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Anal high-grade squamous intraepithelial lesions are the HPV-driven precancer that anal cancer grows from, found by screening people at high risk with cytology and high-resolution anoscopy. The ANCHOR trial showed that treating these lesions, mostly by ablation in the clinic, cuts the number that become anal cancer, so screening and treatment are now recommended for people living with HIV.
Anal high-grade squamous intraepithelial lesions (HSIL, formerly anal intraepithelial neoplasia grades 2 and 3) are the precursor of anal squamous cell carcinoma in the same way that cervical HSIL precedes cervical cancer, and are caused by the same persistent high-risk HPV types, above all HPV 16. They are commonest in people living with HIV, in transplant recipients and in women with a history of cervical, vaginal or vulvar HPV disease. They cause no symptoms and are found by anal cytology followed by high-resolution anoscopy with biopsy, the anal equivalent of colposcopy, and p16 immunohistochemistry helps the pathologist separate HSIL from low-grade change.
Whether treating HSIL prevents cancer was uncertain until the ANCHOR trial (New England Journal of Medicine 2022) randomised 4,459 people living with HIV to treatment or active monitoring: treatment, mostly office-based electrocautery or infrared coagulation with topical fluorouracil or imiquimod for extensive disease, reduced progression to anal cancer by 57 percent. On that evidence the 2024 International Anal Neoplasia Society guidelines recommend screening from age 35 for men who have sex with men and transgender women living with HIV and from 45 for other people with HIV, and HPV vaccination remains the primary prevention. Lesions recur often after treatment, so surveillance continues, and biomarkers such as HPV 16 typing and methylation markers are being studied to decide which lesions most need treatment.
Common in people living with HIV, especially men who have sex with men, and in women with a history of cervical or vulvar HPV disease; only a minority of lesions progress, but anal cancer rates in these groups are many times those of the general population.
Right-sided tumours behave differently from left-sided and rectal ones; the colon drains along its mesenteric vessels, the rectum into the mesorectum and pelvic side wall.
Same organ: Colon cancer (adenocarcinoma of the colon), Micropapillary adenocarcinoma of the colon and rectum, Adenoma-like adenocarcinoma of the colon and rectum, Lynch syndrome-associated colorectal cancer, Familial adenomatous polyposis-associated colorectal cancer, Mucinous adenocarcinoma of the colon and rectum, Signet ring cell carcinoma of the colon and rectum, Medullary carcinoma of the colon, Serrated adenocarcinoma of the colon and rectum, Peritoneal mesothelioma, Colorectal cancer, Rectal cancer, Mismatch-repair deficient (MSI-high) colorectal cancer, BRAF V600E-mutant colorectal cancer, HER2-amplified colorectal cancer, KRAS G12C-mutant colorectal cancer, Early-onset colorectal cancer (under 50), Anal cancer (squamous cell carcinoma), Appendiceal cancer and pseudomyxoma peritonei, Small intestine cancer (small bowel adenocarcinoma), Small intestinal neuroendocrine tumours, Localised anal squamous cell carcinoma (stage I to III), Metastatic and recurrent anal squamous cell carcinoma, Low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei, Appendiceal adenocarcinoma (mucinous and non-mucinous, including signet ring cell), Goblet cell adenocarcinoma of the appendix, Localised small bowel adenocarcinoma (stage I to III, resected), Advanced and metastatic small bowel adenocarcinoma
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Anal cytology or high-risk HPV testing followed by high-resolution anoscopy in people living with HIV and other high-risk groups, following the 2024 International Anal Neoplasia Society guidelines.
Office-based ablation (electrocautery, infrared coagulation) for discrete lesions; topical fluorouracil or imiquimod for extensive or perianal disease; excision for lesions where invasion is suspected (ANCHOR).
HPV vaccination, which protects against the HPV types that cause almost all anal cancer.
Repeat high-resolution anoscopy because recurrence is common; biopsy of any lesion that changes or ulcerates.
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For the first time clinicians have an agreed answer to who to screen for anal cancer and at what age, so that treatment of HSIL can reach the people most likely to benefit.
People living with HIV who have anal HSIL should be offered treatment rather than observation, and screening programmes to find those lesions are now justified. High-resolution anoscopy capacity is the limiting step.
Query for this cancer: (TITLE:"Anal high-grade squamous intraepithelial lesions" OR ABSTRACT:"Anal high-grade squamous intraepithelial lesions" OR TITLE:"precursor" OR ABSTRACT:"precursor" OR TITLE:"Anal HSIL" OR ABSTRACT:"Anal HSIL" OR TITLE:"High-grade anal intraepithelial neoplasia" OR ABSTRACT:"High-grade anal intraepithelial neoplasia" OR TITLE:"AIN 2 to 3" OR ABSTRACT:"AIN 2 to 3" OR TITLE:"Anal dysplasia" OR ABSTRACT:"Anal dysplasia") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Anal high-grade squamous intraepithelial lesions (precursor), not a curated reading list.
No targets or pathways are linked to this cancer yet. Browse the gene hub →
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
Capecitabine: reduce to 75% for CrCl 30-50; contraindicated below 30.
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