By Liz Highleyman

Despite the widespread use of effective combination antiretroviral therapy (ART), people with HIV continue to develop anal cancer, which is caused by the same high-risk human papillomavirus (HPV) types as cervical cancer. Frank anal cancer is preceded by progressive pre-cancerous cell changes, known as anal intraepithelial neoplasia (AIN) or squamous intraepithelial lesions (SIL).

Other types of HPV cause genital and anal condyloma, or warts. Topical 85% trichloroacetic acid is an effective and inexpensive treatment for perianal condyloma, but its efficacy as first-line therapy for intra-anal AIN is unknown.

In the present study, Joel Palefsky and colleagues performed a retrospective review of medical records for all patients with AIN at the University of California at San Francisco Anal Neoplasia Clinic who were treated with TCA as first-line therapy between January 2000 and December 2004. A total of 54 men -- 35 HIV positive (65%) and 19 HIV negative (35%) -- met the enrollment criteria.

Lesion clearance was defined as the absence of AIN confirmed by high-resolution anoscopy (a method of viewing the anal canal) and cytology (examination of cells) after up to 4 TCA treatments administered 1 to 2 weeks apart.

Results

	32% of patients with AIN grade 2 or 3 (moderate to severe) cleared all lesions, and 29% improved to grade 1 (for a total of 61% with improvement).
	HIV positive men were somewhat less likely than HIV negative men to achieve complete clearance of lesions (34% vs 47%), but the difference did not reach statistical significance.
	On a per lesion basis, 73% of AIN grade 1 cleared to no lesions, while 71% of AIN grade 2 or 3 cleared to grade 1 or less.
	Anal lesions cleared after an average of 2 TCA applications.
	72% of HIV positive men and 67% of HIV negative men experienced relapse of lesions, though it was not clear whether these were recurring or new lesions.
	In a multivariate analysis, patients aged 41-48 years were more likely to experience AIN clearance than those age 49 or older (odds ratio [OR] 8.4; P = 0.04].
	Among HIV positive men, those with 1 or 2 lesions were more likely to achieve clearance than those with more lesions (OR 14.3; P = 0.01).
	Higher CD4 cell count was slightly associated with better response, but again the difference did not reach statistical significance.
	TCA was well tolerated, with just 5% reporting adverse events (mostly pain at the site of application).

Based on these findings, the investigators concluded, "Topical 85% TCA was safe and well tolerated."

"It was more effective in younger patients and among HIV positive patients, those with 2 or fewer lesions," they added. "A high proportion of AIN 2/3 lesions responded to TCA treatment."

"Given its ease of use, low cost, and good safety profile, trichloroacetic acid represents a reasonable first-line therapy with carefully selected patients," they suggested.

Department of Internal Medicine, St. Luke's Roosevelt Hospital Center, New York, NY; Yale School of Medicine, New Haven, CT; Department of Medicine, University of California, San Francisco, San Francisco, CA.

10/16/09

Reference
JC Singh, V Kuohung, and JM Palefsky. Efficacy of Trichloroacetic Acid in the Treatment of Anal Intraepithelial Neoplasia in HIV-Positive and HIV-Negative Men Who Have Sex With Men. Journal of Acquired Immune Deficiency Syndromes. September 22, 2009 (epub ahead of print). (Abstract).