Head and neck carcinoma

Summary

Head and neck carcinoma (MONDO:0002038) is a cancer (an umbrella term covering 16 Mondo subtypes) with 1 cohort gene (3 GWAS associations across 2 studies; 1 CIViC-evidence somatic driver) and 124 clinical trials. Molecularly, DDR2 Overexpression confers sensitivity to Dasatinib in Head And Neck Carcinoma (CIViC Level D); 1 further subtype–drug associations are mapped below. Top therapeutic interventions include cetuximab, afatinib, and cabozantinib.

At a glance

• Classification: Cancer
• Umbrella term: 16 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 3
• Clinical trials: 124
• Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	head and neck carcinoma
Mondo ID	MONDO:0002038
DOID	DOID:1542
NCIT	C35850
UMLS	C3887461
MedGen	854345
Anatomy (UBERON)	UBERON:0007811
Is cancer (heuristic)	yes

Also known as: carcinoma of craniocervical region · carcinoma of head and neck · carcinoma of neck · carcinoma of the head and neck · carcinoma of the neck · craniocervical region carcinoma · head and neck carcinoma · neck carcinoma

Data availability: 3 GWAS associations (2 studies).

Disease family

An umbrella term covering 16 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › head and neck carcinoma

Related subtypes (48): retroperitoneum carcinoma, peritoneal carcinoma, neuroendocrine carcinoma, laryngeal carcinoma, bone carcinoma, carcinoma ex pleomorphic adenoma, scrotal carcinoma, skin carcinoma, malignant myoepithelioma, trachea carcinoma, epithelial-myoepithelial carcinoma, lipid-rich carcinoma, comedocarcinoma, in situ carcinoma, adenocarcinoma, urinary bladder carcinoma, breast carcinoma, squamous cell carcinoma, lung carcinoma, prostate carcinoma, renal carcinoma, uterine carcinoma, vulvar carcinoma, large cell carcinoma, undifferentiated carcinoma, basaloid carcinoma, cribriform carcinoma, digestive system carcinoma, fallopian tube carcinoma, penile carcinoma, sarcomatoid carcinoma, thymic carcinoma, transitional cell carcinoma, ureter carcinoma, papillary carcinoma, Krebs 2 carcinoma, thyroid gland carcinoma, vaginal carcinoma, choroid plexus carcinoma, malignant epithelial tumor of ovary, mucin-producing carcinoma, basal cell carcinoma, carcinoma of urethra, combined carcinoid and adenocarcinoma, secondary carcinoma, invasive carcinoma, glycogen-rich carcinoma, lymph node carcinoma

Subtypes (16): eye carcinoma, external ear carcinoma, middle ear carcinoma, nasal cavity carcinoma, growth hormone-producing pituitary gland carcinoma, hypopharyngeal carcinoma, ameloblastic carcinoma, laryngeal small cell carcinoma, pharyngeal adenoid cystic carcinoma, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, pituitary adenocarcinoma, carcinoma of floor of mouth, lip and oral cavity carcinoma, oropharyngeal carcinoma, nasal cavity and paranasal sinus carcinoma

Genetics & variants

GWAS landscape

3 GWAS associations across 2 studies. Top hits map to 4 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs380286	3e-12	CLPTM1L	G
rs3117575	8e-12	MSH5-SAPCD1, MSH5	T
rs2736100	1e-09	TERT	C

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90270344	Guo H	2023	11,348	18,789	A genome-wide cross-cancer meta-analysis highlights the shared genetic links of five solid cancers.
GCST90399471	Zagkos L	2024	1,331	334,378	Exploring the contribution of lifestyle to the impact of education on the risk of cancer through Mendelian randomization analysis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	3

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	3

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs380286	5	1320132	G>A	0.05	intron_variant	CLPTM1L	3e-12	Tier 4: intronic/intergenic
rs3117575	6	31758476	T>C,G	0.05	intron_variant	MSH5-SAPCD1, MSH5	8e-12	Tier 4: intronic/intergenic
rs2736100	5	1286401	C>A,G,T	0.05	intron_variant	TERT	1e-09	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
PTPRD	Act	BRCA,EGC,ESCA,ESCC,LNM,MEL,NHL,OVT,PAAD,SIC,SKCM	CIViC #4692

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PTPRD	HGNC:9668	ENSG00000153707	P23468	Receptor-type tyrosine-protein phosphatase delta	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTPRD	Receptor-type tyrosine-protein phosphatase delta	Can bidirectionally induce pre- and post-synaptic differentiation of neurons by mediating interaction with IL1RAP and IL1RAPL1 trans-synaptically.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTPRD	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	1
cortical plate	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTPRD	160	broad	marker	cortical plate, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPRD	3,052

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPRD	P23468	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Receptor-type tyrosine-protein phosphatases	1	571.0×	0.002	PTPRD
Synaptic adhesion-like molecules	1	543.8×	0.002	PTPRD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
trans-synaptic signaling by trans-synaptic complex	1	5617.3×	0.002	PTPRD
cell surface receptor protein tyrosine phosphatase signaling pathway	1	2106.5×	0.002	PTPRD
presynaptic membrane assembly	1	1685.2×	0.002	PTPRD
presynapse assembly	1	1203.7×	0.002	PTPRD
phosphate-containing compound metabolic process	1	991.3×	0.002	PTPRD
negative regulation of receptor signaling pathway via JAK-STAT	1	887.0×	0.002	PTPRD
positive regulation of dendritic spine morphogenesis	1	887.0×	0.002	PTPRD
regulation of postsynaptic density assembly	1	887.0×	0.002	PTPRD
synaptic membrane adhesion	1	581.1×	0.003	PTPRD
regulation of immune response	1	495.6×	0.003	PTPRD
heterophilic cell-cell adhesion	1	337.0×	0.004	PTPRD
positive regulation of synapse assembly	1	244.2×	0.005	PTPRD
modulation of chemical synaptic transmission	1	183.2×	0.007	PTPRD
neuron differentiation	1	100.3×	0.011	PTPRD
nervous system development	1	45.9×	0.023	PTPRD
signal transduction	1	16.1×	0.062	PTPRD

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTPRD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PTPRD	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPRD	3.1.3.48	protein-tyrosine-phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PTPRD
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PTPRD	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 124.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	57
PHASE2	28
PHASE1	22
PHASE1/PHASE2	9
PHASE3	5
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06258811	PHASE3	RECRUITING	Neoadjuvant Immunochemotherapy for LAOSCC
NCT00050388	PHASE3	COMPLETED	Phase II Trial of Allovectin-7® for Head and Neck Cancer
NCT01228565	PHASE3	COMPLETED	Trial of OTD70DERM® in Radio-dermatitis Induced by Radiotherapy-Erbitux®
NCT01507467	PHASE3	TERMINATED	IAEA-HypoX. Accelerated Radiotherapy With or Without Nimorazole in Squamous Cell Carcinoma of the Head and Neck
NCT02369835	PHASE3	COMPLETED	Modified Dakin’s Solution in Reducing Radiation-Induced Dermatitis in Patients With Head and Neck Cancer Undergoing Radiation Therapy
NCT02465060	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT02713269	PHASE2	ACTIVE_NOT_RECRUITING	Thermal Ablation and Spine Stereotactic Radiosurgery in Treating Patients With Spine Metastases at Risk for Compressing the Spinal Cord
NCT03468218	PHASE2	ACTIVE_NOT_RECRUITING	Pembrolizumab & Cabozantinib in Patients With Head and Neck Squamous Cell Cancer
NCT03556228	PHASE1/PHASE2	RECRUITING	VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma
NCT04140526	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC
NCT04151082	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	High Dose Steroid Therapy (Prednisone or Methylprednisolone) for the Improvement of Symptoms of Late Radiation-Associated Lower Cranial Neuropathy in Oropharyngeal Cancer Survivors
NCT04870762	PHASE2	RECRUITING	Customized 3D Printed Oral Stents During Head and Neck Radiotherapy
NCT05075980	PHASE2	ACTIVE_NOT_RECRUITING	Intensity Modulated Proton or X-Ray Therapy After Surgery for Treatment of Head and Neck Cancer, the HEADLIGHT Study
NCT05077072	PHASE2	ACTIVE_NOT_RECRUITING	Interdisciplinary Interventions to Address Pain Management Among Head and Neck Cancer Patients
NCT05156060	PHASE1/PHASE2	RECRUITING	Gabapentin & Ketamine for Prevention/Treatment of Acute/Chronic Pain in Locally Advanced Head and Neck Cancer
NCT05544136	PHASE2	RECRUITING	A Study of Decreasing Radiation Therapy and Chemotherapy in People With Head and Neck Cancer
NCT05969860	PHASE2	RECRUITING	At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
NCT05980000	PHASE2	ACTIVE_NOT_RECRUITING	Ramucirumab and Pembrolizumab vs Pembrolizumab Monotherapy in PD-L1 Positive Head and Neck Squamous-Cell Carcinoma
NCT06007092	PHASE1/PHASE2	RECRUITING	Therapeutic Vaccine in Patients With Human Papillomavirus HPV-positive Oropharyngeal Cancer
NCT06289049	PHASE2	RECRUITING	Heavy Strength Training in Head and Neck Cancer Survivors
NCT06627270	PHASE2	RECRUITING	Antibiotic Treatment Effects on Intratumoral Bacteria Modulation in Surgical Patients With Oral Cancer
NCT07242365	PHASE2	ACTIVE_NOT_RECRUITING	Soylent in Reducing Gastrostomy Tube Rates in Patients With Locally Advanced Head and Neck Cancer Undergoing Chemoradiotherapy
NCT07285044	PHASE2	RECRUITING	The Cancer Connected Access and Remote Expertise Beyond Walls Program to Provide In-Home Cancer Treatment and Improve Treatment Satisfaction in Cancer Patients Living in the Florida Panhandle and Surrounding Areas
NCT00184028	PHASE2	TERMINATED	Combination of Taxotere and Oxaliplatin in Squamous Cell Carcinoma of the Head and Neck
NCT00257335	PHASE2	WITHDRAWN	Intensity-Modulated Radiotherapy for Recurrent Head and Neck Cancer
NCT00865098	PHASE2	COMPLETED	Study of Cetuximab With Concomitant-boost Radiotherapy in Patients With Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
NCT01696955	PHASE2	COMPLETED	Cetuximab With or Without Tivantinib in Treating Patients With Head and Neck Cancer That Is Recurrent, Metastatic, or Cannot Be Removed by Surgery
NCT02325349	PHASE2	TERMINATED	PET/CT Imaging of Angiogenesis in Lung or Head and Neck Cancers Prior or During Chemotherapy With Antiangiogenic Agents
NCT02706691	PHASE2	TERMINATED	BGJ398 in Treating Patients With FGFR Positive Recurrent Head and Neck Cancer
NCT02718820	PHASE1/PHASE2	COMPLETED	Pembrolizumab Plus Docetaxel for the Treatment of Recurrent or Metastatic Head and Neck Cancer
NCT03001570	PHASE2	UNKNOWN	Accelerated Modulated Fractionation (SIB-IMRT) for Head and Neck District
NCT03049618	PHASE2	COMPLETED	Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475
NCT03164460	PHASE2	SUSPENDED	Stereotactic Body Radiation Therapy or Intensity Modulated Radiation/Proton Therapy in Treating Patients With Recurrent Head and Neck Cancer
NCT03370276	PHASE1/PHASE2	COMPLETED	Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma
NCT03591666	PHASE2	UNKNOWN	A Study of Anlotinib in Recurrent/Metastatic Head and Neck Adenocarcinomas
NCT03602066	PHASE2	TERMINATED	Study Evaluating The Role of ClO2 on Mucositis for Pt. Undergoing Head/Neck Radiotherapy
NCT03602079	PHASE1/PHASE2	COMPLETED	Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene
NCT03745690	PHASE1/PHASE2	WITHDRAWN	Near-Infrared Image Guided Surgical Resection With Indocyanine Green in Treating Patients With Head and Neck Cancer
NCT03795610	PHASE2	COMPLETED	IPI-549 in Patients With Locally Advanced HPV+ and HPV- Head and Neck Squamous Cell Carcinoma
NCT03993353	PHASE2	COMPLETED	Tadalafil and Pembrolizumab in Recurrent or Metastatic Head and Neck Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CETUXIMAB	4	5
AFATINIB	4	2
CABOZANTINIB	4	2
COPANLISIB	4	2
DABRAFENIB	4	2
LAROTRECTINIB	4	2
BINIMETINIB	4	1
CAPIVASERTIB	4	1
CHLORHEXIDINE	4	1
CRIZOTINIB	4	1
ERDAFITINIB	4	1
INFIGRATINIB	4	1
OSIMERTINIB	4	1
PALBOCICLIB	4	1
PORFIMER SODIUM	4	1
RELATLIMAB	4	1
ROMIDEPSIN	4	1
SODIUM HYPOCHLORITE	4	1
SULFADIAZINE, SILVER	4	1
SUNITINIB MALATE	4	1
TALIMOGENE LAHERPAREPVEC	4	1
TISLELIZUMAB	4	1
TRAMETINIB	4	1
TRASTUZUMAB EMTANSINE	4	1
VISMODEGIB	4	1
DEFACTINIB	3	3
CATEQUENTINIB	3	1
IPATASERTIB	3	1
MILADEMETAN	3	1
NIMORAZOLE	3	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 2 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
DDR2 Overexpression	Dasatinib	Sensitivity/Response	CIViC D	EID9854
PTPRD Mutation	JSI-124	Sensitivity/Response	CIViC D	EID807