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 Polesel; Michael Pawlita; Roberta Bertorelle

doi:10.1002/hed.25915

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 journal › Article › peer-review

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 language	English
Pages (from-to)	3833-3841
Number of pages	9
Journal	Head and Neck Surgery
Volume	41
Issue number	11
DOIs	https://doi.org/10.1002/hed.25915
Publication status	Published - Nov 2019

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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

Absence of disruptive TP53 mutations in high-risk human papillomavirus-driven neck squamous cell carcinoma of unknown primary. / Boscolo-Rizzo, Paolo; Schroeder, Lea; Sacchetto, Valeria; Holzinger, Dana; Da Mosto, Maria Cristina; Tirelli, Giancarlo; Dal Cin, Elisa; Mantovani, Monica; Menegaldo, Anna; Del Mistro, Annarosa; Romeo, Salvatore; Dei Tos, Angelo Paolo; Niero, Monia; Rigo, Stefania; Dyckhoff, Gerhard; Hess, Jochen; Alemany, Laia; Quer, Miquel; León, Xavier; Polesel, Jerry; Pawlita, Michael; Bertorelle, Roberta.

In: Head and Neck Surgery, Vol. 41, No. 11, 11.2019, p. 3833-3841.

Research output: Contribution to journal › Article › peer-review

Boscolo-Rizzo, P, Schroeder, L, Sacchetto, V, Holzinger, D, Da Mosto, MC, Tirelli, G, Dal Cin, E, Mantovani, M, Menegaldo, A, Del Mistro, A, Romeo, S, Dei Tos, AP, Niero, M, Rigo, S, Dyckhoff, G, Hess, J, Alemany, L, Quer, M, León, X, Polesel, J, Pawlita, M & 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, vol. 41, no. 11, pp. 3833-3841. https://doi.org/10.1002/hed.25915

Boscolo-Rizzo, Paolo ; Schroeder, Lea ; Sacchetto, Valeria ; Holzinger, Dana ; Da Mosto, Maria Cristina ; Tirelli, Giancarlo ; Dal Cin, Elisa ; Mantovani, Monica ; Menegaldo, Anna ; Del Mistro, Annarosa ; Romeo, Salvatore ; Dei Tos, Angelo Paolo ; Niero, Monia ; Rigo, Stefania ; Dyckhoff, Gerhard ; Hess, Jochen ; Alemany, Laia ; Quer, Miquel ; León, Xavier ; Polesel, Jerry ; Pawlita, Michael ; Bertorelle, Roberta. / Absence of disruptive TP53 mutations in high-risk human papillomavirus-driven neck squamous cell carcinoma of unknown primary. In: Head and Neck Surgery. 2019 ; Vol. 41, No. 11. pp. 3833-3841.

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

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.",

author = "Paolo Boscolo-Rizzo and Lea Schroeder and Valeria Sacchetto and Dana Holzinger and {Da Mosto}, {Maria Cristina} and Giancarlo Tirelli and {Dal Cin}, Elisa and Monica Mantovani and Anna Menegaldo and {Del Mistro}, Annarosa and Salvatore Romeo and {Dei Tos}, {Angelo Paolo} and Monia Niero and Stefania Rigo and Gerhard Dyckhoff and Jochen Hess and Laia Alemany and Miquel Quer and Xavier Le{\'o}n and Jerry Polesel and Michael Pawlita and Roberta Bertorelle",

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AU - Boscolo-Rizzo, Paolo

AU - Schroeder, Lea

AU - Sacchetto, Valeria

AU - Holzinger, Dana

AU - Da Mosto, Maria Cristina

AU - Tirelli, Giancarlo

AU - Dal Cin, Elisa

AU - Mantovani, Monica

AU - Menegaldo, Anna

AU - Del Mistro, Annarosa

AU - Romeo, Salvatore

AU - Dei Tos, Angelo Paolo

AU - Niero, Monia

AU - Rigo, Stefania

AU - Dyckhoff, Gerhard

AU - Hess, Jochen

AU - Alemany, Laia

AU - Quer, Miquel

AU - León, Xavier

AU - Polesel, Jerry

AU - Pawlita, Michael

AU - Bertorelle, Roberta

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

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DO - 10.1002/hed.25915

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SN - 1043-3074

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

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