◆

Subtypes

3

HPV-Associated Endocervical Adenocarcinoma

The dominant subtype of endocervical adenocarcinoma, driven by persistent infection with high-risk HPV (predominantly HPV-16, HPV-18, and HPV-45). Pathologically defined by apical mitoses and apoptotic bodies on the surface of glands and includes the "usual type" and villoglandular/mucinous variants. Better prognosis than HPV-independent adenocarcinoma. The 2020 WHO classification reorganized cervical adenocarcinoma around the HPVA vs HPV-independent axis.

Show evidence (1 reference)

DOI:10.1111/his.13995 SUPPORT Human Clinical

"the separation of cervical adenocarcinomas into HPV‐associated (HPVA) and HPV‐independent has resulted in a transformation of the classification system for cervical adenocarcinomas"

Establishes the HPVA vs HPV-independent dichotomy as the foundational classification of cervical adenocarcinoma.

HPV-Independent Cervical Adenocarcinoma

A minority subtype not driven by HPV infection, comprising the gastric-type, clear-cell, mesonephric, and endometrioid variants. HPV-independent tumors present at older age and more advanced stage, with substantially worse overall survival than HPV-associated adenocarcinoma. Gastric-type is the most clinically important HPV-independent variant; clear-cell has historical association with in utero diethylstilbestrol (DES) exposure.

Show evidence (3 references)

DOI:10.1002/ijgo.14442 SUPPORT Human Clinical

"HPVI cases were more frequent in older patients, presenting at more advanced stages and with worse OS."

140-case retrospective cohort confirms older-age presentation, advanced-stage diagnosis, and worse OS in HPV-independent vs HPV-associated adenocarcinoma.

DOI:10.1002/ijgo.14442 SUPPORT Human Clinical

"The median overall survival (OS) differed between groups: 73.3 months in HPVA and 42.4 months in HPVI (P = 0.005)."

Quantifies the OS gap (73.3 vs 42.4 months) between HPVA and HPVI endocervical adenocarcinoma.

DOI:10.1055/a-1545-4279 SUPPORT Human Clinical

"HPV-independent adenocarcinoma (AC) of the cervix uteri has an unfavorable prognosis."

The WHO 2020 classification explicitly flags HPV-independent cervical adenocarcinoma as a poor-prognosis entity.

Gastric-Type Endocervical Adenocarcinoma

The most clinically prominent HPV-independent adenocarcinoma subtype. Frequently presents with profuse watery vaginal discharge and a barrel-shaped cervix; often eludes HPV-based screening. Recurrent somatic alterations include TP53, KRAS, CDKN2A, and STK11 mutations. Encompasses the older "minimal deviation adenocarcinoma" / "adenoma malignum" terminology.

Show evidence (1 reference)

DOI:10.1111/his.13995 SUPPORT Human Clinical

"Non‐HPV‐associated adenocarcinomas can be divided by their distinct morphology and molecular genomics with very different responses to standard therapies and potential for future targeted therapies. These include gastric‐type, clear‐cell, mesonephric and endometrioid adenocarcinomas."

Park 2020 identifies gastric-type as a distinct HPV-independent cervical adenocarcinoma subtype with characteristic morphology and molecular genomics that differ from HPV-associated tumors.

⚙

Pathophysiology

3

HPV E6/E7-Mediated Oncogenesis in Glandular Epithelium

Persistent infection of endocervical glandular epithelial cells by high-risk HPV (with HPV-16, HPV-18, and HPV-45 dominant) leads to integration of viral DNA and dysregulated expression of E6 and E7. E6 promotes p53 degradation; E7 inactivates pRB. The resulting loss of cell-cycle and apoptotic control, combined with HPV-driven genomic instability, drives progression from adenocarcinoma in situ to invasive HPV-associated adenocarcinoma.

Endocervical glandular epithelial cell link

Viral process link Regulation of cell cycle link ↓ DECREASED Apoptotic process link ↓ DECREASED

Downstream

Silva Pattern of Invasion HPV-associated adenocarcinomas are stratified by the Silva A/B/C pattern of stromal invasion, which directly predicts nodal metastasis risk.

Abnormal Vaginal Bleeding Invasive HPV-driven endocervical adenocarcinoma typically presents with abnormal vaginal bleeding.

Show evidence (1 reference)

DOI:10.1111/his.13995 SUPPORT Human Clinical

"It has become evident that human papillomavirus (HPV) infection does not drive all adenocarcinomas, and appropriate classification is critical for patient management, especially in the era of the HPV vaccine and HPV‐only screening."

Park 2020 frames HPV-driven oncogenesis as the dominant but not exclusive mechanism of cervical adenocarcinoma, motivating subclassification by HPV status.

HPV-Independent Oncogenesis (Gastric-Type, Clear-Cell, Mesonephric)

A subset of cervical adenocarcinomas arises without HPV involvement, driven instead by recurrent somatic alterations in TP53, KRAS, CDKN2A, STK11, and other oncogenes/tumor suppressors. MSK-IMPACT prospective sequencing of 177 cervical cancers found PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%) as the most prevalent alterations across cervical cancer histologies; STK11 alterations were enriched in gastric/clear-cell-associated tumors (33%, 7/21).

Endocervical glandular epithelial cell link

Regulation of cell cycle link ⚠ ABNORMAL Apoptotic process link ↓ DECREASED

Downstream

Abnormal Vaginal Discharge Gastric-type adenocarcinoma, the dominant HPV-independent subtype, characteristically presents with profuse watery vaginal discharge.

Abnormal Vaginal Bleeding HPV-independent cervical adenocarcinoma also presents with abnormal vaginal bleeding, though more often at advanced stage than HPV-associated tumors.

Show evidence (2 references)

DOI:10.1158/1078-0432.ccr-23-1078 SUPPORT Human Clinical

"The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%)."

Prospective MSK-IMPACT sequencing of 177 cervical cancers identifies the most recurrent driver alterations including actionable ERBB2 (HER2) amplifications.

DOI:10.1097/md.0000000000039957 SUPPORT Human Clinical

"HPV-negative cervical cancer has a different pathogenesis from HPV-positive cervical cancer"

Establishes that HPV-negative cervical cancer follows a mechanistically distinct oncogenic trajectory rather than being a screening false-negative artifact.

Silva Pattern of Invasion

The Silva pattern classification (Pattern A, B, C) stratifies HPV-associated endocervical adenocarcinomas by the architecture of stromal invasion and directly predicts the risk of lymph node metastasis. Pattern A tumors are well-demarcated with no lymphovascular invasion or nodal disease; Pattern B shows focal destructive invasion; Pattern C is diffusely destructive and is associated with approximately 22.5% nodal metastasis, driving more aggressive surgical and adjuvant management.

Endocervical glandular epithelial cell link

Downstream

Lymphadenopathy Silva Pattern C adenocarcinomas carry approximately 22.5% risk of regional lymph node metastasis, justifying lymphadenectomy and adjuvant therapy.

Show evidence (1 reference)

DOI:10.1111/his.13995 SUPPORT Human Clinical

"how HPV status, pattern of invasion as described by Silva and colleagues, histological features and molecular markers can be used to refine diagnosis and prognostication for patients with cervical adenocarcinoma"

Park 2020 establishes the Silva pattern of invasion as a clinically actionable stratifier of HPV-associated cervical adenocarcinoma, used together with HPV status and molecular markers for prognostication.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

3

Cardiovascular 1

Lymphadenopathy Lymphadenopathy (HP:0002716)

Regional pelvic and para-aortic lymph node metastasis is the principal locoregional spread route for cervical adenocarcinoma and is strongly associated with Silva Pattern C invasion in HPV-associated tumors.

Other 2

Abnormal Vaginal Bleeding Abnormal vaginal bleeding (HP:0034263)

Abnormal Vaginal Discharge Abnormal vaginal discharge (HP:0034269)

Profuse watery vaginal discharge is a characteristic presenting feature of gastric-type endocervical adenocarcinoma.

🧬

Genetic Associations

5

PIK3CA (Somatic Mutation / Amplification)

Show evidence (1 reference)

DOI:10.1158/1078-0432.ccr-23-1078 SUPPORT Human Clinical

"The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%)."

PIK3CA mutations/amplifications are the most common somatic driver alteration in cervical cancer in the MSK-IMPACT prospective cohort.

ERBB2 (Somatic Mutation / Amplification)

Show evidence (1 reference)

DOI:10.1158/1078-0432.ccr-23-1078 SUPPORT Human Clinical

"The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%)."

ERBB2 alterations occur in 12% of cervical cancers and represent an actionable target for HER2-directed therapy.

KRAS (Somatic Mutation)

Show evidence (1 reference)

DOI:10.1158/1078-0432.ccr-23-1078 SUPPORT Human Clinical

"Tumor genomic profiling can facilitate the selection of targeted/immunotherapies, as well as clinical trial enrollment, for patients with cervical cancer."

The Friedman 2023 abstract supports the general utility of MSK-IMPACT genomic profiling for selecting targeted/immunotherapies and trial enrollment in cervical cancer; specific KRAS prevalence figures are described in the full text and are not quoted here.

STK11 (Somatic Mutation)

Show evidence (1 reference)

DOI:10.1158/1078-0432.ccr-23-1078 SUPPORT Human Clinical

"Thirty-seven percent of cases had at least one potentially actionable alteration designated as a level 3B mutational event according to the FDA-recognized OncoKB tumor mutation database and treatment classification system."

The Friedman 2023 abstract documents that 37% of MSK-IMPACT-profiled cervical cancers carry OncoKB level-3B actionable alterations, supporting the broader rationale for prospective genomic profiling that detects STK11 and other driver alterations.

TP53 (Somatic Mutation)

Show evidence (2 references)

DOI:10.1111/his.13995 SUPPORT Human Clinical

"Non‐HPV‐associated adenocarcinomas can be divided by their distinct morphology and molecular genomics with very different responses to standard therapies and potential for future targeted therapies."

Park 2020 supports the claim that HPV-independent cervical adenocarcinomas (including gastric-type) are distinguished by distinct molecular genomics; TP53 mutation is one such recurrent molecular feature reported in the full classification literature.

DOI:10.1097/md.0000000000039957 SUPPORT Human Clinical

"HPV-negative cervical cancer has a different pathogenesis from HPV-positive cervical cancer"

Shao 2024 supports the broader claim that HPV-negative cervical cancer follows a distinct pathogenesis from HPV-positive disease, consistent with a TP53-mutation-driven mechanism rather than E6-mediated p53 inactivation.

💊

Treatments

4

Radical Hysterectomy

Action: surgical procedure MAXO:0000004

Surgical management for early-stage disease.

Concurrent Chemoradiation

Action: radiation therapy MAXO:0000014

Agent: cisplatin ↗

Concurrent platinum-based chemotherapy with radiotherapy followed by brachytherapy is the cornerstone of curative therapy for locally advanced cervical adenocarcinoma, shared with cervical squamous cell carcinoma.

Pembrolizumab

Action: Pharmacotherapy NCIT:C15986

Agent: pembrolizumab ↗

PD-1 immune checkpoint inhibitor. The KEYNOTE-A18 phase 3 trial (NCT04221945) demonstrated that adding pembrolizumab to cisplatin-based chemoradiation improves progression-free survival in high-risk locally advanced cervical cancer, with adenocarcinoma histology explicitly included. Pembrolizumab is also approved for recurrent/metastatic cervical cancer with PD-L1 expression (CPS >=1) in combination with chemotherapy or as monotherapy after prior therapy.

HPV Vaccination

Action: vaccination MAXO:0001017

Primary prevention via prophylactic HPV vaccines; effective for HPV-associated adenocarcinoma but does not prevent HPV-independent subtypes.

{ }

Source YAML

click to show

name: Cervical Adenocarcinoma
creation_date: "2026-05-12T20:30:00Z"
updated_date: "2026-05-13T12:00:00Z"
category: Complex
disease_term:
  preferred_term: cervical adenocarcinoma
  term:
    id: MONDO:0005153
    label: cervical adenocarcinoma
parents:
- Cervical Cancer
description: >-
  Cervical adenocarcinoma is the second most common histologic type of
  cervical cancer, accounting for approximately 20-25% of cases. It arises
  from the glandular epithelium of the endocervical canal rather than from
  the squamous epithelium of the ectocervix. The majority of cases are
  associated with high-risk human papillomavirus infection, with HPV-18 over-
  represented relative to squamous cell carcinoma. A subset, particularly
  gastric-type adenocarcinoma, is HPV-independent. Because adenocarcinoma
  arises higher in the endocervical canal, it is more often missed by
  cytology-based screening and tends to present at later stage than
  squamous cell carcinoma.
has_subtypes:
- name: HPV-Associated (HPVA)
  display_name: HPV-Associated Endocervical Adenocarcinoma
  description: >-
    The dominant subtype of endocervical adenocarcinoma, driven by
    persistent infection with high-risk HPV (predominantly HPV-16, HPV-18,
    and HPV-45). Pathologically defined by apical mitoses and apoptotic
    bodies on the surface of glands and includes the "usual type" and
    villoglandular/mucinous variants. Better prognosis than HPV-independent
    adenocarcinoma. The 2020 WHO classification reorganized cervical
    adenocarcinoma around the HPVA vs HPV-independent axis.
  evidence:
  - reference: DOI:10.1111/his.13995
    reference_title: "Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the separation of cervical adenocarcinomas into HPV‐associated (HPVA) and HPV‐independent has resulted in a transformation of the classification system for cervical adenocarcinomas"
    explanation: Establishes the HPVA vs HPV-independent dichotomy as the foundational classification of cervical adenocarcinoma.
- name: HPV-Independent (HPVI)
  display_name: HPV-Independent Cervical Adenocarcinoma
  description: >-
    A minority subtype not driven by HPV infection, comprising the
    gastric-type, clear-cell, mesonephric, and endometrioid variants.
    HPV-independent tumors present at older age and more advanced stage,
    with substantially worse overall survival than HPV-associated
    adenocarcinoma. Gastric-type is the most clinically important
    HPV-independent variant; clear-cell has historical association with
    in utero diethylstilbestrol (DES) exposure.
  evidence:
  - reference: DOI:10.1002/ijgo.14442
    reference_title: "Prognosis determination of endocervical adenocarcinomas morphologically reclassified as HPV associated or HPV independent"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "HPVI cases were more frequent in older patients, presenting at more advanced stages and with worse OS."
    explanation: 140-case retrospective cohort confirms older-age presentation, advanced-stage diagnosis, and worse OS in HPV-independent vs HPV-associated adenocarcinoma.
  - reference: DOI:10.1002/ijgo.14442
    reference_title: "Prognosis determination of endocervical adenocarcinomas morphologically reclassified as HPV associated or HPV independent"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The median overall survival (OS) differed between groups: 73.3 months in HPVA and 42.4 months in HPVI (P = 0.005)."
    explanation: Quantifies the OS gap (73.3 vs 42.4 months) between HPVA and HPVI endocervical adenocarcinoma.
  - reference: DOI:10.1055/a-1545-4279
    reference_title: "2020 WHO Classification of Female Genital Tumors"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "HPV-independent adenocarcinoma (AC) of the cervix uteri has an unfavorable prognosis."
    explanation: The WHO 2020 classification explicitly flags HPV-independent cervical adenocarcinoma as a poor-prognosis entity.
- name: Gastric-Type
  display_name: Gastric-Type Endocervical Adenocarcinoma
  description: >-
    The most clinically prominent HPV-independent adenocarcinoma subtype.
    Frequently presents with profuse watery vaginal discharge and a
    barrel-shaped cervix; often eludes HPV-based screening. Recurrent
    somatic alterations include TP53, KRAS, CDKN2A, and STK11 mutations.
    Encompasses the older "minimal deviation adenocarcinoma" / "adenoma
    malignum" terminology.
  evidence:
  - reference: DOI:10.1111/his.13995
    reference_title: "Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Non‐HPV‐associated adenocarcinomas can be divided by their distinct morphology and molecular genomics with very different responses to standard therapies and potential for future targeted therapies. These include gastric‐type, clear‐cell, mesonephric and endometrioid adenocarcinomas."
    explanation: Park 2020 identifies gastric-type as a distinct HPV-independent cervical adenocarcinoma subtype with characteristic morphology and molecular genomics that differ from HPV-associated tumors.
pathophysiology:
- name: HPV E6/E7-Mediated Oncogenesis in Glandular Epithelium
  description: >-
    Persistent infection of endocervical glandular epithelial cells by
    high-risk HPV (with HPV-16, HPV-18, and HPV-45 dominant) leads to
    integration of viral DNA and dysregulated expression of E6 and E7.
    E6 promotes p53 degradation; E7 inactivates pRB. The resulting loss
    of cell-cycle and apoptotic control, combined with HPV-driven genomic
    instability, drives progression from adenocarcinoma in situ to
    invasive HPV-associated adenocarcinoma.
  cell_types:
  - preferred_term: Endocervical glandular epithelial cell
    term:
      id: CL:0000150
      label: glandular secretory epithelial cell
  biological_processes:
  - preferred_term: Viral process
    term:
      id: GO:0016032
      label: viral process
  - preferred_term: Regulation of cell cycle
    term:
      id: GO:0051726
      label: regulation of cell cycle
    modifier: DECREASED
  - preferred_term: Apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
    modifier: DECREASED
  evidence:
  - reference: DOI:10.1111/his.13995
    reference_title: "Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It has become evident that human papillomavirus (HPV) infection does not drive all adenocarcinomas, and appropriate classification is critical for patient management, especially in the era of the HPV vaccine and HPV‐only screening."
    explanation: Park 2020 frames HPV-driven oncogenesis as the dominant but not exclusive mechanism of cervical adenocarcinoma, motivating subclassification by HPV status.
  downstream:
  - target: Silva Pattern of Invasion
    description: HPV-associated adenocarcinomas are stratified by the Silva A/B/C pattern of stromal invasion, which directly predicts nodal metastasis risk.
  - target: Abnormal Vaginal Bleeding
    description: Invasive HPV-driven endocervical adenocarcinoma typically presents with abnormal vaginal bleeding.
- name: HPV-Independent Oncogenesis (Gastric-Type, Clear-Cell, Mesonephric)
  description: >-
    A subset of cervical adenocarcinomas arises without HPV involvement,
    driven instead by recurrent somatic alterations in TP53, KRAS, CDKN2A,
    STK11, and other oncogenes/tumor suppressors. MSK-IMPACT prospective
    sequencing of 177 cervical cancers found PIK3CA (25%), ERBB2 (12%),
    KMT2C (10%), and KMT2D (9%) as the most prevalent alterations across
    cervical cancer histologies; STK11 alterations were enriched in
    gastric/clear-cell-associated tumors (33%, 7/21).
  cell_types:
  - preferred_term: Endocervical glandular epithelial cell
    term:
      id: CL:0000150
      label: glandular secretory epithelial cell
  biological_processes:
  - preferred_term: Regulation of cell cycle
    term:
      id: GO:0051726
      label: regulation of cell cycle
    modifier: ABNORMAL
  - preferred_term: Apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
    modifier: DECREASED
  evidence:
  - reference: DOI:10.1158/1078-0432.ccr-23-1078
    reference_title: "Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%)."
    explanation: Prospective MSK-IMPACT sequencing of 177 cervical cancers identifies the most recurrent driver alterations including actionable ERBB2 (HER2) amplifications.
  - reference: DOI:10.1097/md.0000000000039957
    reference_title: "Research progress on human papillomavirus-negative cervical cancer: A review"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "HPV-negative cervical cancer has a different pathogenesis from HPV-positive cervical cancer"
    explanation: Establishes that HPV-negative cervical cancer follows a mechanistically distinct oncogenic trajectory rather than being a screening false-negative artifact.
  downstream:
  - target: Abnormal Vaginal Discharge
    description: Gastric-type adenocarcinoma, the dominant HPV-independent subtype, characteristically presents with profuse watery vaginal discharge.
  - target: Abnormal Vaginal Bleeding
    description: HPV-independent cervical adenocarcinoma also presents with abnormal vaginal bleeding, though more often at advanced stage than HPV-associated tumors.
- name: Silva Pattern of Invasion
  description: >-
    The Silva pattern classification (Pattern A, B, C) stratifies HPV-associated
    endocervical adenocarcinomas by the architecture of stromal invasion and
    directly predicts the risk of lymph node metastasis. Pattern A tumors are
    well-demarcated with no lymphovascular invasion or nodal disease; Pattern B
    shows focal destructive invasion; Pattern C is diffusely destructive and is
    associated with approximately 22.5% nodal metastasis, driving more
    aggressive surgical and adjuvant management.
  cell_types:
  - preferred_term: Endocervical glandular epithelial cell
    term:
      id: CL:0000150
      label: glandular secretory epithelial cell
  evidence:
  - reference: DOI:10.1111/his.13995
    reference_title: "Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "how HPV status, pattern of invasion as described by Silva and colleagues, histological features and molecular markers can be used to refine diagnosis and prognostication for patients with cervical adenocarcinoma"
    explanation: Park 2020 establishes the Silva pattern of invasion as a clinically actionable stratifier of HPV-associated cervical adenocarcinoma, used together with HPV status and molecular markers for prognostication.
  downstream:
  - target: Lymphadenopathy
    description: Silva Pattern C adenocarcinomas carry approximately 22.5% risk of regional lymph node metastasis, justifying lymphadenectomy and adjuvant therapy.
phenotypes:
- category: Reproductive
  name: Abnormal Vaginal Bleeding
  phenotype_term:
    preferred_term: Abnormal vaginal bleeding
    term:
      id: HP:0034263
      label: Abnormal vaginal bleeding
- category: Reproductive
  name: Abnormal Vaginal Discharge
  subtype: Gastric-Type
  notes: >-
    Profuse watery vaginal discharge is a characteristic presenting
    feature of gastric-type endocervical adenocarcinoma.
  phenotype_term:
    preferred_term: Abnormal vaginal discharge
    term:
      id: HP:0034269
      label: Abnormal vaginal discharge
- category: Neoplastic
  name: Lymphadenopathy
  notes: >-
    Regional pelvic and para-aortic lymph node metastasis is the principal
    locoregional spread route for cervical adenocarcinoma and is strongly
    associated with Silva Pattern C invasion in HPV-associated tumors.
  phenotype_term:
    preferred_term: Lymphadenopathy
    term:
      id: HP:0002716
      label: Lymphadenopathy
genetic:
- name: PIK3CA
  association: Somatic Mutation / Amplification
  gene_term:
    preferred_term: PIK3CA
    term:
      id: hgnc:8975
      label: PIK3CA
  notes: >-
    PIK3CA is the most prevalent driver alteration in cervical cancer
    (25% in MSK-IMPACT), activating PI3K/AKT/mTOR signaling. Represents
    a potentially actionable therapeutic target.
  evidence:
  - reference: DOI:10.1158/1078-0432.ccr-23-1078
    reference_title: "Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%)."
    explanation: PIK3CA mutations/amplifications are the most common somatic driver alteration in cervical cancer in the MSK-IMPACT prospective cohort.
- name: ERBB2
  association: Somatic Mutation / Amplification
  gene_term:
    preferred_term: ERBB2
    term:
      id: hgnc:3430
      label: ERBB2
  notes: >-
    ERBB2 (HER2) is altered in approximately 12% of cervical cancers in
    the MSK-IMPACT cohort. HER2 amplifications create vulnerability to
    HER2-directed therapy (e.g., trastuzumab deruxtecan).
  evidence:
  - reference: DOI:10.1158/1078-0432.ccr-23-1078
    reference_title: "Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%)."
    explanation: ERBB2 alterations occur in 12% of cervical cancers and represent an actionable target for HER2-directed therapy.
- name: KRAS
  association: Somatic Mutation
  gene_term:
    preferred_term: KRAS
    term:
      id: hgnc:6407
      label: KRAS
  notes: >-
    KRAS is reported in the literature as a recurrently altered gene in
    HPV-independent gastric-type cervical adenocarcinoma. In the
    MSK-IMPACT cervical cancer cohort, prospective genomic profiling
    identified actionable alterations supporting trial enrollment and
    targeted-therapy selection across cervical cancer subtypes; specific
    KRAS frequencies are reported in the full text rather than the
    abstract, so this entry cites only the abstract-level conclusion.
  evidence:
  - reference: DOI:10.1158/1078-0432.ccr-23-1078
    reference_title: "Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Tumor genomic profiling can facilitate the selection of targeted/immunotherapies, as well as clinical trial enrollment, for patients with cervical cancer."
    explanation: The Friedman 2023 abstract supports the general utility of MSK-IMPACT genomic profiling for selecting targeted/immunotherapies and trial enrollment in cervical cancer; specific KRAS prevalence figures are described in the full text and are not quoted here.
- name: STK11
  association: Somatic Mutation
  gene_term:
    preferred_term: STK11
    term:
      id: hgnc:11389
      label: STK11
  notes: >-
    STK11 is reported in the literature as enriched in HPV-independent
    gastric-type and clear-cell cervical adenocarcinomas. In the
    MSK-IMPACT cervical cancer cohort, 37% of cases harbored at least one
    potentially actionable OncoKB level-3B alteration. Subtype-specific
    STK11 frequencies are described in the full text and are not quoted
    at the abstract level here.
  evidence:
  - reference: DOI:10.1158/1078-0432.ccr-23-1078
    reference_title: "Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Thirty-seven percent of cases had at least one potentially actionable alteration designated as a level 3B mutational event according to the FDA-recognized OncoKB tumor mutation database and treatment classification system."
    explanation: The Friedman 2023 abstract documents that 37% of MSK-IMPACT-profiled cervical cancers carry OncoKB level-3B actionable alterations, supporting the broader rationale for prospective genomic profiling that detects STK11 and other driver alterations.
- name: TP53
  association: Somatic Mutation
  gene_term:
    preferred_term: TP53
    term:
      id: hgnc:11998
      label: TP53
  notes: >-
    TP53 is reported in the literature as a recurrent somatic mutation in
    HPV-independent cervical adenocarcinoma (particularly gastric-type),
    in contrast to HPV-associated tumors where p53 is functionally
    inactivated via E6-mediated degradation. Quantitative TP53
    frequencies (~41-53% in gastric-type series) come from full-text
    reports outside the abstracts cited here; the cited references
    support the broader claim that HPV-independent adenocarcinomas are
    defined by distinct molecular genomics that include TP53 mutation.
  evidence:
  - reference: DOI:10.1111/his.13995
    reference_title: "Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Non‐HPV‐associated adenocarcinomas can be divided by their distinct morphology and molecular genomics with very different responses to standard therapies and potential for future targeted therapies."
    explanation: Park 2020 supports the claim that HPV-independent cervical adenocarcinomas (including gastric-type) are distinguished by distinct molecular genomics; TP53 mutation is one such recurrent molecular feature reported in the full classification literature.
  - reference: DOI:10.1097/md.0000000000039957
    reference_title: "Research progress on human papillomavirus-negative cervical cancer: A review"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "HPV-negative cervical cancer has a different pathogenesis from HPV-positive cervical cancer"
    explanation: Shao 2024 supports the broader claim that HPV-negative cervical cancer follows a distinct pathogenesis from HPV-positive disease, consistent with a TP53-mutation-driven mechanism rather than E6-mediated p53 inactivation.
treatments:
- name: Radical Hysterectomy
  description: Surgical management for early-stage disease.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
- name: Concurrent Chemoradiation
  description: >-
    Concurrent platinum-based chemotherapy with radiotherapy followed by
    brachytherapy is the cornerstone of curative therapy for locally
    advanced cervical adenocarcinoma, shared with cervical squamous cell
    carcinoma.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
    therapeutic_agent:
    - preferred_term: cisplatin
      term:
        id: CHEBI:27899
        label: cisplatin
- name: Pembrolizumab
  description: >-
    PD-1 immune checkpoint inhibitor. The KEYNOTE-A18 phase 3 trial
    (NCT04221945) demonstrated that adding pembrolizumab to cisplatin-based
    chemoradiation improves progression-free survival in high-risk locally
    advanced cervical cancer, with adenocarcinoma histology explicitly
    included. Pembrolizumab is also approved for recurrent/metastatic
    cervical cancer with PD-L1 expression (CPS >=1) in combination with
    chemotherapy or as monotherapy after prior therapy.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: pembrolizumab
      term:
        id: NCIT:C106432
        label: Pembrolizumab
- name: HPV Vaccination
  description: >-
    Primary prevention via prophylactic HPV vaccines; effective for
    HPV-associated adenocarcinoma but does not prevent HPV-independent
    subtypes.
  treatment_term:
    preferred_term: vaccination
    term:
      id: MAXO:0001017
      label: vaccination
datasets:

📚

References & Deep Research

Deep Research

1

Falcon ▸

Disease Characteristics Research Template

Edison Scientific Literature 53 citations 2026-05-12T17:57:01.336699

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

Disease Name: Cervical Adenocarcinoma
MONDO ID: (if available)
Category: Complex

Research Objectives

Please provide a comprehensive research report on Cervical Adenocarcinoma covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

What is the disease? Provide a concise overview.
What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
What are the common synonyms and alternative names?
Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
Risk Factors:

Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Genetic risk factors (causal variants, susceptibility loci, modifier genes)
Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
Protective Factors:

Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Genetic protective factors (protective variants, modifier alleles)
Environmental protective factors (diet, lifestyle, exposures that reduce risk)
Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Pathogenic Variants:
Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
Variant type/class (missense, frameshift, nonsense, splice-site, structural)
Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
Functional consequences (loss of function, gain of function, dominant negative)
Modifier Genes: Genes that modify disease severity or expression
Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

Search first: CDC databases, WHO, PubMed, NHANES
Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

Search first: PubMed, Gene Ontology, Reactome
Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Molecular Profiling (if available):
Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
Advanced Technologies (if applicable):
Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

Organ Level:
Primary organs directly affected
Secondary organ involvement (complications, secondary effects)
Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Tissue and Cell Level:
Specific tissue types affected (epithelial, connective, muscle, nervous)
Specific cell populations targeted (with Cell Ontology terms)

Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Subcellular Level:
Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Localization:
Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

Onset:
Typical age of onset (congenital, pediatric, adult, geriatric)
Onset pattern (acute, subacute, chronic, insidious)

Search first: OMIM, Orphanet, HPO, PubMed
Progression:
Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
Progression rate (rapid, slow, variable)
Disease course pattern (episodic, relapsing-remitting, progressive, stable)
Disease duration (self-limited, chronic lifelong)

Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Patterns:
Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

Epidemiology:
Prevalence (cases per 100,000 at given time)
Incidence (new cases per 100,000 per year)

Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
For Genetic Etiology:
Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
Population Demographics:
Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
Geographic distribution of specific variants
Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

Clinical Tests:
Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
Genetic Testing:

Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
Overview of recommended genetic testing approach
Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
FISH > Search first: ClinVar, cytogenetics databases, PubMed
Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
Omics-Based Diagnostics (if applicable):
RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
Clinical Criteria:
Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
Screening:
Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

Survival and Mortality:
Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
Morbidity and Function:
Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
Disease Course:
Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
Prediction:
Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

Pharmacotherapy:
Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
Advanced Therapeutics:
Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
Surgical and Interventional:
Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
Supportive and Rehabilitative:
Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
Experimental:
Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
Treatment Outcomes:
Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
Treatment Strategy:
Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

Prevention Levels:
Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
Immunization: Vaccine strategies (if applicable)

Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Screening and Early Detection:
Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
Behavioral Interventions: Lifestyle modifications to reduce risk

Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Counseling: Genetic counseling (risk assessment, family planning guidance)

Search first: NSGC resources, ACMG guidelines, GeneReviews
Public Health:
Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
Prophylaxis: Preventive medications or procedures

Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

Taxonomy: Species affected (with NCBI Taxon identifiers)

Search first: NCBI Taxonomy
Breed: Specific breeds affected (with VBO identifiers if applicable)

Search first: VBO (Vertebrate Breed Ontology)
Gene: Orthologous genes in other species (with NCBI Gene IDs)

Search first: NCBI Gene
Natural Disease:
Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
Comparative Biology:
Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
Transmission (if applicable):
Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

Model Types:
Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
Genetic Models:
Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
Model Characteristics:
Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
Applications:
Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
Resources:
Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

Cite primary literature (PMID preferred) for all mechanistic and clinical claims
Prioritize recent reviews and landmark papers
Include direct quotes from abstracts where possible to support key statements
Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Comprehensive Research Report: Cervical Adenocarcinoma (Endocervical Adenocarcinoma)

Target disease overview

Cervical adenocarcinoma (often termed endocervical adenocarcinoma) is a malignant epithelial tumor arising from the glandular epithelium of the uterine cervix and is now most usefully conceptualized as two biologically distinct groups: HPV-associated (HPVA) and HPV-independent (HPVI) adenocarcinomas, as formalized in the WHO 2020 female genital tumors classification and aligned with the International Endocervical Adenocarcinoma Criteria and Classification (IECC) morphology-based framework. HPVA tumors show characteristic apical mitoses and apoptotic bodies and include “usual type” and certain mucinous/villoglandular variants, whereas HPVI tumors lack abundant apoptosis/mitoses and include gastric-type, clear cell, mesonephric, and endometrioid subtypes. (carvalho2023prognosisdeterminationof pages 2-2, pulkkinenUnknownyearatypicalendocervicalcells pages 24-29)

Current understanding (key concept): HPV-association is not merely etiologic but prognostically and therapeutically relevant, because HPV-independent adenocarcinomas tend to present at later stage and have worse outcomes. In one cohort reclassified by WHO 2020 morphology, HPV-independent tumors had lower survival (e.g., 24-month survival 56.7% HPVI vs 76.7% HPVA; 60-month survival 42.5% vs 64.1%). (carvalho2023prognosisdeterminationof pages 3-3)

Key identifiers, synonyms, and coding

Common synonyms/alternative names: endocervical adenocarcinoma; cervical glandular carcinoma; cervical adenocarcinoma; for a major HPV-independent subtype, gastric-type adenocarcinoma historically overlaps with “minimal deviation adenocarcinoma/adenoma malignum.” (kerwin2023adenocarcinomaofthe pages 1-3)
ICD-O morphology codes (examples; from 2024 guideline tables)
HPV-associated adenocarcinoma: 8140/3, 8483/3; adenocarcinoma in situ: 8140/2, 8483/2 (sznurkowski2024thepolishsociety pages 3-4)
HPV-independent gastric-type adenocarcinoma: 8482/3; gastric-type AIS: 8484/2 (sznurkowski2024thepolishsociety pages 3-4)
Clear cell adenocarcinoma: 8310/3; mesonephric adenocarcinoma: 9110/3 (sznurkowski2024thepolishsociety pages 3-4)

Unavailable in retrieved sources for this run: explicit MONDO ID, MeSH unique IDs, ICD-10/ICD-11, and SNOMED CT codes were not present in the retrieved full-text excerpts; therefore they cannot be provided with evidence-grade citations here.

Evidence provenance: The report synthesizes aggregated disease-level evidence from WHO-aligned pathology literature, SEER population-level analyses, clinical guidelines, and trial registries; it is not derived from individual EHR patient narratives. (carvalho2023prognosisdeterminationof pages 3-3, cohen2023racialandethnic pages 4-5, NCT04221945 chunk 1)

2. Etiology

Primary causal factors

High-risk human papillomavirus (hrHPV) infection is the principal etiologic factor for most cervical adenocarcinomas, particularly usual-type HPV-associated adenocarcinoma, with strong associations reported for HPV16, HPV18, and HPV45. (sznurkowski2024thepolishsociety pages 3-4, shao2024researchprogresson pages 4-4)

Quantitative HPV association: across studies, hrHPV positivity in endocervical adenocarcinoma is reported in the range of ~62–90% overall, with the usual subtype showing the strongest association (~60–95%). HPV16 and HPV18 are dominant worldwide and together account for ~70–98.3% of HPV-positive endocervical adenocarcinomas in reported series; multiple-genotype coinfection is described in ~10% of adenocarcinomas. (pulkkinenUnknownyearatypicalendocervicalcells pages 29-33, sznurkowski2024thepolishsociety pages 3-4)

HPV-negative vs HPV-independent (important distinction)

A minority of cervical cancers are truly HPV-negative; HPV-independent adenocarcinoma subtypes (notably gastric-type) can be hrHPV-negative by sensitive tests and have distinct pathogenesis and clinical behavior. A 2024 review summarizes that “an estimated 3%–8% of cervical cancers are truly HPV-negative” (recognizing the contribution of testing false negatives and diagnostic misclassification). (shao2024researchprogresson pages 1-2)

Risk factors and cofactors

Established cofactors that increase cervical cancer risk (including adenocarcinoma) include sexual behavior/HPV exposure dynamics, co-infections/gynecologic infections, immune suppression (including HIV), and smoking; HPV infection alone is typically insufficient for invasion without additional host cellular and immune alterations. (pulkkinenUnknownyearatypicalendocervicalcells pages 29-33)

Special etiologic association (HPV-independent subtype): clear cell carcinoma of the cervix is reported as associated with prior diethylstilbestrol (DES) exposure in a subset of cases. (shao2024researchprogresson pages 4-5)

Protective factors

Direct quantitative protective-factor estimates for cervical adenocarcinoma specifically were not captured in the retrieved excerpts. However, population-level cervical cancer incidence reductions in vaccinated cohorts (HPV vaccination era) are consistent with prevention of HPV-associated glandular and squamous cancers; for example, US cancer statistics describe a large decline in cervical cancer incidence among the first vaccine-eligible cohort (though not adenocarcinoma-specific in the retrieved excerpt). (shao2024researchprogresson pages 4-4)

Gene–environment interactions

Mechanistically supported, gene-by-exposure interaction estimates specific to cervical adenocarcinoma were not available in the retrieved excerpts; this remains a gap for this run.

3. Phenotypes (clinical presentation)

Common presenting symptoms/signs

Cervical adenocarcinoma may present with abnormal uterine bleeding and/or discharge; a clinically important HPV-independent subtype (gastric-type) is frequently described with profuse watery vaginal discharge and abnormal bleeding. (kerwin2023adenocarcinomaofthe pages 1-3)

Gastric-type clinical phenotype: the cervix may appear enlarged (“barrel-shaped”), and standard screening tools may under-detect due to HPV-negativity and deep stromal growth. (kerwin2023adenocarcinomaofthe pages 1-3, kerwin2023adenocarcinomaofthe pages 3-4)

Phenotype characteristics (typical timing)

HPV-independent adenocarcinomas are repeatedly described as presenting at older age and more advanced stage than HPV-associated tumors. (carvalho2023prognosisdeterminationof pages 3-3, shao2024researchprogresson pages 4-5)

Suggested HPO terms (examples; to support knowledge-base annotation)

Abnormal uterine bleeding — HP:0000132
Vaginal discharge (profuse watery discharge phenotype relevant to gastric-type) — HP:0000155
Pelvic pain (if present clinically; not quantified in retrieved excerpts) — HP:0000233
Lymph node metastasis (disease spread phenotype) — HP:0003003

Frequency/penetrance note: symptom frequency estimates were not provided in the retrieved excerpts and cannot be reliably quantified here.

4. Genetic / Molecular information

High-level molecular stratification

The WHO/IECC separation into HPVA vs HPVI aligns with different driver landscapes and treatment responses. In a large prospective tumor-normal sequencing cohort, subtype-associated enrichment patterns were observed, including STK11 enrichment in a gastric/clear cell–associated subset and ERBB2/HER2 enrichment in uterine endometrioid-like adenocarcinoma patterns. (friedman2023assessingthegenomic pages 11-12)

Recurrent genes and actionable alterations (recent, clinically integrated data)

A prospective clinical sequencing study (MSK-IMPACT) integrating genomic profiling with clinical outcomes reported: * Most prevalent alterations included PIK3CA and ERBB2 (HER2) (statement of prevalence), and quantified frequencies for key genes: ERBB2 12% (22/177) and KRAS 12% (21/177). (friedman2023assessingthegenomic pages 2-3, friedman2023assessingthegenomic pages 11-12) * STK11 alterations were enriched in a gastric/clear cell–associated subset: 33% (7/21) versus lower rates in SCC and uterine endometrioid–like adenocarcinoma. (friedman2023assessingthegenomic pages 11-12) * Actionability: 37% of tumors had at least one potentially actionable alteration (OncoKB level 3B), and sequencing enabled trial enrollment (17% enrolled; 10% genomics-matched). (friedman2023assessingthegenomic pages 2-3)

HPV-independent (HPV-negative) adenocarcinoma mutation patterns

A 2024 review compiled subtype-specific data indicating frequent alterations in HPV-independent gastric-type adenocarcinoma such as TP53 (~41–53%), KRAS (18–36%), CDKN2A (18–27%), and STK11 (10–33%), with PIK3CA less frequent in gastric type; it also summarized actionable alterations in small HPV-negative endocervical-like adenocarcinoma series (e.g., PIK3CA and PTEN at 50% each, MSI-H 12.5%). (shao2024researchprogresson pages 4-4, shao2024researchprogresson pages 4-5)

Epigenetic information

While cervical cancer biomarker reviews emphasize epigenetic-regulator loss-of-function and pathway alterations as outcome-associated in some cervical cancers, gene-specific epigenetic mechanisms for cervical adenocarcinoma were not deeply enumerated in the retrieved excerpts. (scholl2023raidsatlasof pages 1-3)

5. Environmental information

Infectious agent: carcinogenic hrHPV genotypes include 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59. (pulkkinenUnknownyearatypicalendocervicalcells pages 29-33)

Lifestyle/environmental factors: smoking and immune suppression are described as cofactors increasing cervical cancer risk. (pulkkinenUnknownyearatypicalendocervicalcells pages 29-33)

Chemical exposure: DES exposure is linked to cervical clear cell carcinoma (a rare HPV-independent glandular subtype). (shao2024researchprogresson pages 4-5)

6. Mechanism / Pathophysiology

Causal chain (HPV-associated adenocarcinoma; conceptual)

1) Persistent infection by hrHPV (often HPV16/18/45) in cervical glandular epithelium → 2) development of glandular precursor lesions (adenocarcinoma in situ is the recognized precursor for HPV-associated adenocarcinoma) → 3) stromal invasion pattern drives metastatic risk (Silva A/B/C) → 4) lymphovascular invasion and nodal spread contribute to recurrence and mortality. (pulkkinenUnknownyearatypicalendocervicalcells pages 24-29, park2020cervicaladenocarcinomaintegration pages 11-13)

Silva invasion patterns as a mechanism-linked risk stratifier (HPV-associated)

The Silva pattern classification is a morphology-based proxy for invasive behavior: * Pattern A: well-demarcated glands; no destructive invasion; no single-cell detachment; no LVI; initial series showed no nodal metastasis or recurrence. (park2020cervicaladenocarcinomaintegration pages 11-13) * Pattern B: limited destructive invasion; LVI may be present; rare node-positive cases occur; summarized outcomes include ~5% LNM, ~3% recurrence, ~1% death in one overview. (stolnicu2021cervicalcancerwhats pages 4-6) * Pattern C: diffuse destructive invasion with desmoplasia/confluence; associated with higher stage and substantially increased spread; one synthesis reports 22.5% nodal metastasis and 19.7% recurrence. (park2020cervicaladenocarcinomaintegration pages 11-13)

HPV-independent gastric-type biology (conceptual)

Gastric-type adenocarcinoma is HPV-independent and often shows a pancreatobiliary/gastric-like driver spectrum (e.g., STK11, TP53, KRAS in multiple series), deep stromal infiltration with deceptively bland cytology, and may be p16-negative, contributing to under-detection in HPV-based screening. (park2020cervicaladenocarcinomaintegration pages 4-6, kerwin2023adenocarcinomaofthe pages 3-4)

Suggested GO biological process terms (examples)

Viral process / response to virus — GO:0016032 / GO:0009615 (HPV-associated carcinogenesis)
Regulation of cell cycle / apoptotic process — GO:0051726 / GO:0006915 (consistent with morphologic hallmarks and oncogenic progression)
Epithelial cell proliferation — GO:0050673

Suggested Cell Ontology (CL) terms (examples)

Cervical glandular epithelial cell (endocervical epithelium; may require mapping to best available CL term in your ontology stack)
Tumor-associated macrophage / fibroblast involvement is relevant in invasion biology generally but not adenocarcinoma-specific in the retrieved excerpts.

7. Anatomical structures affected

Primary organ/site: uterine cervix (endocervix). Suggested UBERON: uterine cervix (UBERON:0000002).
Locoregional spread: parametrial extension and pelvic lymph nodes are clinically important in more aggressive subtypes (e.g., gastric-type) and in higher-risk invasion patterns. (cho2023gastrictypeendocervicaladenocarcinoma pages 2-4, park2020cervicaladenocarcinomaintegration pages 11-13)

8. Temporal development

Onset: typically adult-onset; HPV-independent tumors skew toward older age at diagnosis relative to HPV-associated tumors. (shao2024researchprogresson pages 4-5)
Progression: progression risk is strongly linked to invasive pattern (Silva A/B/C) in HPV-associated adenocarcinoma, and HPV-independent tumors often present at more advanced stage. (park2020cervicaladenocarcinomaintegration pages 11-13, carvalho2023prognosisdeterminationof pages 3-3)

9. Inheritance and population

Epidemiology and disparities (recent, authoritative population-based evidence)

A large SEER-based, hysterectomy-corrected analysis found that cervical adenocarcinoma incidence and stage-specific survival differ by race/ethnicity; importantly, Black women experienced the lowest 5-year relative survival for adenocarcinoma at regional/distant stages. * Regional-stage adenocarcinoma 5-year relative survival: Black 37.6% vs White 61.5% vs Hispanic 65.1%. (cohen2023racialandethnic pages 4-5) * Distant-stage adenocarcinoma 5-year relative survival: Black 9.2% vs White 21.1% vs Hispanic 24.9%. (cohen2023racialandethnic pages 4-5) * In the same analysis, adenocarcinoma incidence was reported around 0.5 per 100,000 overall in the table excerpt. (cohen2023racialandethnic pages 7-8)

Visual evidence for survival/mortality patterns is shown in the extracted figure/table regions. (cohen2023racialandethnic media b2fbd237, cohen2023racialandethnic media 3662e2f0)

Genetic inheritance

Most cervical adenocarcinoma is not inherited in a Mendelian fashion; it is largely infection-driven and multifactorial. Specific inherited cancer syndromes can be associated with specific subtypes (e.g., Peutz–Jeghers with gastric-type), but detailed germline penetrance statistics were not available in the retrieved excerpts. (kerwin2023adenocarcinomaofthe pages 1-3)

10. Diagnostics

Pathology and immunohistochemistry (key clinical implementation)

HPV-associated adenocarcinoma: strong/diffuse p16 is commonly used as a surrogate for HPV association; one guideline states 95% of HPV-associated carcinomas show diffuse p16 (recognizing occasional exceptions). (sznurkowski2024thepolishsociety pages 3-4)

HPV-independent gastric-type adenocarcinoma (GEA/GAS): * Often HPV-negative and p16 negative or patchy, contributing to delayed detection. (kerwin2023adenocarcinomaofthe pages 3-4, park2020cervicaladenocarcinomaintegration pages 4-6) * Helpful immunophenotypic features include aberrant p53 in ~40–50% and PAX8 positivity (~68%) in one synthesis. (park2020cervicaladenocarcinomaintegration pages 4-6) * Additional gastric-type markers cited as useful include TFF2, HIK1083 (~70%), Claudin 18 (~65%), and HPV RNA ISH is described as a sensitive HPV detection method in difficult cases. (stolnicu2021cervicalcancerwhats pages 3-4)

Cytology (screening/diagnostic challenges; real-world implementation)

Cytologic distinction between gastric-type and usual-type adenocarcinoma has been characterized: * Gastric-type shows flat, honeycomb-like sheets, foamy/vacuolated cytoplasm, vesicular nuclei, and prominent nucleoli more often than usual type; usual type more often shows 3D clusters, peripheral nuclear feathering, and hyperchromasia. (cho2023gastrictypeendocervicaladenocarcinoma pages 1-2, cho2023gastrictypeendocervicaladenocarcinoma pages 2-4)

Imaging (especially relevant to gastric-type)

Gastric-type adenocarcinoma can present as a multicystic cervical mass with solid components; MRI is emphasized as the preferred modality to identify solid components and define extent, supporting differentiation from benign multicystic lesions. (kerwin2023adenocarcinomaofthe pages 1-3)

Differential diagnosis (not exhaustive)

HPV-independent gastric-type carcinoma can be confused with benign glandular lesions (e.g., LEGH) and requires deep sampling plus immunostain correlation; endometrial adenocarcinoma involving cervix is a recognized misclassification issue in HPV-negative cases. (stolnicu2021cervicalcancerwhats pages 3-4, shao2024researchprogresson pages 1-2)

11. Outcome / prognosis

HPV-associated vs HPV-independent prognosis

Reclassification by WHO 2020 morphology is prognostically informative; HPV-independent tumors show worse crude survival and present at more advanced stage. In one cohort, mean OS was 73.3 months (HPVA) vs 42.4 months (HPVI) and the HPVI group had lower 24- and 60-month survival. (carvalho2023prognosisdeterminationof pages 3-3)

Invasion-pattern (Silva) prognosis (HPV-associated)

Silva pattern C is associated with substantially higher nodal metastasis and recurrence than pattern A; pattern A predicts excellent prognosis and may support conservative management in selected settings. (park2020cervicaladenocarcinomaintegration pages 11-13, stolnicu2023villoglandularpatternin pages 6-8)

Disparities

SEER data show profound race/ethnicity disparities in regional/distant adenocarcinoma survival as above. (cohen2023racialandethnic pages 4-5)

12. Treatment

Standard of care (real-world implementation)

Locally advanced cervical cancer (including adenocarcinoma histology): long-standing cornerstone is concurrent cisplatin-based chemoradiation followed by brachytherapy. (ketch2024pharmacotherapyforcervical pages 1-3, sznurkowski2024thepolishsociety pages 1-2)

Recent developments (priority 2023–2024)

Pembrolizumab + chemoradiation (KEYNOTE-A18; practice-changing)

The phase 3, randomized, double-blind KEYNOTE-A18 trial (NCT04221945) evaluated adding pembrolizumab to standard chemoradiotherapy with subsequent maintenance pembrolizumab in high-risk locally advanced cervical cancer (including squamous, adenocarcinoma, and adenosquamous histologies). (NCT04221945 chunk 2) * Trial schema and dosing are described in the registry record (pembrolizumab 200 mg Q3W during CRT then 400 mg Q6W maintenance; cisplatin 40 mg/m² weekly + EBRT + brachytherapy). (NCT04221945 chunk 1) * A linked trial record excerpt reports an 11% absolute 2-year PFS benefit (68% vs 57%) with ~17.9 months median follow-up. (NCT07368985 chunk 1)

Induction chemotherapy before chemoradiation (INTERLACE)

A 2024 expert review summarized INTERLACE: induction weekly dose-dense paclitaxel + carboplatin before chemoradiation improved long-term outcomes (5-year PFS 73% vs 64%; OS 80% vs 72%). Importantly, adenocarcinoma histology was included among eligible histologies. (ang2024evolvingstandardsand pages 1-2)

Antibody–drug conjugate: tisotumab vedotin (Tivdak)

innovaTV 204 (NCT03438396): single-arm phase 2 in previously treated recurrent/metastatic cervical cancer; primary endpoint confirmed objective response by independent review. (NCT03438396 chunk 1)
innovaTV 301 (NCT04697628): randomized open-label phase 3 comparing tisotumab vedotin vs investigator-choice chemotherapy; primary endpoint overall survival. (NCT04697628 chunk 1)
A 2024 review reports key efficacy benchmarks: ORR 24% and DOR 8.3 months in innovaTV204; and interim innovaTV301 OS 11.5 vs 9.5 months (HR 0.70) and PFS 4.2 vs 2.9 months (HR 0.67). (ang2024evolvingstandardsand pages 4-5)

Chemo-immunotherapy + anti-VEGF combinations (advanced disease)

A 2024 review reported BEATcc outcomes for adding atezolizumab to bevacizumab + platinum-taxane chemotherapy: median PFS 13.7 vs 10.4 months (HR 0.62) and OS 32.1 vs 22.8 months (HR 0.68). (ang2024evolvingstandardsand pages 4-5)

Precision oncology (HER2 and others)

Routine tumor genomic profiling can identify targetable alterations; a 2023 prospective sequencing cohort emphasized HER2-directed opportunities and recommended routine HER2 evaluation in advanced/recurrent disease to facilitate targeted trial access. (friedman2023assessingthegenomic pages 17-18)

Suggested MAXO terms (examples)

Concurrent chemoradiotherapy — MAXO:0000045 (radiotherapy) + MAXO:0000058 (chemotherapy) (map to your specific MAXO version)
Brachytherapy — MAXO term for brachytherapy/radiotherapy procedure
Immune checkpoint inhibitor therapy (anti–PD-1) — MAXO term for immunotherapy
Antibody–drug conjugate therapy — MAXO term for targeted drug delivery/antibody therapy

13. Prevention

Primary prevention: HPV vaccination prevents HPV16/18/45-associated cervical cancers; broad vaccination impact is reflected in population statistics showing large declines in cervical cancer incidence in vaccine-era cohorts (not adenocarcinoma-specific in the retrieved excerpt). (shao2024researchprogresson pages 4-4)

Secondary prevention/screening: HPV-based screening is effective for HPV-associated lesions but may under-detect HPV-independent adenocarcinomas (notably gastric-type) because HPV testing can be negative and lesions can be deeply infiltrative with bland cytology; conization and MRI correlation are often needed for suspected gastric-type disease. (kerwin2023adenocarcinomaofthe pages 3-4, kerwin2023adenocarcinomaofthe pages 1-3)

14. Other species / natural disease

No evidence on naturally occurring cervical adenocarcinoma in non-human species was retrieved in the current tool run; therefore no evidence-grade comparative species claims are made.

15. Model organisms / model systems

The retrieved excerpts did not provide a focused, evidence-backed summary of cervical adenocarcinoma model organisms (e.g., specific PDX/organoid systems) beyond noting that preclinical validation and PDX work exist in other cervical cancer histologies (not adenocarcinoma-specific in the extracted evidence). (friedman2023assessingthegenomic pages 2-3)

Expert synthesis and analysis (authoritative perspectives, 2023–2024 emphasis)

1) Pathology has shifted from morphology-only subtyping to etiology-linked classification (HPVA vs HPVI) because it better captures clinically meaningful differences (age/stage at presentation, prognosis, and potential targetable biology). (carvalho2023prognosisdeterminationof pages 2-2, park2020cervicaladenocarcinomaintegration pages 11-13) 2) HPV-independent gastric-type disease is a key unmet need due to frequent screening negativity (p16-/HPV-) and deep infiltrative growth; multimodality diagnosis (deep biopsy/cone + immunostains + MRI) is essential. (kerwin2023adenocarcinomaofthe pages 3-4, kerwin2023adenocarcinomaofthe pages 1-3) 3) 2023–2024 systemic-therapy landscape is rapidly changing: pembrolizumab added to definitive chemoradiation (KEYNOTE-A18) represents a major shift in locally advanced disease management, while ADCs (tisotumab vedotin) and combination immuno-antiangiogenic regimens (BEATcc) are expanding options in recurrent/metastatic disease. (NCT07368985 chunk 1, ang2024evolvingstandardsand pages 4-5, ketch2024pharmacotherapyforcervical pages 1-3)

High-yield facts summary table

Topic	Key points (concise)	Quantitative data	Source (first author year)	URL
High-yield facts for cervical adenocarcinoma	WHO 2020/IECC classifies endocervical adenocarcinoma into HPV-associated (defined morphologically by apical mitoses/apoptotic bodies; includes usual type and mucinous/villoglandular variants) versus HPV-independent (includes gastric, clear cell, mesonephric, endometrioid/NOS); HPV-independent tumors present older/at higher stage and have worse survival. (carvalho2023prognosisdeterminationof pages 2-2, pistolesi2023cervicaladenocarcinomaa pages 1-2, carvalho2023prognosisdeterminationof pages 3-3)	In one 2023 cohort: 24-month survival 76.7% HPVA vs 56.7% HPVI; 60-month survival 64.1% vs 42.5%; mean OS 73.3 vs 42.4 months.	Carvalho 2023	https://doi.org/10.1002/ijgo.14442
HPV genotype association	Most cervical adenocarcinomas are HPV-associated; dominant genotypes are HPV16, HPV18, and HPV45, with HPV18 relatively enriched in adenocarcinoma. hrHPV prevalence is lower than in squamous carcinoma and drops sharply in HPV-independent histologies. (pulkkinenUnknownyearatypicalendocervicalcells pages 29-33, sznurkowski2024thepolishsociety pages 3-4, shao2024researchprogresson pages 4-4)	Overall hrHPV positivity in endocervical adenocarcinoma ~62–90%; usual type 60–95%; HPV16/18 together account for ~70–98.3% of HPV-positive cases; multiple HPV coinfection ~10%.	Shao 2024 / Sznurkowski 2024	https://doi.org/10.1097/md.0000000000039957 ; https://doi.org/10.3390/jcm13154351
Gastric-type adenocarcinoma (GAS)	Rare HPV-independent mucinous endocervical adenocarcinoma, historically including “adenoma malignum/minimal deviation adenocarcinoma”; often bland cytology, deep stromal infiltration, and aggressive behavior. (kerwin2023adenocarcinomaofthe pages 1-3, kerwin2023adenocarcinomaofthe pages 3-4)	HPV-independent tumors ~15% of endocervical adenocarcinomas; GAS ~10–15% of cervical adenocarcinomas; reported 5-year disease-specific survival 38% for GAS vs 74% for non-gastric types; biopsy sensitivity ≈50%.	Kerwin 2023	https://doi.org/10.1007/s00261-022-03724-w
Silva pattern A/B/C	Silva classification applies to HPV-associated adenocarcinoma: A = non-destructive invasion; B = limited destructive invasion; C = diffuse destructive invasion/desmoplasia. Risk rises from A to C and informs conservative vs more extensive surgery. (park2020cervicaladenocarcinomaintegration pages 11-13, stolnicu2021cervicalcancerwhats pages 4-6, pistolesi2023cervicaladenocarcinomaa pages 1-2)	Pattern A: no nodal metastasis or recurrence in initial series; Pattern B: ~5% lymph node metastasis, ~3% recurrence, ~1% death; Pattern C: ~22.5% nodal metastasis and ~19.7% recurrence.	Park 2020 / Stolnicu 2021	https://doi.org/10.1111/his.13995 ; https://doi.org/10.1016/j.mpdhp.2021.09.002
SEER racial disparities	Population-based SEER analysis showed major racial disparities in cervical adenocarcinoma survival; Black women had the worst stage-specific outcomes despite not having the highest incidence. (cohen2023racialandethnic pages 4-5, cohen2023racialandethnic pages 7-8, cohen2023racialandethnic pages 1-2)	Regional adenocarcinoma 5-year relative survival: Black 37.6% vs White 61.5% vs Hispanic 65.1%; distant: Black 9.2% vs White 21.1% vs Hispanic 24.9%. Overall adenocarcinoma incidence ~0.5/100,000.	Cohen 2023	https://doi.org/10.1200/JCO.22.01424
Genomics and actionability	Prospective sequencing identified recurrent actionable alterations; ERBB2 and KRAS were common, and STK11 was enriched in gastric/clear cell-associated subset. Sequencing enabled trial matching in routine practice. (friedman2023assessingthegenomic pages 11-12, friedman2023assessingthegenomic pages 17-18, friedman2023assessingthegenomic pages 2-3)	ERBB2 12% (22/177), KRAS 12% (21/177), STK11 33% in CAS (7/21); 37% had ≥1 potentially actionable alteration; 17% enrolled on trials, 10% matched by sequencing.	Friedman 2023	https://doi.org/10.1158/1078-0432.CCR-23-1078
KEYNOTE-A18	Phase 3 randomized double-blind study of pembrolizumab plus standard cisplatin-based chemoradiotherapy followed by maintenance pembrolizumab vs placebo plus chemoradiotherapy in newly diagnosed high-risk locally advanced cervical cancer; eligible histologies included squamous, adenocarcinoma, and adenosquamous. (NCT04221945 chunk 1, NCT07368985 chunk 1, NCT04221945 chunk 2)	Enrollment 1,060; reported 2-year PFS 68% vs 57% (absolute benefit 11%); primary endpoints PFS and OS.	Merck/NCT04221945 2020	https://clinicaltrials.gov/study/NCT04221945
innovaTV 301	Phase 3 randomized open-label trial of tisotumab vedotin vs investigator’s-choice chemotherapy in second-/third-line recurrent or metastatic cervical cancer. Published interim efficacy figures were highlighted in 2024 review. (ang2024evolvingstandardsand pages 4-5, NCT04697628 chunk 6, NCT04697628 chunk 1)	Enrollment 502; interim OS 11.5 vs 9.5 months (HR 0.70); PFS 4.2 vs 2.9 months (HR 0.67).	Ang 2024 / NCT04697628	https://doi.org/10.3802/jgo.2024.35.e65 ; https://clinicaltrials.gov/study/NCT04697628
innovaTV 204	Multicenter open-label single-arm phase 2 trial of tisotumab vedotin in previously treated recurrent/metastatic cervical cancer. (NCT03438396 chunk 1, NCT03438396 chunk 3)	Enrollment 102; tisotumab vedotin 2.0 mg/kg IV every 3 weeks; primary endpoint confirmed objective response by independent review per RECIST v1.1.	Seagen/NCT03438396 2018	https://clinicaltrials.gov/study/NCT03438396
BEATcc	First-line advanced cervical cancer trial adding atezolizumab to bevacizumab plus platinum-taxane chemotherapy; 2024 review identified this as practice changing. (ang2024evolvingstandardsand pages 4-5)	Median PFS 13.7 vs 10.4 months (HR 0.62); median OS 32.1 vs 22.8 months (HR 0.68).	Ang 2024	https://doi.org/10.3802/jgo.2024.35.e65
Tisotumab vedotin efficacy signal	Anti–tissue factor ADC with clinically meaningful single-agent activity in pretreated recurrent/metastatic cervical cancer; activity summarized in 2024 review and supported later by phase 3 data. (ang2024evolvingstandardsand pages 4-5)	ORR 24%; median duration of response 8.3 months in innovaTV204.	Ang 2024	https://doi.org/10.3802/jgo.2024.35.e65

Table: This table compiles high-yield, citation-backed facts on classification, epidemiology, pathology, genomics, and recent therapeutic trials in cervical adenocarcinoma. It is designed as a compact reference for rapid knowledge-base entry and clinical/research orientation.

Key statistics (quick reference)

hrHPV positivity in endocervical adenocarcinoma: ~62–90% overall, usual type ~60–95%. (pulkkinenUnknownyearatypicalendocervicalcells pages 29-33)
HPV16/18 attribution among HPV-positive EAC: ~70–98.3%. (pulkkinenUnknownyearatypicalendocervicalcells pages 29-33)
Gastric-type proportion: ~10–15% of cervical adenocarcinomas; HPV-independent tumors ~15% of endocervical adenocarcinomas. (kerwin2023adenocarcinomaofthe pages 1-3)
Silva Pattern C: nodal metastasis risk reported ~22.5%; recurrence ~19.7% (HPV-associated). (park2020cervicaladenocarcinomaintegration pages 11-13)
SEER regional-stage adenocarcinoma 5-year survival: Black 37.6% vs White 61.5% vs Hispanic 65.1%. (cohen2023racialandethnic pages 4-5, cohen2023racialandethnic media b2fbd237)
KEYNOTE-A18 linked excerpt: 2-year PFS 68% vs 57% (absolute +11%). (NCT07368985 chunk 1)

Direct abstract quotes (for evidence traceability)

Park (Histopathology, 2020) emphasizes classification transformation: “separation of cervical adenocarcinomas into HPV‐associated (HPVA) and HPV‐independent has resulted in a transformation of the classification system for cervical adenocarcinomas.” ()
Friedman (Clin Cancer Res, 2023) describes clinical utility of prospective profiling: “Tumor genomic profiling can facilitate the selection of targeted/immunotherapies, as well as clinical trial enrollment, for patients with cervical cancer.” (friedman2023assessingthegenomic pages 2-3)

(Note: quotes are limited to abstracts/excerpts available in the retrieved context; additional primary-abstract quotations for other topics would require retrieval of the corresponding full abstracts.)

URLs (selected)

Cohen et al., J Clin Oncol, 2023-02 — https://doi.org/10.1200/JCO.22.01424 (cohen2023racialandethnic pages 4-5)
Friedman et al., Clin Cancer Res, 2023-08 — https://doi.org/10.1158/1078-0432.CCR-23-1078 (friedman2023assessingthegenomic pages 2-3)
Kerwin et al., Abdominal Radiology, 2023-11 — https://doi.org/10.1007/s00261-022-03724-w (kerwin2023adenocarcinomaofthe pages 1-3)
Park, Histopathology, 2020-12 — https://doi.org/10.1111/his.13995 (park2020cervicaladenocarcinomaintegration pages 11-13)
KEYNOTE-A18 trial registry — https://clinicaltrials.gov/study/NCT04221945 (NCT04221945 chunk 1)
innovaTV 301 registry — https://clinicaltrials.gov/study/NCT04697628 (NCT04697628 chunk 1)
innovaTV 204 registry — https://clinicaltrials.gov/study/NCT03438396 (NCT03438396 chunk 1)

References

(carvalho2023prognosisdeterminationof pages 2-2): Carla Fabrine Carvalho, Larissa Bastos Eloy Costa, Natasha Caroline Sanches, Ingrid Iara Damas, Liliana Aparecida Lucci De Angelo Andrade, and Diama Bhadra Vale. Prognosis determination of endocervical adenocarcinomas morphologically reclassified as hpv associated or hpv independent. Sep 2023. URL: https://doi.org/10.1002/ijgo.14442, doi:10.1002/ijgo.14442. This article has 4 citations and is from a peer-reviewed journal.
(pulkkinenUnknownyearatypicalendocervicalcells pages 24-29): J PULKKINEN. Atypical endocervical cells in pap smears. Unknown journal, Unknown year.
(carvalho2023prognosisdeterminationof pages 3-3): Carla Fabrine Carvalho, Larissa Bastos Eloy Costa, Natasha Caroline Sanches, Ingrid Iara Damas, Liliana Aparecida Lucci De Angelo Andrade, and Diama Bhadra Vale. Prognosis determination of endocervical adenocarcinomas morphologically reclassified as hpv associated or hpv independent. Sep 2023. URL: https://doi.org/10.1002/ijgo.14442, doi:10.1002/ijgo.14442. This article has 4 citations and is from a peer-reviewed journal.
(kerwin2023adenocarcinomaofthe pages 1-3): Clara M. Kerwin, Matt Markese, Marisa R. Moroney, Lynelle P. Smith, and Nayana U. Patel. Adenocarcinoma of the uterine cervix, gastric-type (gas): a review of the literature focused on pathology and multimodality imaging. Abdominal Radiology, 48:713-723, Nov 2023. URL: https://doi.org/10.1007/s00261-022-03724-w, doi:10.1007/s00261-022-03724-w. This article has 23 citations and is from a peer-reviewed journal.
(sznurkowski2024thepolishsociety pages 3-4): Jacek J. Sznurkowski, Lubomir Bodnar, Łukasz Szylberg, Agnieszka Zołciak-Siwinska, Anna Dańska-Bidzińska, Dagmara Klasa-Mazurkiewicz, Agnieszka Rychlik, Artur Kowalik, Joanna Streb, Mariusz Bidziński, and Włodzimierz Sawicki. The polish society of gynecological oncology guidelines for the diagnosis and treatment of cervical cancer (v2024.0). Journal of Clinical Medicine, 13:4351, Jul 2024. URL: https://doi.org/10.3390/jcm13154351, doi:10.3390/jcm13154351. This article has 10 citations.
(cohen2023racialandethnic pages 4-5): Camryn M. Cohen, Nicolas Wentzensen, Philip E. Castle, Mark Schiffman, Rosemary Zuna, Rebecca C. Arend, and Megan A. Clarke. Racial and ethnic disparities in cervical cancer incidence, survival, and mortality by histologic subtype. Journal of Clinical Oncology, 41:1059-1068, Feb 2023. URL: https://doi.org/10.1200/jco.22.01424, doi:10.1200/jco.22.01424. This article has 171 citations and is from a highest quality peer-reviewed journal.
(NCT04221945 chunk 1): Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047). Merck Sharp & Dohme LLC. 2020. ClinicalTrials.gov Identifier: NCT04221945
(shao2024researchprogresson pages 4-4): Ning Shao. Research progress on human papillomavirus-negative cervical cancer: a review. Medicine, 103:e39957, Oct 2024. URL: https://doi.org/10.1097/md.0000000000039957, doi:10.1097/md.0000000000039957. This article has 11 citations and is from a peer-reviewed journal.
(pulkkinenUnknownyearatypicalendocervicalcells pages 29-33): J PULKKINEN. Atypical endocervical cells in pap smears. Unknown journal, Unknown year.
(shao2024researchprogresson pages 1-2): Ning Shao. Research progress on human papillomavirus-negative cervical cancer: a review. Medicine, 103:e39957, Oct 2024. URL: https://doi.org/10.1097/md.0000000000039957, doi:10.1097/md.0000000000039957. This article has 11 citations and is from a peer-reviewed journal.
(shao2024researchprogresson pages 4-5): Ning Shao. Research progress on human papillomavirus-negative cervical cancer: a review. Medicine, 103:e39957, Oct 2024. URL: https://doi.org/10.1097/md.0000000000039957, doi:10.1097/md.0000000000039957. This article has 11 citations and is from a peer-reviewed journal.
(kerwin2023adenocarcinomaofthe pages 3-4): Clara M. Kerwin, Matt Markese, Marisa R. Moroney, Lynelle P. Smith, and Nayana U. Patel. Adenocarcinoma of the uterine cervix, gastric-type (gas): a review of the literature focused on pathology and multimodality imaging. Abdominal Radiology, 48:713-723, Nov 2023. URL: https://doi.org/10.1007/s00261-022-03724-w, doi:10.1007/s00261-022-03724-w. This article has 23 citations and is from a peer-reviewed journal.
(friedman2023assessingthegenomic pages 11-12): Claire F. Friedman, Vignesh Ravichandran, Kathryn Miller, Chad Vanderbilt, Qin Zhou, Alexia Iasonos, Malavika Vivek, Pamela Mishra, Mario M. Leitao, Vance Broach, Yukio Sonoda, Chrisann Kyi, Dmitriy Zamarin, Roisin E. O'Cearbhaill, Jason Konner, Michael F. Berger, Britta Weigelt, Amir Momeni Boroujeni, Kay J. Park, Carol Aghajanian, David B. Solit, and Mark T.A. Donoghue. Assessing the genomic landscape of cervical cancers: clinical opportunities and therapeutic targets. Clinical Cancer Research, 29:4660-4668, Aug 2023. URL: https://doi.org/10.1158/1078-0432.ccr-23-1078, doi:10.1158/1078-0432.ccr-23-1078. This article has 23 citations and is from a highest quality peer-reviewed journal.
(friedman2023assessingthegenomic pages 2-3): Claire F. Friedman, Vignesh Ravichandran, Kathryn Miller, Chad Vanderbilt, Qin Zhou, Alexia Iasonos, Malavika Vivek, Pamela Mishra, Mario M. Leitao, Vance Broach, Yukio Sonoda, Chrisann Kyi, Dmitriy Zamarin, Roisin E. O'Cearbhaill, Jason Konner, Michael F. Berger, Britta Weigelt, Amir Momeni Boroujeni, Kay J. Park, Carol Aghajanian, David B. Solit, and Mark T.A. Donoghue. Assessing the genomic landscape of cervical cancers: clinical opportunities and therapeutic targets. Clinical Cancer Research, 29:4660-4668, Aug 2023. URL: https://doi.org/10.1158/1078-0432.ccr-23-1078, doi:10.1158/1078-0432.ccr-23-1078. This article has 23 citations and is from a highest quality peer-reviewed journal.
(scholl2023raidsatlasof pages 1-3): Suzy Scholl, Diana Bello Roufai, Linda Larbi Chérif, and Maud Kamal. Raids atlas of significant genetic and protein biomarkers in cervical cancer. Journal of Gynecologic Oncology, Aug 2023. URL: https://doi.org/10.3802/jgo.2023.34.e74, doi:10.3802/jgo.2023.34.e74. This article has 4 citations and is from a peer-reviewed journal.
(park2020cervicaladenocarcinomaintegration pages 11-13): Kay J. Park. Cervical adenocarcinoma: integration of hpv status, pattern of invasion, morphology and molecular markers into classification. Histopathology, 76:112-127, Dec 2020. URL: https://doi.org/10.1111/his.13995, doi:10.1111/his.13995. This article has 155 citations and is from a domain leading peer-reviewed journal.
(stolnicu2021cervicalcancerwhats pages 4-6): Simona Stolnicu. Cervical cancer: what's new in classification, morphology, molecular findings and prognosis of glandular precursor and invasive lesions. Diagnostic Histopathology, 27:483-492, Dec 2021. URL: https://doi.org/10.1016/j.mpdhp.2021.09.002, doi:10.1016/j.mpdhp.2021.09.002. This article has 4 citations.
(park2020cervicaladenocarcinomaintegration pages 4-6): Kay J. Park. Cervical adenocarcinoma: integration of hpv status, pattern of invasion, morphology and molecular markers into classification. Histopathology, 76:112-127, Dec 2020. URL: https://doi.org/10.1111/his.13995, doi:10.1111/his.13995. This article has 155 citations and is from a domain leading peer-reviewed journal.
(cho2023gastrictypeendocervicaladenocarcinoma pages 2-4): HAEYON CHO, SUJIN PARK, and HYUN-SOO KIM. Gastric-type endocervical adenocarcinoma: comprehensive cytopathological analysis and comparison with usual-type endocervical adenocarcinoma. In Vivo, 37:1173-1181, Jan 2023. URL: https://doi.org/10.21873/invivo.13192, doi:10.21873/invivo.13192. This article has 10 citations and is from a peer-reviewed journal.
(cohen2023racialandethnic pages 7-8): Camryn M. Cohen, Nicolas Wentzensen, Philip E. Castle, Mark Schiffman, Rosemary Zuna, Rebecca C. Arend, and Megan A. Clarke. Racial and ethnic disparities in cervical cancer incidence, survival, and mortality by histologic subtype. Journal of Clinical Oncology, 41:1059-1068, Feb 2023. URL: https://doi.org/10.1200/jco.22.01424, doi:10.1200/jco.22.01424. This article has 171 citations and is from a highest quality peer-reviewed journal.
(cohen2023racialandethnic media b2fbd237): Camryn M. Cohen, Nicolas Wentzensen, Philip E. Castle, Mark Schiffman, Rosemary Zuna, Rebecca C. Arend, and Megan A. Clarke. Racial and ethnic disparities in cervical cancer incidence, survival, and mortality by histologic subtype. Journal of Clinical Oncology, 41:1059-1068, Feb 2023. URL: https://doi.org/10.1200/jco.22.01424, doi:10.1200/jco.22.01424. This article has 171 citations and is from a highest quality peer-reviewed journal.
(cohen2023racialandethnic media 3662e2f0): Camryn M. Cohen, Nicolas Wentzensen, Philip E. Castle, Mark Schiffman, Rosemary Zuna, Rebecca C. Arend, and Megan A. Clarke. Racial and ethnic disparities in cervical cancer incidence, survival, and mortality by histologic subtype. Journal of Clinical Oncology, 41:1059-1068, Feb 2023. URL: https://doi.org/10.1200/jco.22.01424, doi:10.1200/jco.22.01424. This article has 171 citations and is from a highest quality peer-reviewed journal.
(stolnicu2021cervicalcancerwhats pages 3-4): Simona Stolnicu. Cervical cancer: what's new in classification, morphology, molecular findings and prognosis of glandular precursor and invasive lesions. Diagnostic Histopathology, 27:483-492, Dec 2021. URL: https://doi.org/10.1016/j.mpdhp.2021.09.002, doi:10.1016/j.mpdhp.2021.09.002. This article has 4 citations.
(cho2023gastrictypeendocervicaladenocarcinoma pages 1-2): HAEYON CHO, SUJIN PARK, and HYUN-SOO KIM. Gastric-type endocervical adenocarcinoma: comprehensive cytopathological analysis and comparison with usual-type endocervical adenocarcinoma. In Vivo, 37:1173-1181, Jan 2023. URL: https://doi.org/10.21873/invivo.13192, doi:10.21873/invivo.13192. This article has 10 citations and is from a peer-reviewed journal.
(stolnicu2023villoglandularpatternin pages 6-8): Simona Stolnicu, Maria J. Brito, Georgia Karpathiou, Lynn Hoang, Ana Felix, Claudia Mateoiu, Daniela Fanni, Armando Reques, Angel Garcia, David Hardisson, Canan K. Talu, Antonia Furtado, Nadeem Abu-Rustum, Robert A. Soslow, and Kay J. Park. Villoglandular pattern in hpv-associated endocervical adenocarcinoma is associated with excellent prognosis: a reappraisal of 31 cases using iecc and silva pattern classification. International Journal of Gynecological Pathology, 42:270-277, Nov 2023. URL: https://doi.org/10.1097/pgp.0000000000000916, doi:10.1097/pgp.0000000000000916. This article has 10 citations and is from a peer-reviewed journal.
(ketch2024pharmacotherapyforcervical pages 1-3): Peter W. Ketch, Rennan S. Zaharias, and Charles A. Leath. Pharmacotherapy for cervical cancer: current standard of care and new perspectives. Expert Opinion on Pharmacotherapy, 25:1591-1603, Aug 2024. URL: https://doi.org/10.1080/14656566.2024.2395379, doi:10.1080/14656566.2024.2395379. This article has 2 citations and is from a peer-reviewed journal.
(sznurkowski2024thepolishsociety pages 1-2): Jacek J. Sznurkowski, Lubomir Bodnar, Łukasz Szylberg, Agnieszka Zołciak-Siwinska, Anna Dańska-Bidzińska, Dagmara Klasa-Mazurkiewicz, Agnieszka Rychlik, Artur Kowalik, Joanna Streb, Mariusz Bidziński, and Włodzimierz Sawicki. The polish society of gynecological oncology guidelines for the diagnosis and treatment of cervical cancer (v2024.0). Journal of Clinical Medicine, 13:4351, Jul 2024. URL: https://doi.org/10.3390/jcm13154351, doi:10.3390/jcm13154351. This article has 10 citations.
(NCT04221945 chunk 2): Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047). Merck Sharp & Dohme LLC. 2020. ClinicalTrials.gov Identifier: NCT04221945
(NCT07368985 chunk 1): Prof. Dr. Remi A. Nout. Pembrolizumab and Lenvatinib in Patients With High Risk Locally Advanced Cervix Cancer. Prof. Dr. Remi A. Nout. 2026. ClinicalTrials.gov Identifier: NCT07368985
(ang2024evolvingstandardsand pages 1-2): Daniel Jia Ming Ang and Jack Junjie Chan. Evolving standards and future directions for systemic therapies in cervical cancer. Journal of Gynecologic Oncology, Jan 2024. URL: https://doi.org/10.3802/jgo.2024.35.e65, doi:10.3802/jgo.2024.35.e65. This article has 21 citations and is from a peer-reviewed journal.
(NCT03438396 chunk 1): A Trial of Tisotumab Vedotin in Cervical Cancer. Seagen Inc.. 2018. ClinicalTrials.gov Identifier: NCT03438396
(NCT04697628 chunk 1): Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer. Seagen, a wholly owned subsidiary of Pfizer. 2021. ClinicalTrials.gov Identifier: NCT04697628
(ang2024evolvingstandardsand pages 4-5): Daniel Jia Ming Ang and Jack Junjie Chan. Evolving standards and future directions for systemic therapies in cervical cancer. Journal of Gynecologic Oncology, Jan 2024. URL: https://doi.org/10.3802/jgo.2024.35.e65, doi:10.3802/jgo.2024.35.e65. This article has 21 citations and is from a peer-reviewed journal.
(friedman2023assessingthegenomic pages 17-18): Claire F. Friedman, Vignesh Ravichandran, Kathryn Miller, Chad Vanderbilt, Qin Zhou, Alexia Iasonos, Malavika Vivek, Pamela Mishra, Mario M. Leitao, Vance Broach, Yukio Sonoda, Chrisann Kyi, Dmitriy Zamarin, Roisin E. O'Cearbhaill, Jason Konner, Michael F. Berger, Britta Weigelt, Amir Momeni Boroujeni, Kay J. Park, Carol Aghajanian, David B. Solit, and Mark T.A. Donoghue. Assessing the genomic landscape of cervical cancers: clinical opportunities and therapeutic targets. Clinical Cancer Research, 29:4660-4668, Aug 2023. URL: https://doi.org/10.1158/1078-0432.ccr-23-1078, doi:10.1158/1078-0432.ccr-23-1078. This article has 23 citations and is from a highest quality peer-reviewed journal.
(pistolesi2023cervicaladenocarcinomaa pages 1-2): SABINA PISTOLESI, GIUSEPPE NICOLÒ FANELLI, FRANCESCO GIUDICE, FRANCESCA GARBINI, ANTONIO GIUSEPPE NACCARATO, STEFANIA COSIO, MARTA CARETTO, and ANGIOLO GADDUCCI. Cervical adenocarcinoma: a still under-investigated malignancy. AntiCancer Research, 43:53-58, Dec 2023. URL: https://doi.org/10.21873/anticanres.16133, doi:10.21873/anticanres.16133. This article has 3 citations and is from a peer-reviewed journal.
(cohen2023racialandethnic pages 1-2): Camryn M. Cohen, Nicolas Wentzensen, Philip E. Castle, Mark Schiffman, Rosemary Zuna, Rebecca C. Arend, and Megan A. Clarke. Racial and ethnic disparities in cervical cancer incidence, survival, and mortality by histologic subtype. Journal of Clinical Oncology, 41:1059-1068, Feb 2023. URL: https://doi.org/10.1200/jco.22.01424, doi:10.1200/jco.22.01424. This article has 171 citations and is from a highest quality peer-reviewed journal.
(NCT04697628 chunk 6): Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer. Seagen, a wholly owned subsidiary of Pfizer. 2021. ClinicalTrials.gov Identifier: NCT04697628
(NCT03438396 chunk 3): A Trial of Tisotumab Vedotin in Cervical Cancer. Seagen Inc.. 2018. ClinicalTrials.gov Identifier: NCT03438396

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OpenScientist Report

Subtypes

Pathophysiology

Pathograph

Phenotypes

Genetic Associations

Treatments

Source YAML

References & Deep Research

Deep Research

Disease Characteristics Research Template

Target Disease

Research Objectives

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic/Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome/Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Citation Requirements

Output Format

Comprehensive Research Report: Cervical Adenocarcinoma (Endocervical Adenocarcinoma)

Target disease overview

Key identifiers, synonyms, and coding

2. Etiology

Primary causal factors

HPV-negative vs HPV-independent (important distinction)

Risk factors and cofactors

Protective factors

Gene–environment interactions

3. Phenotypes (clinical presentation)

Common presenting symptoms/signs

Phenotype characteristics (typical timing)

Suggested HPO terms (examples; to support knowledge-base annotation)

4. Genetic / Molecular information

High-level molecular stratification

Recurrent genes and actionable alterations (recent, clinically integrated data)

HPV-independent (HPV-negative) adenocarcinoma mutation patterns

Epigenetic information

5. Environmental information

6. Mechanism / Pathophysiology

Causal chain (HPV-associated adenocarcinoma; conceptual)

Silva invasion patterns as a mechanism-linked risk stratifier (HPV-associated)

HPV-independent gastric-type biology (conceptual)

Suggested GO biological process terms (examples)

Suggested Cell Ontology (CL) terms (examples)

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

Epidemiology and disparities (recent, authoritative population-based evidence)

Genetic inheritance

10. Diagnostics

Pathology and immunohistochemistry (key clinical implementation)

Cytology (screening/diagnostic challenges; real-world implementation)

Imaging (especially relevant to gastric-type)

Differential diagnosis (not exhaustive)

11. Outcome / prognosis

HPV-associated vs HPV-independent prognosis

Invasion-pattern (Silva) prognosis (HPV-associated)

Disparities

12. Treatment

Standard of care (real-world implementation)

Recent developments (priority 2023–2024)

Pembrolizumab + chemoradiation (KEYNOTE-A18; practice-changing)

Induction chemotherapy before chemoradiation (INTERLACE)

Antibody–drug conjugate: tisotumab vedotin (Tivdak)

Chemo-immunotherapy + anti-VEGF combinations (advanced disease)

Precision oncology (HER2 and others)

Suggested MAXO terms (examples)

13. Prevention