Anal high-grade squamous intraepithelial lesions (precursor)
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.
Overview
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.
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.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowBlood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
- Check before combiningFood and drink: Fluorouracil (5-FU)
Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
- Check before combiningKidneys: Fluorouracil (5-FU)
Capecitabine: reduce to 75% for CrCl 30-50; contraindicated below 30.
See all on the product pages:Fluorouracil (5-FU)·Printable cards in the navigator
Anatomy and lymph node drainage
- Right colon (MSI-high, BRAF commoner)
- Left colon and sigmoid
- Rectum
- Anal canal (HPV squamous)
- Appendix
- Peritoneum and omentum (mesothelioma, peritoneal spread)
- Nodes: pericolic
- Nodes: mesenteric root
- Nodes: para-aortic
- Nodes: mesorectal
- Nodes: lateral pelvic and inguinal (anal)
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.
- Right colon (MSI-high, BRAF commoner)
- Left colon and sigmoid
- Rectum
- Anal canal (HPV squamous)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)
- Appendix
- Peritoneum and omentum (mesothelioma, peritoneal spread)
- pericolic
- mesenteric root
- para-aortic
- mesorectal
- lateral pelvic and inguinal (anal)
Same organ: 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
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.
- HPV & HBV vaccinationStandard of care
- HPV DNA testing and self-samplingStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
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.
Subtypes & biomarkers
top- 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)
- 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)
How often this target appears
- 2006Quadrivalent HPV vaccine approved; later trials show protection against anal precancer
- 2012Lower Anogenital Squamous Terminology (LAST) unifies HSIL and LSIL across anogenital sites
- 2022ANCHOR: treating anal HSIL in people living with HIV cuts progression to anal cancer by 57 percent
- 2024International Anal Neoplasia Society screening guidelines for people at high risk
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 5 changes by month →- 2026-09-18This recordAnal high-grade squamous intraepithelial lesions (precursor)Facts on this page last checked
When this page itself was last checked or edited.
- 2024MilestoneHPV DNA testing and self-samplingInternational Anal Neoplasia Society screening guidelines for people at high risk
A milestone in how this cancer is treated.
- 2022MilestoneThermal ablation and cryotherapy for cervical precancerANCHOR: treating anal HSIL in people living with HIV cuts progression to anal cancer by 57 percent
A milestone in how this cancer is treated.
- 2012MilestoneHPV-positive (p16) head and neck cancerLower Anogenital Squamous Terminology (LAST) unifies HSIL and LSIL across anogenital sites
A milestone in how this cancer is treated.
- 2006MilestoneHPV & HBV vaccinationQuadrivalent HPV vaccine approved; later trials show protection against anal precancer
A milestone in how this cancer is treated.
What is in development for Anal high-grade squamous intraepithelial lesions (precursor), drawn from the whole corpus: 0 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Nothing recorded in development for this cancer yet.
Open problems and what is being done
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.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable now- Circulating tumour HPV DNA (ctHPV-DNA)Established
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Treatment journeys · Survivorship planner.
Whether screening helps people at high risk who do not have HIV is unproven.
and how the field plans to fix it →What is being done about thisFinding cancer earlierAvailable now- HPV & HBV vaccinationStandard of care
- HPV DNA testing and self-samplingStandard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Expert centres
topExpert centres
Wuhan · hospital | China | none recorded | 0 | 2,478 | 31,527 | - | |
Heidelberg · research institute | Germany | none recorded | 0 | 2,202 | 32,575 | - | |
New Delhi · government | India | none recorded | 0 | 2,028 | 15,043 | - | |
Bethesda, MD · government | United States | none recorded | 0 | 1,312 | 26,262 | - | |
Leiden · university | Netherlands | none recorded | 0 | 1,245 | 16,125 | - | |
L'Hospitalet de Llobregat · cancer center | Spain | 0 | 988 | 14,310 | - | ||
Oakland, CA · research institute | United States | none recorded | 0 | 908 | 10,296 | - | |
New Delhi · hospital | India | none recorded | 0 | 880 | 5,143 | - | |
Taipei · hospital | Taiwan | none recorded | 0 | 746 | 8,966 | - | |
Chennai · cancer center | India | none recorded | 0 | 691 | 13,919 | - | |
Geneva · government | Switzerland | none recorded | 0 | 599 | 45,298 | - | |
Rio de Janeiro · government | Brazil | none recorded | 0 | 364 | 2,172 | - | |
Vancouver, BC · cancer center | Canada | none recorded | 0 | 305 | 2,733 | - | |
Ljubljana · cancer center | Slovenia | none recorded | 0 | 187 | 2,566 | - | |
Barretos · cancer center | Brazil | none recorded | 0 | 178 | 1,511 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Anal high-grade squamous intraepithelial lesions but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Anal high-grade squamous intraepithelial lesions
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Anal cytology, High-resolution anoscopy with biopsy, p16 immunohistochemistry, HPV 16 typing, HIV status and CD4 count), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Anal canal HSIL, Perianal HSIL, HSIL in people living with HIV.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Screening
- For my situation (screening), which of the standard options do you recommend and why?Why: Guideline options include: 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.
Treatment of HSIL
- For my situation (treatment of hsil), which of the standard options do you recommend and why?Why: Guideline options include: 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).
- Am I a candidate for Fluorouracil (5-FU), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Prevention
- For my situation (prevention), which of the standard options do you recommend and why?Why: Guideline options include: HPV vaccination, which protects against the HPV types that cause almost all anal cancer.
- Am I a candidate for Nonavalent HPV vaccine, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
After treatment
- For my situation (after treatment), which of the standard options do you recommend and why?Why: Guideline options include: Repeat high-resolution anoscopy because recurrence is common; biopsy of any lesion that changes or ulcerates.
Any stage
- Are there clinical trials I could join, for example of Circulating tumour HPV DNA (ctHPV-DNA), HPV & HBV vaccination, HPV DNA testing and self-sampling?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Most HSIL never progresses, and no marker yet says which lesions to treat and which to watch”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “High-resolution anoscopy is scarce outside specialist centres”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Anal high-grade squamous intraepithelial lesions, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
5drugs
2companies
2terms
3key papers
2For 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.
Latest papers
topQuery 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.
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