Screening HIV-infected MSM with annual anal cytology has been shown to be cost-effective, with an incremental cost-effectiveness ratio compared to no screening of $16,600 per quality –adjusted life year (QALY) saved, which is similar to other accepted screening test such as colorectal cancer screening [10].

Currently, there are no randomized controlled trials comparing the efficacy of HRA versus clinical follow-up with regards to ASCC prevention. We are thus left with observational studies and retrospective reviews. A meta-analysis of published studies suggests that the pooled prevalence of histological high grade AIN in MSM with HIV was 29.1 % [7], with incidences of 8.5 % and 15.4 % per year respectively in two estimates [19, 20]. The pooled anal cancer incidence was 45.9 per 100,000 men [7]. This number is corroborated by a pilot study which found that high grade AIN (AIN II and III) was found on histological analysis after HRA in approximately 32 % of asymptomatic MSM living with HIV. In this population of 368 asymptomatic MSM, 1.4 % developed invasive anal cancer at a median follow up of 4.2 years after HRA. All patients had high grade AIN at initial HRA screening. Additionally, during this study, the cumulative risk of anal cancer following HSIL diagnosis was 0.6 % at 5 years [14]. It is clear from this and other studies that AIN II-III represents a significant risk factor for development of ASCC.

However, does the incidence of ASCC support the widespread usage of HRA, and does the cost outweigh the benefit? A recent large retrospective review addresses the utility of routinely performing HRA. Crawshaw et al performed a single institution retrospective analysis of 424 patients from 2007 to 2013 comparing HRA to clinical follow-up. Surgeons in the group differed in their views on this controversy and their use of HRA, creating a natural experiment of sorts. 220 patients underwent HRA after abnormal pap smear, and 204 patients underwent clinical follow-up. The authors found no significant difference in progression to ASCC among the two groups [12]. It is important to note, however, that the surgeons in the clinical follow-up group performed mapping biopsies, ablated all visible lesions, and readily used imiquimod. Therefore, the only real difference between the groups was the use of HRA. HRA was not associated with prevention of ASCC when compared to the non HRA arm.

A recent Markov model analysis suggests that surveillance strategies after treatment for HGAIN that included HRA at 6 and 12 month intervals, with or without anal cytology testing, were more effective than using HRA only for confirmatory testing of abnormal anal cytology testing. However, a combined strategy of HRA and anal cytology extended life expectancy and quality-adjusted life expectancy (QALE) while remaining below the commonly-cited threshold of 100,000/QALY gained [21]. Similarly, Lam et al built a decision analytic model, and found that of 18 screening strategies, the direct use of HRA was the most cost-effective approach for the detection of high grade AIN [22]. However, neither of these analyses compare HRA to that of clinical follow-up.

Proponents of clinical management without HRA cite the increased morbidity as well as the additional cost incurred with repeated procedures often seen with HRA, as well as the low rate of disease progression to ASCC in compliant patients [1]. However, whilst HRA has been shown to be more effective in the detection of AIN than standard anoscopy with biopsies, this has failed to translate into lower rates of disease progression to ASCC [14, 16, 17]. The purpose of cancer screening is to reduce cancer-related mortality; there is a paucity of high quality evidence to make clear recommendations regarding the true benefit of HRA.