Key messages
• Several treatments for anal intraepithelial neoplasia (AIN) are available. None has been proven better in terms of removing AIN or preventing the return of the disease.
• Overall, few people with AIN will develop anal cancer. However, people receiving treatment for AIN have a lower risk of developing anal cancer.
What is anal intraepithelial neoplasia?
Anal intraepithelial neoplasia (AIN) is a rare condition in the anal skin or anal mucosa (the moist tissue that lines the anal canal) caused by infection with human papillomavirus. However, certain population groups have a higher risk of AIN, including people living with HIV, men who have sex with men, and immunosuppressed people (i.e. when the immune system is weaker than normal). AIN is most often without symptoms, but may lead to itching, bleeding, or the sensation of an anal mass. AIN is not cancer, but the abnormal cells are believed to be able to develop into anal cancer (squamous cell carcinoma).
How is anal intraepithelial neoplasia treated?
There are several treatments for AIN. It can be removed surgically or destroyed with heat by infrared coagulation or electrocauterisation devices (i.e. tools that use heat or electricity to safely burn, seal, or destroy tissue). AIN can also be treated with topical ointments (locally applied gels or creams) with imiquimod, a medication that stimulates the immune system, or topical fluorouracil ointment, which stops the growth of the AIN cells.
What did we want to find out?
We wanted to find out which treatments are best to remove AIN, prevent the development of anal cancer, and remove human papillomavirus. We also wanted to know if the treatments cause any unwanted effects.
What did we do?
We searched for studies that investigated and compared different treatments for AIN and the development of cancer. We compared and summarised the results, and rated our confidence in the evidence, based on factors such as study methods, precision, and study sizes.
What did we find?
We found five studies eligible for inclusion, involving 4907 participants. All participants in the studies were people living with HIV. Most were men with a median age of 45 to 51 years. The studies were conducted in the USA, Spain, the UK, and the Netherlands.
The main results came from one study comparing high-resolution anoscopy-guided treatments (where a powerful magnifying device is used to spot problem areas in or around the anus) to active monitoring. The study included 4446 participants, and its main focus was the development of anal cancer. Researchers found that the number of people with AIN who develop anal cancer is low, but also that people who received treatment for AIN had a lower risk of developing anal cancer than those in the active monitoring group. However, the evidence is very uncertain.
The study also asked 124 people about their health-related quality of life while they participated in the study. Researchers found that those in the active monitoring group reported a worsening in psychological functioning in the 28 days after joining the study, whereas people in the treatment group reported no change in quality of life measures in the same timeframe. However, the evidence is very uncertain.
Two per cent (43 of 2227) of participants in the treatment group and 0.2% (4 of 2219) in the active monitoring group reported unwanted events, mostly mild pain. However, the evidence is very uncertain.
The study did not assess other important outcomes we were interested in, including the removal of AIN, the removal of human papillomavirus, whether AIN became less severe, or the recurrence of AIN.
Details about treatments and results in the other four studies are available in the review.
What are the limitations of the evidence?
We are not confident in the evidence because all participants in the studies were people living with HIV, whereas the question we wanted to answer was broader. The studies also did not assess all the outcomes we were interested in.
How current is this evidence?
This review updates the previous Cochrane review of treatments for anal canal intraepithelial neoplasia. This evidence is current to April 2025.