{"entity":{"id":"anal","kind":"cancer","name":"Anal cancer (squamous cell carcinoma)","aka":[],"tldr":"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.\n\nDefinitive 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.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Anal_cancer","links":[{"label":"NCCN Guidelines: Anal Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1414"},{"label":"ANCHOR (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2201048"},{"label":"NCI PDQ: anal cancer","url":"https://www.cancer.gov/types/anal/patient/anal-treatment-pdq"}],"tags":["gap-fill","gastrointestinal","hpv"],"related":["urethral"],"cancers":[],"sections":[],"technologies":["imrt-igrt","cytotoxic-chemotherapy","checkpoint-inhibitor","hpv-vaccine","hpv-testing","precancer-ablation","cthpv-dna"],"targets":["pd1","pdl1"],"drugs":["mitomycin","fluorouracil","carboplatin","paclitaxel","retifanlimab","nivolumab","pembrolizumab","gardasil-9"],"companies":["incyte","merck","bms","oncolytics-biotech"],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["hpv-p16","clinical-complete-response"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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)"],"standardOfCare":[{"setting":"Precancer (HSIL) in people with HIV","approach":"Screening with anal cytology / high-resolution anoscopy and treatment of HSIL (ablation, topical therapy) reduces progression to cancer by 57% (ANCHOR).","refs":["hpv-testing","precancer-ablation","hpv-vaccine","anchor"],"guideline":{"version":"ANCHOR (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2201048"}},{"setting":"Localised (stage I-III)","approach":"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).","refs":["mitomycin","fluorouracil","imrt-igrt"],"guideline":{"nccn":"Category 1 (5-FU/mitomycin + RT)","version":"NCCN Guidelines: Anal Carcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1414"}},{"setting":"Persistent or recurrent local disease","approach":"Salvage abdominoperineal resection with permanent colostomy; flap reconstruction.","refs":["robotic-surgery"]},{"setting":"Metastatic, first line","approach":"Retifanlimab + carboplatin-paclitaxel (POD1UM-303, PFS and OS benefit); carboplatin-paclitaxel alone if immunotherapy contraindicated.","refs":["retifanlimab","carboplatin","paclitaxel","pod1um-303"],"guideline":{"nccn":"Category 1","version":"NCCN Guidelines: Anal Carcinoma"}},{"setting":"Metastatic, later lines","approach":"Nivolumab or pembrolizumab if not previously given; clinical trials.","refs":["nivolumab","pembrolizumab"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Anal Carcinoma"}}],"stateOfArt":["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."],"history":[{"year":1974,"title":"Nigro: chemoradiation instead of surgery","note":"Three patients with complete response to 5-FU, mitomycin and radiation; abdominoperineal resection abandoned as first treatment.","refs":["fluorouracil","mitomycin"]},{"year":1996,"title":"UKCCCR ACT I and EORTC: chemoradiation beats radiation alone","refs":[]},{"year":2013,"title":"ACT II: mitomycin-5-FU standard; no maintenance benefit","refs":["mitomycin","fluorouracil"]},{"year":2017,"title":"Nivolumab active in refractory disease (NCI9673)","refs":["nivolumab"]},{"year":2020,"title":"InterAAct: carboplatin-paclitaxel first-line standard","refs":["carboplatin","paclitaxel"]},{"year":2022,"title":"ANCHOR: treating HSIL prevents anal cancer in people with HIV","refs":["precancer-ablation"]},{"year":2024,"title":"POD1UM-303: retifanlimab + chemotherapy improves PFS/OS","note":"FDA approval 2025.","refs":["retifanlimab"]}],"pipeline":["retifanlimab","cthpv-dna","hpv-vaccine"],"openProblems":["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."]},"route":"/cancers/anal/","neighbours":{"cancer":[{"id":"anal-hsil-precursor","kind":"cancer","name":"Anal high-grade squamous intraepithelial lesions (precursor)","route":"/cancers/anal-hsil-precursor/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"localised-anal-cancer","kind":"cancer","name":"Localised anal squamous cell carcinoma (stage I to III)","route":"/cancers/localised-anal-cancer/"},{"id":"metastatic-anal-cancer","kind":"cancer","name":"Metastatic and recurrent anal squamous cell carcinoma","route":"/cancers/metastatic-anal-cancer/"},{"id":"penile","kind":"cancer","name":"Penile cancer","route":"/cancers/penile/"},{"id":"urethral-squamous-cell-carcinoma","kind":"cancer","name":"Squamous cell carcinoma of the urethra","route":"/cancers/urethral-squamous-cell-carcinoma/"},{"id":"urethral","kind":"cancer","name":"Urethral cancer","route":"/cancers/urethral/"},{"id":"vaginal","kind":"cancer","name":"Vaginal cancer","route":"/cancers/vaginal/"}],"technology":[{"id":"cthpv-dna","kind":"technology","name":"Circulating tumour HPV DNA (ctHPV-DNA)","route":"/technologies/cthpv-dna/"},{"id":"colposcopes-digital-cervical-screening","kind":"technology","name":"Colposcopes and digital cervical screening devices (DYSIS, EVA System, AVE)","route":"/technologies/colposcopes-digital-cervical-screening/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"dpyd-genotyping","kind":"technology","name":"DPYD genotyping and DPD phenotyping before fluoropyrimidines","route":"/technologies/dpyd-genotyping/"},{"id":"hpv-vaccine","kind":"technology","name":"HPV & HBV vaccination","route":"/technologies/hpv-vaccine/"},{"id":"hpv-testing","kind":"technology","name":"HPV DNA testing and self-sampling","route":"/technologies/hpv-testing/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"radiosensitisers","kind":"technology","name":"Radiosensitisers","route":"/technologies/radiosensitisers/"},{"id":"rejuv-recon-pelvic-exenteration","kind":"technology","name":"Recovery after pelvic exenteration","route":"/technologies/rejuv-recon-pelvic-exenteration/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"},{"id":"rejuv-recon-stoma-reversal","kind":"technology","name":"Stoma reversal after rectal cancer surgery: who gets the bowel joined up again","route":"/technologies/rejuv-recon-stoma-reversal/"},{"id":"precancer-ablation","kind":"technology","name":"Thermal ablation and cryotherapy for cervical precancer","route":"/technologies/precancer-ablation/"}],"target":[{"id":"apc","kind":"target","name":"APC","route":"/targets/apc/"},{"id":"birc6","kind":"target","name":"BIRC6","route":"/targets/birc6/"},{"id":"col1a1","kind":"target","name":"COL1A1","route":"/targets/col1a1/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"ptprc","kind":"target","name":"PTPRC","route":"/targets/ptprc/"},{"id":"stk11","kind":"target","name":"STK11","route":"/targets/stk11/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"hpv-quadrivalent-vaccine","kind":"drug","name":"HPV quadrivalent vaccine (types 6, 11, 16 and 18)","route":"/drugs/hpv-quadrivalent-vaccine/"},{"id":"mitomycin","kind":"drug","name":"Mitomycin C","route":"/drugs/mitomycin/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"gardasil-9","kind":"drug","name":"Nonavalent HPV vaccine","route":"/drugs/gardasil-9/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"retifanlimab","kind":"drug","name":"Retifanlimab","route":"/drugs/retifanlimab/"}],"company":[{"id":"aids-malignancy-consortium","kind":"company","name":"AIDS Malignancy Consortium","route":"/companies/aids-malignancy-consortium/"},{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"incyte","kind":"company","name":"Incyte","route":"/companies/incyte/"},{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"},{"id":"oncolytics-biotech","kind":"company","name":"Oncolytics Biotech","route":"/companies/oncolytics-biotech/"}],"pathway":[{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"term":[{"id":"clinical-complete-response","kind":"term","name":"Clinical complete response (cCR)","route":"/terms/clinical-complete-response/"},{"id":"hpv-p16","kind":"term","name":"HPV-positive (p16) head and neck cancer","route":"/terms/hpv-p16/"},{"id":"radiation-dermatitis","kind":"term","name":"Radiation dermatitis (skin reaction)","route":"/terms/radiation-dermatitis/"}],"trial":[{"id":"nct07280377","kind":"trial","name":"A Study in Advanced or Metastatic Gastrointestinal Cancers Exploring Treatment Combinations With Pelareorep and Atezolizumab","route":"/trials/nct07280377/"},{"id":"act-ii","kind":"trial","name":"ACT II","route":"/trials/act-ii/"},{"id":"anchor","kind":"trial","name":"ANCHOR","route":"/trials/anchor/"},{"id":"interaact","kind":"trial","name":"InterAACT","route":"/trials/interaact/"},{"id":"nci9673","kind":"trial","name":"NCI9673","route":"/trials/nci9673/"},{"id":"nhs-galleri","kind":"trial","name":"NHS-Galleri","route":"/trials/nhs-galleri/"},{"id":"pod1um-303","kind":"trial","name":"POD1UM-303/InterAACT-2","route":"/trials/pod1um-303/"}],"person":[{"id":"harald-zur-hausen","kind":"person","name":"Harald zur Hausen","route":"/people/harald-zur-hausen/"}],"paper":[{"id":"paper-anchor-anal-hsil-treatment-nejm-2022","kind":"paper","name":"ANCHOR: treating anal high-grade squamous intraepithelial lesions to prevent anal cancer in people living with HIV","route":"/key-papers/paper-anchor-anal-hsil-treatment-nejm-2022/"},{"id":"paper-interaact-carboplatin-paclitaxel-advanced-anal-cancer-rao-jco-2020","kind":"paper","name":"InterAACT: cisplatin and fluorouracil versus carboplatin and paclitaxel in advanced anal cancer","route":"/key-papers/paper-interaact-carboplatin-paclitaxel-advanced-anal-cancer-rao-jco-2020/"},{"id":"paper-nci9673-part-b-nivolumab-ipilimumab-anal-cancer-morris-jco-2026","kind":"paper","name":"NCI9673 part B: randomised phase 2 study of nivolumab with or without ipilimumab in refractory metastatic anal cancer","route":"/key-papers/paper-nci9673-part-b-nivolumab-ipilimumab-anal-cancer-morris-jco-2026/"},{"id":"paper-nci9673-nivolumab-metastatic-anal-cancer-morris-lancet-oncol-2017","kind":"paper","name":"NCI9673: nivolumab for previously treated unresectable metastatic anal cancer","route":"/key-papers/paper-nci9673-nivolumab-metastatic-anal-cancer-morris-lancet-oncol-2017/"},{"id":"paper-nhs-galleri-performance-nat-med-2026","kind":"paper","name":"Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial","route":"/key-papers/paper-nhs-galleri-performance-nat-med-2026/"},{"id":"paper-pod1um-303-retifanlimab-anal-cancer-rao-lancet-2025","kind":"paper","name":"POD1UM-303/InterAACT-2: retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic anal squamous cell carcinoma","route":"/key-papers/paper-pod1um-303-retifanlimab-anal-cancer-rao-lancet-2025/"}],"journal":[{"id":"clinical-colorectal-cancer","kind":"journal","name":"Clinical colorectal cancer","route":"/journals/clinical-colorectal-cancer/"},{"id":"journal-of-gastrointestinal-cancer","kind":"journal","name":"Journal of gastrointestinal cancer","route":"/journals/journal-of-gastrointestinal-cancer/"}]}}