Penile Cancer

MONDO:0001325 Pathograph 8 Show in embeddings browser male reproductive organ cancer penile neoplasm

Penile cancer is a primary malignant neoplasm of the penis. Squamous cell carcinoma accounts for approximately 95% of cases, while sarcomas, basal cell carcinomas, and melanoma are rare. Two largely distinct carcinogenic pathways are recognized: an HPV-associated pathway driven by high-risk human papillomavirus E6/E7 oncoproteins (which inactivate p53 and Rb and produce p16INK4a overexpression), and an HPV-independent pathway arising in the background of chronic inflammatory dermatoses such as lichen sclerosus and characterized by somatic TP53, CDKN2A, and HRAS mutations. Penile intraepithelial neoplasia (PeIN) is the recognized precursor lesion. The disease typically arises on the glans, coronal sulcus, or foreskin, presents with diverse clinical lesions, and spreads in a stepwise fashion to inguinal lymph nodes, making nodal assessment central to staging, treatment, and prognosis.

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1
Definitions
4
Pathophys.
1
Histopath.
3
Phenotypes
8
Pathograph
3
Genes
7
Medical Actions
2
Subtypes
1
Deep Research
📘

Definitions

1
Clinicopathologic definition
Penile cancer is a primary malignant neoplasm of the penis, most commonly squamous cell carcinoma, diagnosed by clinical examination of the primary lesion and regional lymph nodes followed by tissue biopsy for histologic classification.
CASE_DEFINITION Adult genitourinary oncology
Show evidence (2 references)
PMID:38841163 SUPPORT Human Clinical
"While the penis can be affected by sarcomas, basal cell carcinomas or even melanoma, Penile Squamous Cell Carcinoma (PSCC) represents approximately 95% of all penile neoplasms."
This review establishes squamous cell carcinoma as the dominant histology of penile cancer while noting rarer histologies, supporting the scope of the root entity.
PMID:38841163 SUPPORT Human Clinical
"Diagnosis of PSCC is done through clinical examination, including lymph node palpation, followed by a biopsy, which is essential for the classification."
This supports the biopsy-based clinicopathologic definition and the nodal examination component.
◆

Subtypes

2
HPV-associated penile squamous cell carcinoma
Carcinogenic pathway driven by high-risk human papillomavirus (chiefly HPV-16) E6/E7 oncoproteins, which inactivate p53 and Rb and produce characteristic p16INK4a overexpression. Encompasses warty and basaloid histologic variants and arises from undifferentiated PeIN. Tumors carry few somatic driver mutations because viral oncoproteins substitute for them.
Show evidence (2 references)
PMID:37353203 SUPPORT Human Clinical
"oncogenic action of E6 and E7 substitute for mutations in HPV-induced SCC."
This directly supports the HPV-associated pathway in which viral E6/E7 oncoproteins drive carcinogenesis in place of somatic driver mutations.
PMID:39758591 SUPPORT Human Clinical
"undifferentiated PeIN and warty/basaloid PeSCC are thought to be HPV related"
This supports the HPV-associated subtype encompassing warty/basaloid histology arising from undifferentiated PeIN.
HPV-independent penile squamous cell carcinoma
Carcinogenic pathway not driven by HPV, arising in the background of chronic inflammatory dermatoses such as lichen sclerosus. Encompasses usual (keratinizing) and verrucous histologic variants and arises from differentiated PeIN. Tumors are characterized by somatic mutations in tumor suppressor genes including TP53 and CDKN2A.
Show evidence (2 references)
PMID:37353203 SUPPORT Human Clinical
"genetic mutations in tumor suppressor genes drive HPV-independent penile carcinogenesis"
This supports the HPV-independent pathway being driven by tumor suppressor gene mutations rather than viral oncoproteins.
PMID:39758591 SUPPORT Human Clinical
"differentiated PeIN and usual PeSCC are considered HPV independent"
This supports the HPV-independent subtype encompassing usual-type histology arising from differentiated PeIN.
⚙

Pathophysiology

4
HPV E6/E7 Oncoprotein-Driven Transformation
In the HPV-associated pathway, persistent high-risk HPV infection of penile squamous epithelium expresses the E6 and E7 oncoproteins. E6 targets p53 for ubiquitin-mediated degradation and E7 inactivates the Rb tumor suppressor, abrogating cell-cycle checkpoints and producing compensatory p16INK4a overexpression. These viral oncoproteins substitute for the somatic driver mutations seen in HPV-independent tumors.
penile squamous epithelial cell CL:0000076
ubiquitin-dependent degradation of p53 GO:0006511 ↑ INCREASED cell cycle checkpoint signaling GO:0000075 ↓ DECREASED
penis epithelium UBERON:0004803
Downstream
Invasive Squamous Cell Proliferation and Nodal Spread HPV-driven checkpoint loss converges on malignant squamous proliferation and local invasion.
Immune-Checkpoint Biomarker Enrichment HPV status stratifies tumor mutational burden and immune-checkpoint biomarker patterns.
Show evidence (2 references)
PMID:37353203 SUPPORT Human Clinical
"oncogenic action of E6 and E7 substitute for mutations in HPV-induced SCC."
This supports E6/E7 oncoprotein action as the transforming mechanism in HPV-induced penile carcinogenesis.
PMID:39758591 SUPPORT Human Clinical
"Strong p16 positivity was a reliable surrogate marker for the detection of transcriptionally active high-risk HPV."
This supports p16 overexpression as a surrogate for transcriptionally active high-risk HPV, consistent with E7-mediated Rb inactivation.
HPV-Independent Somatic Tumor Suppressor Loss
In the HPV-independent pathway, chronic inflammation (e.g., lichen sclerosus) is the background for accumulation of somatic mutations in tumor suppressor and cell-cycle genes. TP53, CDKN2A, and HRAS mutations occur almost exclusively in HPV-independent tumors, with frequent co-occurrence of TP53 and CDKN2A, driving checkpoint loss and proliferation.
TP53 hgnc:11998 CDKN2A hgnc:1787 HRAS hgnc:5173
cell cycle checkpoint signaling GO:0000075 ↓ DECREASED positive regulation of cell population proliferation GO:0008284 ↑ INCREASED
Downstream
Invasive Squamous Cell Proliferation and Nodal Spread Tumor suppressor loss supports malignant proliferation, invasion, and nodal dissemination.
Show evidence (2 references)
PMID:37353203 SUPPORT Human Clinical
"mutations in TP53 (44/77; 57%), CDKN2A (35/77; 45%), and HRAS (13/77; 17%) genes occurred with one exception of a HIV positive patient exclusively in HPV-independent SCC"
This directly supports TP53, CDKN2A, and HRAS mutations as near-exclusive drivers of the HPV-independent pathway.
PMID:37353203 SUPPORT Human Clinical
"genetic mutations in tumor suppressor genes drive HPV-independent penile carcinogenesis"
This supports tumor suppressor gene loss as the central mechanism of the HPV-independent pathway.
Immune-Checkpoint Biomarker Enrichment
A substantial subset of penile cancers shows PD-L1 positivity, and high tumor mutational burden is enriched in HPV-positive tumors. These immune-checkpoint biomarkers provide a rationale for immune-checkpoint inhibitor therapy and patient stratification.
negative regulation of T cell mediated immunity GO:0002710 ↑ INCREASED
Show evidence (2 references)
PMID:37565840 SUPPORT Human Clinical
"Overall, 51% of tumors were PD-L1+, 10.7% had high TMB, and 1.1% had mismatch repair-deficient (dMMR)/MSI-high status."
This supports PD-L1 positivity and high TMB as immune-checkpoint-related biomarkers in penile cancer.
PMID:37565840 SUPPORT Human Clinical
"Increased tumor mutational burden is associated with HPV-positive tumors, and could serve as a biomarker for predicting therapeutic response to ICI-based therapies."
This supports the HPV-associated immune biomarker rationale for immune-checkpoint inhibitor therapy selection.
Invasive Squamous Cell Proliferation and Nodal Spread
Both carcinogenic pathways converge on malignant squamous cell proliferation with local invasion of the glans, coronal sulcus, or foreskin, followed by stepwise lymphatic dissemination to inguinal lymph nodes. Occult inguinal nodal metastasis in clinically node-negative disease is common, making nodal staging central to prognosis.
penile squamous epithelial cell CL:0000076
cell population proliferation GO:0008283 ↑ INCREASED
glans penis UBERON:0001299
Show evidence (2 references)
PMID:38841163 SUPPORT Human Clinical
"Lymph node involvement is a common finding at first presentation and investigation of spread to deep nodes is important and can be done with the aid of PET-CT."
This supports inguinal/deep nodal spread as a clinically important manifestation of invasive penile cancer.
PMID:39272796 SUPPORT Human Clinical
"The diagnosis of occult inguinal lymph node metastasis in clinically node-negative invasive penile squamous cell carcinoma (PSCC) has remained a challenge, with substantial perioperative complications."
This supports occult inguinal lymph-node metastasis as a key feature of invasive penile cancer.
✶

Histopathology

1
Squamous Cell Carcinoma Histology
Squamous cell carcinoma is the dominant penile cancer histology (~95%), classified by HPV-associated (warty, basaloid) and HPV-independent (usual, verrucous) pathways and variants. Rare histologies include sarcoma, basal cell carcinoma, and melanoma.
Show evidence (1 reference)
PMID:38841163 SUPPORT Human Clinical
"While the penis can be affected by sarcomas, basal cell carcinomas or even melanoma, Penile Squamous Cell Carcinoma (PSCC) represents approximately 95% of all penile neoplasms."
This supports squamous cell carcinoma as the dominant histology and notes the rarer histologic types of penile cancer.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Penile Cancer Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

3
Primary Penile Lesion Clinical HP:0000032
Show evidence (1 reference)
PMID:38841163 SUPPORT Human Clinical
"Penile Squamous Cell Carcinoma (PSCC) represents approximately 95% of all penile neoplasms."
This supports penile cancer as a primary penile neoplastic abnormality.
Variable Clinical Presentation Clinical HP:0000078
Show evidence (1 reference)
PMID:39339000 SUPPORT Human Clinical
"Diagnosing PC remains challenging due to its rarity and variety of clinical presentations."
This supports variable clinical presentation as a practical phenotype of penile cancer.
Inguinal Lymphadenopathy Clinical HP:0034751
Show evidence (1 reference)
PMID:39272796 SUPPORT Human Clinical
"Although DSLNB, if available, has been endorsed as the preferred method for nodal staging in patients with invasive PSCC and no palpable inguinal lymphadenopathy in the recent penile cancer guidelines, its utilization has been quite limited so far."
This directly references palpable inguinal lymphadenopathy status in penile cancer nodal staging.
🧬

Genetic Associations

3
TP53 (Somatic Driver Mutation)
Gene: TP53 hgnc:11998
Show evidence (1 reference)
PMID:37565840 SUPPORT Human Clinical
"revealed TP53 (46%), CDKN2A (26%), and PIK3CA (25%) to be the most common mutations."
This NGS cohort identifies TP53 as the most common recurrent somatic alteration in penile squamous cell carcinoma.
CDKN2A (Somatic Driver Mutation)
Gene: CDKN2A hgnc:1787
Show evidence (1 reference)
PMID:37565840 SUPPORT Human Clinical
"CDKN2A mutations (0% vs. 37.5%) were exclusive to HPV16/18- tumors."
This supports CDKN2A mutation as a recurrent HPV-independent penile cancer molecular feature.
HRAS (Somatic Driver Mutation)
Gene: HRAS hgnc:5173
Show evidence (1 reference)
PMID:37353203 SUPPORT Human Clinical
"mutations in TP53 (44/77; 57%), CDKN2A (35/77; 45%), and HRAS (13/77; 17%) genes occurred with one exception of a HIV positive patient exclusively in HPV-independent SCC"
This supports HRAS as a recurrent somatic driver in the HPV-independent penile cancer pathway.
💊

Medical Actions

7
Organ-Sparing Surgery
Action: surgical procedure MAXO:0000004
Penile-preserving local excision, glansectomy, or partial penectomy provides primary local control of resectable disease while preserving as much penile function and quality of life as oncologically feasible.
Show evidence (1 reference)
PMID:38841163 SUPPORT Human Clinical
"Surgical removal of the tumor is considered the most effective however can lead to severe decrease of quality of life."
This supports surgery as the core local treatment, motivating organ-sparing approaches to mitigate the quality-of-life burden.
Inguinal Lymphadenectomy
Action: lymphadenectomy MAXO:0001063
Inguinal lymph node dissection (ILND), increasingly performed with minimally invasive techniques, is used for nodal staging and management of nodal metastasis. Dynamic sentinel lymph node biopsy is the preferred staging method in clinically node-negative invasive disease.
Show evidence (1 reference)
PMID:39272796 SUPPORT Human Clinical
"For management of nodal metastasis in patients with clinically palpable inguinal lymph nodes, minimally invasive ILND has shown promising results as well."
This supports inguinal lymphadenectomy as a treatment for nodal metastasis in penile cancer.
Platinum-Based Chemotherapy
Action: chemotherapy MAXO:0000647
Agent: platinum compound NCIT:C1450
Platinum-based systemic chemotherapy is used for fixed or bulky nodal disease and distant metastatic penile cancer, and as part of chemoradiation and chemo-immunotherapy regimens.
Show evidence (1 reference)
PMID:38841163 SUPPORT Human Clinical
"Chemotherapy is used in the case of fixed or bulky lymph nodes, where surgery is not indicated, and for distant metastasis."
This supports chemotherapy in advanced nodal or metastatic penile cancer.
Radiation Therapy
Action: Radiation Therapy NCIT:C15313
Radiation therapy is used in selected penile cancer contexts, including organ-preservation strategies and combined chemoradiation, with particular relevance in HPV-positive disease.
Show evidence (1 reference)
PMID:38841163 SUPPORT Human Clinical
"Radiation therapy is particularly effective in the case of HPV-positive PSCC."
This supports radiation therapy as a modality with relevance in HPV-positive penile cancer.
EGFR-Targeted Therapy
Action: Pharmacotherapy NCIT:C15986
Agent: cetuximab NCIT:C1723
EGFR-targeted agents such as cetuximab are used in advanced or refractory penile squamous cell carcinoma; a subgroup of advanced tumors may be candidates for targeted therapy and clinical trials.
Show evidence (1 reference)
PMID:37353203 PARTIAL Human Clinical
"A subgroup of patients with advanced SCC may be candidates for targeted therapy and clinical trials, although the majority of advanced penile SCC remain a therapeutic challenge."
This supports targeted therapy (including EGFR-directed agents) as an option for a subgroup of advanced penile cancer, while noting that most advanced disease remains a therapeutic challenge.
Immune Checkpoint Inhibitor Therapy
Action: Pharmacotherapy NCIT:C15986
Agent: pembrolizumab NCIT:C106432
Immune-checkpoint inhibitors such as pembrolizumab have shown efficacy in HPV-associated penile cancer and are used, often in combination, in advanced disease, motivated by PD-L1 and TMB biomarker findings.
Mechanism Target:
MODULATES Immune-Checkpoint Biomarker Enrichment — Immune-checkpoint inhibitors are intended to restore anti-tumor immune activity in biomarker-selected or advanced penile cancer.
Show evidence (1 reference)
PMID:39339000 SUPPORT Human Clinical
"recent advancements in immune checkpoint inhibitors (ICIs) have shown some efficacy in treating HPV-associated PC."
This supports immune-checkpoint inhibitors as showing efficacy in HPV-associated penile cancer.
Prophylactic HPV Vaccination
Action: vaccination MAXO:0001017
Prophylactic HPV vaccination is a primary-prevention strategy that blocks high-risk HPV transmission and reduces the incidence of HPV-related cancers, including penile cancer, by preventing the persistent infections that drive the HPV-associated carcinogenic pathway.
Show evidence (2 references)
PMID:39591193 SUPPORT Human Clinical
"Human papillomavirus (HPV) persistent infection is a major pathogenic factor for HPV-related cancers, such as cervical cancer (CC), vaginal cancer, vulvar cancer, anal cancer, penile cancer, and head and neck cancer (HNC)."
This identifies penile cancer as an HPV-related cancer driven by persistent HPV infection, the target of prophylactic vaccination.
PMID:39591193 SUPPORT Human Clinical
"Vaccination against HPV can effectively block the transmission of the virus and prevent HPV-related cancers."
This supports prophylactic HPV vaccination as an effective prevention strategy for HPV-related cancers including penile cancer.
🌍

Environmental Factors

3
Chronic Inflammatory Dermatosis (Lichen Sclerosus)
Male genital lichen sclerosus and other chronic inflammatory dermatoses provide the tissue background from which HPV-independent penile squamous cell carcinoma arises.
Show evidence (1 reference)
PMID:37353203 SUPPORT Human Clinical
"independent of HPV in the background of chronic dermatoses"
This supports chronic dermatoses (including lichen sclerosus) as the inflammatory background for HPV-independent penile carcinogenesis.
Lack of Neonatal Circumcision and Poor Genital Hygiene
Absence of neonatal circumcision and poor genital hygiene are established risk contexts that can coexist with chronic local inflammation, phimosis, and HPV exposure.
Show evidence (1 reference)
PMID:38841163 SUPPORT Human Clinical
"The list of associated risk factors is long and includes among others, lack of neonatal circumcision, poor genital hygiene, socioeconomic status, history of human papillomavirus (HPV) infection and penile intraepithelial neoplasia (PeIN)."
This exact abstract sentence lists lack of neonatal circumcision and poor genital hygiene among penile cancer risk factors.
Penile Intraepithelial Neoplasia (Precursor Lesion)
Penile intraepithelial neoplasia (PeIN) is the recognized precursor lesion for invasive penile squamous cell carcinoma and forms part of the classification system. Undifferentiated PeIN is HPV-related while differentiated PeIN is HPV-independent.
Show evidence (1 reference)
PMID:38841163 SUPPORT Human Clinical
"HPV and PeIN are indisputable risk factors, and both also form part of the classification system for PSCC."
This directly supports PeIN as an established precursor/risk lesion and classification component for penile cancer.
{ }

Source YAML

click to show 
name: Penile Cancer
creation_date: "2026-06-08T00:00:00Z"
synonyms:
- Cancer of penis
- Malignant neoplasm of penis
- Penile neoplasm
- Penis cancer
description: >-
  Penile cancer is a primary malignant neoplasm of the penis. Squamous cell
  carcinoma accounts for approximately 95% of cases, while sarcomas, basal cell
  carcinomas, and melanoma are rare. Two largely distinct carcinogenic pathways
  are recognized: an HPV-associated pathway driven by high-risk human
  papillomavirus E6/E7 oncoproteins (which inactivate p53 and Rb and produce
  p16INK4a overexpression), and an HPV-independent pathway arising in the
  background of chronic inflammatory dermatoses such as lichen sclerosus and
  characterized by somatic TP53, CDKN2A, and HRAS mutations. Penile
  intraepithelial neoplasia (PeIN) is the recognized precursor lesion. The
  disease typically arises on the glans, coronal sulcus, or foreskin, presents
  with diverse clinical lesions, and spreads in a stepwise fashion to inguinal
  lymph nodes, making nodal assessment central to staging, treatment, and
  prognosis.
categories:
- Urogenital Cancer
- Solid Tumor
- HPV-Related Cancer
disease_term:
  preferred_term: penile cancer
  term:
    id: MONDO:0001325
    label: penile cancer
parents:
- male reproductive organ cancer
- penile neoplasm
definitions:
- name: Clinicopathologic definition
  definition_type: CASE_DEFINITION
  description: >-
    Penile cancer is a primary malignant neoplasm of the penis, most commonly
    squamous cell carcinoma, diagnosed by clinical examination of the primary
    lesion and regional lymph nodes followed by tissue biopsy for histologic
    classification.
  scope: Adult genitourinary oncology
  evidence:
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      While the penis can be affected by sarcomas, basal cell carcinomas or
      even melanoma, Penile Squamous Cell Carcinoma (PSCC) represents
      approximately 95% of all penile neoplasms.
    explanation: >-
      This review establishes squamous cell carcinoma as the dominant histology
      of penile cancer while noting rarer histologies, supporting the scope of
      the root entity.
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diagnosis of PSCC is done through clinical examination, including lymph
      node palpation, followed by a biopsy, which is essential for the
      classification.
    explanation: >-
      This supports the biopsy-based clinicopathologic definition and the nodal
      examination component.
has_subtypes:
- name: HPV-Associated
  display_name: HPV-associated penile squamous cell carcinoma
  description: >-
    Carcinogenic pathway driven by high-risk human papillomavirus (chiefly
    HPV-16) E6/E7 oncoproteins, which inactivate p53 and Rb and produce
    characteristic p16INK4a overexpression. Encompasses warty and basaloid
    histologic variants and arises from undifferentiated PeIN. Tumors carry few
    somatic driver mutations because viral oncoproteins substitute for them.
  evidence:
  - reference: PMID:37353203
    reference_title: "Different Mutational Landscapes in Human Papillomavirus-Induced and Human Papillomavirus-Independent Invasive Penile Squamous Cell Cancers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      oncogenic action of E6 and E7 substitute for mutations in HPV-induced SCC.
    explanation: >-
      This directly supports the HPV-associated pathway in which viral E6/E7
      oncoproteins drive carcinogenesis in place of somatic driver mutations.
  - reference: PMID:39758591
    reference_title: "Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      undifferentiated PeIN and warty/basaloid PeSCC are thought to be HPV
      related
    explanation: >-
      This supports the HPV-associated subtype encompassing warty/basaloid
      histology arising from undifferentiated PeIN.
- name: HPV-Independent
  display_name: HPV-independent penile squamous cell carcinoma
  description: >-
    Carcinogenic pathway not driven by HPV, arising in the background of chronic
    inflammatory dermatoses such as lichen sclerosus. Encompasses usual
    (keratinizing) and verrucous histologic variants and arises from
    differentiated PeIN. Tumors are characterized by somatic mutations in tumor
    suppressor genes including TP53 and CDKN2A.
  evidence:
  - reference: PMID:37353203
    reference_title: "Different Mutational Landscapes in Human Papillomavirus-Induced and Human Papillomavirus-Independent Invasive Penile Squamous Cell Cancers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      genetic mutations in tumor suppressor genes drive HPV-independent penile
      carcinogenesis
    explanation: >-
      This supports the HPV-independent pathway being driven by tumor suppressor
      gene mutations rather than viral oncoproteins.
  - reference: PMID:39758591
    reference_title: "Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      differentiated PeIN and usual PeSCC are considered HPV independent
    explanation: >-
      This supports the HPV-independent subtype encompassing usual-type
      histology arising from differentiated PeIN.
infectious_agent:
- name: High-Risk Human Papillomavirus
  description: >-
    High-risk HPV infection, predominantly HPV-16, contributes to a substantial
    subset of penile cancers and defines the HPV-associated carcinogenic
    pathway.
  infectious_agent_term:
    preferred_term: Human papillomavirus 16
    term:
      id: NCBITaxon:333760
      label: Human papillomavirus 16
  evidence:
  - reference: PMID:39339000
    reference_title: "HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Approximately 40% of penile tumors are associated with human
      papillomavirus (HPV) infection.
    explanation: >-
      This review directly supports high-risk HPV as a common infectious
      contributor to penile cancer.
environmental:
- name: Chronic Inflammatory Dermatosis (Lichen Sclerosus)
  description: >-
    Male genital lichen sclerosus and other chronic inflammatory dermatoses
    provide the tissue background from which HPV-independent penile squamous
    cell carcinoma arises.
  evidence:
  - reference: PMID:37353203
    reference_title: "Different Mutational Landscapes in Human Papillomavirus-Induced and Human Papillomavirus-Independent Invasive Penile Squamous Cell Cancers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      independent of HPV in the background of chronic dermatoses
    explanation: >-
      This supports chronic dermatoses (including lichen sclerosus) as the
      inflammatory background for HPV-independent penile carcinogenesis.
- name: Lack of Neonatal Circumcision and Poor Genital Hygiene
  description: >-
    Absence of neonatal circumcision and poor genital hygiene are established
    risk contexts that can coexist with chronic local inflammation, phimosis,
    and HPV exposure.
  evidence:
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The list of associated risk factors is long and includes among others,
      lack of neonatal circumcision, poor genital hygiene, socioeconomic status,
      history of human papillomavirus (HPV) infection and penile
      intraepithelial neoplasia (PeIN).
    explanation: >-
      This exact abstract sentence lists lack of neonatal circumcision and poor
      genital hygiene among penile cancer risk factors.
- name: Penile Intraepithelial Neoplasia (Precursor Lesion)
  description: >-
    Penile intraepithelial neoplasia (PeIN) is the recognized precursor lesion
    for invasive penile squamous cell carcinoma and forms part of the
    classification system. Undifferentiated PeIN is HPV-related while
    differentiated PeIN is HPV-independent.
  evidence:
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      HPV and PeIN are indisputable risk factors, and both also form part of the
      classification system for PSCC.
    explanation: >-
      This directly supports PeIN as an established precursor/risk lesion and
      classification component for penile cancer.
pathophysiology:
- name: HPV E6/E7 Oncoprotein-Driven Transformation
  conforms_to: "viral_oncogenesis#Host Tumor Suppressor Inactivation and Signaling Hijack"
  description: >-
    In the HPV-associated pathway, persistent high-risk HPV infection of penile
    squamous epithelium expresses the E6 and E7 oncoproteins. E6 targets p53 for
    ubiquitin-mediated degradation and E7 inactivates the Rb tumor suppressor,
    abrogating cell-cycle checkpoints and producing compensatory p16INK4a
    overexpression. These viral oncoproteins substitute for the somatic driver
    mutations seen in HPV-independent tumors.
  cell_types:
  - preferred_term: penile squamous epithelial cell
    term:
      id: CL:0000076
      label: squamous epithelial cell
  locations:
  - preferred_term: penis epithelium
    term:
      id: UBERON:0004803
      label: penis epithelium
  biological_processes:
  - preferred_term: ubiquitin-dependent degradation of p53
    modifier: INCREASED
    term:
      id: GO:0006511
      label: ubiquitin-dependent protein catabolic process
  - preferred_term: cell cycle checkpoint signaling
    modifier: DECREASED
    term:
      id: GO:0000075
      label: cell cycle checkpoint signaling
  evidence:
  - reference: PMID:37353203
    reference_title: "Different Mutational Landscapes in Human Papillomavirus-Induced and Human Papillomavirus-Independent Invasive Penile Squamous Cell Cancers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      oncogenic action of E6 and E7 substitute for mutations in HPV-induced SCC.
    explanation: >-
      This supports E6/E7 oncoprotein action as the transforming mechanism in
      HPV-induced penile carcinogenesis.
  - reference: PMID:39758591
    reference_title: "Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Strong p16 positivity was a reliable surrogate marker for the detection of
      transcriptionally active high-risk HPV.
    explanation: >-
      This supports p16 overexpression as a surrogate for transcriptionally
      active high-risk HPV, consistent with E7-mediated Rb inactivation.
  downstream:
  - target: Invasive Squamous Cell Proliferation and Nodal Spread
    description: >-
      HPV-driven checkpoint loss converges on malignant squamous proliferation
      and local invasion.
  - target: Immune-Checkpoint Biomarker Enrichment
    description: >-
      HPV status stratifies tumor mutational burden and immune-checkpoint
      biomarker patterns.
- name: HPV-Independent Somatic Tumor Suppressor Loss
  description: >-
    In the HPV-independent pathway, chronic inflammation (e.g., lichen
    sclerosus) is the background for accumulation of somatic mutations in tumor
    suppressor and cell-cycle genes. TP53, CDKN2A, and HRAS mutations occur
    almost exclusively in HPV-independent tumors, with frequent co-occurrence of
    TP53 and CDKN2A, driving checkpoint loss and proliferation.
  genes:
  - preferred_term: TP53
    term:
      id: hgnc:11998
      label: TP53
  - preferred_term: CDKN2A
    term:
      id: hgnc:1787
      label: CDKN2A
  - preferred_term: HRAS
    term:
      id: hgnc:5173
      label: HRAS
  biological_processes:
  - preferred_term: cell cycle checkpoint signaling
    modifier: DECREASED
    term:
      id: GO:0000075
      label: cell cycle checkpoint signaling
  - preferred_term: positive regulation of cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
  evidence:
  - reference: PMID:37353203
    reference_title: "Different Mutational Landscapes in Human Papillomavirus-Induced and Human Papillomavirus-Independent Invasive Penile Squamous Cell Cancers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      mutations in TP53 (44/77; 57%), CDKN2A (35/77; 45%), and HRAS (13/77; 17%)
      genes occurred with one exception of a HIV positive patient exclusively in
      HPV-independent SCC
    explanation: >-
      This directly supports TP53, CDKN2A, and HRAS mutations as near-exclusive
      drivers of the HPV-independent pathway.
  - reference: PMID:37353203
    reference_title: "Different Mutational Landscapes in Human Papillomavirus-Induced and Human Papillomavirus-Independent Invasive Penile Squamous Cell Cancers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      genetic mutations in tumor suppressor genes drive HPV-independent penile
      carcinogenesis
    explanation: >-
      This supports tumor suppressor gene loss as the central mechanism of the
      HPV-independent pathway.
  downstream:
  - target: Invasive Squamous Cell Proliferation and Nodal Spread
    description: >-
      Tumor suppressor loss supports malignant proliferation, invasion, and
      nodal dissemination.
- name: Immune-Checkpoint Biomarker Enrichment
  conforms_to: "immune_checkpoint_blockade#Adaptive Immune Resistance"
  description: >-
    A substantial subset of penile cancers shows PD-L1 positivity, and high
    tumor mutational burden is enriched in HPV-positive tumors. These
    immune-checkpoint biomarkers provide a rationale for immune-checkpoint
    inhibitor therapy and patient stratification.
  biological_processes:
  - preferred_term: negative regulation of T cell mediated immunity
    modifier: INCREASED
    term:
      id: GO:0002710
      label: negative regulation of T cell mediated immunity
  evidence:
  - reference: PMID:37565840
    reference_title: "Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall, 51% of tumors were PD-L1+, 10.7% had high TMB, and 1.1% had
      mismatch repair-deficient (dMMR)/MSI-high status.
    explanation: >-
      This supports PD-L1 positivity and high TMB as immune-checkpoint-related
      biomarkers in penile cancer.
  - reference: PMID:37565840
    reference_title: "Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Increased tumor mutational burden is associated with HPV-positive tumors,
      and could serve as a biomarker for predicting therapeutic response to
      ICI-based therapies.
    explanation: >-
      This supports the HPV-associated immune biomarker rationale for
      immune-checkpoint inhibitor therapy selection.
- name: Invasive Squamous Cell Proliferation and Nodal Spread
  description: >-
    Both carcinogenic pathways converge on malignant squamous cell proliferation
    with local invasion of the glans, coronal sulcus, or foreskin, followed by
    stepwise lymphatic dissemination to inguinal lymph nodes. Occult inguinal
    nodal metastasis in clinically node-negative disease is common, making nodal
    staging central to prognosis.
  cell_types:
  - preferred_term: penile squamous epithelial cell
    term:
      id: CL:0000076
      label: squamous epithelial cell
  locations:
  - preferred_term: glans penis
    term:
      id: UBERON:0001299
      label: glans penis
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  evidence:
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Lymph node involvement is a common finding at first presentation and
      investigation of spread to deep nodes is important and can be done with
      the aid of PET-CT.
    explanation: >-
      This supports inguinal/deep nodal spread as a clinically important
      manifestation of invasive penile cancer.
  - reference: PMID:39272796
    reference_title: "Minimally Invasive Management of Inguinal Lymph Nodes in Penile Cancer: Recent Progress and Remaining Challenges."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The diagnosis of occult inguinal lymph node metastasis in clinically
      node-negative invasive penile squamous cell carcinoma (PSCC) has remained
      a challenge, with substantial perioperative complications.
    explanation: >-
      This supports occult inguinal lymph-node metastasis as a key feature of
      invasive penile cancer.
histopathology:
- name: Squamous Cell Carcinoma Histology
  finding_term:
    preferred_term: Squamous cell carcinoma
    term:
      id: NCIT:C2929
      label: Squamous Cell Carcinoma
  description: >-
    Squamous cell carcinoma is the dominant penile cancer histology (~95%),
    classified by HPV-associated (warty, basaloid) and HPV-independent (usual,
    verrucous) pathways and variants. Rare histologies include sarcoma, basal
    cell carcinoma, and melanoma.
  evidence:
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      While the penis can be affected by sarcomas, basal cell carcinomas or
      even melanoma, Penile Squamous Cell Carcinoma (PSCC) represents
      approximately 95% of all penile neoplasms.
    explanation: >-
      This supports squamous cell carcinoma as the dominant histology and notes
      the rarer histologic types of penile cancer.
phenotypes:
- category: Clinical
  name: Primary Penile Lesion
  description: >-
    The primary clinical abnormality is a penile neoplasm involving external
    male genital tissues, typically on the glans, coronal sulcus, or foreskin,
    requiring examination and biopsy for classification.
  phenotype_term:
    preferred_term: primary penile lesion
    term:
      id: HP:0000032
      label: Abnormal male external genitalia morphology
  evidence:
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Penile Squamous Cell Carcinoma (PSCC) represents approximately 95% of all
      penile neoplasms.
    explanation: >-
      This supports penile cancer as a primary penile neoplastic abnormality.
- category: Clinical
  name: Variable Clinical Presentation
  description: >-
    Penile cancer can present in diverse clinical forms, which can delay
    diagnosis and requires direct examination and biopsy of suspicious penile
    lesions.
  phenotype_term:
    preferred_term: variable penile clinical presentation
    term:
      id: HP:0000078
      label: Abnormality of the genital system
  evidence:
  - reference: PMID:39339000
    reference_title: "HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diagnosing PC remains challenging due to its rarity and variety of
      clinical presentations.
    explanation: >-
      This supports variable clinical presentation as a practical phenotype of
      penile cancer.
- category: Clinical
  name: Inguinal Lymphadenopathy
  description: >-
    Regional nodal spread may manifest as clinically palpable inguinal
    lymphadenopathy and can also be occult in clinically node-negative invasive
    disease.
  phenotype_term:
    preferred_term: inguinal lymphadenopathy
    term:
      id: HP:0034751
      label: Inguinal lymphadenopathy
  evidence:
  - reference: PMID:39272796
    reference_title: "Minimally Invasive Management of Inguinal Lymph Nodes in Penile Cancer: Recent Progress and Remaining Challenges."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Although DSLNB, if available, has been endorsed as the preferred method
      for nodal staging in patients with invasive PSCC and no palpable inguinal
      lymphadenopathy in the recent penile cancer guidelines, its utilization
      has been quite limited so far.
    explanation: >-
      This directly references palpable inguinal lymphadenopathy status in
      penile cancer nodal staging.
genetic:
- name: TP53
  association: Somatic Driver Mutation
  gene_term:
    preferred_term: TP53
    term:
      id: hgnc:11998
      label: TP53
  notes: >-
    TP53 is the most frequent somatic alteration in penile squamous cell
    carcinoma overall and occurs near-exclusively in the HPV-independent
    pathway.
  evidence:
  - reference: PMID:37565840
    reference_title: "Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      revealed TP53 (46%), CDKN2A (26%), and PIK3CA (25%) to be the most
      common mutations.
    explanation: >-
      This NGS cohort identifies TP53 as the most common recurrent somatic
      alteration in penile squamous cell carcinoma.
- name: CDKN2A
  association: Somatic Driver Mutation
  gene_term:
    preferred_term: CDKN2A
    term:
      id: hgnc:1787
      label: CDKN2A
  notes: >-
    CDKN2A mutation disrupts cell-cycle control and is enriched in the
    HPV-negative subset, frequently co-occurring with TP53.
  evidence:
  - reference: PMID:37565840
    reference_title: "Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      CDKN2A mutations (0% vs. 37.5%) were exclusive to HPV16/18- tumors.
    explanation: >-
      This supports CDKN2A mutation as a recurrent HPV-independent penile cancer
      molecular feature.
- name: HRAS
  association: Somatic Driver Mutation
  gene_term:
    preferred_term: HRAS
    term:
      id: hgnc:5173
      label: HRAS
  notes: >-
    HRAS mutation occurs near-exclusively in HPV-independent penile squamous
    cell carcinoma, contributing to RAS-pathway activation.
  evidence:
  - reference: PMID:37353203
    reference_title: "Different Mutational Landscapes in Human Papillomavirus-Induced and Human Papillomavirus-Independent Invasive Penile Squamous Cell Cancers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      mutations in TP53 (44/77; 57%), CDKN2A (35/77; 45%), and HRAS (13/77; 17%)
      genes occurred with one exception of a HIV positive patient exclusively in
      HPV-independent SCC
    explanation: >-
      This supports HRAS as a recurrent somatic driver in the HPV-independent
      penile cancer pathway.
treatments:
- name: Organ-Sparing Surgery
  description: >-
    Penile-preserving local excision, glansectomy, or partial penectomy provides
    primary local control of resectable disease while preserving as much penile
    function and quality of life as oncologically feasible.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  evidence:
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Surgical removal of the tumor is considered the most effective however
      can lead to severe decrease of quality of life.
    explanation: >-
      This supports surgery as the core local treatment, motivating
      organ-sparing approaches to mitigate the quality-of-life burden.
- name: Inguinal Lymphadenectomy
  description: >-
    Inguinal lymph node dissection (ILND), increasingly performed with minimally
    invasive techniques, is used for nodal staging and management of nodal
    metastasis. Dynamic sentinel lymph node biopsy is the preferred staging
    method in clinically node-negative invasive disease.
  treatment_term:
    preferred_term: lymphadenectomy
    term:
      id: MAXO:0001063
      label: lymphadenectomy
  evidence:
  - reference: PMID:39272796
    reference_title: "Minimally Invasive Management of Inguinal Lymph Nodes in Penile Cancer: Recent Progress and Remaining Challenges."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      For management of nodal metastasis in patients with clinically palpable
      inguinal lymph nodes, minimally invasive ILND has shown promising results
      as well.
    explanation: >-
      This supports inguinal lymphadenectomy as a treatment for nodal metastasis
      in penile cancer.
- name: Platinum-Based Chemotherapy
  description: >-
    Platinum-based systemic chemotherapy is used for fixed or bulky nodal
    disease and distant metastatic penile cancer, and as part of chemoradiation
    and chemo-immunotherapy regimens.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: MAXO:0000647
      label: chemotherapy
    therapeutic_agent:
    - preferred_term: platinum compound
      term:
        id: NCIT:C1450
        label: Platinum Compound
  evidence:
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Chemotherapy is used in the case of fixed or bulky lymph nodes, where
      surgery is not indicated, and for distant metastasis.
    explanation: >-
      This supports chemotherapy in advanced nodal or metastatic penile cancer.
- name: Radiation Therapy
  description: >-
    Radiation therapy is used in selected penile cancer contexts, including
    organ-preservation strategies and combined chemoradiation, with particular
    relevance in HPV-positive disease.
  treatment_term:
    preferred_term: Radiation Therapy
    term:
      id: NCIT:C15313
      label: Radiation Therapy
  evidence:
  - reference: PMID:38841163
    reference_title: "A comprehensive review of current knowledge on penile squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Radiation therapy is particularly effective in the case of HPV-positive
      PSCC.
    explanation: >-
      This supports radiation therapy as a modality with relevance in
      HPV-positive penile cancer.
- name: EGFR-Targeted Therapy
  description: >-
    EGFR-targeted agents such as cetuximab are used in advanced or refractory
    penile squamous cell carcinoma; a subgroup of advanced tumors may be
    candidates for targeted therapy and clinical trials.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: cetuximab
      term:
        id: NCIT:C1723
        label: Cetuximab
  evidence:
  - reference: PMID:37353203
    reference_title: "Different Mutational Landscapes in Human Papillomavirus-Induced and Human Papillomavirus-Independent Invasive Penile Squamous Cell Cancers."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A subgroup of patients with advanced SCC may be candidates for targeted
      therapy and clinical trials, although the majority of advanced penile SCC
      remain a therapeutic challenge.
    explanation: >-
      This supports targeted therapy (including EGFR-directed agents) as an
      option for a subgroup of advanced penile cancer, while noting that most
      advanced disease remains a therapeutic challenge.
- name: Immune Checkpoint Inhibitor Therapy
  description: >-
    Immune-checkpoint inhibitors such as pembrolizumab have shown efficacy in
    HPV-associated penile cancer and are used, often in combination, in advanced
    disease, motivated by PD-L1 and TMB biomarker findings.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: pembrolizumab
      term:
        id: NCIT:C106432
        label: Pembrolizumab
  target_mechanisms:
  - target: Immune-Checkpoint Biomarker Enrichment
    treatment_effect: MODULATES
    description: >-
      Immune-checkpoint inhibitors are intended to restore anti-tumor immune
      activity in biomarker-selected or advanced penile cancer.
  evidence:
  - reference: PMID:39339000
    reference_title: "HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      recent advancements in immune checkpoint inhibitors (ICIs) have shown some
      efficacy in treating HPV-associated PC.
    explanation: >-
      This supports immune-checkpoint inhibitors as showing efficacy in
      HPV-associated penile cancer.
- name: Prophylactic HPV Vaccination
  description: >-
    Prophylactic HPV vaccination is a primary-prevention strategy that blocks
    high-risk HPV transmission and reduces the incidence of HPV-related cancers,
    including penile cancer, by preventing the persistent infections that drive
    the HPV-associated carcinogenic pathway.
  treatment_term:
    preferred_term: vaccination
    term:
      id: MAXO:0001017
      label: vaccination
  evidence:
  - reference: PMID:39591193
    reference_title: "Human Papillomavirus-Related Cancer Vaccine Strategies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Human papillomavirus (HPV) persistent infection is a major pathogenic
      factor for HPV-related cancers, such as cervical cancer (CC), vaginal
      cancer, vulvar cancer, anal cancer, penile cancer, and head and neck
      cancer (HNC).
    explanation: >-
      This identifies penile cancer as an HPV-related cancer driven by
      persistent HPV infection, the target of prophylactic vaccination.
  - reference: PMID:39591193
    reference_title: "Human Papillomavirus-Related Cancer Vaccine Strategies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vaccination against HPV can effectively block the transmission of the
      virus and prevent HPV-related cancers.
    explanation: >-
      This supports prophylactic HPV vaccination as an effective prevention
      strategy for HPV-related cancers including penile cancer.
📚

References & Deep Research

Deep Research

1
Falcon ▸
1. Disease Information
Edison Scientific Literature 60 citations 2026-06-08T12:50:43.097317

1. Disease Information

1.1 What is the disease?

Penile cancer is a malignant tumor arising in penile tissues, most commonly penile squamous cell carcinoma (PSCC). Contemporary guidance emphasizes classifying PSCC into HPV-associated and HPV-independent subtypes, reflecting distinct etiologic pathways. (taghizadeh2025immunotherapyinthe pages 1-2, brouwer2024penilecancereauasco pages 1-2)

Key definition statements (abstract-derived): - A 2024 HPV-focused review states: “Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin.” (Pathogens; Sep 2024; https://doi.org/10.3390/pathogens13090809) (mannam2024hpvandpenile pages 1-2) - EAU-ASCO 2023 update summary notes PSCC is divided into HPV-associated and HPV-independent (e.g., lichen sclerosus) pathways and that HPV status determination is required at diagnosis. (JCO Oncology Practice; Jan 2024; https://doi.org/10.1200/op.23.00585) (brouwer2024penilecancereauasco pages 1-2)

1.2 Key identifiers

Evidence in the retrieved sources directly supports guideline-level and MeSH/ICD usage but did not return explicit ontology IDs. - ICD-10: C60 (Malignant neoplasm of penis) (not explicitly printed in retrieved texts; standard coding) - MeSH: Penile Neoplasms (not explicitly printed in retrieved texts; standard MeSH heading) - MONDO: Not located in retrieved sources during this run (see caveat above). (brouwer2024penilecancereauasco pages 1-2)

1.3 Common synonyms / alternative names

  • Penile squamous cell carcinoma (PSCC)
  • Squamous cell carcinoma of the penis
  • Carcinoma of the penis
  • Penile intraepithelial neoplasia (PeIN) for precancerous lesions (gerdtsson2025theswedishnational pages 2-4, gerdtsson2025theswedishnational pages 1-2)

1.4 Evidence provenance

This report is derived from aggregated disease-level resources: peer-reviewed reviews, guideline summaries, registry/population-based studies, and retrospective cohorts. It is not EHR-derived. (brouwer2024penilecancereauasco pages 1-2, huang2024incidenceriskfactors pages 1-2)

2. Etiology

2.1 Disease causal factors (mechanistic/etiologic)

HPV-associated carcinogenesis

A major causal pathway is persistent infection with high-risk HPV (most commonly HPV16). A key mechanistic chain is: HPV infection → integration/oncogene expression (E6/E7) → functional inhibition of TP53 and RB1 tumor suppressor pathways → dysregulated cell cycle and genomic instability; p16INK4a overexpression is used as a surrogate marker reflecting RB pathway disruption. (mannam2024hpvandpenile pages 5-6, brouwer2024penilecancereauasco pages 1-2)

Abstract quote: the Pathogens 2024 review states: “Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection.” (Sep 2024; https://doi.org/10.3390/pathogens13090809) (mannam2024hpvandpenile pages 1-2)

HPV-independent carcinogenesis

HPV-independent disease is commonly linked to chronic inflammatory/scarring dermatoses (e.g., lichen sclerosus) and other non-viral exposures; it corresponds to distinct PeIN subtype biology (differentiated PeIN). (uppal2026penilecancer—apreventable pages 1-2, brouwer2024penilecancereauasco pages 1-2)

2.2 Risk factors

Infectious

  • HPV infection: HPV-associated penile cancers estimated at ~38.5% with HPV16 predominant in one synthesis. (mannam2024hpvandpenile pages 1-2)

Environmental/lifestyle/clinical

  • Phimosis: reported substantially more frequent in cases than controls (e.g., 35.2% vs 7.6% in one cited dataset). (mannam2024hpvandpenile pages 2-4)
  • Smoking: associated with HPV acquisition and cancer risk; the review notes dose-response patterns and odds ratios for HPV infection (e.g., OR ~1.19 for any HPV; OR ~1.24 for oncogenic HPV among current smokers). (mannam2024hpvandpenile pages 2-4)
  • Poor genital hygiene / smegma and low socioeconomic status: consistently listed risk correlates. (mannam2024hpvandpenile pages 1-2, mannam2024hpvandpenile pages 2-4)
  • HIV infection, unsafe sex, alcohol drinking (ecologic association): national-level incidence associations were reported in a 2024 global population-based analysis. (huang2024incidenceriskfactors pages 1-2)

2.3 Protective factors

  • Circumcision: childhood/adolescent circumcision protective (reported OR 0.33 for invasive penile cancer in a cited synthesis). (uppal2026penilecancer—apreventable pages 1-2, mannam2024hpvandpenile pages 2-4)
  • HPV vaccination: prophylactic vaccination is positioned as a key preventive strategy for HPV-related cancers; a vaccine-strategy review notes expanding program adoption globally (e.g., “By the end of 2023, 143 member states had included HPV [vaccination]...”). (mannam2024hpvandpenile pages 2-4)

2.4 Gene–environment interactions

Direct gene–environment interaction studies specific to penile cancer were not retrieved here. However, the dual-pathway model implies interaction of host genomic susceptibility and inflammatory microenvironment (HPV-independent) versus viral oncogene-driven pathway (HPV-associated). (brouwer2024penilecancereauasco pages 1-2)

3. Phenotypes

3.1 Core clinical phenotypes (with HPO suggestions)

A Swedish guideline summary highlights presentation patterns that should trigger suspicion: - Penile ulcer or lump (HPO suggestion: genital ulceration, penile mass) (gerdtsson2025theswedishnational pages 2-4) - Reddish rash refractory to topical corticosteroids (HPO: erythema, rash) (gerdtsson2025theswedishnational pages 2-4) - Bleeding or foul-smelling discharge under a phimotic prepuce (HPO: genital bleeding, malodorous discharge) (gerdtsson2025theswedishnational pages 2-4) - Penile pain (HPO: penile pain) (gerdtsson2025theswedishnational pages 2-4)

3.2 Age of onset and course

  • Typically diagnosed in later decades; global analyses show much higher incidence in older men with an old:young incidence ratio ~9.7:1. (huang2024incidenceriskfactors pages 2-3)
  • Disease is often delayed in presentation due to psychosocial/structural factors (not quantified in retrieved primary evidence here). (jaimecasas2025evaluatingtheevolving pages 9-11)

3.3 Nodal disease (key phenotype for prognosis)

Penile cancer has early lymphatic dissemination; in intermediate/high-risk primary tumors with cN0 groins, micro-metastatic risk is described as 6–30%. (gebruers2023accuracyofdynamic pages 1-2)

3.4 Quality of life (QoL) impact

The EAU-ASCO summary and follow-up review emphasize significant QoL impacts, including: - Psychological distress related to mutilation and perceived loss of masculinity - Sexual and urinary dysfunction - Lymphedema associated with nodal procedures - Need for multidisciplinary supportive/rehabilitative interventions (sexual therapy, counseling). (brouwer2024penilecancereauasco pages 1-2, lasorsa2024followupcare pages 4-5)

4. Genetic / Molecular Information

4.1 Causal genes

Penile cancer is not typically a monogenic inherited disorder; rather it is driven by somatic alterations and, in a subset, viral oncogene effects. No germline causal gene set was established in the retrieved evidence. (brouwer2024penilecancereauasco pages 1-2, nazha2023comprehensivegenomicprofiling pages 1-2)

4.2 Somatic genomic alterations (with frequencies)

Large-scale profiling (Nazha et al., Cancer, Aug 2023)

In 108 pSCC tumors: - TP53 altered: 46% - CDKN2A altered: 26% - PIK3CA altered: 25% Immunotherapy biomarkers in the overall cohort: - PD-L1 positive: 51% - TMB-high (≥10 mut/Mb): 10.7% - dMMR/MSI-high: 1.1% (https://doi.org/10.1002/cncr.34982; Aug 2023) (nazha2023comprehensivegenomicprofiling pages 1-2)

HPV-stratified differences (WES HPV status subset; n=29): - TP53 alterations: 62.5% (HPV−) vs 7.7% (HPV+) (p=0.006) - TERT alterations: 76.9% (HPV−) vs 25.0% (HPV+) (p=0.032) - CDKN2A mutations: 37.5% only in HPV− (0% in HPV+) - TMB-high: 0% (HPV−) vs 30.8% (HPV+) (p=0.035) The authors explicitly caution: “Our finding that TMB-high is exclusive to HPV16/18þ tumors requires confirmation in larger data sets.” (nazha2023comprehensivegenomicprofiling pages 1-2, nazha2023comprehensivegenomicprofiling pages 5-6)

Metastatic cohort from developing-country centers (Monteiro et al., The Oncologist, Sep 2025)

In 18 NGS-profiled metastatic tumors: - TP53: 66.7% - TERT: 50% - CDKN2A: 50% - PIK3CA: 33.3% - NOTCH1: 27.8% (reported only in HPV-negative tumors) Biomarkers: - PD-L1 CPS≥1%: 63.6% - Median TMB: 3.85 mut/Mb (range 0–8.83); no TMB-high cases (https://doi.org/10.1093/oncolo/oyae220; Sep 2025) (monteiro2025molecularcharacterizationof pages 4-6)

4.3 Epigenetic information

Epigenetic biomarker claims (e.g., methylation markers) were referenced in the HPV/p16 systematic review’s citation list but were not extractable as primary quantified findings from the retrieved pages in this run. (parza2023theprognosticrole pages 11-12)

4.4 Mechanism / causal chains (GO/CL suggestions)

HPV-dependent chain

HPV infection → E6/E7 expression → p53/Rb inhibition → cell cycle dysregulation and uncontrolled proliferation; p16 overexpression as surrogate; immune evasion and altered cytokine signaling may shape response to therapy. (mannam2024hpvandpenile pages 5-6, mannam2024hpvandpenile pages 13-14)

Suggested GO biological process terms (examples): - cell cycle checkpoint signaling; regulation of epithelial cell proliferation; response to virus; antigen processing and presentation; interferon-gamma-mediated signaling pathway; negative regulation of immune response. (mannam2024hpvandpenile pages 13-14, jaimecasas2025evaluatingtheevolving pages 9-11)

Suggested CL cell types: - keratinocyte (tumor cell-of-origin in SCC), CD8-positive alpha-beta T cell, regulatory T cell, natural killer cell, tumor-associated macrophage, myeloid-derived suppressor cell. (jaimecasas2025evaluatingtheevolving pages 9-11)

5. Environmental Information

  • Lifestyle/behavioral: smoking; sexual behavior/unsafe sex; hygiene practices; factors leading to chronic occlusion under foreskin. (mannam2024hpvandpenile pages 2-4, huang2024incidenceriskfactors pages 1-2)
  • Infectious agent: high-risk HPV (NCBI Taxon: Human papillomavirus; specific genotypes HPV16/18 prominent). (mannam2024hpvandpenile pages 1-2)

6. Mechanism / Pathophysiology

Penile cancer pathophysiology can be organized into two principal routes: 1) HPV-associated route: viral oncogene-driven cell-cycle disruption and immune microenvironment modulation; may exhibit differing TIL composition and exhaustion signatures as stage advances. (mannam2024hpvandpenile pages 13-14, mannam2024hpvandpenile pages 5-6) 2) HPV-independent route: chronic inflammation/scarring (e.g., lichen sclerosus), with higher rates of TP53/TERT pathway alterations and distinct precursor lesions (differentiated PeIN). (brouwer2024penilecancereauasco pages 1-2, nazha2023comprehensivegenomicprofiling pages 5-6)

Key pathways repeatedly implicated in profiling include TP53, RTK–RAS, PI3K/mTOR, and cell-cycle pathways. (nazha2023comprehensivegenomicprofiling pages 4-5)

7. Anatomical Structures Affected

  • Primary organ: penis (UBERON: penis; common sites include glans and inner prepuce). (gerdtsson2025theswedishnational pages 2-4)
  • Regional spread: superficial and deep inguinal lymph nodes; pelvic nodes in advanced nodal disease. (gerdtsson2025theswedishnational pages 2-4, brouwer2024penilecancereauasco pages 1-2)

8. Temporal Development

  • Progression/staging: prognosis is stage dependent. 2024 global analysis summarizes survival gradients: ~90% 5-year overall survival for localized disease and <10% for metastatic disease. (huang2024incidenceriskfactors pages 1-2)
  • Recurrence timing and surveillance: most local/regional recurrences occur within the first 2 years; EAU-oriented follow-up includes physical exam every 3 months for 2 years then every 6 months for 3 years. (lasorsa2024followupcare pages 4-5)

9. Inheritance and Population

9.1 Epidemiology

Global burden and distribution (Huang et al., BJU International, Dec 2024)

  • Estimated new cases in 2020: 36,068
  • Global ASR (2020): 0.80 per 100,000
  • Highest regional ASRs include South America (1.5), Caribbean (1.4), Melanesia (1.4), South-Central Asia (1.3), Eastern Africa (1.2); Northern America ~0.5. (https://doi.org/10.1111/bju.16224; Dec 2024) (huang2024incidenceriskfactors pages 2-3, huang2024incidenceriskfactors pages 1-2)

A figure from the paper illustrates global ASR variation across age strata. (huang2024incidenceriskfactors media 3423e6f1)

Temporal trends (Huang et al., 2024)

Rising incidence among younger males (15–49) was emphasized, with examples of large AAPC in several jurisdictions (e.g., Martinique AAPC ~29.84; Turkey ~27.14; Japan ~12.84). (huang2024incidenceriskfactors pages 7-7)

9.2 Population demographics

  • Strong age gradient: old:young incidence ratio ~9.7:1 (global). (huang2024incidenceriskfactors pages 2-3)

9.3 Genetic inheritance

Penile cancer is primarily multifactorial/somatic; no Mendelian inheritance pattern is supported by the retrieved evidence. (nazha2023comprehensivegenomicprofiling pages 1-2)

10. Diagnostics

10.1 Clinical diagnosis and pathology

  • Biopsy is essential for diagnosis and classification.
  • The EAU-ASCO 2023 update summary states it is mandatory to determine HPV status at diagnosis; direct HPV detection uses PCR/ISH and p16INK4a immunohistochemistry is a reliable surrogate and should be reported. (brouwer2024penilecancereauasco pages 1-2)

10.2 Nodal staging and DSNB performance (real-world implementation)

A key real-world implementation is DSNB for cN0 intermediate/high-risk patients.

Performance metrics (Gebruers et al., EJNMMI Research, Jun 2023; https://doi.org/10.1186/s13550-023-01013-1): - Detection rate: 91% per procedure, 96% per groin - Sensitivity 79%, specificity 100%, NPV 97%, PPV 100% - DSNB-related adverse events: 1% (1/75 patients) These are reported in the abstract and results extracts. (gebruers2023accuracyofdynamic pages 1-2, gebruers2023accuracyofdynamic pages 4-6)

10.3 Imaging and follow-up

  • Follow-up after penile-sparing surgery: “EAU guidelines recommend physical examination to be performed every 3 months in the first 2 years and every 6 months in the following 3 years.” (Oct 2024; https://doi.org/10.2147/RRU.S465546) (lasorsa2024followupcare pages 4-5)
  • Swedish guideline summary includes groin ultrasound schedules for pN0 surveillance and CT-based follow-up for pN+ disease. (gerdtsson2025theswedishnational pages 5-6)

10.4 Differential diagnosis

Not comprehensively retrievable from the evidence excerpts in this run; however, chronic inflammatory/dermatologic penile lesions (e.g., lichen sclerosus-related changes) can mimic malignancy and warrant low biopsy threshold, especially when refractory. (marques2023clinicalandepidemologic pages 13-18, gerdtsson2025theswedishnational pages 2-4)

11. Outcome / Prognosis

11.1 Stage-based survival

A 2024 global analysis summarizes: ~90% 5-year overall survival for localized penile cancer and <10% for metastatic disease. (huang2024incidenceriskfactors pages 1-2)

11.2 Prognostic factors

  • Lymph node involvement is repeatedly emphasized as central to prognosis and treatment intensity. (brouwer2024penilecancereauasco pages 1-2)
  • Biomarker-driven prognosis is emerging: in a metastatic cohort, NOTCH1 alteration associated with worse survival (mOS 5.4 vs 12.7 months). (monteiro2025molecularcharacterizationof pages 4-6)

11.3 Immunotherapy outcomes in advanced disease (authoritative cohort)

A 2023 JNCI multicenter retrospective cohort (92 patients) reported: - Median OS 9.8 months (95% CI 7.7–12.8) - Median PFS 3.2 months (95% CI 2.5–4.2) - ORR 13% (11/85 evaluable) - ORR 35% in lymph-node–only metastases subgroup - Treatment-related AEs: 29% any grade; 9.8% grade ≥3 (https://doi.org/10.1093/jnci/djad155; Aug 2023) (zarif2023safetyandefficacy pages 1-2)

12. Treatment

12.1 Standards of care (current applications)

  • Localized disease: penile-sparing techniques increasingly recommended; historic 2 cm margins are no longer universally required; local recurrence rates may be higher with sparing approaches but without clear detriment to metastasis-free or overall survival in selected series. (lasorsa2024followupcare pages 4-5)
  • Nodal management: DSNB for staging when indicated; ILND when DSNB unavailable or per informed choice. (brouwer2024penilecancereauasco pages 1-2)
  • Advanced disease: platinum-based chemotherapy regimens are guideline-referenced; bleomycin is discouraged in contemporary guidance. (brouwer2024penilecancereauasco pages 1-2)

12.2 Immunotherapy (emerging/real-world)

ICIs show activity in a subset (see Prognosis section), driving ongoing clinical trials. (zarif2023safetyandefficacy pages 1-2)

12.3 MAXO term suggestions (examples)

  • penile biopsy; immunohistochemistry assay; HPV testing; dynamic sentinel lymph node biopsy; inguinal lymph node dissection; partial penectomy; total penectomy; radiotherapy; platinum-based chemotherapy; immune checkpoint inhibitor therapy; smoking cessation intervention; HPV vaccination. (brouwer2024penilecancereauasco pages 1-2, gebruers2023accuracyofdynamic pages 1-2)

13. Prevention

13.1 Primary prevention

  • HPV vaccination and circumcision and smoking cessation are emphasized prevention levers. (uppal2026penilecancer—apreventable pages 1-2, mannam2024hpvandpenile pages 2-4)

13.2 Secondary prevention

  • Earlier diagnosis of suspicious penile lesions and management of precursor lesions (PeIN) and chronic inflammatory penile dermatoses. (gerdtsson2025theswedishnational pages 2-4, gerdtsson2025theswedishnational pages 1-2)

14. Other Species / Natural Disease

Not addressed in the retrieved sources for this run. No evidence-supported cross-species natural penile cancer summary can be provided without additional targeted veterinary literature retrieval. (brouwer2024penilecancereauasco pages 1-2)

15. Model Organisms

Dedicated animal models were not retrieved in this run. A relevant in vitro direction exists via penile cancer cell line development and chemoresistance modeling (paper retrieved but not extracted here); however, providing specifics without direct evidence excerpts would be speculative. This section should be populated after targeted model-system literature retrieval (e.g., Cellosaurus-listed penile SCC lines; xenograft/organoid reports). (brouwer2024penilecancereauasco pages 1-2)

Key Evidence Table

The table below consolidates knowledge-base-ready facts with citations, ontology suggestions, and key numeric findings.

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. (taghizadeh2025immunotherapyinthe pages 1-2, brouwer2024penilecancereauasco pages 1-2) 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). (mannam2024hpvandpenile pages 1-2, marques2023clinicalandepidemologic pages 13-18, uppal2026penilecancer—apreventable pages 1-2, mannam2024hpvandpenile pages 2-4, huang2024incidenceriskfactors pages 1-2) 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. (huang2024incidenceriskfactors pages 2-3, huang2024incidenceriskfactors pages 1-2, huang2024incidenceriskfactors pages 7-7, lasorsa2024followupcare pages 4-5, huang2024incidenceriskfactors media 3423e6f1) 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%. (gerdtsson2025theswedishnational pages 2-4, gerdtsson2025theswedishnational pages 1-2) 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. (nazha2023comprehensivegenomicprofiling pages 1-2, monteiro2025molecularcharacterizationof pages 4-6, nazha2023comprehensivegenomicprofiling pages 4-5) 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%. (brouwer2024penilecancereauasco pages 1-2, brouwer2024penilecancereauasco pages 3-4, gebruers2023accuracyofdynamic pages 4-6) 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). (huang2024incidenceriskfactors pages 1-2, monteiro2025molecularcharacterizationof pages 4-6, lasorsa2024followupcare pages 4-5) 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%. (brouwer2024penilecancereauasco pages 1-2, lasorsa2024followupcare pages 4-5, taghizadeh2025immunotherapyinthe pages 2-4) 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. (uppal2026penilecancer—apreventable pages 1-2, mannam2024hpvandpenile pages 2-4) 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). (gebruers2023accuracyofdynamic pages 4-6) 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. (gerdtsson2025theswedishnational pages 5-6, lasorsa2024followupcare pages 4-5) 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.

High-value recent sources (2023–2024 prioritized)

  • Huang J et al. BJU International. Incidence, risk factors, and temporal trends of penile cancer: a global population-based study. Dec 2024. https://doi.org/10.1111/bju.16224 (huang2024incidenceriskfactors pages 2-3, huang2024incidenceriskfactors pages 7-7, huang2024incidenceriskfactors media 3423e6f1)
  • Brouwer OR et al. JCO Oncology Practice. Penile Cancer: EAU-ASCO Collaborative Guidelines Update Q and A. Jan 2024. https://doi.org/10.1200/op.23.00585 (brouwer2024penilecancereauasco pages 1-2)
  • Mannam G et al. Pathogens. HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights. Sep 2024. https://doi.org/10.3390/pathogens13090809 (mannam2024hpvandpenile pages 1-2, mannam2024hpvandpenile pages 2-4, mannam2024hpvandpenile pages 5-6)
  • Gebruers J et al. EJNMMI Research. Accuracy of dynamic sentinel lymph node biopsy… Jun 2023. https://doi.org/10.1186/s13550-023-01013-1 (gebruers2023accuracyofdynamic pages 1-2)
  • Nazha B et al. Cancer. Comprehensive genomic profiling… Aug 2023. https://doi.org/10.1002/cncr.34982 (nazha2023comprehensivegenomicprofiling pages 1-2)
  • El Zarif T et al. JNCI. Safety and efficacy of immune checkpoint inhibitors… Aug 2023. https://doi.org/10.1093/jnci/djad155 (zarif2023safetyandefficacy pages 1-2)

Notes on evidence gaps

  • MONDO ID and Orphanet identifiers were not available in retrieved texts; these should be directly queried from MONDO/Orphanet for database completion.
  • Animal models / comparative species information was not retrieved; additional targeted searches are needed for a complete knowledge base entry.
  • Several topics (epigenetics, differential diagnosis, omics diagnostics, protective genetic variants) were only indirectly referenced and require dedicated primary literature retrieval for fully PMID-anchored claims.

References

  1. (taghizadeh2025immunotherapyinthe pages 1-2): Hossein Taghizadeh and Harun Fajkovic. Immunotherapy in the management of penile cancer—a systematic review. Cancers, 17:883, Mar 2025. URL: https://doi.org/10.3390/cancers17050883, doi:10.3390/cancers17050883. This article has 8 citations.

  2. (brouwer2024penilecancereauasco pages 1-2): Oscar R. Brouwer, R. Bryan Rumble, Benjamin Ayres, Diego F. Sánchez Martínez, Pedro Oliveira, Philippe E. Spiess, Peter A.S. Johnstone, Juanita Crook, Curtis A. Pettaway, Scott T. Tagawa, Oscar R. Brouwer, Scott T. Tagawa, Maarten Albersen, Tiago Antunes-Lopes, Benjamin Ayres, Lenka Barreto, Riccardo Campi, Juanita Crook, Sergio Fernández-Pello, Herney A. Garcia-Perdomo, Isabella Greco, Peter A.S. Johnstone, Kenneth Manzie, Jack David Marcus, Andrea Necchi, Pedro Oliveira, John Osborne, Lance C. Pagliaro, Arie Parnham, Curtis A. Pettaway, Chris Protzel, Ashwin Sachdeva, Vasileios I. Sakalis, Diego F. Sánchez Martínez, Philippe E. Spiess, Michiel S. van der Heijden, Łukasz Zapala, and R. Bryan Rumble. Penile cancer: eau-asco collaborative guidelines update q and a. JCO Oncology Practice, 20:33-37, Jan 2024. URL: https://doi.org/10.1200/op.23.00585, doi:10.1200/op.23.00585. This article has 34 citations and is from a peer-reviewed journal.

  3. (mannam2024hpvandpenile pages 1-2): Gowtam Mannam, Justin W. Miller, Jeffrey S. Johnson, Keerthi Gullapalli, Adnan Fazili, Philippe E. Spiess, and Jad Chahoud. Hpv and penile cancer: epidemiology, risk factors, and clinical insights. Pathogens, 13:809, Sep 2024. URL: https://doi.org/10.3390/pathogens13090809, doi:10.3390/pathogens13090809. This article has 28 citations.

  4. (mannam2024hpvandpenile pages 2-4): Gowtam Mannam, Justin W. Miller, Jeffrey S. Johnson, Keerthi Gullapalli, Adnan Fazili, Philippe E. Spiess, and Jad Chahoud. Hpv and penile cancer: epidemiology, risk factors, and clinical insights. Pathogens, 13:809, Sep 2024. URL: https://doi.org/10.3390/pathogens13090809, doi:10.3390/pathogens13090809. This article has 28 citations.

  5. (huang2024incidenceriskfactors pages 1-2): Junjie Huang, Sze Chai Chan, Wing Sze Pang, Xianjing Liu, Lin Zhang, Don Eliseo Lucero‐Prisno, Wanghong Xu, Zhi‐Jie Zheng, Anthony Chi‐Fai Ng, Andrea Necchi, Philippe E. Spiess, Jeremy Yuen‐Chun Teoh, and Martin C.S. Wong. Incidence, risk factors, and temporal trends of penile cancer: a global population‐based study. BJU International, 133:314-323, Dec 2024. URL: https://doi.org/10.1111/bju.16224, doi:10.1111/bju.16224. This article has 35 citations and is from a domain leading peer-reviewed journal.

  6. (gebruers2023accuracyofdynamic pages 1-2): Juanito Gebruers, Laura Elst, Marcella Baldewijns, Liesbeth De Wever, Koen Van Laere, Maarten Albersen, and Karolien Goffin. Accuracy of dynamic sentinel lymph node biopsy for inguinal lymph node staging in cn0 penile cancer. EJNMMI Research, Jun 2023. URL: https://doi.org/10.1186/s13550-023-01013-1, doi:10.1186/s13550-023-01013-1. This article has 7 citations and is from a peer-reviewed journal.

  7. (zarif2023safetyandefficacy pages 1-2): Talal El Zarif, Amin H Nassar, Gregory R Pond, Tony Zibo Zhuang, Viraj Master, Bassel Nazha, Scot Niglio, Nicholas Simon, Andrew W Hahn, Curtis A Pettaway, Shi-Ming Tu, Noha Abdel-Wahab, Maud Velev, Ronan Flippot, Sebastiano Buti, Marco Maruzzo, Arjun Mittra, Jinesh Gheeya, Yuanquan Yang, Pablo Alvarez Rodriguez, Daniel Castellano, Guillermo de Velasco, Giandomenico Roviello, Lorenzo Antonuzzo, Rana R McKay, Bruno Vincenzi, Alessio Cortellini, Gavin Hui, Alexandra Drakaki, Michael Glover, Ali Raza Khaki, Edward El-Am, Nabil Adra, Tarek H Mouhieddine, Vaibhav Patel, Aida Piedra, Angela Gernone, Nancy B Davis, Harrison Matthews, Michael R Harrison, Ravindran Kanesvaran, Giulia Claire Giudice, Pedro Barata, Alberto Farolfi, Jae Lyun Lee, Matthew I Milowsky, Charlotte Stahlfeld, Leonard Appleman, Joseph W Kim, Dory Freeman, Toni K Choueiri, Philippe E Spiess, Andrea Necchi, Andrea B Apolo, and Guru P Sonpavde. Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the global society of rare genitourinary tumors. Journal of the National Cancer Institute, 115:1605-1615, Aug 2023. URL: https://doi.org/10.1093/jnci/djad155, doi:10.1093/jnci/djad155. This article has 56 citations and is from a highest quality peer-reviewed journal.

  8. (gerdtsson2025theswedishnational pages 2-4): Axel Gerdtsson, Eliya Abedi, Gediminas Baseckas, Håkan Brorson, Luiza Dorofte, Sofia Fall, Emelie Filipsson, Johan Forssell, Dominik Glombik, Diane Grelaud, Fatou Hellman, Anna-Karin Jakobsson, Kimia Kohestani, Sinja Kristiansen, Jenny Magnusson, Kajsa Nilsson, Per Nordlund, Erik Persson, Theodoros Psarias, Elisabeth Skeppner, Elin Trägårdh, Emma Ulvskog, Åsa Warnolf, Elisabeth Öfverholm, and Peter Kirrander. The swedish national guidelines on penile cancer. Scandinavian Journal of Urology, 60:189-194, Sep 2025. URL: https://doi.org/10.2340/sju.v60.44463, doi:10.2340/sju.v60.44463. This article has 3 citations and is from a peer-reviewed journal.

  9. (gerdtsson2025theswedishnational pages 1-2): Axel Gerdtsson, Eliya Abedi, Gediminas Baseckas, Håkan Brorson, Luiza Dorofte, Sofia Fall, Emelie Filipsson, Johan Forssell, Dominik Glombik, Diane Grelaud, Fatou Hellman, Anna-Karin Jakobsson, Kimia Kohestani, Sinja Kristiansen, Jenny Magnusson, Kajsa Nilsson, Per Nordlund, Erik Persson, Theodoros Psarias, Elisabeth Skeppner, Elin Trägårdh, Emma Ulvskog, Åsa Warnolf, Elisabeth Öfverholm, and Peter Kirrander. The swedish national guidelines on penile cancer. Scandinavian Journal of Urology, 60:189-194, Sep 2025. URL: https://doi.org/10.2340/sju.v60.44463, doi:10.2340/sju.v60.44463. This article has 3 citations and is from a peer-reviewed journal.

  10. (mannam2024hpvandpenile pages 5-6): Gowtam Mannam, Justin W. Miller, Jeffrey S. Johnson, Keerthi Gullapalli, Adnan Fazili, Philippe E. Spiess, and Jad Chahoud. Hpv and penile cancer: epidemiology, risk factors, and clinical insights. Pathogens, 13:809, Sep 2024. URL: https://doi.org/10.3390/pathogens13090809, doi:10.3390/pathogens13090809. This article has 28 citations.

  11. (uppal2026penilecancer—apreventable pages 1-2): Encarl Uppal, Georgios Kravvas, Hussain Alnajjar, Asif Muneer, and Christopher Bunker. Penile cancer—a preventable cause of death in elderly men. British Journal of Hospital Medicine, Mar 2026. URL: https://doi.org/10.31083/bjhm51831, doi:10.31083/bjhm51831. This article has 0 citations and is from a peer-reviewed journal.

  12. (huang2024incidenceriskfactors pages 2-3): Junjie Huang, Sze Chai Chan, Wing Sze Pang, Xianjing Liu, Lin Zhang, Don Eliseo Lucero‐Prisno, Wanghong Xu, Zhi‐Jie Zheng, Anthony Chi‐Fai Ng, Andrea Necchi, Philippe E. Spiess, Jeremy Yuen‐Chun Teoh, and Martin C.S. Wong. Incidence, risk factors, and temporal trends of penile cancer: a global population‐based study. BJU International, 133:314-323, Dec 2024. URL: https://doi.org/10.1111/bju.16224, doi:10.1111/bju.16224. This article has 35 citations and is from a domain leading peer-reviewed journal.

  13. (jaimecasas2025evaluatingtheevolving pages 9-11): Salvador Jaime-Casas, Regina Barragan-Carrillo, Federico Eskenazi, Juan P. Dugarte, Jad Chahoud, Philippe E. Spiess, and Luis G. Medina. Evaluating the evolving treatment landscape of systemic therapies in penile cancer. Cancers, 17:2956, Sep 2025. URL: https://doi.org/10.3390/cancers17182956, doi:10.3390/cancers17182956. This article has 5 citations.

  14. (lasorsa2024followupcare pages 4-5): Francesco Lasorsa, Gabriele Bignante, Angelo Orsini, Sofia Rossetti, Michele Marchioni, Francesco Porpiglia, Pasquale Ditonno, Giuseppe Lucarelli, Riccardo Autorino, and Celeste Manfredi. Follow up care after penile sparing surgery for penile cancer: current perspectives. Research and Reports in Urology, 16:225-233, Oct 2024. URL: https://doi.org/10.2147/rru.s465546, doi:10.2147/rru.s465546. This article has 3 citations.

  15. (nazha2023comprehensivegenomicprofiling pages 1-2): Bassel Nazha, Tony Zhuang, Sharon Wu, Jacqueline T. Brown, Daniel Magee, Bradley C. Carthon, Omer Kucuk, Chadi Nabhan, Pedro C. Barata, Elisabeth I. Heath, Charles J. Ryan, Rana R. McKay, Viraj A. Master, and Mehmet Asim Bilen. Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune‐checkpoint inhibitor‐related biomarkers. Cancer, 129:3884-3893, Aug 2023. URL: https://doi.org/10.1002/cncr.34982, doi:10.1002/cncr.34982. This article has 45 citations and is from a domain leading peer-reviewed journal.

  16. (nazha2023comprehensivegenomicprofiling pages 5-6): Bassel Nazha, Tony Zhuang, Sharon Wu, Jacqueline T. Brown, Daniel Magee, Bradley C. Carthon, Omer Kucuk, Chadi Nabhan, Pedro C. Barata, Elisabeth I. Heath, Charles J. Ryan, Rana R. McKay, Viraj A. Master, and Mehmet Asim Bilen. Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune‐checkpoint inhibitor‐related biomarkers. Cancer, 129:3884-3893, Aug 2023. URL: https://doi.org/10.1002/cncr.34982, doi:10.1002/cncr.34982. This article has 45 citations and is from a domain leading peer-reviewed journal.

  17. (monteiro2025molecularcharacterizationof pages 4-6): Fernando Sabino Marques Monteiro, Antonio Machado Alencar Junior, Karine Martins da Trindade, Taiane Francieli Rebelatto, Fernando C Maluf, Antonia A Gazzola, Pablo M Barrios, Joaquim Bellmunt, Rafaela Gomes de Jesus, Gyl Eanes Barros Silva, Antonio Augusto Lima Teixeira Junior, Philippe E Spiess, and Andre P Fay. Molecular characterization of metastatic penile squamous cell carcinoma in developing countries and its impact on clinical outcomes: lacog 2018 translational study. The Oncologist, Sep 2025. URL: https://doi.org/10.1093/oncolo/oyae220, doi:10.1093/oncolo/oyae220. This article has 10 citations.

  18. (parza2023theprognosticrole pages 11-12): Kevin Parza, Arfa Mustasam, Filip Ionescu, Mahati Paravathaneni, Reagan Sandstrom, Houssein Safa, G. Daniel Grass, Peter A. Johnstone, Steven A. Eschrich, Juskaran Chadha, Niki Zacharias, Curtis A. Pettaway, Philippe E. Spiess, and Jad Chahoud. The prognostic role of human papillomavirus and p16 status in penile squamous cell carcinoma—a systematic review. Cancers, 15:3713, Jul 2023. URL: https://doi.org/10.3390/cancers15143713, doi:10.3390/cancers15143713. This article has 27 citations.

  19. (mannam2024hpvandpenile pages 13-14): Gowtam Mannam, Justin W. Miller, Jeffrey S. Johnson, Keerthi Gullapalli, Adnan Fazili, Philippe E. Spiess, and Jad Chahoud. Hpv and penile cancer: epidemiology, risk factors, and clinical insights. Pathogens, 13:809, Sep 2024. URL: https://doi.org/10.3390/pathogens13090809, doi:10.3390/pathogens13090809. This article has 28 citations.

  20. (nazha2023comprehensivegenomicprofiling pages 4-5): Bassel Nazha, Tony Zhuang, Sharon Wu, Jacqueline T. Brown, Daniel Magee, Bradley C. Carthon, Omer Kucuk, Chadi Nabhan, Pedro C. Barata, Elisabeth I. Heath, Charles J. Ryan, Rana R. McKay, Viraj A. Master, and Mehmet Asim Bilen. Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune‐checkpoint inhibitor‐related biomarkers. Cancer, 129:3884-3893, Aug 2023. URL: https://doi.org/10.1002/cncr.34982, doi:10.1002/cncr.34982. This article has 45 citations and is from a domain leading peer-reviewed journal.

  21. (huang2024incidenceriskfactors media 3423e6f1): Junjie Huang, Sze Chai Chan, Wing Sze Pang, Xianjing Liu, Lin Zhang, Don Eliseo Lucero‐Prisno, Wanghong Xu, Zhi‐Jie Zheng, Anthony Chi‐Fai Ng, Andrea Necchi, Philippe E. Spiess, Jeremy Yuen‐Chun Teoh, and Martin C.S. Wong. Incidence, risk factors, and temporal trends of penile cancer: a global population‐based study. BJU International, 133:314-323, Dec 2024. URL: https://doi.org/10.1111/bju.16224, doi:10.1111/bju.16224. This article has 35 citations and is from a domain leading peer-reviewed journal.

  22. (huang2024incidenceriskfactors pages 7-7): Junjie Huang, Sze Chai Chan, Wing Sze Pang, Xianjing Liu, Lin Zhang, Don Eliseo Lucero‐Prisno, Wanghong Xu, Zhi‐Jie Zheng, Anthony Chi‐Fai Ng, Andrea Necchi, Philippe E. Spiess, Jeremy Yuen‐Chun Teoh, and Martin C.S. Wong. Incidence, risk factors, and temporal trends of penile cancer: a global population‐based study. BJU International, 133:314-323, Dec 2024. URL: https://doi.org/10.1111/bju.16224, doi:10.1111/bju.16224. This article has 35 citations and is from a domain leading peer-reviewed journal.

  23. (gebruers2023accuracyofdynamic pages 4-6): Juanito Gebruers, Laura Elst, Marcella Baldewijns, Liesbeth De Wever, Koen Van Laere, Maarten Albersen, and Karolien Goffin. Accuracy of dynamic sentinel lymph node biopsy for inguinal lymph node staging in cn0 penile cancer. EJNMMI Research, Jun 2023. URL: https://doi.org/10.1186/s13550-023-01013-1, doi:10.1186/s13550-023-01013-1. This article has 7 citations and is from a peer-reviewed journal.

  24. (gerdtsson2025theswedishnational pages 5-6): Axel Gerdtsson, Eliya Abedi, Gediminas Baseckas, Håkan Brorson, Luiza Dorofte, Sofia Fall, Emelie Filipsson, Johan Forssell, Dominik Glombik, Diane Grelaud, Fatou Hellman, Anna-Karin Jakobsson, Kimia Kohestani, Sinja Kristiansen, Jenny Magnusson, Kajsa Nilsson, Per Nordlund, Erik Persson, Theodoros Psarias, Elisabeth Skeppner, Elin Trägårdh, Emma Ulvskog, Åsa Warnolf, Elisabeth Öfverholm, and Peter Kirrander. The swedish national guidelines on penile cancer. Scandinavian Journal of Urology, 60:189-194, Sep 2025. URL: https://doi.org/10.2340/sju.v60.44463, doi:10.2340/sju.v60.44463. This article has 3 citations and is from a peer-reviewed journal.

  25. (marques2023clinicalandepidemologic pages 13-18): ARM Marques. Clinical and epidemologic relevance of hpv in penile cancer: a retrospective study. Unknown journal, 2023.

  26. (brouwer2024penilecancereauasco pages 3-4): Oscar R. Brouwer, R. Bryan Rumble, Benjamin Ayres, Diego F. Sánchez Martínez, Pedro Oliveira, Philippe E. Spiess, Peter A.S. Johnstone, Juanita Crook, Curtis A. Pettaway, Scott T. Tagawa, Oscar R. Brouwer, Scott T. Tagawa, Maarten Albersen, Tiago Antunes-Lopes, Benjamin Ayres, Lenka Barreto, Riccardo Campi, Juanita Crook, Sergio Fernández-Pello, Herney A. Garcia-Perdomo, Isabella Greco, Peter A.S. Johnstone, Kenneth Manzie, Jack David Marcus, Andrea Necchi, Pedro Oliveira, John Osborne, Lance C. Pagliaro, Arie Parnham, Curtis A. Pettaway, Chris Protzel, Ashwin Sachdeva, Vasileios I. Sakalis, Diego F. Sánchez Martínez, Philippe E. Spiess, Michiel S. van der Heijden, Łukasz Zapala, and R. Bryan Rumble. Penile cancer: eau-asco collaborative guidelines update q and a. JCO Oncology Practice, 20:33-37, Jan 2024. URL: https://doi.org/10.1200/op.23.00585, doi:10.1200/op.23.00585. This article has 34 citations and is from a peer-reviewed journal.

  27. (taghizadeh2025immunotherapyinthe pages 2-4): Hossein Taghizadeh and Harun Fajkovic. Immunotherapy in the management of penile cancer—a systematic review. Cancers, 17:883, Mar 2025. URL: https://doi.org/10.3390/cancers17050883, doi:10.3390/cancers17050883. This article has 8 citations.

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