Background:  The incidence of anal cancer is higher among HIV⁺ men who have sex with men (MSM) than the general population, and is continuing to increase since the introduction of ART. Several studies have shown a high prevalence and incidence of high-grade anal intraepithelial neoplasia (HGAIN), the putative anal cancer precursor, in HIV⁺ MSM. Anal and cervical cancer are biologically similar, and the treatment of HGAIN may prevent development of anal cancer, similar to treatment of high-grade cervical intraepithelial neoplasia to prevent cervical cancer. One of the barriers to implementing routine screening and treatment of HGAIN in HIV⁺ MSM is the paucity of data on progression of HGAIN to cancer.

Methods:  To determine whether HGAIN has the potential to progress to invasive cancer, medical records of patients at the University of California–San Francisco, who developed invasive anal cancer from 1997 to 2007, were reviewed to determine whether cancer developed at the same location as previously biopsied HGAIN. Patients diagnosed with HGAIN were either referred for, or offered treatment, but not all patients were treated. All were asked to return to clinic at regular intervals for anal cytology, digital rectal examination, and high-resolution anoscopy with biopsy of suspicious lesions, but some were lost to follow-up. 

Results:  Among approximately 1700 HIV⁺ MSM, 65 cancers were diagnosed. Adequate documentation of the relationship of HGAIN to the site of cancer was available for 27 patients. We identified 21 patients with cancer in a site of biopsy of HGAIN, and 6 patients had a well-documented history but no recent biopsy of HGAIN at the site of anal cancer. Invasive cancers were intra-anal in 17 patients, peri-anal in 7, and metachronous in 3. Median age at diagnosis was 49 years (range 39 to 68). Median CD4⁺ lymphocyte count was 240 cells/mm³ in 25 of 27 subjects with available results (range 49 to 1000 cells/mm³). Patients diagnosed with HGAIN progressed to cancer after an average of 47.1 months (range 4 to 139 months) but since most patients presented with HGAIN, the total time that HGAIN was present prior to progression is unknown. 15 of 27 (56%) patients were asymptomatic and their cancers were detected during routine follow-up.

Conclusions:  Both intra-anal and peri-anal HGAIN have potential to progress to invasive anal cancer. Carefully controlled clinical trials are needed to evaluate screening and treatment of HGAIN in HIV⁺ MSM to prevent anal cancer.