Oral Cavity Squamous Cell Carcinoma (OCSC)

Overview

Oral Cavity Squamous Cell Carcinoma (OCSC) is a subtype of Head and Neck Squamous Cell Carcinoma (HNSC) arising from the oral cavity epithelium. It is classified under the Head and Neck Cancer main type in OncoTree (parent node HNSC). OCSC is characterized by high genomic instability (74% of tumors with ≥20 copy-number alterations), four major driver pathways (mitogenic signaling, Notch, cell cycle, TP53), and a high proportion of targetable alterations.

Cohorts in the corpus

  • hnsc_mdanderson_2013 — 40 OSCC patients from MD Anderson Cancer Center; multi-platform analysis including Affymetrix SNP6 copy-number arrays (38 tumors), whole-exome sequencing, Illumina 450k methylation arrays, Affymetrix exon expression arrays, and Agilent miRNA arrays. PMID:23619168

Recurrent alterations

  • Multi-platform genomic analysis of 40 OSCC (an HNSC subtype) identified four major driver pathways (mitogenic signaling 63%, Notch 66%, cell cycle 94%, TP53 60%), novel FAT1 inactivation in 46% and CASP8 mutations in 10% defining a CN-quiet subtype; 80% of tumors harbored at least one targetable alteration PMID:23619168
  • TP53 mutated in 60% (24/40); 13% splice-site mutations (markedly enriched vs. 2% baseline across tumor types); TP53 mutations associated with higher CNA burden (p=0.0051). PMID:23619168
  • FAT1 mutated in 30% (12/40), the highest frequency reported for HNSCC at time of publication; two-thirds were inactivating; 46% combined inactivation including focal deletions. PMID:23619168
  • NOTCH1 mutated in 9% of primary OSCC; 16/44 HNSCC cell lines had NOTCH1 alterations; functional NOTCH1 signaling (ICN1) inhibited proliferation in vitro and in orthotopic xenograft models via G1 arrest and p21 induction. PMID:23619168
  • CASP8 mutations in 10% (4/40) define a low-CNA subtype co-occurring with HRAS mutations (p=0.0016 in discovery cohort; validated in TCGA HNSC p<0.0001). PMID:23619168
  • Arm-level CNAs in >50% of tumors: 3p loss (76%), 8q gain (63%), 3q gain (58%), 18q loss (58%), 8p loss (53%); 8p loss associated with reduced disease-free survival (p=0.047). PMID:23619168
  • Focal high-level amplifications: CCND1 (22%), EGFR (16%); cell-cycle pathway altered in 94% (33/35) via CCND1 amplification and/or CDKN2A loss. PMID:23619168
  • Oral cavity squamous cell carcinoma (OCSC) comprised 172/279 (62%) of the TCGA HNSC cohort; CASP8 inactivating mutations were highly enriched in OCSC (92% of all CASP8 mutations), and HRAS+CASP8+wild-type TP53 co-mutation defined a favourable-outcome M-class subset predominantly in this site. PMID:25631445

Subtypes

  • CASP8-mutant subtype (~10%): Low copy-number alteration burden; HRAS co-mutation; more aggressive orthotopic xenograft phenotype with CASP8 loss-of-function. PMID:23619168
  • mRNA/miRNA expression cluster 1 (poorly differentiated): Higher ploidy (3.33 vs. 2.62), fewer mutations (median 53 vs. 81, p=0.0073); all non-tobacco users in this cluster (p<0.007). PMID:23619168
  • CIMP-like methylation subgroup: Higher methylation frequency, fewer CNAs; tobacco use associated with methylation cluster (p<0.009). PMID:23619168

Therapeutic landscape

  • 80% (28/35) of OSCC tumors harbored ≥1 targetable alteration; 54% (19/35) had ≥2; notable targets include PI3K signaling (PIK3CA/AKT1-3, 34%), SRC-family kinases (SRC/LYN/YES1, 29%), TNK2 (17%), PTK2/FAK (14%), Aurora kinases (AURKA/C, 14%). PMID:23619168
  • cetuximab (anti-EGFR) is an established HNSCC therapy; EGFR amplified in 16% of OSCC, but downstream PI3K alterations (HRAS, PIK3CA, BRAF, AKT1) may explain limited EGFR-inhibitor benefit. PMID:23619168
  • cisplatin remains backbone therapy alongside surgery and radiation. PMID:23619168

Sources

  • PMID:23619168 — Pickering et al. Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov 2013.

This page was processed by crosslinker on 2026-05-14. - PMID:25631445

This page was processed by crosslinker on 2026-05-14.