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.
Baca abstrak penuh
Anal intraepithelial neoplasia (AIN) is a dysplasia of the anal transitional epithelium that is associated with human papillomavirus (HPV) infection. High-grade lesions have the potential to develop into anal cancer. The incidence and prevalence of AIN and anal cancer has been increasing over the last decades. Certain groups – including people living with HIV, men who have sex with men (MSM), and those with suppressed immune systems – are at high risk of developing AIN. Targeted excisions using ablative treatments such as electrocauterisation, infrared coagulation, or cryotherapy have been used as first-line therapeutic strategies. Other options include topical treatment with immunomodulators such as imiquimod or cytostatics such as fluorouracil. Ideally, treatment of AIN should have a low risk of complications and result in a low risk of recurrence. This is the first update of a review originally published in 2012.
Matlamat
To assess the effects of any therapeutic intervention for anal intraepithelial neoplasia, regardless of gender, age, and comorbidity.
Kaedah Pencarian
We used CENTRAL, MEDLINE, Embase, and five trials registers, together with reference checking, citation searching and contact with study authors to identify the studies that are included in the review. The latest search date was 16 April 2025.
Kriteria Pemilihan
We included randomised controlled trials (RCTs) that assessed any type of intervention for AIN. We excluded cluster-randomised and cross-over trials. We excluded people with a histological diagnosis of anal carcinoma, Paget's disease, or Bowenoid papulosis.
Pengumpulan Data dan Analisis
We used standard methodological procedures expected by Cochrane. Our primary outcomes of interest were: AIN eradication (defined by the absence of histologic criteria OR the presence of a normal epithelium or scarring OR the complete absence of dysplasia); development of anal cancer; and human papillomavirus (HPV) eradication. We assessed the certainty of the evidence using GRADE.
Keputusan Utama
Five RCTs met our inclusion criteria, randomising a total of 4907 participants. All included participants were adults living with HIV with a CD4 cell count above 300 cells/μL. The median participant age ranged from 45 to 51 years. Most participants were male. Two studies were multicentre, both conducted in the USA. The remaining studies were conducted in outpatient clinics in Spain, the Netherlands, and the UK. We considered the overall risk of bias as high in one study and moderate in four. The main reasons for concerns of bias were open-label design and high dropout rates.
All studies had different interventions and outcomes, precluding meta-analysis. The inclusion of two multi-armed studies means that we synthesised evidence for nine separate comparisons. Here, we summarise only the results from the largest study, with 4459 randomised participants, comparing high-resolution anoscopy-guided treatment to active monitoring. We summarise results from the other studies in the main review.
The study comparing high-resolution anoscopy (HRA)-guided treatment to active monitoring did not assess four of the review's outcomes of interest: AIN eradication, HPV eradication, histological downgrading of AIN lesions, and recurrence of AIN. Results for the three remaining outcomes – development of anal cancer, quality of life, and adverse events – are as follows.
In the HRA-guided treatment group, four per 1000 (0.4%) participants developed anal cancer, while in the active monitoring group, nine per 1000 (0.9%) participants developed anal cancer, with a median follow-up of 25 to 28 months (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.20 to 0.93; P = 0.03; 1 study, 4446 participants; very low-certainty evidence).
In the active monitoring group, there was an increased impact on psychological functions from inclusion to 28 days after inclusion. In the treatment group, there was no difference in physical symptoms, impact on physical functioning, or impact on psychological functioning from inclusion to 28 days after inclusion.
Two per cent of participants in the treatment arm and 0.2% in the active monitoring arm reported adverse events. Most adverse events were mild pain (RR 10.7, 95% CI 3.85 to 29.79; P < 0.001; 1 study, 4446 participants; very low-certainty evidence).
Kesimpulan Pengarang
All included studies focused on people living with HIV. This may limit the applicability of the results to HIV-negative people. We assessed the certainty of evidence as very low for all outcomes across all nine comparisons, highlighting a lack of high-quality evidence on interventions for AIN.
Our findings suggest that HRA-guided treatment may lower anal cancer risk, but the evidence is very uncertain.
We evaluated the efficacy of cidofovir, sinecatechins, infrared coagulation, HRA-guided electrocautery, imiquimod, and fluorouracil in eradicating AIN. With eradication rates between 14% and 62% and follow-up periods ranging from four weeks to 33 months, the evidence on the effectiveness of these treatments is very uncertain.
Further studies on interventions for AIN with sufficient power and duration are required to determine the efficacy of interventions. Studies addressing treatments in HIV-negative cohorts are also needed.
