Prognostic Markers and Driver Genes and Options for Targeted Therapy in Human-Papillomavirus-Positive Tonsillar and Base-of-Tongue Squamous Cell Carcinoma

Viruses. 2021 May 14;13(5):910. doi: 10.3390/v13050910.


The incidence of Human-papillomavirus-positive (HPV+) tonsillar and base-of-tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) is increasing epidemically, but they have better prognosis than equivalent HPV-negative (HPV-) cancers, with roughly 80% vs. 50% 3-year disease-free survival, respectively. The majority of HPV+ TSCC and BOTSCC patients therefore most likely do not require the intensified chemoradiotherapy given today to head and neck cancer patients and would with de-escalated therapy avoid several severe side effects. Moreover, for those with poor prognosis, survival has not improved, so better-tailored alternatives are urgently needed. In line with refined personalized medicine, recent studies have focused on identifying predictive markers and driver cancer genes useful for better stratifying patient treatment as well as for targeted therapy. This review presents some of these endeavors and briefly describes some recent experimental progress and some clinical trials with targeted therapy.

Keywords: base-of-tongue squamous cell carcinoma; driver genes; human papillomavirus; mutations; oropharyngeal squamous cell carcinoma; prognostic marker; targeted therapy; tonsillar squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / etiology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / therapy
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Viral
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Molecular Targeted Therapy
  • Mutation
  • Oncogenes*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Tongue Neoplasms / diagnosis
  • Tongue Neoplasms / etiology*
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / therapy
  • Tonsillar Neoplasms / diagnosis
  • Tonsillar Neoplasms / etiology*
  • Tonsillar Neoplasms / metabolism
  • Tonsillar Neoplasms / therapy
  • Treatment Outcome


  • Biomarkers, Tumor
  • Protein Kinase Inhibitors