To treat limited perianal HGAIN at UCSF, we would start with 85 % trichloroacetic acid (TCA) [28] or liquid nitrogen. A combination of the two modalities may be helpful, with the lesions frozen first, followed by application of TCA. TCA is reapplied as needed up to four times at 2- to 3-week intervals, and if it is not successful, a different modality should be tried. If there is uncertainty about whether the disease has been cleared, the treatment areas should be biopsied. If available, some clinicians would use hyfrecation (low-power, high-frequency, alternating current electrical pulse therapy) in the office or IRC. Imiquimod cream is another modality that may be used if the patient knows where to apply it. Studies in Europe have shown some success with imiquimod for treatment of HGAIN [29–31], but we have had relatively limited success with it at the UCSF Anal Neoplasia Clinic. HIV-positive patients may not respond as well to imiquimod as HIV-negative patients because the mechanism of action is immune-mediated through toll-like receptors. If the patient does not experience pain or inflammation with standard dosing regimens and has not experienced a therapeutic effect, some have increased the number of treatment days per week beyond the standard 3 days/week. Treatment should be discontinued if the patient is experiencing excessive discomfort, but mild discomfort may be a sign that the treatment is working. Treated areas should be biopsied to confirm a treatment response. Like other topical treatments, imiquimod has not specifically been approved by the U.S. Food and Drug Administration for this purpose.

Larger perianal HGAIN lesions usually require more aggressive approaches. IRC is growing in popularity because it can be performed in the office setting and does not create smoke or require a smoke evacuator. Large lesions that would in the past have required referral to surgery may be treated using this approach. Retrospective chart review studies and a multicenter phase I safety study indicate that the efficacy of IRC to treat individual HGAIN lesions is about 65 % within a year, with up to three treatments [32, 33]. The efficacy of laser or electrocautery for treatment of perianal HGAIN has not been reported.