# Penile cancer

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

## TL;DR

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.

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: Penile squamous cell carcinoma; Carcinoma of the penis
- Tags: nci-coverage; rare; genitourinary; hpv
- 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)

## 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/penile/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/penile/#overview [2 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/penile/#what-it-is [6 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/penile/#finding-it [5 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/penile/#treating-it [4 settings, 2 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/penile/#evidence [3 trials, 5 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/penile/#science [3 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/penile/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/penile/#living-with-it [16 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/penile/coming/ [7 medicines, 3 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/penile/data/ [36 connected records]

## Standard of care

- Primary tumour: Organ-sparing treatment where feasible (glansectomy, glans resurfacing, wide local excision, laser or brachytherapy); partial or total penectomy reserved for extensive tumours. ([Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Mohs surgery](https://onco.cc/terms/mohs-surgery/))
- Clinically node-negative, intermediate or high-risk primary: Dynamic sentinel node biopsy (or modified inguinal lymphadenectomy where unavailable); observation only for low-risk primaries. ([Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/))
- Node-positive: 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). ([Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [InPACT](https://onco.cc/trials/inpact/))
- Metastatic or recurrent: Cisplatin-based chemotherapy (TIP); checkpoint inhibitors in trials or where approved for tumour-agnostic indications; palliative radiotherapy. ([Cisplatin](https://onco.cc/drugs/cisplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Penile_cancer
- NCI PDQ: penile cancer: https://www.cancer.gov/types/penile
- EAU-ASCO collaborative guideline (Eur Urol 2023): https://doi.org/10.1016/j.eururo.2023.02.027
- InPACT (NCT02305654): https://clinicaltrials.gov/study/NCT02305654
- NCCN: Penile Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1456

## Connected records

- cancers: [Anal cancer (squamous cell carcinoma)](https://onco.cc/cancers/anal/), [Cervical cancer](https://onco.cc/cancers/cervical/), [Cutaneous squamous cell carcinoma](https://onco.cc/cancers/cutaneous-scc/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Localised penile cancer (organ-confined, node-negative)](https://onco.cc/cancers/localised-penile-cancer/), [Node-positive and metastatic penile cancer](https://onco.cc/cancers/node-positive-penile-cancer/), [Squamous cell carcinoma of the urethra](https://onco.cc/cancers/urethral-squamous-cell-carcinoma/), [Urethral cancer](https://onco.cc/cancers/urethral/), [Vulvar cancer](https://onco.cc/cancers/vulvar/)
- technologies: [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [HPV & HBV vaccination](https://onco.cc/technologies/hpv-vaccine/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [Sentinel lymph node biopsy](https://onco.cc/technologies/sentinel-node/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [PD-1](https://onco.cc/targets/pd1/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Ifosfamide](https://onco.cc/drugs/ifosfamide/), [Nonavalent HPV vaccine](https://onco.cc/drugs/gardasil-9/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- pathways: [Oncogenic viruses](https://onco.cc/pathways/oncogenic-viruses/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/)
- terms: [HPV status (HPV-positive / HPV-negative)](https://onco.cc/terms/hpv-status/), [HPV-positive (p16) head and neck cancer](https://onco.cc/terms/hpv-p16/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/), [Mohs surgery](https://onco.cc/terms/mohs-surgery/)
- trials: [A Phase III Study to Evaluate the Efficacy, Immunogenicity and Safety of the 9-valent HPV Vaccine in Chinese Males](https://onco.cc/trials/nct06465914/), [InPACT](https://onco.cc/trials/inpact/), [Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers](https://onco.cc/trials/nct03260023/)
- bottlenecks: [Prevention we already have is not deployed](https://onco.cc/bottlenecks/b-prevention-adoption/), [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)
- journals: [Clinical genitourinary cancer](https://onco.cc/journals/clinical-genitourinary-cancer/), [Urologic oncology](https://onco.cc/journals/urologic-oncology/)
- companies: [Shanghai Bovax Biotechnology](https://onco.cc/companies/shanghai-bovax-biotechnology/)

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