Penile cancer
Penile cancer is a skin-type (squamous) cancer, about half of it caused by HPV, the same virus behind cervical cancer. It is highly curable when caught early, surgery has become far less mutilating, and the disease is preventable through HPV vaccination and hygiene. The hard cases are those with lymph-node spread, where chemotherapy plus surgery and now immunotherapy are being tested.
Overview
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.
The 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.
The 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.
State of the art today
- 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.
Where it starts and where it drains
Renal cell carcinoma comes from the kidney's filtering cortex, urothelial cancer from the lining of the collecting system and bladder, and the adrenal on top hosts cortical and medullary (neuroblastoma) tumours.
- Renal cortex (RCC)HPV-independent squamous cell carcinoma (usual type, verrucous, sarcomatoid)
- Renal pelvis and ureter (upper tract urothelial)
- Bladder lining (non-muscle-invasive)HPV-associated squamous cell carcinoma (basaloid, warty) · Penile intraepithelial neoplasia (PeIN; precursor) · Rare: melanoma, basal cell carcinoma, sarcoma, urethral carcinoma of the penis
- Bladder muscle wall (muscle-invasive)HPV-associated squamous cell carcinoma (basaloid, warty) · HPV-independent squamous cell carcinoma (usual type, verrucous, sarcomatoid)
- Adrenal cortex
- Adrenal medulla and sympathetic chain (neuroblastoma)
- Developing kidney (Wilms tumour)
- renal hilar
- para-aortic and paracaval
- obturator and iliac (bladder)
Same organ: Bladder & urothelial cancer, Renal cell carcinoma, Wilms tumour (nephroblastoma), Neuroblastoma (paediatric), Adrenocortical carcinoma, Pheochromocytoma and paraganglioma (PPGL), Urethral cancer
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.
- HPV & HBV vaccinationStandard of care
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Organ-sparing treatment where feasible (glansectomy, glans resurfacing, wide local excision, laser or brachytherapy); partial or total penectomy reserved for extensive tumours.
Dynamic sentinel node biopsy (or modified inguinal lymphadenectomy where unavailable); observation only for low-risk primaries.
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).
Cisplatin-based chemotherapy (TIP); checkpoint inhibitors in trials or where approved for tumour-agnostic indications; palliative radiotherapy.
Subtypes & biomarkers
top- 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
- 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)
Target prevalence in this cancer
- 1932Squamous origin and HPV precursors described
Bowen's disease and erythroplasia of Queyrat recognised as penile carcinoma in situ.
- 1994Dynamic sentinel node biopsy for penile cancer
Horenblas and colleagues (Netherlands Cancer Institute) introduce lymphatic mapping.
- 2010TIP neoadjuvant chemotherapy
Pagliaro and colleagues (JCO 2010) report responses and resectability in bulky nodal disease.
- 2017InPACT opens
International phase 3 platform for node-positive penile cancer (NCT02305654).
- 2023EAU-ASCO collaborative guideline
First joint European and American guideline for penile cancer.
Open problems, and what is being done about each
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.
and how the field plans to fix it →What is being done about thisFinding cancer earlierAvailable now- HPV & HBV vaccinationStandard of care
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
In trialsIdeas and roadmaps- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Lymphoedema and sexual function after treatment; sentinel node biopsy and organ preservation reduce the toll.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterBaltimore, USNewsweek oncology #10NCI comprehensivevia Pembrolizumab
- via Sentinel lymph node biopsy
- Alliance for Clinical Trials in OncologyChicago, IL, USvia Pembrolizumab, Sentinel lymph node biopsy
- Cancer Institute (WIA), AdyarChennai, INvia HPV & HBV vaccination, Brachytherapy
- Dharmais National Cancer CenterJakarta, IDvia HPV & HBV vaccination, Brachytherapy
- Institut National d'Oncologie, RabatRabat, MAvia HPV & HBV vaccination, Brachytherapy
- Institute of Oncology LjubljanaLjubljana, SIvia HPV & HBV vaccination, Brachytherapy
- via HPV & HBV vaccination, Brachytherapy
- Instituto Nacional de Cancerología (Mexico)Mexico City, MXvia HPV & HBV vaccination, Brachytherapy
- via HPV & HBV vaccination, Brachytherapy
- Kenyatta National HospitalNairobi, KEvia HPV & HBV vaccination, Brachytherapy
- Ocean Road Cancer InstituteDar es Salaam, TZvia HPV & HBV vaccination, Brachytherapy
- Uganda Cancer InstituteKampala, UGvia HPV & HBV vaccination, Brachytherapy
- All India Institute of Medical Sciences, New DelhiNew Delhi, INvia HPV & HBV vaccination
- American Society for Radiation OncologyArlington, VA, USvia Brachytherapy
- Catalan Institute of Oncology (ICO)L'Hospitalet de Llobregat, ESvia HPV & HBV vaccination
- Centre Oscar LambretLille, FRvia Brachytherapy
- via HPV & HBV vaccination
- Department of Biotechnology, Government of IndiaNew Delhi, INvia HPV & HBV vaccination
- European Cancer OrganisationBrussels, BEvia HPV & HBV vaccination
- European Society for Radiotherapy and OncologyBrussels, BEvia Brachytherapy
- via Brachytherapy
- European Society of Surgical OncologyBrussels, BEvia Sentinel lymph node biopsy
- Gates FoundationSeattle, WA, USvia HPV & HBV vaccination
- German Cancer Research Center (DKFZ)Heidelberg, DEvia HPV & HBV vaccination
- GOG FoundationPhiladelphia, PA, USvia Pembrolizumab
- Groote Schuur Hospital / University of Cape TownCape Town, ZAvia Brachytherapy
- Hacettepe University Cancer InstituteAnkara, TRvia Brachytherapy
- Ho Chi Minh City Oncology HospitalHo Chi Minh City, VNvia Brachytherapy
- Hospital de Amor (Barretos Cancer Hospital)Barretos, BRvia HPV & HBV vaccination
- via HPV & HBV vaccination
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensivevia Cisplatin
- Institut BergoniéBordeaux, FRvia Brachytherapy
- Institut Jules BordetBrussels, BEvia Pembrolizumab
- Institut PasteurParis, FRvia HPV & HBV vaccination
- Institut Salah AzaïezTunis, TNvia Brachytherapy
- Instituto Nacional de Câncer (INCA)Rio de Janeiro, BRvia HPV & HBV vaccination
- via Brachytherapy
- via Brachytherapy
- Istanbul University Institute of OncologyIstanbul, TRvia Brachytherapy
- Kaiser Permanente Division of ResearchOakland, CA, USvia HPV & HBV vaccination
- Keio University HospitalTokyo, JPvia Sentinel lymph node biopsy
- Koo Foundation Sun Yat-Sen Cancer CenterTaipei, TWvia Brachytherapy
- Korle Bu Teaching HospitalAccra, GHvia Brachytherapy
- Lagos University Teaching HospitalLagos, NGvia Brachytherapy
- via Pembrolizumab
- Leiden University Medical CenterLeiden, NLvia HPV & HBV vaccination
- via Brachytherapy
- via HPV & HBV vaccination
- via Brachytherapy
- National Institute of Oncology, HungaryBudapest, HUvia Brachytherapy
- National Taiwan University HospitalTaipei, TWvia HPV & HBV vaccination
- NCI Center for Cancer Research (intramural programme)Bethesda, MD, USvia HPV & HBV vaccination
- NSABP FoundationPittsburgh, PA, USvia Sentinel lymph node biopsy
- Philippine General HospitalManila, PHvia HPV & HBV vaccination
- via Brachytherapy
- Society of Gynecologic OncologyChicago, IL, USvia HPV & HBV vaccination
- Society of Surgical OncologyRosemont, IL, USvia Sentinel lymph node biopsy
- Sunnybrook Odette Cancer CentreToronto, ON, CAvia Brachytherapy
- via HPV & HBV vaccination
- via HPV & HBV vaccination
- Velindre Cancer CentreCardiff, GBvia Brachytherapy
- via HPV & HBV vaccination
Questions to ask
topQuestions to ask your oncologist about Penile cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example p16 IHC / HPV DNA status, Grade and lymphovascular invasion of the primary, Inguinal and pelvic nodal stage, PD-L1 expression, TP53 and CDKN2A status), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include HPV-associated squamous cell carcinoma, HPV-independent squamous cell carcinoma, Penile intraepithelial neoplasia.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Primary tumour
- For my situation (primary tumour), which of the standard options do you recommend and why?Why: Guideline options include: Organ-sparing treatment where feasible (glansectomy, glans resurfacing, wide local excision, laser or brachytherapy); partial or total penectomy reserved for extensive tumours.
Clinically node-negative, intermediate or high-risk primary
- For my situation (clinically node-negative, intermediate or high-risk primary), which of the standard options do you recommend and why?Why: Guideline options include: Dynamic sentinel node biopsy (or modified inguinal lymphadenectomy where unavailable); observation only for low-risk primaries.
Node-positive
- For my situation (node-positive), which of the standard options do you recommend and why?Why: Guideline options include: 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).
- Am I a candidate for Paclitaxel / nab-paclitaxel, Cisplatin, Ifosfamide, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic or recurrent
- For my situation (metastatic or recurrent), which of the standard options do you recommend and why?Why: Guideline options include: Cisplatin-based chemotherapy (TIP); checkpoint inhibitors in trials or where approved for tumour-agnostic indications; palliative radiotherapy.
- Am I a candidate for Cisplatin, Paclitaxel / nab-paclitaxel, Pembrolizumab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Pembrolizumab, Cemiplimab, HPV & HBV vaccination?Why: Trials are how the next standard of care is set; asking early keeps options open.
- 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.
- 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.
- I read that “Node-positive disease: the best sequence of chemotherapy, radiotherapy and surgery is unknown; InPACT is designed to answer it”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “No approved systemic therapy beyond cisplatin combinations; checkpoint inhibitor trials (often HPV-stratified) are recruiting”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
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3drugs
7companies
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2terms
4bottlenecks
2Latest papers
topQuery for this cancer: (TITLE:"Penile cancer" OR ABSTRACT:"Penile cancer" OR TITLE:"Penile squamous cell carcinoma" OR ABSTRACT:"Penile squamous cell carcinoma" OR TITLE:"Carcinoma of the penis" OR ABSTRACT:"Carcinoma of the penis") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Penile cancer, not a curated reading list.
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