Anal intraepithelial neoplasia

AIN; anal squamous intraepithelial lesion (anal SIL); AIN1 = LSIL; AIN2/3 = HSIL; perianal Bowen's disease

Anal intraepithelial neoplasia (AIN) is squamous intraepithelial dysplasia of the anal canal and perianal skin driven, in the great majority of cases, by high-risk human papillomavirus — most commonly HPV-16. The 2012 LAST consensus reclassified AIN1 as low-grade SIL (LSIL — usually transient HPV cytopathic effect) and AIN2/3 as high-grade SIL (HSIL — the true precursor of invasive anal SCC). The condition is markedly over-represented in HIV-positive men who have sex with men, in whom multifocal high-grade disease is the norm and progression to invasive anal SCC reaches ~1% per year. The 2022 ANCHOR trial demonstrated that treatment of HSIL in HIV-positive adults reduces invasive anal cancer by ~46% (intention-to-treat hazard reduction) / ~57% (per-protocol). UK practice now embraces HSIL screening for high-risk groups using high-resolution anoscopy and treatment of detected HSIL with imiquimod, infrared coagulation, electrocautery or surgical excision, with HPV vaccination as primary prevention.

CurrentLast reviewed 26 April 2026

Terminology (LAST 2012)

LSIL (AIN1) — basal-third atypia; usually transient HPV-related; low progression risk.
HSIL (AIN2/3) — full-thickness or near-full-thickness atypia; the true precursor of invasive anal SCC; treatment indicated.
p16 immunohistochemistry strongly diffuse positive supports HSIL classification of borderline cases.
"Perianal Bowen's disease" describes HSIL on the keratinised perianal skin (outside the anal verge); same biology, same management principles.

Risk groups

HIV-positive men who have sex with men (MSM) — highest risk; anal HSIL prevalence 30–50%.
HIV-positive women.
HIV-negative MSM.
Women with high-grade cervical / vulval / vaginal intraepithelial neoplasia or invasive cancer.
Solid-organ transplant recipients.
Smokers.
Immunosuppression (autoimmune disease therapy, primary immunodeficiency).

Clinical features

Most patients are asymptomatic.
Pruritus, soreness, bleeding, tenesmus or discharge in some.
Lesions: white (acetowhite after acetic acid), red, pigmented or warty plaques on the anal canal squamocolumnar junction or perianal skin.
Frequently multifocal in immunocompromised / HIV-positive patients.
Examine the entire anogenital area (vulva, vagina, cervix, penis, scrotum, perianal) — synchronous lesions common.

Diagnosis

High-resolution anoscopy (HRA) — the gold standard. After application of acetic acid and Lugol's iodine, the squamocolumnar junction is examined under colposcopic magnification; suspicious lesions are biopsied.
Anal cytology (cytobrush) — adjunctive screening, similar to cervical cytology; abnormal results trigger HRA.
HPV typing (high-risk HPV especially HPV-16) supports diagnosis.
HIV testing if not already known.
Cervical / vulval examination in women.

Management

HSIL (AIN2/3): active treatment is preferred over watchful waiting, particularly in HIV-positive patients (ANCHOR trial 2022).
- Topical imiquimod 5% 3 nights/week for 12–16 weeks — 50–60% complete response.
- Topical 5-fluorouracil — alternative.
- Infrared coagulation (IRC) in clinic under HRA guidance.
- Electrocautery, CO₂ laser, cryotherapy.
- Surgical excision for unifocal accessible lesions.
- Combination / sequential approaches for multifocal disease.
LSIL (AIN1): surveillance only.
HPV vaccination — primary prevention; emerging evidence for therapeutic / secondary prevention of recurrence post-treatment.
Discuss with anal dysplasia / colorectal MDT in HIV-positive or recurrent cases.

Surveillance

HIV-positive MSM and other high-risk groups — annual HRA; lifelong.
Post-treatment HSIL — 6-monthly HRA for 2 years, then annually.
Smoking cessation.
HIV viral suppression and immune reconstitution.