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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.
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.
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), Appendiceal cancer and pseudomyxoma peritonei, Small intestine cancer (small bowel adenocarcinoma), Small intestinal neuroendocrine tumours, Anal high-grade squamous intraepithelial lesions (precursor), 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.
Screening with anal cytology / high-resolution anoscopy and treatment of HSIL (ablation, topical therapy) reduces progression to cancer by 57% (ANCHOR).
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).
Salvage abdominoperineal resection with permanent colostomy; flap reconstruction.
Retifanlimab + carboplatin-paclitaxel (POD1UM-303, PFS and OS benefit); carboplatin-paclitaxel alone if immunotherapy contraindicated.
Nivolumab or pembrolizumab if not previously given; clinical trials.
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Single-agent PD-1 blockade remains the immunotherapy standard after chemotherapy in metastatic anal cancer; CTLA-4 blockade adds toxicity without benefit.
For someone offered the test, these are the numbers that describe what a result means in an NHS population: about 1 in 100 tests came back positive each year, between 46 and 58 in 100 positives were cancer, and a negative result left about 1 in 100 with an undetected cancer within the year. The test found between a quarter and a third of all cancers diagnosed in a screening round, and about half to two thirds of the 12 cancer types it was designed to find. Whether finding them this way reduces late-stage diagnoses is the primary question, and this paper says only that the answer was no; the primary-endpoint paper had not appeared on Europe PMC by 23 September 2026.
Retifanlimab with carboplatin-paclitaxel is the new first-line standard for advanced anal squamous cell carcinoma; approved in the United States in May 2025.
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.
Carboplatin plus weekly paclitaxel is the chemotherapy backbone for advanced anal cancer and the base on which retifanlimab was added in POD1UM-303.
PD-1 blockade is an option for metastatic anal cancer after chemotherapy, and the basis for later immunotherapy combinations in the disease.
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.
Three patients with complete response to 5-FU, mitomycin and radiation; abdominoperineal resection abandoned as first treatment.
FDA approval 2025.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Dose by Calvert formula using GFR (see the calculators).
Capecitabine: reduce to 75% for CrCl 30-50; contraindicated below 30.
See all on the product pages:CarboplatinFluorouracil (5-FU)Mitomycin CNivolumabPaclitaxel / nab-paclitaxelPembrolizumabRetifanlimab·Printable cards in the navigator
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