# Anal cancer (squamous cell carcinoma)

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

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; gastrointestinal; hpv
- Group: gastrointestinal
- Burden: 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.
- Subtypes: Anal canal SCC (HPV-positive, ~90%); Perianal skin SCC; HPV-negative anal SCC (worse prognosis, TP53-mutant); Anal adenocarcinoma (treated as rectal cancer); High-grade anal intraepithelial neoplasia (precursor)
- Biomarkers: 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/anal/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/anal/#overview [3 subtypes, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/anal/#what-it-is [8 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/anal/#finding-it [6 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/anal/#treating-it [5 settings, 1 regimen, 4 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/anal/#evidence [7 trials, 6 key papers, 7 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/anal/#science [7 targets, 2 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/anal/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/anal/#living-with-it [19 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/anal/coming/ [9 medicines, 7 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/anal/data/ [59 connected records]

## Standard of care

- 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). ([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/), [HPV & HBV vaccination](https://onco.cc/technologies/hpv-vaccine/), [ANCHOR](https://onco.cc/trials/anchor/))
- 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). ([Mitomycin C](https://onco.cc/drugs/mitomycin/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- Persistent or recurrent local disease: Salvage abdominoperineal resection with permanent colostomy; flap reconstruction. ([Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/))
- Metastatic, first line: Retifanlimab + carboplatin-paclitaxel (POD1UM-303, PFS and OS benefit); carboplatin-paclitaxel alone if immunotherapy contraindicated. ([Retifanlimab](https://onco.cc/drugs/retifanlimab/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [POD1UM-303/InterAACT-2](https://onco.cc/trials/pod1um-303/))
- Metastatic, later lines: Nivolumab or pembrolizumab if not previously given; clinical trials. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/))

## State of the art

- 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.

## 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Anal_cancer
- NCCN Guidelines: Anal Carcinoma: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1414
- ANCHOR (NEJM 2022): https://doi.org/10.1056/NEJMoa2201048
- NCI PDQ: anal cancer: https://www.cancer.gov/types/anal/patient/anal-treatment-pdq

## Connected records

- cancers: [Anal high-grade squamous intraepithelial lesions (precursor)](https://onco.cc/cancers/anal-hsil-precursor/), [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/), [Penile cancer](https://onco.cc/cancers/penile/), [Squamous cell carcinoma of the urethra](https://onco.cc/cancers/urethral-squamous-cell-carcinoma/), [Urethral cancer](https://onco.cc/cancers/urethral/), [Vaginal cancer](https://onco.cc/cancers/vaginal/)
- technologies: [Circulating tumour HPV DNA (ctHPV-DNA)](https://onco.cc/technologies/cthpv-dna/), [Colposcopes and digital cervical screening devices (DYSIS, EVA System, AVE)](https://onco.cc/technologies/colposcopes-digital-cervical-screening/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [DPYD genotyping and DPD phenotyping before fluoropyrimidines](https://onco.cc/technologies/dpyd-genotyping/), [HPV & HBV vaccination](https://onco.cc/technologies/hpv-vaccine/), [HPV DNA testing and self-sampling](https://onco.cc/technologies/hpv-testing/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Radiosensitisers](https://onco.cc/technologies/radiosensitisers/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [Thermal ablation and cryotherapy for cervical precancer](https://onco.cc/technologies/precancer-ablation/)
- targets: [APC](https://onco.cc/targets/apc/), [BIRC6](https://onco.cc/targets/birc6/), [COL1A1](https://onco.cc/targets/col1a1/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/), [PTPRC](https://onco.cc/targets/ptprc/), [STK11](https://onco.cc/targets/stk11/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [HPV quadrivalent vaccine (types 6, 11, 16 and 18)](https://onco.cc/drugs/hpv-quadrivalent-vaccine/), [Mitomycin C](https://onco.cc/drugs/mitomycin/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Nonavalent HPV vaccine](https://onco.cc/drugs/gardasil-9/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Retifanlimab](https://onco.cc/drugs/retifanlimab/)
- companies: [AIDS Malignancy Consortium](https://onco.cc/companies/aids-malignancy-consortium/), [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Incyte](https://onco.cc/companies/incyte/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [Oncolytics Biotech](https://onco.cc/companies/oncolytics-biotech/)
- pathways: [Oncogenic viruses](https://onco.cc/pathways/oncogenic-viruses/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- terms: [Clinical complete response (cCR)](https://onco.cc/terms/clinical-complete-response/), [HPV-positive (p16) head and neck cancer](https://onco.cc/terms/hpv-p16/), [Radiation dermatitis (skin reaction)](https://onco.cc/terms/radiation-dermatitis/)
- trials: [A Study in Advanced or Metastatic Gastrointestinal Cancers Exploring Treatment Combinations With Pelareorep and Atezolizumab](https://onco.cc/trials/nct07280377/), [ACT II](https://onco.cc/trials/act-ii/), [ANCHOR](https://onco.cc/trials/anchor/), [InterAACT](https://onco.cc/trials/interaact/), [NCI9673](https://onco.cc/trials/nci9673/), [NHS-Galleri](https://onco.cc/trials/nhs-galleri/), [POD1UM-303/InterAACT-2](https://onco.cc/trials/pod1um-303/)
- people: [Harald zur Hausen](https://onco.cc/people/harald-zur-hausen/)
- key papers: [ANCHOR: treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer](https://onco.cc/key-papers/paper-anchor-treatment-of-anal-hsil-prevents-cancer-palefsky-nejm-2022/), [InterAACT: cisplatin and fluorouracil versus carboplatin and paclitaxel in advanced anal cancer](https://onco.cc/key-papers/paper-interaact-carboplatin-paclitaxel-advanced-anal-cancer-rao-jco-2020/), [NCI9673 part B: randomised phase 2 study of nivolumab with or without ipilimumab in refractory metastatic anal cancer](https://onco.cc/key-papers/paper-nci9673-part-b-nivolumab-ipilimumab-anal-cancer-morris-jco-2026/), [NCI9673: nivolumab for previously treated unresectable metastatic anal cancer](https://onco.cc/key-papers/paper-nci9673-nivolumab-metastatic-anal-cancer-morris-lancet-oncol-2017/), [Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial](https://onco.cc/key-papers/paper-nhs-galleri-performance-nat-med-2026/), [POD1UM-303/InterAACT-2: retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic anal squamous cell carcinoma](https://onco.cc/key-papers/paper-pod1um-303-retifanlimab-anal-cancer-rao-lancet-2025/)
- journals: [Clinical colorectal cancer](https://onco.cc/journals/clinical-colorectal-cancer/), [Journal of gastrointestinal cancer](https://onco.cc/journals/journal-of-gastrointestinal-cancer/)

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JSON: https://onco.cc/api/v1/entities/anal.json