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High-Grade Anal Intraepithelial Neoplasia Recurrence
Christopher J. Hoffmann, MD, MPH 

HIV-infected men who have sex with men (MSM) have a higher risk of anal cancer than men in the general population (65 to 130 per 100,000 person-years versus 5 to 15 per 100,000 person-years). High-grade anal intraepithelial neoplasia (AIN) is considered the precursor to anal cancer, which has high morbidity and mortality rates. High-grade AIN can be suspected on the basis of an abnormal anal cytology result (generally, high-grade squamous intraepithelial lesion or SIL). Although limited data are available to support a specific screening and management approach, abnormal anal cytology is generally followed-up with anal biopsy via high-resolution anoscopy (HRA). Histologically proven high-grade AIN lesions can be ablated using electrocautery, cryotherapy, or chemical means. However, recurrence after treatment persists, as shown in a recently published study that examined factors associated with high-grade AIN recurrence after successful ablation.

The study authors [Burgos J, et al. AIDS 2017 Jun 1;32(9)] used data collected from an observational cohort of MSM with HIV infection whose care was managed in an anal dysplasia clinic at a hospital in Spain. All patients were diagnosed with high-grade AIN and had biopsy-proven response to electrocautery 6 to 8 weeks after their last treatment session. Follow-up with HRA continued every 3 to 6 months. Recurrent high-grade AIN was defined by biopsy either at the previously treated site or an untreated site.

The study included 141 participants with high-grade AIN who accepted treatment. Of these, 100 (71%) had successful treatment. The median age of successfully treated patients 43 years; the mean CD4 count was 629 cells/mm3, and 70% had an undetectable viral load at the time of treatment. The participants were followed for a median of 13.6 months. During the follow-up period, 39 (39%) developed recurrent high-grade AIN; no patients progressed to invasive anal cancer.

Of those with recurrent high-grade AIN, 37/39 (95%) had a larger initial lesion (lesion affecting two or more octants of the anal canal circumference) than did those without recurrence (45/61 [74%]). Those with recurrence also had a lower nadir CD4 count (232 vs. 326 cells/mm3) and were more likely to have HCV antibodies present (16% vs. 2%). 

Factors not associated with recurrence of high-grade AIN included age, undetectable viral load, a current and stable sex partner, and routine use of condoms.

After 1 year of treatment, 57% of participants had high-grade neoplasia (41 patients did not respond to initial treatment and 39 patients experienced recurrence). This appears to be a remarkable failure rate for any therapy. This result raises several questions regarding the most effective management of anal neoplasia: What is achieved through electrocautery ablation? Is the risk of anal cancer being reduced with this treatment? How frequently should follow-up occur? What risk factors predict progression to anal cancer?

The take-home message for me is that high-grade anal neoplasia is common and the success with current treatment approaches is limited. There remains a need for improved data and guidance on optimal approaches to managing and preventing anal cancer among MSM.
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HIV Clinical Guidelines Program 
New York State Department of Health AIDS Institute
In collaboration with the Division of Infectious Diseases
Johns Hopkins University School of Medicine

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