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

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

Paolo Boscolo-Rizzo  1 , Lea Schroeder  2 , Valeria Sacchetto  3 , Dana Holzinger  2 , Maria Cristina Da Mosto  1 , Giancarlo Tirelli  4 , Elisa Dal Cin  4 , Monica Mantovani  1 , Anna Menegaldo  1 , Annarosa Del Mistro  3 , Salvatore Romeo  5 , Angelo Paolo Dei Tos  6 , Monia Niero  6 , Stefania Rigo  4 , Gerhard Dyckhoff  7 , Jochen Hess  8 , Laia Alemany  9   10 , Miquel Quer  11 , Xavier León  11 , Jerry Polesel  12 , Michael Pawlita  2 , Roberta Bertorelle  3
Affiliations
Multicenter Study

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

Paolo Boscolo-Rizzo et al. Head Neck. 2019 Nov.

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.

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

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References

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