Absence of disruptive TP53 mutations in high-risk human papillomavirus-driven neck squamous cell carcinoma of unknown primary

Head Neck. 2019 Nov;41(11):3833-3841. doi: 10.1002/hed.25915. Epub 2019 Aug 15.


Background: To enforce the evidence for causality between high-risk human papillomavirus (hrHPV) infections and neck squamous cell carcinoma from unknown primary (NSCCUP) and provide biological basis for treatment de-intensification, we searched for TP53 mutations in association with HPV status.

Methods: TP53 mutations were searched for by amplification of exons 4 to 10.

Results: Of the 70 NSCCUP, 27 (39%) harbored HPV infection. TP53 sequencing resulted in the identification of 19 patients harboring single mutations including 16 disruptive alterations (84%). The association of TP53 mutations and HPV could be evaluated in 48 NSCCUP including those with disruptive mutation in any exon (n = 16) and those without mutations but with complete sequence of exons 4 to 9 (n = 32): no disruptive mutations were found in the 17 HPV-driven NSCCUP but in 16 of the 31 non-HPV-driven NSCCUP (P = .0002).

Conclusion: In a fraction of cases, NSCCUP is an HPV-driven entity harboring wild-type TP53 gene or nondisruptive TP53 mutations. HPV-driven NSCCUP might benefit from treatment de-intensification.

Keywords: CUP; HPV; head and neck; mutation; p53.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / virology
  • Female
  • Genes, p53 / genetics*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / secondary
  • Head and Neck Neoplasms / virology
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasms, Unknown Primary / genetics*
  • Neoplasms, Unknown Primary / virology
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / genetics
  • Retrospective Studies