy findings. AIDS 24(3): 373-379 (Abstract). January 28, 2010.

L Pantanowitz and BJ Dezube. The anal Pap test as a screening tool (Editorial comment). AIDS 24(3): 463-465. January 28, 2010.