Comparison of interventions for patients diagnosed with pre-cancerous changes of the anal canal (anal intraepithelial neoplasia)

Persistent infection with some types of human papillomavirus (HPV) can cause anal canal intraepithelial neoplasia (AIN), a condition which may become cancerous. HPV is transmitted via skin-to-skin contact. There are over 100 different types of HPV virus. At least 30 of these can be sexually transmitted. HPV transmission occurs easily among sexual partners. Despite this, spontaneous clearance of the infection is generally the rule.

In some cases, HPV may produce genital warts or even some anogenital pre-malignant or malignant lesions. The latter is especially the case when some HPV types (which are named 'high-risk' HPV, like HPV types 16, 18, 31 and 33) persist on anogenital mucosa or skin over long periods of time. Viral persistence is very common in an HIV-positive population, particularly in the anal mucosa of men who have sex with men. The incidence of AIN is reaching epidemic proportions in this population group. AIN is usually asymptomatic. People at risk need to be under prevention screening programs in order to identify and treat those pre-cancerous lesions.

To date there is no consensus on AIN management. The most used strategies are ablative treatments. Lesions in the anal canal are treated with cautery, infrared coagulation, laser or cryotherapy. Other available options include surgical excision, topical treatments (imiquimod, trichloroacetic acid, 5-fluorouracil), interferon and HPV vaccines. We identified many studies that examined all the interventions mentioned above. Only one trial with 53 patients was randomized and placebo-controlled and could be included in this review. The trial compared self-application of imiquimod cream in the anal canal with placebo. The analysis of the findings could not demonstrate a definitive superior effect of imiquimod compared with placebo in terms or cure. Some effectiveness could be observed in terms of improvement, with high-risk stages of AIN being reduced to low-risk stages.

We conclude that the available information on AIN treatment does not meet evidence-based medicine requirements. Future trials should be designed as randomized controlled trials, and should include data about HPV load and the types affecting the treated patients, recurrence rates, progression to anal cancer and quality of life of patients.

Authors' conclusions: 

The included trial failed to demonstrate any statistically significant efficacy of imiquimod in the management of anal intraepithelial neoplasia (AIN). The absence of reliable evidence for any of the interventions used in AIN precludes any definitive guidance or recommendations for clinical practice. Prospective cohort studies and retrospective studies have not been included in this review as they are considered to provide lower quality evidence. Well designed RCTs are needed.

Read the full abstract...

Anal canal intraepithelial neoplasia (AIN) is a pre-malignant condition of the anal canal transitional epithelium that is associated with human papillomavirus (HPV) infection. The incidence and prevalence of AIN and anal cancer are increasing rapidly in HIV-positive men who have sex with men (MSM). Other groups like HIV-negative MSM, immunosuppressed patients and people affected by other HPV diseases like genital warts and cervical intraepithelial neoplasia (CIN) may also develop AIN. The condition is complicated by its multicentric and multifocal nature and high rates of relapse and morbidity. Targeted excisions using ablative treatments such as cautery, infrared coagulation (IRC) and cryotherapy have been used as first-line therapeutic strategies, and there are many other options. There is no consensus about the optimal management of AIN.


To evaluate the effects of therapeutic interventions for anal canal intraepithelial neoplasia (AIN).

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4), MEDLINE and EMBASE (to October 2011). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and contacted experts in the field and manufacturers of any AIN and HPV-specific treatments.

Selection criteria: 

Randomized controlled trials (RCTs) that assessed any type of intervention for AIN.

Data collection and analysis: 

Two review authors independently abstracted data and assessed risk of bias. If it was possible, the data were synthesised in a meta-analysis.

Main results: 

We found only one RCT, which included 53 patients, that met our inclusion criteria. This trial reported data on imiquimod versus placebo. There was no statistically significant difference in the risk of disease cure but there was a trend for imiquimod to downgrade the AIN to a low-risk stage. The lack of statistical power of the trial may be due to the small number of patients in each group. The risk of bias was estimated as moderate.