Prior to discussing treatment of AIN, brief mention will be made of prevention. A quadrivalent HPV vaccine is currently available, and has been proven effective in preventing high-grade cervical intraepithelial neoplasia related to HPV strains 6, 11, 16 or 18 in women, and genital lesions associated with the same HPV strains in men [9–11]. Thus, a study was prompted to look at the efficacy of the vaccine for prevention of HSIL and ASCC in MSM [12]. Although none of the 602 healthy men aged 16 to 26 developed ASCC within the 3-year follow-up period, there were 5 cases of grade HSIL in the vaccine arm and 24 cases in the placebo arm. This amounted to an observed efficacy of 77.5 % for prevention of HSIL, suggesting the quadrivalent HPV vaccine may reduce the risk of ASCC in this patient population.

Recently, the quadrivalent HPV vaccine has been tested in HIV positive children, a group at high risk for HPV, and subsequent associated cervical and anal cancer. A randomized clinical trial found the vaccine to be safe and immunogenic in 126 HIV positive aged 7–12 years. Initially, antibody titers were lower for HPV 6 and 18 compared with historic age-matched immunocompetent controls [13], but this difference was lost after the fourth dose of vaccine [14]. The success of vaccines could lead to a significant decrease or near elimination of ASCC if used early and universally. Thus, their clinical importance cannot be underscored enough.

Patients with condyloma acuminatum or low-grade squamous intraepithelial lesion (LSIL) have very low potential for malignancy [15]. It is not clear that LSIL actually directly progresses to HSIL or ASCC. Rather, LSIL may be a marker in certain at risk groups for the presence of virus. Those patients that are symptomatic may wish to have the lesions excised or destroyed and this can be done with cautery, IRC or chemical agents. Follow up of these patients depends heavily on age, risk factors, underlying disease states and behavior patterns.

The goal of treating HSIL is the prevention of ASCC while maintaining anal function, including continence of stool and gas. Several therapies are available for the treatment of HSIL including surgical excision, electrocautery, topical imiquimod, trichloracetic acid and topical fluorouracil (5-FU). Limited studies, largely in the form of case series, have addressed the relative efficacy of the potential treatment options.

In 2000, a survey of 663 members of the ASCRS found that 87 % of respondents chose surgical excision with clear margins as the optimal treatment for HSIL [16]. However, a number of subsequent studies have suggested that surgery may not be the best treatment approach. Brown reported 34 patients with HSIL treated surgically in the UK. Within 41 months, 14 of 34 patients had macroscopic recurrences and 25 % of patients had anal function deficits postoperatively [17]. Scholefield reported on 35 patients who underwent limited excision for HSIL and were followed for 63 months. Three of 35 (9 %) had progression to ASCC [2]. Watson reported their experience with 72 patients treated surgically, of whom nine developed incontinence; four of these required a colostomy. Despite their aggressive surgical approach, 8 patients (11 %) progressed to invasive ASCC [3]. These studies have suggested surgical excision is not an ideal treatment due to incomplete excisions, frequent recurrences, and complications including stenosis and incontinence. They argued further that because chemoradiation for small invasive anal carcinoma is effective, a less radical approach may be warranted, because early surgical intervention with the associated complications may compromise later definitive treatment.

Other investigators suggest that rather than using an excisional approach, the use of HRA allows targeted destruction of suspicious lesions with the lowest reported rates of progression to cancer and preservation of anorectal function. HRA is used to identify dysplastic epithelium under the magnification of a standard colposcope or operating microscope. The technical application of HRA itself is discussed in more detail in the section regarding our treatment approach; but, briefly, HRA can be used with either targeted infrared coagulation (IRC) or electrocautery (EC). Both procedures are outpatient with only enemas given in preparation. IRC can be used with facility for lesions above the dentate line although local anesthesia is often necessary because the heat generated by the instrument causes pain. It coagulates lesions using 1.6 s pulses until the entire surface and an approximately 3 mm surrounding border are coagulated. The coagulated tissue is then scraped off with a small cotton Q-tip or forceps. This is repeated until the submucosal vessels are identified and coagulated. HRA directed EC, unlike IRC, uses bipolar cautery creating a smoke plume that requires a smoke evacuator to prevent transmission of HPV. Across the four listed studies (Table 23.1) regarding HRA targeted IRC for HSIL, there was no reported anal function compromise, 10–38 % had recurrence of HSIL, and none had progression to ASCC [18–21]. Similarly, in the two listed studies regarding HRA targeted EC, there was no reported anal function compromise, 17–31 % had recurrence of HSIL, and 0.4 % had progression to anal squamous cell carcinoma [22, 23]. Of note, recurrence of HSIL was higher in HIV patients and patients with higher burden of disease.