Vulvar carcinoma is a rare epithelial malignancy of the vulva. Vulvar squamous cell carcinoma is the dominant histologic subtype, and current molecular classification separates HPV-associated tumors from HPV-independent tumors, the latter often involving TP53 pathway disruption and chronic vulvar dermatoses such as lichen sclerosus.
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name: Vulvar Carcinoma
creation_date: "2026-05-07T18:59:34Z"
updated_date: "2026-05-07T19:58:48Z"
synonyms:
- Vulvar cancer
- Carcinoma of the vulva
- Vulvar squamous cell carcinoma
- VSCC
description: >-
Vulvar carcinoma is a rare epithelial malignancy of the vulva. Vulvar
squamous cell carcinoma is the dominant histologic subtype, and current
molecular classification separates HPV-associated tumors from
HPV-independent tumors, the latter often involving TP53 pathway disruption
and chronic vulvar dermatoses such as lichen sclerosus.
categories:
- Gynecologic Malignancy
- Solid Tumor
- HPV-Related Cancer
parents:
- vulva cancer
disease_term:
preferred_term: vulvar carcinoma
term:
id: MONDO:0005215
label: vulvar carcinoma
definitions:
- name: Clinicopathologic definition
definition_type: CASE_DEFINITION
description: >-
Vulvar carcinoma is a vulvar epithelial cancer, most commonly squamous
cell carcinoma, diagnosed by biopsy of a suspicious vulvar lesion and
staged with clinical, pathologic, and imaging assessment of local and
nodal disease.
scope: General adult gynecologic oncology definition
evidence:
- reference: PMID:38791925
reference_title: "Current Preoperative Management of Vulvar Squamous Cell Carcinoma: An Overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Vulvar carcinoma is a rare cancer affecting the genital tract,
constituting 4% of gynecological tumors. Vulvar squamous cell carcinoma
(VSCC) is the most common type. Diagnosis relies on biopsy during
vulvoscopy, plus imaging such as ultrasonography (USG), magnetic
resonance imaging (MRI) and positron emission tomography (PET).
explanation: >-
This review defines vulvar carcinoma as a rare gynecologic cancer,
identifies VSCC as the most common type, and summarizes biopsy and
imaging-based preoperative assessment.
- reference: DOI:10.1055/a-1545-4279
reference_title: "2020 WHO Classification of Female Genital Tumors"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The 2020 WHO classification is focused on the distinction between
HPV-associated and HPV-independent squamous cell carcinoma of the lower
female genital organs.
explanation: >-
The WHO classification review supports HPV-associated versus
HPV-independent classification for lower female genital squamous cell
carcinoma, including vulvar squamous carcinoma.
has_subtypes:
- name: HPV-Associated VSCC
display_name: HPV-associated vulvar squamous cell carcinoma
description: >-
Molecular subtype associated with high-risk human papillomavirus,
p16INK4A positivity, and generally better prognosis than HPV-independent
disease.
evidence:
- reference: PMID:37840151
reference_title: "TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Vulva squamous cell carcinoma (VSCC) develops through two separate
molecular pathways-one involving high-risk human papilloma virus
infection (HPV-associated), and the other without HPV infection
(HPV-independent) often involving TP53 mutation. HPV-associated VSCC
generally has a better progression-free survival than HPV-independent
VSCC.
explanation: >-
The cohort paper directly supports HPV-associated VSCC as a distinct
molecular pathway and links it to better progression-free survival.
- name: HPV-Independent TP53-Altered VSCC
display_name: HPV-independent TP53-altered vulvar squamous cell carcinoma
description: >-
Molecular subtype not driven by HPV, commonly keratinizing, enriched for
TP53 alteration and other somatic lesions, and often associated with
differentiated VIN and lichen sclerosus.
evidence:
- reference: PMID:37840151
reference_title: "TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Vulva squamous cell carcinoma (VSCC) develops through two separate
molecular pathways-one involving high-risk human papilloma virus
infection (HPV-associated), and the other without HPV infection
(HPV-independent) often involving TP53 mutation.
explanation: >-
This abstract explicitly distinguishes the HPV-independent pathway and
notes frequent TP53 mutation involvement.
- name: HPV-Independent p53-Wild-Type VSCC
display_name: HPV-independent p53-wild-type vulvar squamous cell carcinoma
description: >-
Uncommon HPV-independent molecular subtype lacking abnormal p53
immunophenotype, with intermediate prognosis between HPV-associated and
HPV-independent TP53-altered disease.
evidence:
- reference: DOI:10.3390/cancers16244216
reference_title: "Molecular Subtypes of Vulvar Squamous Cell Carcinoma: The Significance of HPV-Independent/p53 Wild Type"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
These three molecular subtypes of VSCC (HPVa, HPVi p53 abnormal, and HPVi
p53 wild type), as well as their precursor lesions, cannot be diagnosed
based on a routine histopathological examination or immunostaining for p53
and p16 as surrogate markers for TP53 mutation and high-risk HPV
infection, respectively, are required.
explanation: >-
The review explicitly describes HPV-independent p53-wild-type VSCC as a
third molecular subtype requiring p16 and p53 immunostaining.
infectious_agent:
- name: High-Risk Human Papillomavirus
description: >-
High-risk HPV infection drives the HPV-associated pathway of vulvar
squamous cell carcinoma through viral oncogene effects and is commonly
assessed by p16 immunohistochemistry or HPV RNA/DNA testing.
infectious_agent_term:
preferred_term: Human papillomavirus 16
term:
id: NCBITaxon:333760
label: Human papillomavirus 16
evidence:
- reference: PMID:37840151
reference_title: "TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Immunohistochemistry for p53, Ki67 and p16INK4A (a surrogate marker for
HPV infection) was performed on formalin-fixed paraffin-embedded tissues
from a cohort of surgically treated VSCC patients to identify molecular
subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR
and HPV mRNA in situ hybridization (ISH).
explanation: >-
This cohort operationalizes HPV-associated VSCC using p16, HPV DNA PCR,
and HPV mRNA ISH, supporting high-risk HPV as the infectious driver in
this molecular subtype.
pathophysiology:
- name: HPV-Associated Tumor Suppressor Disruption
description: >-
Persistent high-risk HPV infection defines one major VSCC pathway. Viral
oncogene activity is reflected by p16INK4A positivity and produces cell
cycle deregulation in vulvar squamous epithelium.
evidence:
- reference: PMID:37840151
reference_title: "TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
p16INK4A immunohistochemistry, mRNA ISH, and DNA PCR had excellent
concordance in terms of HPV detection.
explanation: >-
Concordance of p16 with HPV detection supports p16-marked HPV-associated
biology as a major VSCC pathway.
cell_types:
- preferred_term: vulvar keratinocyte
term:
id: CL:0000312
label: keratinocyte
locations:
- preferred_term: vulva
term:
id: UBERON:0000997
label: mammalian vulva
biological_processes:
- preferred_term: response to virus
term:
id: GO:0009615
label: response to virus
- preferred_term: G1/S transition of mitotic cell cycle
modifier: INCREASED
term:
id: GO:0000082
label: G1/S transition of mitotic cell cycle
downstream:
- target: Clonal Squamous Cell Proliferation
description: HPV-associated cell-cycle deregulation promotes expansion of transformed vulvar keratinocytes.
- name: Lichen Sclerosus Inflammatory Microenvironment
description: >-
Lichen sclerosus creates chronic vulvar inflammation, tissue remodeling,
oxidative stress, scarring, and symptoms that can precede or accompany
HPV-independent vulvar squamous carcinogenesis.
evidence:
- reference: DOI:10.3389/fmed.2023.1106318
reference_title: "Lichen sclerosus: The 2023 update"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Oxidative stress with lipid and DNA peroxidation provides an enabling
microenvironment to autoimmunity and carcinogenesis.
explanation: >-
The review supports oxidative stress and immune-mediated tissue injury
as a carcinogenesis-enabling microenvironment in lichen sclerosus.
- reference: DOI:10.3389/fmed.2023.1106318
reference_title: "Lichen sclerosus: The 2023 update"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In addition to genital scarring, and sexual and urinary dysfunction, LS
may also lead to squamous cell carcinoma.
explanation: >-
This explicitly links lichen sclerosus to squamous cell carcinoma risk.
cell_types:
- preferred_term: vulvar keratinocyte
term:
id: CL:0000312
label: keratinocyte
locations:
- preferred_term: vulva
term:
id: UBERON:0000997
label: mammalian vulva
biological_processes:
- preferred_term: extracellular matrix organization
modifier: ABNORMAL
term:
id: GO:0030198
label: extracellular matrix organization
downstream:
- target: HPV-Independent Somatic Driver Accumulation
description: Chronic inflammatory and oxidative injury can create a permissive context for somatic driver selection.
- name: HPV-Independent Somatic Driver Accumulation
description: >-
HPV-independent VSCC is enriched for TERT promoter, TP53, CDKN2A, NOTCH1,
and FAT1 alterations, supporting a tumor-suppressor and differentiation
failure pathway distinct from HPV-driven tumors.
evidence:
- reference: PMID:34650187
reference_title: "Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Other common abnormalities in HPV-independent tumors were TP53 mutations
(13/15, 87%), CDKN2A alterations (10/15, 67%), and NOTCH1 and FAT1
mutations (7/15, 47% each).
explanation: >-
Sequencing of vulvovaginal squamous carcinomas identifies recurrent
TP53, CDKN2A, NOTCH1, and FAT1 alterations in HPV-independent tumors.
- reference: PMID:34650187
reference_title: "Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Cancer cell fraction analysis of HPV-independent squamous carcinomas
suggests that TERT and/or NOTCH1 alterations along with TP53 alterations
can be the initiating event in these tumors.
explanation: >-
The paper places TERT, NOTCH1, and TP53 alterations early in the
HPV-independent carcinogenic pathway.
genes:
- preferred_term: TP53
term:
id: hgnc:11998
label: TP53
- preferred_term: TERT
term:
id: hgnc:11730
label: TERT
- preferred_term: CDKN2A
term:
id: hgnc:1787
label: CDKN2A
- preferred_term: NOTCH1
term:
id: hgnc:7881
label: NOTCH1
- preferred_term: FAT1
term:
id: hgnc:3595
label: FAT1
cell_types:
- preferred_term: vulvar keratinocyte
term:
id: CL:0000312
label: keratinocyte
biological_processes:
- preferred_term: apoptotic process
modifier: DECREASED
term:
id: GO:0006915
label: apoptotic process
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
downstream:
- target: Clonal Squamous Cell Proliferation
description: Somatic driver alterations support malignant clonal expansion in vulvar keratinocytes.
- name: PIK3CA-Activated HPV-Associated Signaling
description: >-
HPV-associated vulvovaginal squamous carcinomas are enriched for PIK3CA
activating mutations, implicating PI3K pathway activation in a subset of
HPV-driven tumors.
evidence:
- reference: PMID:34650187
reference_title: "Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
HPV-associated vulvovaginal squamous cell carcinoma had PIK3CA
activating mutations (7/11, 64%) as the most common genomic event
explanation: >-
This sequencing cohort supports PIK3CA activation as a recurrent event
in HPV-associated vulvovaginal squamous carcinoma.
genes:
- preferred_term: PIK3CA
term:
id: hgnc:8975
label: PIK3CA
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
downstream:
- target: Clonal Squamous Cell Proliferation
description: PI3K pathway activation supports tumor cell growth and survival.
- name: HRAS/RAS-MAPK Signaling Activation
description: >-
HRAS mutations occur in a subset of VSCC and implicate RAS/MAPK signaling as
an additional proliferation pathway in vulvar squamous carcinoma.
evidence:
- reference: DOI:10.1038/s41598-024-63913-z
reference_title: "Genomic profiles of Japanese patients with vulvar squamous cell carcinoma"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Somatic mutations were identified by targeted or panel sequencing, and TP53
was identified as the most common mutation (52–81%), followed by HRAS
(7–26%), CDKN2A (21–24%), and PIK3CA (5–10%).
explanation: >-
The Japanese VSCC sequencing cohort identifies recurrent HRAS mutations,
supporting a RAS/MAPK-linked somatic driver mechanism.
genes:
- preferred_term: HRAS
term:
id: hgnc:5173
label: HRAS
biological_processes:
- preferred_term: MAPK cascade
modifier: INCREASED
term:
id: GO:0000165
label: MAPK cascade
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
downstream:
- target: Clonal Squamous Cell Proliferation
description: HRAS-driven MAPK signaling can promote transformed keratinocyte proliferation.
- name: Clonal Squamous Cell Proliferation
description: >-
HPV-driven cell-cycle deregulation or HPV-independent somatic driver
accumulation leads to clonal proliferation and invasive squamous carcinoma
in the vulvar epithelium.
cell_types:
- preferred_term: vulvar keratinocyte
term:
id: CL:0000312
label: keratinocyte
locations:
- preferred_term: vulva
term:
id: UBERON:0000997
label: mammalian vulva
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
histopathology:
- name: Squamous Cell Carcinoma
finding_term:
preferred_term: Squamous Cell Carcinoma
term:
id: NCIT:C2929
label: Squamous Cell Carcinoma
diagnostic: true
description: >-
Vulvar squamous cell carcinoma is the most common histologic type of
vulvar carcinoma.
evidence:
- reference: PMID:38791925
reference_title: "Current Preoperative Management of Vulvar Squamous Cell Carcinoma: An Overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Vulvar squamous cell carcinoma (VSCC) is the most common type.
explanation: >-
This review supports squamous cell carcinoma as the dominant vulvar
carcinoma histology.
phenotypes:
- category: Gynecologic
name: Biopsy-Requiring Vulvar Lesion
diagnostic: true
description: >-
A persistent or suspicious vulvar lesion requires biopsy to establish or
exclude vulvar carcinoma.
phenotype_term:
preferred_term: vulvar lesion
term:
id: HP:0011355
label: Localized skin lesion
evidence:
- reference: PMID:38791925
reference_title: "Current Preoperative Management of Vulvar Squamous Cell Carcinoma: An Overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Diagnosis relies on biopsy during vulvoscopy, plus imaging such as
ultrasonography (USG), magnetic resonance imaging (MRI) and positron
emission tomography (PET).
explanation: >-
The need for vulvoscopy-directed biopsy supports a visible or clinically
suspicious vulvar lesion as the diagnostic presentation.
- category: Gynecologic
name: Vulvar Lump or Mass
description: >-
Patients with vulvar cancer may notice a vulvar lump or mass as part of the
presenting lesion complex.
phenotype_term:
preferred_term: vulvar lump or mass
term:
id: HP:0002664
label: Neoplasm
evidence:
- reference: DOI:10.1002/ijgo.13881
reference_title: "Cancer of the vulva: 2021 update"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
While vulvar cancer may be asymptomatic, most women present with vulvar
pruritus or pain, or have noticed a lump or ulcer.
explanation: >-
The clinical update identifies a noticed lump as a presenting feature of
vulvar cancer; the HPO binding uses the broad neoplasm term because local
HPO did not provide a vulvar-specific mass term.
- category: Dermatologic
name: Vulvar Ulcer
description: >-
Ulceration can be part of the presenting vulvar lesion complex in vulvar
cancer.
phenotype_term:
preferred_term: vulvar ulcer
term:
id: HP:0200042
label: Skin ulcer
evidence:
- reference: DOI:10.1002/ijgo.13881
reference_title: "Cancer of the vulva: 2021 update"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
While vulvar cancer may be asymptomatic, most women present with vulvar
pruritus or pain, or have noticed a lump or ulcer.
explanation: >-
The clinical update identifies ulcer as a presenting feature; the HPO
binding uses the broader skin-ulcer term because local HPO did not provide
a vulvar-specific ulcer term.
- category: Dermatologic
name: Vulvar Pruritus
description: >-
Itching is common in lichen sclerosus and other vulvar dermatoses that can
underlie HPV-independent vulvar carcinogenesis.
phenotype_term:
preferred_term: Vulvar pruritus
term:
id: HP:0000989
label: Pruritus
evidence:
- reference: DOI:10.3389/fmed.2023.1106318
reference_title: "Lichen sclerosus: The 2023 update"
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
The typical clinical picture includes chronic whitish atrophic patches
along with itching and soreness in the vulvar, perianal and penile
regions.
explanation: >-
This supports pruritus in lichen sclerosus, an important associated
precursor/risk setting for HPV-independent vulvar carcinoma.
- category: Dermatologic
name: Vulvar Pain or Soreness
description: >-
Vulvar soreness or pain may occur in associated dermatoses and can
contribute to impaired sexual and urinary function.
phenotype_term:
preferred_term: Vulvar pain
term:
id: HP:0012531
label: Pain
evidence:
- reference: DOI:10.3389/fmed.2023.1106318
reference_title: "Lichen sclerosus: The 2023 update"
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
The typical clinical picture includes chronic whitish atrophic patches
along with itching and soreness in the vulvar, perianal and penile
regions.
explanation: >-
This supports vulvar soreness in lichen sclerosus, a clinically relevant
associated dermatosis in the HPV-independent disease pathway.
genetic:
- name: TP53
association: Somatic Mutation
gene_term:
preferred_term: TP53
term:
id: hgnc:11998
label: TP53
notes: >-
TP53 mutations are frequent in HPV-independent VSCC and correlate with
poorer progression-free survival.
evidence:
- reference: PMID:37840151
reference_title: "TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The TP53 mutation status was identified as an independent prognostic
factor of worse progression-free survival (p = 0.024) after adjustment
for FIGO stage.
explanation: >-
This cohort supports TP53 mutation as a prognostic somatic alteration in
VSCC.
- name: PIK3CA
association: Somatic Activating Mutation
gene_term:
preferred_term: PIK3CA
term:
id: hgnc:8975
label: PIK3CA
notes: >-
PIK3CA activating mutations are enriched in HPV-associated vulvovaginal
squamous carcinomas.
evidence:
- reference: PMID:34650187
reference_title: "Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
HPV-associated vulvovaginal squamous cell carcinoma had PIK3CA
activating mutations (7/11, 64%) as the most common genomic event
explanation: >-
This supports PIK3CA activation as a recurrent molecular event in the
HPV-associated pathway.
- name: TERT
association: Somatic Promoter Alteration
gene_term:
preferred_term: TERT
term:
id: hgnc:11730
label: TERT
notes: >-
TERT promoter alterations are highly enriched in HPV-independent
vulvovaginal squamous carcinomas.
evidence:
- reference: PMID:34650187
reference_title: "Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
TERT gene alterations, mainly TERT promoter mutations (14/15 cases, 93%)
featured significantly in HPV-independent carcinomas.
explanation: >-
This supports TERT promoter alteration as a frequent HPV-independent
VSCC driver event.
- name: CDKN2A
association: Somatic Alteration
gene_term:
preferred_term: CDKN2A
term:
id: hgnc:1787
label: CDKN2A
notes: >-
CDKN2A alterations occur in HPV-independent tumors and remove an important
cell-cycle restraint.
evidence:
- reference: PMID:34650187
reference_title: "Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Other common abnormalities in HPV-independent tumors were TP53 mutations
(13/15, 87%), CDKN2A alterations (10/15, 67%), and NOTCH1 and FAT1
mutations (7/15, 47% each).
explanation: >-
This supports CDKN2A alteration as a recurrent somatic event in the
HPV-independent molecular subgroup.
- name: NOTCH1
association: Somatic Mutation
gene_term:
preferred_term: NOTCH1
term:
id: hgnc:7881
label: NOTCH1
notes: >-
NOTCH1 mutations are recurrent in HPV-independent vulvovaginal squamous
carcinomas and may occur early with TP53 alterations.
evidence:
- reference: PMID:34650187
reference_title: "Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Other common abnormalities in HPV-independent tumors were TP53 mutations
(13/15, 87%), CDKN2A alterations (10/15, 67%), and NOTCH1 and FAT1
mutations (7/15, 47% each).
explanation: >-
This supports NOTCH1 mutation as a recurrent somatic event in
HPV-independent vulvovaginal squamous carcinoma.
- name: FAT1
association: Somatic Mutation
gene_term:
preferred_term: FAT1
term:
id: hgnc:3595
label: FAT1
notes: >-
FAT1 mutations recur in HPV-independent vulvovaginal squamous carcinomas.
evidence:
- reference: PMID:34650187
reference_title: "Molecular landscape of vulvovaginal squamous cell carcinoma: new insights into molecular mechanisms of HPV-associated and HPV-independent squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Other common abnormalities in HPV-independent tumors were TP53 mutations
(13/15, 87%), CDKN2A alterations (10/15, 67%), and NOTCH1 and FAT1
mutations (7/15, 47% each).
explanation: >-
This supports FAT1 mutation as a recurrent somatic event in
HPV-independent vulvovaginal squamous carcinoma.
- name: HRAS
association: Somatic Mutation
gene_term:
preferred_term: HRAS
term:
id: hgnc:5173
label: HRAS
notes: >-
HRAS mutations occur in a subset of VSCC and support RAS/MAPK pathway
involvement.
evidence:
- reference: DOI:10.1038/s41598-024-63913-z
reference_title: "Genomic profiles of Japanese patients with vulvar squamous cell carcinoma"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Somatic mutations were identified by targeted or panel sequencing, and TP53
was identified as the most common mutation (52–81%), followed by HRAS
(7–26%), CDKN2A (21–24%), and PIK3CA (5–10%).
explanation: >-
This supports HRAS as a recurrent somatic mutation in Japanese VSCC
sequencing cohorts.
biochemical:
- name: p16 Immunohistochemistry
notes: >-
p16INK4A immunohistochemistry is used as a surrogate marker for HPV
infection in VSCC molecular subtyping.
evidence:
- reference: PMID:37840151
reference_title: "TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Immunohistochemistry for p53, Ki67 and p16INK4A (a surrogate marker for
HPV infection) was performed on formalin-fixed paraffin-embedded tissues
from a cohort of surgically treated VSCC patients to identify molecular
subtypes of VSCC.
explanation: >-
The study supports p16INK4A immunohistochemistry as an HPV-associated
subtype marker in VSCC.
- name: p53 Immunohistochemistry
notes: >-
p53 immunohistochemistry is used to infer TP53 mutation status and helps
stratify HPV-independent VSCC prognosis.
evidence:
- reference: PMID:37840151
reference_title: "TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The results of p53 and p16INK4A immunohistochemistry confirmed three
VSCC subtypes associated with different prognosis.
explanation: >-
This supports combined p53 and p16 immunohistochemistry for molecular
stratification of VSCC.
treatments:
- name: Local Excision With Sentinel Node Biopsy
description: >-
Early-stage vulvar cancer is treated by local excision of the primary
tumor with sentinel node biopsy when nodal assessment is indicated, reducing
morbidity compared with inguinofemoral lymphadenectomy in appropriate
patients.
evidence:
- reference: DOI:10.6004/jnccn.2024.7002
reference_title: "Update on the Sentinel Node Procedure in Vulvar Cancer"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Early-stage vulvar cancer is managed by a local excision of the primary
tumor and, if indicated, a sentinel node (SN) biopsy to assess the need
for further groin treatment.
explanation: >-
This review supports local excision and sentinel node biopsy as standard
early-stage management.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Definitive or Adjuvant Radiotherapy
description: >-
Radiotherapy is used in vulvar cancer management for local-regional disease
control, including definitive, adjuvant, or groin-treatment contexts
depending on stage and nodal status.
evidence:
- reference: DOI:10.6004/jnccn.2024.7002
reference_title: "Update on the Sentinel Node Procedure in Vulvar Cancer"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Inguinofemoral radiotherapy is a good alternative to IFL in patients
with micrometastases in the SN, with comparable efficacy and less
treatment-related morbidity.
explanation: >-
The sentinel-node review supports radiotherapy as a morbidity-sparing
groin-treatment option for selected node-positive early VSCC.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
- name: Guideline-Based Multidisciplinary Treatment
description: >-
Management commonly requires coordinated gynecologic oncology, pathology,
imaging, radiation oncology, medical oncology, reconstructive surgery, and
supportive-care input.
evidence:
- reference: DOI:10.3390/cancers17020186
reference_title: "Management of Patients with Vulvar Cancers: A Systematic Comparison of International Guidelines (NCCN-ASCO-ESGO-BGCS-IGCS-FIGO-French Guidelines-RCOG)"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
From the systematic comparison of the main international guidelines, a
strong heterogeneity emerged in the diagnostic and therapeutic
recommendations as well as for the multidisciplinary approach that today
is essential.
explanation: >-
This guideline comparison supports multidisciplinary management as an
essential part of vulvar cancer care.
treatment_term:
preferred_term: therapeutic procedure
term:
id: NCIT:C49236
label: Therapeutic Procedure
- name: Platinum-Based Chemotherapy
description: >-
First-line platinum-based chemotherapy is used for advanced or recurrent
vulvar squamous cell carcinoma not amenable to curative surgery.
evidence:
- reference: clinicaltrials:NCT07101848
reference_title: "A PHASE II, RANDOMIZED TRIAL TO ASSESS MAINTENANCE THERAPY WITH CEMIPLIMAB VERSUS BEST SUPPORTIVE CARE AFTER 1ST LINE PLATINUM-BASED CHEMOTHERAPY IN ADVANCED/RECURRENT VULVAR CANCER"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This is a phase II, randomized study that will include 42 participants who
have received 4 to 6 cycles of first-line platinum-based chemotherapy for
advanced vulvar squamous cell carcinoma (SCC) not amenable to curative
surgical treatment (FIGO 2018 stages III-IV - International Federation of
Gynecology and Obstetrics) /
explanation: >-
The trial summary explicitly requires prior first-line platinum-based
chemotherapy for advanced VSCC, supporting this systemic treatment context.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
therapeutic_agent:
- preferred_term: platinum compound
term:
id: NCIT:C1450
label: Platinum Compound
- name: HPV Vaccination
description: >-
Prophylactic HPV vaccination is a prevention strategy intended to reduce the
future burden of HPV-related cancers, including HPV-associated vulvar cancer.
evidence:
- reference: DOI:10.1001/jamanetworkopen.2024.31807
reference_title: "Human Papillomavirus Vaccination and Human Papillomavirus–Related Cancer Rates"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Designing and implementing targeted interventions to increase uptake and
completion of HPV vaccination series across counties with low HPV
vaccination rates may help to reduce future the burden of HPV-related
cancers.
explanation: >-
This population-based study supports HPV vaccination uptake as a strategy
to reduce future HPV-related cancer burden, which includes HPV-associated
vulvar carcinoma.
treatment_term:
preferred_term: vaccination
term:
id: MAXO:0001017
label: vaccination
therapeutic_agent:
- preferred_term: human papillomavirus vaccine
term:
id: NCIT:C1951
label: Human Papilloma Virus Vaccine
clinical_trials:
- name: NCT05903833
phase: PHASE_II
status: RECRUITING
description: >-
Phase II trial of pembrolizumab plus lenvatinib in recurrent, persistent,
metastatic, or locally advanced vulvar cancer not amenable to curative
surgery or radiotherapy. ClinicalTrials.gov listed status as RECRUITING on
2026-05-07.
target_phenotypes:
- preferred_term: Recurrent, persistent, metastatic, or locally advanced vulvar cancer
evidence:
- reference: clinicaltrials:NCT05903833
reference_title: "Pembrolizumab in Combination With Lenvatinib in Pts With Recurrent, Persistent, Metastatic or Locally Advanced Vulvar Cancer Not Amenable to Curative Surgery or Radiotherapy"
supports: SUPPORT
snippet: >-
Evaluation of efficacy and safety of pembrolizumab in combination with
lenvatinib in patients with recurrent, persistent, metastatic or locally
advanced vulva cancer.
explanation: >-
This ClinicalTrials.gov summary directly describes the study population
and pembrolizumab-lenvatinib intervention.
- name: NCT07101848
phase: PHASE_II
status: NOT_RECRUITING
description: >-
Phase II randomized trial of cemiplimab maintenance plus best supportive
care versus best supportive care after first-line platinum chemotherapy in
advanced or recurrent vulvar squamous cell carcinoma. ClinicalTrials.gov
listed status as NOT_YET_RECRUITING on 2026-05-07, represented here by the
schema's NOT_RECRUITING status enum.
target_phenotypes:
- preferred_term: Advanced or recurrent vulvar squamous cell carcinoma
evidence:
- reference: clinicaltrials:NCT07101848
reference_title: "A PHASE II, RANDOMIZED TRIAL TO ASSESS MAINTENANCE THERAPY WITH CEMIPLIMAB VERSUS BEST SUPPORTIVE CARE AFTER 1ST LINE PLATINUM-BASED CHEMOTHERAPY IN ADVANCED/RECURRENT VULVAR CANCER"
supports: SUPPORT
snippet: >-
This is a phase II, randomized study that will include 42 participants
who have received 4 to 6 cycles of first-line platinum-based
chemotherapy for advanced vulvar squamous cell carcinoma (SCC) not
amenable to curative surgical treatment (FIGO 2018 stages III-IV -
International Federation of Gynecology and Obstetrics) /
explanation: >-
This ClinicalTrials.gov summary supports the trial design and population
for cemiplimab maintenance in advanced or recurrent VSCC.
- name: NCT07290894
phase: PHASE_II
status: RECRUITING
description: >-
Phase II single-arm, multi-cohort trial of lenvatinib plus pembrolizumab in
patients with vulvar cancer. ClinicalTrials.gov listed status as RECRUITING
on 2026-05-07.
target_phenotypes:
- preferred_term: Vulvar cancer
evidence:
- reference: clinicaltrials:NCT07290894
reference_title: "Pembrolizumab Plus Lenvatinib in Vulvar Cancer Patients: MITO VULVA-01 Study."
supports: SUPPORT
snippet: >-
MITO VULVA-1 is a prospective, single arm, multi-cohorts, phase II trial
that aims to assess the activity and the safety of Lenvatinib plus
Pembrolizumab in patients with vulvar cancer.
explanation: >-
This ClinicalTrials.gov summary directly supports the MITO VULVA-01 trial
and intervention for patients with vulvar cancer.
Vulvar carcinoma is an uncommon malignant tumor arising in vulvar tissues; vulvar squamous cell carcinoma (VSCC) is the predominant histologic subtype (≈90% of vulvar cancers in multiple reviews). (corte2024currentpreoperativemanagement pages 1-2)
This report is derived from aggregated disease-level resources (reviews, guidelines syntheses, cohort/registry studies, and clinical trial registry entries) plus some single-center retrospective cohorts and experimental model studies. (corte2024currentpreoperativemanagement pages 1-2, dongre2024tp53mutationand pages 1-2, meng2024overallsurvivalassociated pages 1-2, dongre2020establishmentofa pages 1-7)
Modern classification recognizes two main etiologic pathways for VSCC: 1. HPV-associated VSCC: often basaloid/warty morphology; typically p16 “block” positive; generally occurs in younger patients and is associated with precursor high-grade squamous intraepithelial lesions (HSIL/usual VIN). (dongre2024tp53mutationand pages 1-2, horn2024molecularsubtypesof pages 12-14, hohn20212020whoclassification pages 4-6) 2. HPV-independent VSCC: often keratinizing morphology; frequently linked to chronic inflammatory vulvar dermatoses (notably lichen sclerosus) and to differentiated VIN (dVIN); commonly shows aberrant p53 patterns consistent with TP53 alteration; generally associated with poorer prognosis. (dongre2024tp53mutationand pages 1-2, horn2024molecularsubtypesof pages 12-14, horn2024molecularsubtypesof pages 16-18)
A recent focus is the less common HPV-independent/p53-wild-type subtype, emphasizing that not all HPV-independent tumors are p53-abnormal. (horn2024molecularsubtypesof pages 12-14)
Infectious: high-risk HPV infection is a major risk factor for HPV-associated disease; HPV16 is predominant among HPV-positive high-grade vulvar lesions in one 2024 review (HPV16 ≈80% of HPV-positive cases). (scurtu2024squamouscellcarcinoma pages 5-7)
Inflammatory/dermatologic: lichen sclerosus (LS) is strongly associated with HPV-independent precancers and cancer and can lead to SCC development; LS causes chronic inflammation and tissue remodeling that may support carcinogenesis. (luca2023lichensclerosusthe pages 1-2, scurtu2024squamouscellcarcinoma pages 5-7)
Precursor lesions: differentiated VIN (dVIN) is a high-risk HPV-independent precursor; one 2024 review reports much higher progression for dVIN than HSIL (43.2% vs 9.7%). (scurtu2024squamouscellcarcinoma pages 4-5)
Host factors: immunosuppression is highlighted as a critical cofactor for HPV-associated lesions in a recent review. (scurtu2024squamouscellcarcinoma pages 5-7)
HPV vaccination: Multiple sources support prophylactic HPV vaccination as a key protective factor against HPV-associated disease, with very high efficacy in HPV-naïve individuals. - A large 2024 cross-sectional study notes vaccine efficacy “close to 100%” for preventing HPV-associated cancers among those without prior infection with vaccine HPV types. (adekanmbi2024humanpapillomavirusvaccination pages 1-2) - A 2024 review of HPV vaccine strategies states that vaccination blocks transmission and prevents HPV-related cancers and reports global implementation but limited coverage (143 member states by end of 2023; ~15% of young girls vaccinated). (cai2024humanpapillomavirusrelatedcancer pages 1-2)
Management of lichen sclerosus (risk reduction plausibility): LS reviews and cohorts emphasize the need for early diagnosis, adequate treatment, and follow-up to reduce malignant evolution risk. - A 2024 LS review reports markedly elevated vulvar cancer risk in LS (example population-based SIR 33.6 for vulvar cancer) and suggests that consistent long-term potent topical corticosteroid (TCS) use may reduce recurrence compared with historical recurrence rates. (popa2024vulvarlichensclerosus pages 21-22)
Direct quantitative gene–environment interaction estimates were not present in the retrieved evidence. Mechanistically, LS-associated chronic inflammation/oxidative stress provides an enabling microenvironment for carcinogenesis and can co-occur with TP53 pathway alterations typical of HPV-independent disease. (luca2023lichensclerosusthe pages 1-2, scurtu2024squamouscellcarcinoma pages 5-7)
Recent clinical updates emphasize that presentation ranges from asymptomatic lesions detected on exam to symptomatic disease with: - vulvar pruritus (itching) - pain/burning - lump/mass - ulcer These features are highlighted in recent clinical overviews and updates. (corte2024currentpreoperativemanagement pages 1-2, olawaiye2021cancerofthe pages 1-2)
VSCC predominantly affects postmenopausal women with mean/median ages often >65–70 years in clinical series and reviews; HPV-associated cases skew younger. (corte2024currentpreoperativemanagement pages 1-2, cebollaverdugo2024multidisciplinaryvulvarcancer pages 2-4, dongre2024tp53mutationand pages 1-2)
Major QoL burdens stem from symptoms (pain/pruritus), genital functional impairment, and treatment morbidity. - Conservative approaches (e.g., sentinel node biopsy) are emphasized to reduce long-term morbidity such as chronic lymphedema, wound issues, and sexual dysfunction. (cebollaverdugo2024multidisciplinaryvulvarcancer pages 2-4, kolk2024updateonthe pages 1-2)
(These are ontology suggestions; HPO IDs are provided where commonly used—verify in HPO browser for exact IDs.) - Pruritus (HP:0000989) - Vulvar pain (term exists in HPO; verify exact ID) - Genital ulcer (HP:0000211, general mucosal ulceration; vulvar-specific term should be checked) - Vulvar mass (term exists; verify exact ID) - Lymphedema (HP:0001004) (treatment complication) (cebollaverdugo2024multidisciplinaryvulvarcancer pages 2-4) - Dyspareunia (HP:0000148) (common in LS and survivorship context) (luca2023lichensclerosusthe pages 1-2)
WHO-era classification of vulvar SCC emphasizes HPV association using p16 as a surrogate marker and p53 immunophenotyping for HPV-independent disease (with a recognized “uncertain” group). (hohn20212020whoclassification pages 4-6, horn2024molecularsubtypesof pages 16-18)
2024 Japanese VSCC genomic profiling: TP53 (52–81%), HRAS (7–26%), CDKN2A (21–24%), PIK3CA (5–10%). (fujii2024genomicprofilesof pages 1-2)
HPV-status–linked molecular profiles (tumor sequencing cohort): HPV-independent tumors show high rates of TP53, TERT promoter, CDKN2A, NOTCH1, FAT1 alterations, while HPV-associated tumors are enriched for activating PIK3CA mutations (PI3K pathway). (salama2022molecularlandscapeof pages 1-3)
Experimental evidence supports a strong role for tumor–stroma interaction: a LS-associated VSCC cell line (VCC1) showed fibroblast-dependent invasion and tumor formation in 3D organotypic models and xenografts. (dongre2020establishmentofa pages 1-7)
Genetic inheritance is not applicable in a Mendelian sense for most vulvar carcinoma; this is primarily a sporadic, multifactorial cancer with somatic driver alterations.
Imaging recommendations vary by stage and clinical question; a 2024 preoperative management review identifies MRI and PET as gold-standard imaging for local extension and nodal evaluation, with expert-performed ultrasound increasingly used for groin node assessment. (corte2024currentpreoperativemanagement pages 1-2)
The FIGO 2021 staging revision explicitly allows staging to incorporate cross-sectional imaging findings. (olawaiye2021figostagingfor pages 1-2)
The following table (from the 2024 imaging review) summarizes FIGO 2021 staging.
(ha2024imaginginvulval media e360c86b)
Vulvar lesions that can mimic malignant or premalignant disease include inflammatory dermatoses (e.g., lichen sclerosus) and premalignant vulvar intraepithelial lesions; biopsy is required when neoplasia is suspected. (luca2023lichensclerosusthe pages 1-2)
Surgery - Early-stage disease: local excision / radical local excision with attention to margins, plus groin staging when indicated. (kolk2024updateonthe pages 1-2, ferrari2024adjuvantradiotherapyfor pages 1-2)
Sentinel lymph node biopsy (SLNB) - SLNB is an established, less morbid alternative to inguinofemoral lymphadenectomy in selected early-stage VSCC; it reduces complications such as lymphedema while maintaining oncologic safety. (kolk2024updateonthe pages 1-2)
Radiotherapy / chemoradiotherapy - Adjuvant radiotherapy for nodal disease has limited RCT evidence but suggests reduction in cancer-related deaths and groin recurrences; one RCT reported 6-year cancer-related deaths 29% vs 51% (HR 0.49) and groin recurrences 5.3% vs 24.1% favoring radiotherapy. (ferrari2024adjuvantradiotherapyfor pages 1-2) - For locally advanced unresectable disease, multiple guideline sets recommend definitive chemoradiation. (restaino2025managementofpatients pages 14-16)
Systemic therapy and immunotherapy (emerging) - Modern guidance notes emerging immunotherapy options for advanced disease, but evidence remains limited and often extrapolated from other SCC sites; clinical trials are ongoing. (restaino2025managementofpatients pages 2-4)
(Provide as ontology suggestions; confirm IDs in MAXO.) - Surgical excision / wide local excision; radical vulvectomy - Sentinel lymph node biopsy - External beam radiotherapy - Concurrent chemoradiotherapy - Immune checkpoint inhibitor therapy (anti–PD-1)
No naturally occurring non-human species disease data were identified in the retrieved sources for vulvar carcinoma specifically.
| Section | Item | Summary | Notes/Citations |
|---|---|---|---|
| Identifiers/terminology | Standard disease name | Vulvar carcinoma / vulval cancer; most cases are vulvar squamous cell carcinoma (VSCC), the predominant histology (~90%). | ICD-10 C51 is reported for vulval cancer; VSCC predominance noted in recent reviews (corte2024currentpreoperativemanagement pages 1-2) |
| Identifiers/terminology | Controlled vocabulary / search term | A 2024 imaging review explicitly used the MeSH search terms “vulval neoplasm” and “diagnostic imaging.” | Useful for literature retrieval, though no MeSH UID was provided in retrieved text (ha2024imaginginvulval pages 1-2) |
| Identifiers/terminology | Staging/classification | FIGO 2021 is the current staging framework for vulvar carcinoma and permits incorporation of cross-sectional imaging into staging. | Data-derived revision; imaging incorporation specifically noted (olawaiye2021figostagingfor pages 1-2, ha2024imaginginvulval pages 1-2, faruqiUnknownyear2021figostaging pages 1-5) |
| Identifiers/terminology | ICD-related coding context | Additional ICD-related references in retrieved literature include ICD-10 groupings for vulvar cancer and ICD-O-3 site code C51.0 in HPV-related cancer analyses. | ICD-10 C51 reported in economic analysis; ICD-O-3 C51.0 cited in HPV-related cancer rate study (steinkasserer2023characterizationofpatients pages 1-2, adekanmbi2024humanpapillomavirusvaccination pages 1-2) |
| Molecular subtype | HPV-associated VSCC | Typically younger women; often basaloid/warty morphology; precursor lesions are HSIL/uVIN (usual-type VIN); usually block-positive p16, generally non-aberrant/wild-type p53 pattern; often better prognosis and better radiotherapy response. | HPV-associated tumors usually occur in younger patients and have improved prognosis/radiosensitivity (dongre2024tp53mutationand pages 1-2, horn2024molecularsubtypesof pages 12-14, hohn20212020whoclassification pages 4-6, scurtu2024squamouscellcarcinoma pages 5-7) |
| Molecular subtype | HPV-independent, p53-abnormal VSCC | Typically older/postmenopausal women; usually keratinizing morphology; precursor lesions are dVIN and often lichen sclerosus; usually p16 negative/non-block with aberrant p53 (overexpression, null, or cytoplasmic pattern); generally worse prognosis and less radiosensitive. | Strongly associated with TP53 alterations, poorer outcomes, and lower radiosensitivity (dongre2024tp53mutationand pages 1-2, hohn20212020whoclassification pages 4-6, horn2024molecularsubtypesof pages 16-18) |
| Molecular subtype | HPV-independent, p53-wild-type VSCC | Uncommon third molecular subtype within HPV-independent disease; lacks HPV association and lacks classic p53-abnormal pattern; still falls within the HPV-independent spectrum but is molecularly distinct and under active study. | Recent 2024 review emphasizes diagnostic/treatment significance of this subtype (horn2024molecularsubtypesof pages 12-14, horn2024molecularsubtypesof pages 1-5) |
| Biomarker framework | p16 / p53 interpretation | p16 is a surrogate marker of HPV-driven disease; p53 IHC helps identify HPV-independent/TP53-altered disease. Combined p16/p53 stratification supports classification into clinically meaningful subgroups. | WHO/CAP-aligned approach summarized in recent reviews and cohort work (dongre2024tp53mutationand pages 1-2, hohn20212020whoclassification pages 4-6, horn2024molecularsubtypesof pages 16-18, hohn20212020whoclassification pages 1-2) |
| Genomics: 2024 Japanese cohort | TP53 | Most common alteration in Japanese VSCC cohorts: 52–81%. | 2024 Scientific Reports cohort; predominantly HPV-independent tumors (fujii2024genomicprofilesof pages 1-2) |
| Genomics: 2024 Japanese cohort | HRAS | Recurrent alteration: 7–26%. | Suggests RTK/RAS pathway involvement in a subset (fujii2024genomicprofilesof pages 1-2) |
| Genomics: 2024 Japanese cohort | CDKN2A | Recurrent alteration: 21–24%. | Cell-cycle dysregulation signal (fujii2024genomicprofilesof pages 1-2) |
| Genomics: 2024 Japanese cohort | PIK3CA | Recurrent alteration: 5–10%. | Supports PI3K pathway targetability in a subset (fujii2024genomicprofilesof pages 1-2) |
| Genomics: 2022 MSK cohort | HPV-associated profile | Enriched for PIK3CA activating mutations 7/11 (64%); NOTCH-pathway alterations also present 6/11 (55%) but involving different genes than HPV-independent tumors. | HPV-associated tumors favor PI3K-pathway activation (salama2022molecularlandscapeof pages 4-6, salama2022molecularlandscapeof pages 8-10, salama2022molecularlandscapeof pages 1-3) |
| Genomics: 2022 MSK cohort | HPV-independent profile | Strong enrichment for TERT alterations 14/15 (93%), TP53 13/15 (87%), CDKN2A 10/15 (67%), NOTCH1 7/15 (47%), FAT1 7/15 (47%); NOTCH-pathway alterations overall 10/15 (67%). | Distinct molecular program from HPV-associated tumors; TERT/TP53/CDKN2A/NOTCH1 argue against HPV-driven etiology (salama2022molecularlandscapeof pages 4-6, salama2022molecularlandscapeof pages 8-10, salama2022molecularlandscapeof pages 1-3) |
| Genomics: additional recent cohort | HPV-independent vs HPV-associated differences | In an additional recent cohort, HPV-negative tumors showed TP53 86% vs 0%, POLE 50% vs 6%, NOTCH1 43% vs 19%, CDKN2A 36% vs 0%; HPV-associated tumors more often had CNVs, especially cMYC, plus CDK2/CDK4 amplifications. | Useful supporting comparison for subtype-specific molecular architecture (farkas2025pathologicalvariantsin pages 8-9, farkas2025pathologicalvariantsin pages 7-8) |
Table: This table compiles core identifiers, current subtype terminology, biomarker definitions, and recurrent genomic alterations for vulvar carcinoma/VSCC. It is useful as a compact reference for disease ontology, clinicopathologic stratification, and precision-oncology annotation.
References
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(NCT07101848 chunk 1): A PHASE II, RANDOMIZED TRIAL TO ASSESS MAINTENANCE THERAPY WITH CEMIPLIMAB VERSUS BEST SUPPORTIVE CARE AFTER 1ST LINE PLATINUM-BASED CHEMOTHERAPY IN ADVANCED/RECURRENT VULVAR CANCER. Hospital Israelita Albert Einstein. 2025. ClinicalTrials.gov Identifier: NCT07101848
(NCT05903833 chunk 1): Pembrolizumab Combination With Lenvatinib in Pts With Recurrent,Persistent,Metastatic or Locally Advanced Vulvar Cancer Not Amenable to Curative Surgery or Radiotherapy. AGO Research GmbH. 2025. ClinicalTrials.gov Identifier: NCT05903833
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