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Anal cancer (squamous cell carcinoma)

An HPV-caused cancer of the anal canal that is usually cured without surgery by combined chemotherapy and radiation. Prevention (HPV vaccination, screening of high-risk groups) and immunotherapy for advanced disease are the new fronts.

Anal squamous cell carcinoma is an HPV-driven cancer (HPV16 in most), biologically closer to cervical cancer than to rectal adenocarcinoma. Risk factors are HPV persistence, HIV, immunosuppression, receptive anal intercourse and smoking; high-grade anal intraepithelial neoplasia is the precursor, and the ANCHOR trial (2022) showed treating it in people with HIV cuts progression to cancer by more than half.

Definitive chemoradiation with mitomycin and 5-fluorouracil (Nigro regimen 1974; ACT II confirmed mitomycin-5-FU and no benefit of maintenance) cures ~70-80% and preserves the sphincter; salvage abdominoperineal resection is reserved for persistent or recurrent disease. Metastatic disease was treated with carboplatin-paclitaxel (InterAAct, 2020); PD-1 blockade showed activity in refractory disease (nivolumab NCI9673, pembrolizumab KEYNOTE-158), and POD1UM-303 (2024) established retifanlimab plus carboplatin-paclitaxel as first-line standard (FDA approval 2025). Response-adapted radiotherapy dose (PLATO trials) and ctHPV DNA monitoring are being developed.

State of the art today

  • Chemoradiation cures most patients with sphincter preservation; the 1974 Nigro insight still holds.
  • ANCHOR proved that anal cancer is preventable in the highest-risk group by screening and treating precancer.
  • Retifanlimab-chemotherapy is the first immunotherapy standard in first-line metastatic disease.
  • Radiotherapy dose de-escalation for small tumours and escalation for bulky disease (PLATO) is under test.
Who it affects

About 50,000 cases per year worldwide and rising ~2-3% a year in high-income countries; over 90% caused by HPV; higher in people living with HIV and in women.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Precancer (HSIL) in people with HIV

Screening with anal cytology / high-resolution anoscopy and treatment of HSIL (ablation, topical therapy) reduces progression to cancer by 57% (ANCHOR).

ANCHOR (NEJM 2022)
HPV DNA testing and self-samplingThermal ablation and cryotherapy for cervical precancerHPV & HBV vaccination
Localised (stage I-III)

Definitive IMRT chemoradiation with concurrent mitomycin + 5-FU (or capecitabine); small T1 perianal lesions may be excised; assess response at 26 weeks before declaring failure (ACT II).

NCCN · Category 1 (5-FU/mitomycin + RT)
Mitomycin CFluorouracil (5-FU)IMRT / IGRT (modern external beam)
Persistent or recurrent local disease

Salvage abdominoperineal resection with permanent colostomy; flap reconstruction.

Robotic & minimally invasive surgery
Metastatic, first line

Retifanlimab + carboplatin-paclitaxel (POD1UM-303, PFS and OS benefit); carboplatin-paclitaxel alone if immunotherapy contraindicated.

NCCN · Category 1
RetifanlimabCarboplatinPaclitaxel / nab-paclitaxel
Metastatic, later lines

Nivolumab or pembrolizumab if not previously given; clinical trials.

NCCN · Category 2A
NivolumabPembrolizumab

Subtypes & biomarkers

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Subtypes
Biomarkers clinicians test
  • HPV / p16 status
  • HIV status and CD4 count
  • T and N stage (MRI, PET-CT)
  • PD-L1 (not required)
  • ctHPV DNA (emerging)
  • Anal cytology / high-resolution anoscopy (screening in high-risk groups)

Target prevalence in this cancer

History

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  1. 1974Nigro: chemoradiation instead of surgery

    Three patients with complete response to 5-FU, mitomycin and radiation; abdominoperineal resection abandoned as first treatment.

    Fluorouracil (5-FU)Mitomycin C
  2. 1996UKCCCR ACT I and EORTC: chemoradiation beats radiation alone
  3. 2013ACT II: mitomycin-5-FU standard; no maintenance benefit
    Mitomycin CFluorouracil (5-FU)
  4. 2017Nivolumab active in refractory disease (NCI9673)
    Nivolumab
  5. 2020InterAAct: carboplatin-paclitaxel first-line standard
    CarboplatinPaclitaxel / nab-paclitaxel
  6. 2022ANCHOR: treating HSIL prevents anal cancer in people with HIV
    Thermal ablation and cryotherapy for cervical precancer
  7. 2024POD1UM-303: retifanlimab + chemotherapy improves PFS/OS

    FDA approval 2025.

    Retifanlimab

Pipeline

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Not mapped hereAnti-PD-1 monoclonal antibody (IgG4)
Retifanlimab · Zynyz
Circulating tumour HPV DNA (ctHPV-DNA)HPV & HBV vaccination

Open problems

  • Screening programmes for high-risk groups exist almost nowhere despite ANCHOR.
  • Late toxicity of pelvic chemoradiation (bowel, sexual, bone).
  • HPV-negative anal cancer does poorly.
  • Stigma and delayed diagnosis.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Anal cancer (squamous cell carcinoma)
condition: Anal cancer
Open on ClinicalTrials.gov →

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

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Anal cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 17 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example HPV / p16 status, HIV status and CD4 count, T and N stage, PD-L1, ctHPV DNA), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Anal canal SCC, Perianal skin SCC, HPV-negative anal SCC.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Precancer (HSIL) in people with HIV

  1. For my situation (precancer (hsil) in people with hiv), which of the standard options do you recommend and why?
    Why: Guideline options include: Screening with anal cytology / high-resolution anoscopy and treatment of HSIL (ablation, topical therapy) reduces progression to cancer by 57% (ANCHOR).

Localised (stage I-III)

  1. For my situation (localised (stage i-iii)), which of the standard options do you recommend and why?
    Why: Guideline options include: Definitive IMRT chemoradiation with concurrent mitomycin + 5-FU (or capecitabine); small T1 perianal lesions may be excised; assess response at 26 weeks before declaring failure (ACT II).
  2. Am I a candidate for Mitomycin C, Fluorouracil (5-FU), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Persistent or recurrent local disease

  1. For my situation (persistent or recurrent local disease), which of the standard options do you recommend and why?
    Why: Guideline options include: Salvage abdominoperineal resection with permanent colostomy; flap reconstruction.

Metastatic, first line

  1. For my situation (metastatic, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: Retifanlimab + carboplatin-paclitaxel (POD1UM-303, PFS and OS benefit); carboplatin-paclitaxel alone if immunotherapy contraindicated.
  2. Am I a candidate for Retifanlimab, Carboplatin, Paclitaxel / nab-paclitaxel, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, later lines

  1. For my situation (metastatic, later lines), which of the standard options do you recommend and why?
    Why: Guideline options include: Nivolumab or pembrolizumab if not previously given; clinical trials.
  2. Am I a candidate for Nivolumab, Pembrolizumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

  1. Are there clinical trials I could join, for example of Retifanlimab, Circulating tumour HPV DNA (ctHPV-DNA), HPV & HBV vaccination?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. 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.
  3. 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.
  4. I read that “Screening programmes for high-risk groups exist almost nowhere despite ANCHOR”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Late toxicity of pelvic chemoradiation (bowel, sexual, bone)”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

11
Circulating tumour HPV DNA (ctHPV-DNA)Cytotoxic chemotherapyHIPEC / PIPAC (intraperitoneal chemotherapy)HPV & HBV vaccinationHPV DNA testing and self-samplingImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Intravesical therapy (BCG, chemotherapy, devices, gene and viral therapy)Platinum agentsRobotic & minimally invasive surgeryThermal ablation and cryotherapy for cervical precancer

targets

2
PD-1PD-L1

drugs

8
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
Not mapped hereFluoropyrimidine antimetabolite
Fluorouracil (5-FU) · Adrucil / Efudex
Not mapped hereAlkylating antibiotic (bioreductive)
Mitomycin C · Mutamycin / Jelmyto / Zusduri
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedProphylactic vaccine (virus-like particles)
Nonavalent HPV vaccine · Gardasil 9
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Not mapped hereAnti-PD-1 monoclonal antibody (IgG4)
Retifanlimab · Zynyz

companies

3
Bristol Myers SquibbIncyteMerck & Co. (MSD)

pathways

2
Oncogenic virusesPD-1 / PD-L1 immune checkpoint & T-cell activation

terms

2
Clinical complete response (cCR)HPV-positive (p16) head and neck cancer

people

1
Harald zur Hausen

Latest papers

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Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Anal cancer" OR ABSTRACT:"Anal cancer" OR TITLE:"squamous cell carcinoma" OR ABSTRACT:"squamous cell carcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Anal cancer (squamous cell carcinoma), not a curated reading list.

Connected

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technologies

8
Circulating tumour HPV DNA (ctHPV-DNA)Cytotoxic chemotherapyHPV & HBV vaccinationHPV DNA testing and self-samplingImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Robotic & minimally invasive surgeryThermal ablation and cryotherapy for cervical precancer

targets

2
PD-1PD-L1

drugs

8
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
Not mapped hereFluoropyrimidine antimetabolite
Fluorouracil (5-FU) · Adrucil / Efudex
Not mapped hereAlkylating antibiotic (bioreductive)
Mitomycin C · Mutamycin / Jelmyto / Zusduri
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedProphylactic vaccine (virus-like particles)
Nonavalent HPV vaccine · Gardasil 9
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Not mapped hereAnti-PD-1 monoclonal antibody (IgG4)
Retifanlimab · Zynyz

companies

3
Bristol Myers SquibbIncyteMerck & Co. (MSD)

pathways

2
Oncogenic virusesPD-1 / PD-L1 immune checkpoint & T-cell activation

terms

2
Clinical complete response (cCR)HPV-positive (p16) head and neck cancer

people

1
Harald zur Hausen