Management of High‑Grade Anal Intraepithelial Neoplasia (AIN) in People Living with HIV

Evaluation and Diagnosis

Digital rectal examination (DRE) is essential for detecting anal lesions and should be performed in every patient with suspected AIN. – NCCN Guidelines (expert consensus) 4
High‑resolution anoscopy (HRA) with targeted biopsy is mandatory in high‑risk groups (e.g., PLWH, transplant recipients) to exclude invasive cancer and confirm the AIN diagnosis. – NCCN Guidelines (expert consensus) 4
Histologic confirmation by biopsy of any suspicious lesion is required before initiating treatment. – NCCN Guidelines (expert consensus) 4
Anal cytology is an effective screening tool for AIN in high‑risk populations, although its diagnostic performance is highly operator‑dependent. – NCCN Guidelines (expert consensus) 1
Screening programs have not yet demonstrated a mortality benefit for anal cancer in randomized trials, making the overall benefit of routine screening uncertain. – NCCN Guidelines (expert consensus) 1
HIV testing should be considered in patients presenting with recurrent or multifocal AIN lesions. – Annals of Oncology (Level III evidence) 5
Women diagnosed with AIN should be screened concurrently for cervical, vulvar, and vaginal intra‑epithelial neoplasia. – NCCN Guidelines (expert consensus) 4

Topical or ablative therapy reduces progression to anal cancer by 57 % compared with active monitoring in PLWH with high‑grade AIN (9/4 459 vs 21/4 459 cases; median follow‑up 25.8 mo, p = 0.03). – Phase III randomized trial, Level I evidence 1
Electrocautery is superior to topical agents (imiquimod, 5‑fluorouracil) for overall clearance of AIN, based on a randomized trial of 246 HIV‑positive MSM. – Randomized trial, Level I evidence 1
Imiquimod shows a higher response rate for perianal AIN than for intra‑anal AIN. – Randomized trial, Level I evidence 1
Recurrence of AIN is common after any treatment modality, necessitating lifelong surveillance. – Phase III trial follow‑up, Level I evidence 1

People living with HIV (PLWH):
- HIV‑positive MSM have an 18 % conversion rate from high‑grade AIN to anal cancer over a median 2.3‑year follow‑up despite treatment. – Cohort data, Level II evidence 1
Solid‑organ transplant recipients:
- Initiate anal cancer screening 10 years after transplantation; incidence rises to 24.5–29.6 per 100 000 person‑years after this interval. – Cohort data, Level II evidence 2

Quadrivalent HPV vaccine provides 77.5 % efficacy in preventing grade 2/3 AIN among MSM aged 16–26 years. – Vaccine efficacy trial, Level I evidence 1
The 9‑valent HPV vaccine is projected to prevent an additional 464 anal cancer cases per year compared with the quadrivalent formulation. – Modeling study, Level II evidence 1

Given the high recurrence rates, patients treated for high‑grade AIN require intensive, long‑term follow‑up; the 57 % risk reduction still leaves a substantial residual cancer risk. – Phase III trial, Level I evidence 1

No randomized trial has yet shown that screening reduces anal‑cancer mortality; clinicians should convey this uncertainty when discussing screening benefits. – NCCN Guidelines (expert consensus) 1
Abnormal screening results can temporarily worsen health‑related quality of life in the weeks following testing. – Prospective QoL study, Level III evidence 5
The accuracy of both anal cytology and HRA is strongly dependent on the operator’s training and experience. – Observational study, Level III evidence 5