RNA TargetsHead & Neck OncologyResearch Use Only
Head & Neck Cancer (HNSCC)
Gene Expression Reference Targets
Gene Expression Reference Targets
A biologically curated RNA target reference for head and neck cancer spanning EGFR/PI3K driver pathways, HPV+ vs HPV− molecular biology, immune checkpoint biology (KEYNOTE-048/890 biomarkers), and squamous lineage markers — enabling researchers to configure custom Tapestri assays for precision IO stratification and resistance mechanism studies.
240
Total Genes
7
Functional Categories
5
HNSCC Subtypes Covered
6+
Curation Sources
1
Panel Power Scorecard & Functional Categories
● Panel Power Scorecard
Panel Score: 71 / 100
87%
Landmark
Biomarker
Coverage
Biomarker
Coverage
82%
COSMIC
Tier-1
Coverage
Tier-1
Coverage
9 genes
FDA
Biomarker
Genes
Biomarker
Genes
14 genes
Clinical Trial
Biomarkers
Biomarkers
7 states
Cell States
Resolvable
Resolvable
240 genes
Total Panel
Genes
Genes
Published precedent — targeted panels are sufficient
Cohen et al. 2019 Lancet (KEYNOTE-048 pembrolizumab HNSCC)
Cillo et al. 2020 Cell (HNSCC TIL single-cell atlas)
52
Driver / EGFR
48
Squamous Lineage
52
Immune TME
32
HPV+ Biology
38
Stroma / CAF
24
Cell Cycle
19
DDR / HRD
2
Background & Curation Principles
Commercial Assays
- FoundationOne CDx (HNSCC panel)
- Tempus xT (solid tumor)
- Illumina TruSight Oncology 500
- QIAGEN QIAseq HNSCC Panel
Public Databases
- TCGA HNSC (279 tumors)
- COSMIC (head & neck mutations)
- MSigDB squamous signatures
- Human Cell Atlas (oral/pharyngeal)
- TISCH2 HNSCC TME
Peer-Reviewed Literature
- HNSCC molecular subtypes (Seiwert 2015)
- Pembrolizumab first-line (KEYNOTE-048, Cohen 2019 Lancet)
- EGFR/cetuximab resistance (Ferris 2019)
- HPV+ vs HPV- biology (Gillison 2019 Nature)
Why Single-Cell RNA for Head & Neck Cancer?
HNSCC has one of the highest TIL infiltration rates among solid tumors, but ICI response rates remain ~20% in unselected patients. The critical question is not whether TILs are present but whether they are functional or exhausted — and bulk RNA cannot distinguish functional vs terminally exhausted CD8+ T cells in the same biopsy. Tapestri resolves HPV+ vs HPV- tumor cells by co-detecting HPV-driven transcriptional state alongside immune cell activation, enabling per-cell mapping of the immune exclusion that drives resistance.
HPV+ vs HPV− — Two Diseases in One ICD Code
HPV+ oropharyngeal HNSCC has better survival, higher TIL infiltration, PIK3CA as primary driver, and higher ICI response rate. HPV− HNSCC is TP53-mutant, CDKN2A-deleted, and EGFR-amplified. Panel covers both: E6/E7-driven CDK pathway (HPV+) and TP53/EGFR (HPV−) — enabling subtype-specific single-cell analysis and per-cell co-detection of driver mutation + immune TME state.
3
Target Reference Structure — Gene Table
1 · Driver / EGFR / PI3K2 · Squamous Lineage / Subtype3 · Immune TME / Checkpoint4 · HPV+ Biology5 · Stroma / EMT6 · Cell Cycle7 · DDR / HRD
| Category | Representative Genes (n) | Biological Function | Disease Relevance | scD+R Use Case |
|---|---|---|---|---|
| 1 · Driver / EGFR / PIK3CA / TP53 · 52 genes | ||||
| Driver | EGFR, ERBB2, ERBB3, MET, FGFR1, FGFR2, FGFR3, PIK3CA, PTEN, AKT1, MTOR, TP53, CDKN2A, RB1, MDM2, HRAS, KRAS, NFE2L2, KEAP1, NOTCH1, FAT1, CASP8, NSD1, MYC, CCND1 (25) + 27 accessory | EGFR/ErbB; PI3K/mTOR; TP53/CDKN2A tumor suppressor; Notch/Wnt | EGFR amp = cetuximab target; PIK3CA = alpelisib; NFE2L2/KEAP1 = antioxidant pathway (HPV-); NOTCH1 = HNSCC tumor suppressor; FAT1 = Wnt activating | Co-detect EGFR amp status + epithelial-to-mesenchymal state per tumor cell |
| 2 · Squamous Lineage / HNSCC Molecular Subtypes · 48 genes | ||||
| Lineage | KRT5, KRT14, KRT6A, KRT6B, TP63, SOX2, SNAI1, SNAI2, ZEB1, ZEB2, TWIST1, CDH1, CDH2, VIM, EPCAM, MUC1, S100A2, S100A4, LAMC2, ITGB4, FN1, EGFR, MKI67, FGFR1 (24) + 24 accessory | Classical/basal/atypical/mesenchymal subtype markers; epithelial squamous identity | KRT5/TP63 = classical squamous; SOX2 amp = classical subtype; ZEB1 = mesenchymal subtype; SNAI1/2 = EMT; classical/basal = EGFR-driven | Classify HNSCC molecular subtype per tumor cell; track EMT at single-cell resolution |
| 3 · Immune TME / Checkpoint · 52 genes | ||||
| Immune | CD3E, CD8A, CD4, GZMB, IFNG, TOX, PDCD1, LAG3, HAVCR2, TIGIT, CD274, CTLA4, FOXP3, IL2RA, TCF7, CXCL13, TREM2, SPP1, CD68, CD163, ARG1, IDO1, B2M, HLA-A, MS4A1, NCAM1 (26) + 26 accessory | TIL / checkpoint / myeloid / TLS | CD274 CPS score = KEYNOTE-048/890 pembrolizumab eligibility; TCF7+/TOX+ = progenitor-exhausted T cells (ICI response); IDO1 = immunosuppression | Measure CPS-equivalent biomarkers per cell; resolve TIL functional states |
| 4 · HPV+ Biology / E6/E7 Pathway · 32 genes | ||||
| Resistance | RB1, E2F1, CDKN1A, CDK4, CDK6, CCND1, CCNE1, TP53, MDM2, TERT, PIK3CA, MAPK1, MYC, MCM2, TOP2A, CDC20 (16) + 16 accessory | HPV E6 degrades TP53; HPV E7 inactivates RB1; CDK pathway | RB1 loss (E7) = CDK4/6i opportunity in HPV+; TP53 degradation (E6) = HPV+ distinguisher; PIK3CA hot-spot = HPV+ specific co-driver | Identify HPV+ tumor cells (RB1-low/CDK-high) vs HPV- (TP53-mutant) at single-cell level |
| 5 · Stroma / CAF / Angiogenesis · 38 genes | ||||
| Stromal | ACTA2, FAP, PDGFRA, PDGFRB, CXCL12, VEGFA, KDR, COL1A1, MMP2, MMP9, POSTN, LRRC15, TGFB1, CDH11, THY1, SPARC, FN1, MMP14 (18) + 20 accessory | CAF subtypes; invasion/angiogenesis; T cell exclusion stroma | TGFB1 = T cell exclusion (stroma-mediated resistance); FAP+ CAF = immunosuppressive; VEGFA = bevacizumab; CXCL12 = T cell trapping | Resolve iCAF vs myCAF subtypes; map T cell exclusion mechanisms |
| 6 · Cell Cycle / Proliferation · 24 genes | ||||
| Cell Cycle | MKI67, TOP2A, AURKA, CCNB1, CDK2, E2F1, FOXM1, MCM2, PLK1, BUB1, CDC20, UBE2C (12) + 12 accessory | WHO grade / mitotic index | MKI67 = proliferative index; FOXM1 = cetuximab resistance; AURKA = alisertib target | Score proliferating tumor cells; link to cetuximab resistance mechanisms |
| 7 · DDR / HRD / TMB · 19 genes | ||||
| DDR | BRCA1, BRCA2, ATM, CHEK1, CHEK2, PARP1, MLH1, MSH2, POLE, TP53, CDKN2A, CASP8, RAD51 (13) + 6 accessory | DNA damage repair; HRD; TMB; PARP sensitivity | POLE mutation = high TMB / ICI predictor; BRCA1/2 = HRD / PARP inhibitor; MSH2 = MSI-H | Identify DDR-deficient subclones; assess POLE/MSI-H hypermutation states |
Total: 240 genesCat 1: 52 · Cat 2: 48 · Cat 3: 52 · Cat 4: 32 · Cat 5: 38 · Cat 6: 24 · Cat 7: 19
ⓘ Select genes appear in more than one functional category reflecting their multi-role biology. The total above counts unique genes; per-category counts include all category-relevant entries.