| Domain | Key points | Ontology terms | Key sources |
|---|---|---|---|
| Identifiers/Definition | Penile cancer is a rare malignancy; ~95% are penile squamous cell carcinomas (PSCC). Current pathology framework separates HPV-associated and HPV-independent disease; precursor lesions include penile intraepithelial neoplasia (PeIN). MONDO ID was not available from retrieved sources. Aggregated disease-level literature/guidelines, not individual EHR-derived data. (pqac-00000005, pqac-00000014) | MONDO: not available from retrieved sources; MeSH: Penile Neoplasms; ICD-10: C60; ICD-11: malignant neoplasm of penis; UBERON: penis; HPO: HP:0030358 Neoplasm of the penis | Mannam 2024; URL: https://doi.org/10.3390/pathogens13090809. Brouwer 2024; URL: https://doi.org/10.1200/op.23.00585 |
| Etiology/Risk | HPV is implicated in ~38.5%–50.8% of penile cancers; high-risk HPV16 predominates. Major risks: phimosis, smoking, poor hygiene, low socioeconomic status; chronic inflammatory dermatoses/lichen sclerosus contribute to HPV-independent disease. Childhood/adolescent circumcision is protective (OR 0.33). (pqac-00000000, pqac-00000003, pqac-00000006, pqac-00000007, pqac-00000020) | CHEBI: tobacco smoke; NCBITaxon: Human papillomavirus; HPO: HP:0100513 Phimosis; GO: response to virus, epithelial cell proliferation | Mannam 2024; URL: https://doi.org/10.3390/pathogens13090809. Huang 2024; URL: https://doi.org/10.1111/bju.16224 |
| Epidemiology/Trends | Global 2020 burden: 36,068 new cases; ASR 0.80/100,000. Highest regional ASRs: South America 1.5, Caribbean 1.4, Melanesia 1.4, South-Central Asia 1.3, Eastern Africa 1.2; Northern America 0.5. Younger-male incidence is rising in several countries; overall old:young incidence ratio 9.7:1. US estimate cited in 2024 review: ~2,100 new cases and ~500 deaths in 2024. (pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000017, pqac-00000033) | MONDO: not available; MeSH: Penile Neoplasms; ICD-10: C60 | Huang 2024; URL: https://doi.org/10.1111/bju.16224. Lasorsa 2024; URL: https://doi.org/10.2147/RRU.S465546 |
| Phenotypes | Typical presentations raising suspicion: penile ulcer or lump, reddish rash refractory to topical corticosteroids, bleeding or foul-smelling discharge under phimotic prepuce, penile pain. Glans is a common primary site. Untreated PeIN may progress to invasive cancer in ~30%. (pqac-00000013, pqac-00000018) | HPO: penile pain, genital ulceration, penile mass, malodorous discharge, erythroplasia; UBERON: glans penis, prepuce | Gerdtsson 2025; URL: https://doi.org/10.2340/sju.v60.44463 |
| Molecular/Genetics | Overall genomic profile (Nazha 2023): TP53 46%, CDKN2A 26%, PIK3CA 25%; TERT promoter ~22%; NOTCH1 ~14%; EGFR amplification 7.8%; pathways: TP53 44.6%, RTK-RAS 36.6%, PI3K/mTOR 31.7%. By HPV status: HPV-negative tumors had higher TP53 alterations (62.5% vs 7.7%) and TERT alterations (76.9% vs 25.0%); CDKN2A mutations only in HPV-negative tumors (37.5% vs 0%); TMB-high only in HPV16/18-positive tumors (30.8% vs 0%). Metastatic cohort (Monteiro 2025): TP53 66.7%, TERT 50%, CDKN2A 50%, PIK3CA 33.3%, NOTCH1 27.8%; PD-L1 CPS≥1 in 63.6%; no TMB-high identified; NOTCH1 only in HPV-negative tumors. (pqac-00000028, pqac-00000029, pqac-00000030) | HGNC: TP53, CDKN2A, PIK3CA, TERT, NOTCH1, EGFR, FGFR3; GO: cell cycle checkpoint signaling, PI3K signaling, keratinocyte proliferation, viral carcinogenesis; CL: keratinocyte, CD8-positive T cell, macrophage | Nazha 2023; PMID not available in retrieved context; URL: https://doi.org/10.1002/cncr.34982. Monteiro 2025; PMID not available in retrieved context; URL: https://doi.org/10.1093/oncolo/oyae220 |
| Diagnostics/Staging | EAU-ASCO 2023 update recommends determining HPV status at diagnosis; direct HPV testing by PCR/ISH, with p16 IHC as a reliable surrogate. For cN0 intermediate/high-risk tumors, DSNB is recommended when surgical staging is indicated; if unavailable, offer ILND. In a 2023 DSNB series, detection rate was 91% per procedure and 96% per groin; sensitivity 79%, specificity 100%, NPV 97%, PPV 100%; adverse events 1%. (pqac-00000014, pqac-00000015, pqac-00000034) | MAXO: biopsy of penis, immunohistochemistry, HPV testing, sentinel lymph node biopsy, inguinal lymph node dissection; HPO: inguinal lymphadenopathy; UBERON: inguinal lymph node | Brouwer 2024; URL: https://doi.org/10.1200/op.23.00585. Gebruers 2023; URL: https://doi.org/10.1186/s13550-023-01013-1 |
| Prognosis | Survival is highly stage-dependent: ~90% 5-year OS for localized disease and <10% for metastatic disease. In metastatic ICI-treated patients, median OS 9.8 months and median PFS 3.2 months; ORR 13% overall, 35% in lymph-node-only metastases. NOTCH1 alteration in metastatic PSCC associated with worse OS (5.5 vs 12.8 months) and PFS (5.5 vs 11.7 months). PeIN-positive surgical margins after penile-sparing surgery increased local recurrence risk (HR 1.51, 95% CI 1.07–2.12). (pqac-00000020, pqac-00000029, pqac-00000017) | HPO: local recurrence, lymph node metastasis, distant metastasis; GO: negative regulation of apoptotic process | Huang 2024; URL: https://doi.org/10.1111/bju.16224. Zarif 2023; URL: https://doi.org/10.1093/jnci/djad155. Lee 2023; URL: https://doi.org/10.1097/JU.0000000000003635 |
| Treatment | Localized disease: penile-sparing surgery/topical therapy for selected Ta/Tis/PeIN; advanced disease: platinum-based chemotherapy, surgery/radiotherapy in multimodal pathways. TIP remains a key neoadjuvant regimen; modern guidelines advise avoiding bleomycin. ICI real-world/global cohort: pembrolizumab, nivolumab±ipilimumab, cemiplimab used; trAEs 29%, grade ≥3 trAEs 9.8%. (pqac-00000014, pqac-00000017, pqac-00000012) | MAXO: partial penectomy, total penectomy, glansectomy, topical imiquimod therapy, topical fluorouracil therapy, platinum-based chemotherapy, radiotherapy, immune checkpoint inhibitor therapy | Brouwer 2024; URL: https://doi.org/10.1200/op.23.00585. Lasorsa 2024; URL: https://doi.org/10.2147/RRU.S465546. Zarif 2023; URL: https://doi.org/10.1093/jnci/djad155 |
| Prevention | Preventive priorities: HPV vaccination, circumcision, smoking cessation, genital hygiene, early diagnosis/treatment of PeIN and lichen sclerosus. WHO-linked review notes prophylactic HPV vaccination is effective and expanding globally; by end of 2023, 143 WHO member states had introduced HPV vaccine programs. (pqac-00000006, pqac-00000007) | MAXO: HPV vaccination, smoking cessation intervention, circumcision, health education; CHEBI: tobacco; NCBITaxon: HPV | Mannam 2024; URL: https://doi.org/10.3390/pathogens13090809. Cai 2024; URL: https://doi.org/10.3390/vaccines12111291 |
| Trials | Recent/active studies include pembrolizumab + cisplatin-based chemotherapy (NCT04224740, phase 2, completed, n=37), carboplatin/paclitaxel + pembrolizumab for locoregionally advanced disease (NCT06353906, phase 2, recruiting, n=27), maintenance cemiplimab vs best supportive care after platinum chemotherapy (NCT07101822, phase 2, not yet recruiting, n=42), dostarlimab + niraparib (NCT05526989, phase 2, recruiting, n=25), TIP + toripalimab/triplizumab neoadjuvant therapy (NCT06415318, phase 2, recruiting, n=25), and multiple EGFR-ADC/PD-1 studies in EGFR-positive advanced disease (NCT07497919; NCT07518979). (pqac-00000034) | MAXO: clinical trial enrollment, PD-1 inhibitor therapy, combination chemotherapy, antibody-drug conjugate therapy, PARP inhibitor therapy | ClinicalTrials.gov records: NCT04224740, NCT06353906, NCT07101822, NCT05526989, NCT06415318, NCT07497919, NCT07518979 |
| Follow-up/Implementation | Follow-up after penile-sparing surgery emphasizes intensive early surveillance because most local/regional recurrences occur within 2 years. EAU-based schedule: physical exam every 3 months for 2 years, then every 6 months for 3 years; node-positive follow-up may include CT and visits every 3 months for 2 years then every 6 months to 5 years, while pN0 surveillance can use groin US every 6 months for 2 years then annually. Centralization of care improves DSNB use and specialized pathology. (pqac-00000016, pqac-00000017) | MAXO: follow-up visit, ultrasonography, computed tomography; UBERON: groin/inguinal region, penis | Lasorsa 2024; URL: https://doi.org/10.2147/RRU.S465546. Gerdtsson 2025; URL: https://doi.org/10.2340/sju.v60.44463 |


*Table: This table summarizes core disease-knowledge-base facts for penile cancer, including epidemiology, risk factors, phenotypes, molecular features, diagnostics, prognosis, treatment, prevention, and ongoing trials. It highlights quantitative findings such as DSNB performance and HPV-stratified genomic differences from recent authoritative sources.*