# Anal high-grade squamous intraepithelial lesions (precursor)

Source: https://onco.cc/cancers/anal-hsil-precursor/  
OnCo record `anal-hsil-precursor` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Anal HSIL; High-grade anal intraepithelial neoplasia; AIN 2 to 3; Anal dysplasia; Anal precancer
- Tags: subtype-page; gastrointestinal
- Group: gastrointestinal
- Burden: 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.
- Subtypes: Anal canal HSIL (HPV 16 in most, p16 positive); Perianal HSIL (perianal skin, treated with topical agents or excision); HSIL in people living with HIV (highest progression risk, ANCHOR population); HSIL in women with prior cervical or vulvar HPV disease; Low-grade squamous intraepithelial lesion (LSIL, AIN 1, not a cancer precursor in itself)
- Biomarkers: Anal cytology (screening); High-resolution anoscopy with biopsy (diagnosis); p16 immunohistochemistry (confirms HSIL); HPV 16 typing (highest progression risk, investigational triage); HIV status and CD4 count; Host and viral DNA methylation markers (investigational)

## Standard of care

- Screening: 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. ([HPV DNA testing and self-sampling](https://onco.cc/technologies/hpv-testing/), [HPV-positive (p16) head and neck cancer](https://onco.cc/terms/hpv-p16/), [Circulating tumour HPV DNA (ctHPV-DNA)](https://onco.cc/technologies/cthpv-dna/))
- Treatment of HSIL: 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). ([Thermal ablation and cryotherapy for cervical precancer](https://onco.cc/technologies/precancer-ablation/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/))
- Prevention: HPV vaccination, which protects against the HPV types that cause almost all anal cancer. ([HPV & HBV vaccination](https://onco.cc/technologies/hpv-vaccine/), [Nonavalent HPV vaccine](https://onco.cc/drugs/gardasil-9/))
- After treatment: Repeat high-resolution anoscopy because recurrence is common; biopsy of any lesion that changes or ulcerates. ([HPV DNA testing and self-sampling](https://onco.cc/technologies/hpv-testing/), [HPV-positive (p16) head and neck cancer](https://onco.cc/terms/hpv-p16/))

## State of the art

- ANCHOR is the first randomised proof that treating an HPV precancer outside the cervix prevents cancer.
- Screening programmes for people living with HIV now have guideline backing, though high-resolution anoscopy capacity is the limiting step.
- HPV vaccination prevents the infection that starts the whole sequence.

## Open problems

- Most HSIL never progresses, and no marker yet says which lesions to treat and which to watch.
- High-resolution anoscopy is scarce outside specialist centres.
- Recurrence after ablation is common and the best retreatment strategy is untested.
- Whether screening helps people at high risk who do not have HIV is unproven.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Anal_cancer
- ANCHOR (NEJM 2022): https://doi.org/10.1056/NEJMoa2201048
- IANS screening guidelines 2024: https://doi.org/10.1002/ijc.34850
- Wikipedia: https://en.wikipedia.org/wiki/Anal_cancer

## Connected records

- cancers: [Anal cancer (squamous cell carcinoma)](https://onco.cc/cancers/anal/), [Localised anal squamous cell carcinoma (stage I to III)](https://onco.cc/cancers/localised-anal-cancer/), [Metastatic and recurrent anal squamous cell carcinoma](https://onco.cc/cancers/metastatic-anal-cancer/)
- technologies: [Circulating tumour HPV DNA (ctHPV-DNA)](https://onco.cc/technologies/cthpv-dna/), [HPV & HBV vaccination](https://onco.cc/technologies/hpv-vaccine/), [HPV DNA testing and self-sampling](https://onco.cc/technologies/hpv-testing/), [Thermal ablation and cryotherapy for cervical precancer](https://onco.cc/technologies/precancer-ablation/)
- drugs: [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Nonavalent HPV vaccine](https://onco.cc/drugs/gardasil-9/)
- terms: [Cervical precancer (CIN, HSIL/LSIL)](https://onco.cc/terms/cin-hsil/), [HPV status (HPV-positive / HPV-negative)](https://onco.cc/terms/hpv-status/), [HPV-positive (p16) head and neck cancer](https://onco.cc/terms/hpv-p16/)
- key papers: [ANCHOR: treating anal high-grade squamous intraepithelial lesions to prevent anal cancer in people living with HIV](https://onco.cc/key-papers/paper-anchor-anal-hsil-treatment-nejm-2022/), [International Anal Neoplasia Society consensus guidelines for anal cancer screening](https://onco.cc/key-papers/paper-ians-anal-cancer-screening-guidelines-ijc-2024/)

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