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CROI 2013: Random Anal Biopsies Improve Detection of Pre-cancerous Lesions

Performing random anal biopsies increases the rate of diagnosis of high-grade squamous intraepithelial lesions (HSIL) during high-resolution anoscopy, researchers from Mt. Sinai School of Medicine in New York City reported at the recent 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013).

Anal squamous cell cancer is a common malignancy seen in people with HIV today, with an estimated 7060 new cases in the U.S. in 2013. Detection of HSIL enables treatment and control of precursor lesions before they progress to anal cancer. Abnormal-appearing anal tissue is typically biopsied to test for disease, but the aim of this study was to see if performing random anal biopsies of normal-looking tissue could improve diagnosis. Random biopsies, collected without any visible abnormality, have been shown to increase diagnosis of high-grade dysplasia in previous studies; this is the first study to evaluate use of random biopsies during high-resolution anoscopy (HRA).

The trial included 391 participants who presented for HRA. Most (82%) were men who have sex with men, 63% were white, and nearly 73% were HIV positive. They did not have a history of anal squamous cell cancer or extensive disease requiring 4-quadrant anal biopsy. They also did not have known bleeding disorders and were not taking anticoagulant drugs.

The procedure was performed by dividing the anal canal into 4 quadrants. Standard biopsies were collected where there were visual cues of potential abnormality, while random biopsies were collected from regions that appeared normal. High-grade lesions were reviewed by a single expert pathologist. All participants underwent at least 1 random and at least 4 total biopsies. They were also screened for 13 high and intermediate risk human papillomavirus (HPV) strains.

Risk assessment variables included patient sex, race, sexual orientation, HIV status, use of antiretroviral therapy, previous HSIL or condyloma (anal warts) screening and disease, monogamy, anal sex, condom use, and tobacco use.

Results

• 878 non-random biopsies (mean 2.25 per participant) identified 220 HSILs (25.1%).
• 883 random biopsies (mean 2.26 per participant) identified 33 HSILs (3.7%).
• Random biopsy vs standard biopsy alone significantly increased total HSILs identified per patient (mean 2.0 vs 1.0, respectively).
• Random biopsy also significantly increased the total number of patients identified as having HSIL (132 vs 119, respectively).
• 33 HSILs (13.0%) and 13 participants (9.8%) were diagnosed solely through random biopsy.
• A greater total number of HSILs by standard biopsy was found to be associated with an increased risk of HSIL by random biopsy.
• In univariate and multivariate analyses, oncogenic (cancer-causing) HPV infection was associated with increased risk of HSIL detection by standard or random biopsy.
• There was no association between HSIL risk and race, sexual orientation, gender of sexual partners, sexual practices, history of sexually transmitted infections, smoking history, or HIV status.

The limitations of this study were borne out in more practical rather than medical issues. The study population was not heterogeneous, and therefore not generalizable. Other limitations were related to biopsies themselves. There might have been provider bias in determining which biopsies were truly random. Not every biopsy was subjected to expert review, and there was no adjudication of diagnostic discrepancies. In addition, the researchers did not do a cost/benefit analysis of adding random biopsies to the standard HRA procedure.

At the end of the presentation, an audience member asked about side effects of the high number of biopsies, given that only 3%-10% of HSILs will progress to cancer. Presenter Richard Silvera responded that while they did not consider all the ramification of random biopsies, since there was an increase in higher grade lesions diagnosed -- and given the serious consequences of not treating such lesions -- the investigators think there is a benefit.

Another practical consideration raised by the audience was the ongoing challenge of providing even the standard biopsy procedure for suspicious lesions, and that this new technique would only increase the challenges some providers face in busy clinics.

4/10/13

Reference

R Silvera, M Gaisa, and SE Goldstone. Random Biopsy Increases Diagnostic Rate and Total Anal High-grade Squamous Intraepithelial Lesions Found by High-resolution Anoscopy. 20th Conference on Retroviruses and Opportunistic Infections. Atlanta, March 3-6, 2013. Abstract 142.

Other Sources

R Siegel, D Naishadham, and A Jemal. Cancer Statistics, 2013. CA Cancer J Clin. 63(1):11-30. January-February 2013.

WC Mathews, W Agmas, and E Cachay. Comparative accuracy of anal and cervical cytology in screening for moderate to severe dysplasia by magnification guided punch biopsy: a meta-analysis. PLoS One 6(9):e24946. September 19, 2011.

AJ Cagle, SY Hu, JW Sellors, et al. Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid. International Journal of Cancer 126(1):156-161. January 1, 2010.