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

Paolo Boscolo-Rizzo, Lea Schroeder, Valeria Sacchetto, Dana Holzinger, Maria Cristina Da Mosto, Giancarlo Tirelli, Elisa Dal Cin, Monica Mantovani, Anna Menegaldo, Annarosa Del Mistro, Salvatore Romeo, Angelo Paolo Dei Tos, Monia Niero, Stefania Rigo, Gerhard Dyckhoff, Jochen Hess, Laia Alemany, Miquel Quer, Xavier León, Jerry PoleselMichael Pawlita, Roberta Bertorelle

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)3833-3841
Number of pages9
JournalHead and Neck Surgery
Volume41
Issue number11
DOIs
Publication statusPublished - Nov 2019

Keywords

  • *CUP
  • *HPV
  • *head and neck
  • *mutation
  • *p53

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    Boscolo-Rizzo, P., Schroeder, L., Sacchetto, V., Holzinger, D., Da Mosto, M. C., Tirelli, G., Dal Cin, E., Mantovani, M., Menegaldo, A., Del Mistro, A., Romeo, S., Dei Tos, A. P., Niero, M., Rigo, S., Dyckhoff, G., Hess, J., Alemany, L., Quer, M., León, X., ... Bertorelle, R. (2019). Absence of disruptive TP53 mutations in high-risk human papillomavirus-driven neck squamous cell carcinoma of unknown primary. Head and Neck Surgery, 41(11), 3833-3841. https://doi.org/10.1002/hed.25915