Progression of High-grade Anal Intraepithelial Neoplasia to Invasive Anal Cancer among HIV+ Men Who Have Sex with Men
M Berry1, N Jay1, R Cranston2, T Darragh1, E Holly1, M Welton3, and Joel Palefsky*1
1Univ of California, San Francisco, US; 2Univ of Pittsburgh, PA, US; and 3Stanford Univ, CA, US
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
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.