Anal intraepithelial neoplasia

Anal intraepithelial neoplasia (AIN) is a premalignant squamous lesion of the anal mucosa, most often caused by persistent human papillomavirus (HPV) infection, particularly HPV 16. The high-grade form of AIN, high-grade squamous intraepithelial lesion (HSIL; AIN II–III), is the direct precursor to anal cancer and is especially prevalent in groups at high risk, such as people living with HIV. At-risk individuals are screened with anal cytology, high-risk HPV testing, or both, with high-resolution anoscopy (HRA) and biopsy used to confirm the diagnosis. Ablative therapy is the most common treatment and significantly reduces the progression to cancer compared with observation. Periodic HRA monitoring is required to detect and manage recurrence.

• Pathogen: human papillomavirus (HPV), particularly HPV 16 ^[1]
• Risk factors ^[1]
  • HIV infection
  • Immunosuppression (e.g., following solid-organ transplantation)
  • History of other HPV-associated diseases
  • History of receptive anal intercourse
  • Smoking
  • History of anal fissures or fistulas

A two-tiered system is used to classify the grade of AIN. ^[1][2]

• Low-grade squamous intraepithelial lesion
  • Corresponds to grade AIN I
  • Not premalignant but has the potential to progress to HSIL
• HSIL
  • Corresponds to grades AIN II and AIN III
  • Premalignant precursor to anal cancer

See “Screening for anal cancer” for details.

Indications ^[3]

• Offer screening to individuals at risk of AIN, e.g.:
  • People living with HIV
  • Men who have sex with men
  • Transgender women
  • Solid-organ transplant recipients
  • Individuals with a history of vulvar precancer or cancer
• Consider screening individuals aged ≥ 45 years with a history of :
  • Cervical or vaginal HSIL or cancer
  • Perianal warts
  • Persistent (> 1 year) cervical HPV 16 infection
  • Autoimmune conditions

Screening methods ^[3]

• Anal cytology, high-risk HPV testing, or both
• Digital rectal examination at all screening visits

Diagnostics for anal cancer are discussed separately.

High-resolution anoscopy ^[2]

• Indication: follow-up after an abnormal screening test to localize the source of atypical cells
• Procedure
  • Examination of the anal canal and perianal skin with a colposcope
  • Application of 3–5% acetic acid: Abnormal epithelium appears white.
  • Application of Lugol's iodine: Dysplastic lesions typically do not stain.
  • Biopsy of suspicious lesions under direct visualization
• Histopathology ^[2]
  • Nuclear pleomorphism
  • Numerous mitoses
  • Lack of epithelial maturation

Treatment of anal cancer is discussed separately.

General principles ^[1]

• Expectant management may be considered for patients with LSIL. ^[4]
• Refer to a specialist (e.g., gastroenterologist, colorectal surgeon) for active treatment of HSIL. ^[2]
• Periodic HRA is necessary to detect and treat any recurrence.

Progression to anal cancer in patients with HSIL is 57% lower with treatment compared to active monitoring. ^[1]

Treatment modalities ^[1][2]

• Ablative therapy (most common approach)
• Topical therapy (e.g., trichloroacetic acid, imiquimod, 5-fluorouracil)
• Surgical excision (rare)

A larger lesion size is associated with an increased risk of progression to anal cancer. ^[1]

• Educate all individuals on prevention of HPV infection.
• Offer HPV vaccination to all eligible individuals.