Oropharynx Squamous Cell Carcinoma (OPHSC)

Overview

Oropharynx squamous cell carcinoma arises from the squamous epithelium of the oropharynx (base of tongue, tonsils, soft palate, posterior pharyngeal wall). It is classified in OncoTree under HNSC (Head and Neck Squamous Cell Carcinoma). Oropharyngeal HNSCC is notable for its high frequency of HPV-driven disease (~64% HPV-positive in the TCGA cohort), which defines a biologically and clinically distinct subgroup with favorable outcomes relative to HPV-negative tumors.

Cohorts in the corpus

  • TCGA HNSCC 2015 publication (hnsc_tcga_pub): 33/279 tumors (12%) were oropharyngeal; 64% HPV-positive vs 6% in non-oropharyngeal sites. PMID:25631445

Recurrent alterations

  • HPV+ oropharyngeal tumors are enriched for helical-domain PIK3CA mutations (E542K/E545K; 56% HPV+ vs 34% HPV−), recurrent TRAF3 deletions (14%) and truncating mutations (8%), and focal E2F1 amplification; intact 9p21.3 (CDKN2A) distinguishes HPV+ from HPV− oropharyngeal tumors. PMID:25631445
  • FGFR3 alterations enriched in HPV+ vs HPV− oropharyngeal tumors (11% vs 2%), including FGFR3–TACC3 fusions in 2 HPV+ cases. PMID:25631445
  • TP53 mutation rate reduced in oropharyngeal tumors relative to oral cavity and larynx (P<0.001), reflecting HPV E6-mediated TP53 degradation in the HPV+ majority. PMID:25631445
  • NSD1 and CASP8 mutations also had reduced rates in oropharyngeal tumors compared with other HNSCC subsites. PMID:25631445
  • Included in the MSK-IMPACT cohort of 53 recurrent/metastatic HNSC (Morris et al., N=151 total); overall NGS-guided therapy rate was 25% for HNSC; HPV-positive oropharyngeal tumors were enriched in the advanced disease cohort and 43% acquired an HPV-negative-like genotype PMID:27442865.

Subtypes

  • HPV+ oropharyngeal tumors cluster in the “atypical” mRNA expression subtype: enriched for PIK3CA helical-domain mutations, NSD1 LOF, DNA hypomethylation, wild-type NOTCH1, and APOBEC-like TpC mutational signature. PMID:25631445
  • HPV+ tumors show favorable overall survival compared with HPV−/TP53-mutant and 11q13/CCND1-amplified tumors. PMID:25631445

Therapeutic landscape

  • HPV+ oropharyngeal cancers harbor aberrant NF-κB activation via TRAF3 loss and PI3K pathway activation via PIK3CA, motivating PI3K-pathway and cell-cycle-targeted therapy evaluation. PMID:25631445

Sources

  • TCGA multi-platform profiling of 279 HNSCCs; oropharynx site (n=33, 12% of cohort) was the most HPV-enriched subsite (64% HPV+); HPV+ biology defined by TRAF3 loss, PIK3CA helical-domain mutations, and E2F1 amplification, with favorable survival outcomes. PMID:25631445

This page was processed by crosslinker on 2026-05-14. - PMID:27442865 — Morris et al. 2017 (JAMA Oncol). MSK-IMPACT of 151 advanced head and neck tumors; HPV-positive oropharyngeal tumors predominate and 43% acquire HPV-negative-like genotype.

This page was processed by entity-page-writer on 2026-05-15.