{"entity":{"id":"penile","kind":"cancer","name":"Penile cancer","aka":["Penile squamous cell carcinoma","Carcinoma of the penis"],"tldr":"Penile cancer is a squamous skin-type cancer, about half of it caused by HPV. Caught early it is usually cured with organ-sparing surgery that has replaced amputation, and HPV vaccination and circumcision prevent it; the hard cases are those with lymph-node spread, where cisplatin-based chemotherapy plus surgery and now immunotherapy are being tested in the InPACT trial.","summary":"Penile squamous cell carcinoma arises on the glans or foreskin and follows two pathways: HPV-related (HPV16 predominant, p16-positive, basaloid or warty histology) and HPV-independent (differentiated PeIN linked to lichen sclerosus and chronic inflammation, TP53 and CDKN2A alterations). The disease spreads predictably to inguinal then pelvic nodes, and nodal stage is the dominant prognostic factor. Management has shifted from amputation to organ-sparing surgery for most primary tumours (glansectomy, glans resurfacing, laser, Mohs, or brachytherapy), which preserves function without compromising cure when margins are clear.\n\nThe inguinal nodes decide outcome. Dynamic sentinel node biopsy stages clinically node-negative patients with intermediate- or high-risk primaries, sparing most of them a morbid lymphadenectomy; palpable or proven nodal disease is treated with radical inguinal (and, when indicated, pelvic) lymphadenectomy, with adjuvant chemotherapy or chemoradiation for extensive nodal disease. Cisplatin-based combinations (TIP: paclitaxel, ifosfamide, cisplatin) are the standard neoadjuvant and first-line regimens; the international InPACT trial (NCT02305654) is the first randomised study to define the sequence of surgery, chemotherapy and radiotherapy in node-positive disease. Immune checkpoint inhibitors (pembrolizumab, cemiplimab) have produced responses in small series and are being combined with chemotherapy and radiotherapy in trials, and HPV-directed vaccines and cell therapies are being explored.\n\nThe EAU-ASCO 2023 collaborative guideline is the current reference. Prevention is straightforward in principle: HPV vaccination of boys, neonatal or childhood circumcision where culturally appropriate, phimosis treatment and smoking cessation.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Penile_cancer","links":[{"label":"NCI PDQ: penile cancer","url":"https://www.cancer.gov/types/penile"},{"label":"EAU-ASCO collaborative guideline (Eur Urol 2023)","url":"https://doi.org/10.1016/j.eururo.2023.02.027"},{"label":"InPACT (NCT02305654)","url":"https://clinicaltrials.gov/study/NCT02305654"},{"label":"NCCN: Penile Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1456"}],"tags":["nci-coverage","rare","genitourinary","hpv"],"related":["cervical","vulvar","anal","head-and-neck","cutaneous-scc"],"cancers":[],"sections":[],"technologies":["sentinel-node","brachytherapy","cytotoxic-chemotherapy","checkpoint-inhibitor","hpv-vaccine","robotic-surgery"],"targets":["pd1","egfr","tp53"],"drugs":["cisplatin","paclitaxel","ifosfamide","pembrolizumab","cemiplimab","gardasil-9","fluorouracil"],"companies":[],"institutions":[],"pathways":["oncogenic-viruses","p53-cell-cycle"],"terms":["hpv-p16","hpv-status","lymphadenectomy","mohs-surgery"],"trials":["nct06465914"],"people":[],"bottlenecks":["b-rare-cancers","b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"genitourinary","burden":"Rare in high-income countries (well under one per 100,000 men per year) and several times more common in parts of South America, sub-Saharan Africa and South Asia, tracking HPV prevalence, phimosis and low circumcision rates.","subtypes":["HPV-associated squamous cell carcinoma (basaloid, warty)","HPV-independent squamous cell carcinoma (usual type, verrucous, sarcomatoid)","Penile intraepithelial neoplasia (PeIN; precursor)","Rare: melanoma, basal cell carcinoma, sarcoma, urethral carcinoma of the penis"],"biomarkers":["p16 IHC / HPV DNA status","Grade and lymphovascular invasion of the primary (decides sentinel node biopsy)","Inguinal and pelvic nodal stage (extranodal extension, number of nodes)","PD-L1 expression (investigational)","TP53 and CDKN2A status (HPV-independent tumours)"],"standardOfCare":[{"setting":"Primary tumour","approach":"Organ-sparing treatment where feasible (glansectomy, glans resurfacing, wide local excision, laser or brachytherapy); partial or total penectomy reserved for extensive tumours.","refs":["brachytherapy","mohs-surgery"],"guideline":{"version":"EAU-ASCO Collaborative Guideline on Penile Cancer 2023","url":"https://doi.org/10.1016/j.eururo.2023.02.027"}},{"setting":"Clinically node-negative, intermediate or high-risk primary","approach":"Dynamic sentinel node biopsy (or modified inguinal lymphadenectomy where unavailable); observation only for low-risk primaries.","refs":["sentinel-node"],"guideline":{"version":"EAU-ASCO 2023; NCCN Guidelines: Penile Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1456"}},{"setting":"Node-positive","approach":"Radical inguinal lymphadenectomy; pelvic lymphadenectomy and adjuvant chemotherapy or chemoradiation for extensive disease; neoadjuvant TIP for bulky or fixed nodes (InPACT is testing the sequence).","refs":["lymphadenectomy","paclitaxel","cisplatin","ifosfamide","inpact"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Penile Cancer"}},{"setting":"Metastatic or recurrent","approach":"Cisplatin-based chemotherapy (TIP); checkpoint inhibitors in trials or where approved for tumour-agnostic indications; palliative radiotherapy.","refs":["cisplatin","paclitaxel","pembrolizumab","cemiplimab"]}],"stateOfArt":["Organ-sparing surgery has replaced amputation for most primary tumours without loss of cure, a quiet revolution in quality of life.","Dynamic sentinel node biopsy spares most node-negative men a lymphadenectomy and its lifelong lymphoedema risk.","InPACT, a UK-US-led academic trial, is the first randomised study in node-positive penile cancer, testing neoadjuvant chemotherapy and chemoradiation before surgery.","HPV vaccination of boys and men is the prevention lever; several countries adopted gender-neutral vaccination in the 2010s and 2020s."],"history":[{"year":1932,"title":"Squamous origin and HPV precursors described","note":"Bowen's disease and erythroplasia of Queyrat recognised as penile carcinoma in situ.","refs":[]},{"year":1994,"title":"Dynamic sentinel node biopsy for penile cancer","note":"Horenblas and colleagues (Netherlands Cancer Institute) introduce lymphatic mapping.","refs":["sentinel-node"]},{"year":2010,"title":"TIP neoadjuvant chemotherapy","note":"Pagliaro and colleagues (JCO 2010) report responses and resectability in bulky nodal disease.","refs":["paclitaxel","cisplatin","ifosfamide"]},{"year":2017,"title":"InPACT opens","note":"International phase 3 platform for node-positive penile cancer (NCT02305654).","refs":[]},{"year":2023,"title":"EAU-ASCO collaborative guideline","note":"First joint European and American guideline for penile cancer.","refs":[]}],"pipeline":["pembrolizumab","cemiplimab","hpv-vaccine"],"openProblems":["Node-positive disease: the best sequence of chemotherapy, radiotherapy and surgery is unknown; InPACT is designed to answer it.","No approved systemic therapy beyond cisplatin combinations; checkpoint inhibitor trials (often HPV-stratified) are recruiting.","Late presentation from stigma and delayed referral; awareness campaigns and rapid-access clinics are the response.","Lymphoedema and sexual function after treatment; sentinel node biopsy and organ preservation reduce the toll."]},"route":"/cancers/penile/","neighbours":{"cancer":[{"id":"anal","kind":"cancer","name":"Anal cancer (squamous cell carcinoma)","route":"/cancers/anal/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"cutaneous-scc","kind":"cancer","name":"Cutaneous squamous cell carcinoma","route":"/cancers/cutaneous-scc/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"localised-penile-cancer","kind":"cancer","name":"Localised penile cancer (organ-confined, node-negative)","route":"/cancers/localised-penile-cancer/"},{"id":"node-positive-penile-cancer","kind":"cancer","name":"Node-positive and metastatic penile cancer","route":"/cancers/node-positive-penile-cancer/"},{"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":"vulvar","kind":"cancer","name":"Vulvar cancer","route":"/cancers/vulvar/"}],"technology":[{"id":"brachytherapy","kind":"technology","name":"Brachytherapy","route":"/technologies/brachytherapy/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"hpv-vaccine","kind":"technology","name":"HPV & HBV vaccination","route":"/technologies/hpv-vaccine/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"},{"id":"sentinel-node","kind":"technology","name":"Sentinel lymph node biopsy","route":"/technologies/sentinel-node/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"drug":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"ifosfamide","kind":"drug","name":"Ifosfamide","route":"/drugs/ifosfamide/"},{"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/"}],"pathway":[{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"},{"id":"p53-cell-cycle","kind":"pathway","name":"p53 / RB / cell-cycle checkpoint","route":"/pathways/p53-cell-cycle/"}],"term":[{"id":"hpv-status","kind":"term","name":"HPV status (HPV-positive / HPV-negative)","route":"/terms/hpv-status/"},{"id":"hpv-p16","kind":"term","name":"HPV-positive (p16) head and neck cancer","route":"/terms/hpv-p16/"},{"id":"lymphadenectomy","kind":"term","name":"Lymphadenectomy (lymph node dissection)","route":"/terms/lymphadenectomy/"},{"id":"mohs-surgery","kind":"term","name":"Mohs surgery","route":"/terms/mohs-surgery/"}],"trial":[{"id":"nct06465914","kind":"trial","name":"A Phase III Study to Evaluate the Efficacy, Immunogenicity and Safety of the 9-valent HPV Vaccine in Chinese Males","route":"/trials/nct06465914/"},{"id":"inpact","kind":"trial","name":"InPACT","route":"/trials/inpact/"},{"id":"nct03260023","kind":"trial","name":"Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers","route":"/trials/nct03260023/"}],"bottleneck":[{"id":"b-prevention-adoption","kind":"bottleneck","name":"Prevention we already have is not deployed","route":"/bottlenecks/b-prevention-adoption/"},{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"}],"journal":[{"id":"clinical-genitourinary-cancer","kind":"journal","name":"Clinical genitourinary cancer","route":"/journals/clinical-genitourinary-cancer/"},{"id":"urologic-oncology","kind":"journal","name":"Urologic oncology","route":"/journals/urologic-oncology/"}],"company":[{"id":"shanghai-bovax-biotechnology","kind":"company","name":"Shanghai Bovax Biotechnology","route":"/companies/shanghai-bovax-biotechnology/"}]}}