HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas

D. M. Filippini; B. Cabarrou; C. Dupain; M. Halladjian; E. Coquan; M. P. Sablin; L. Mazzarella; M. Francisco; N. Servant; M. M. Tonini; A. F. Hundt; Z. Castel-Ajgal; B. You; F. Bigot; F. Ghiringhelli; D. Vansteene; C. Gomez-Roca; S. Cousin; A. Lambert; E. Saada-Bouzid; X. Durando; C. Abdeddaim; C. Borel; R. Chaltiel; E. Borcoman; F. Legrand; S. Bernhart; M. Jimenez; I. Bièche; T. Filleron; C. Le Tourneau; M. Kamal; E. Jeannot

doi:10.1016/j.esmoop.2025.106024

HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas

D. M. Filippini
, B. Cabarrou
, C. Dupain
, M. Halladjian
, E. Coquan
, M. P. Sablin
, L. Mazzarella
, M. Francisco
, N. Servant
, M. M. Tonini
, A. F. Hundt
, Z. Castel-Ajgal
, B. You
, F. Bigot
, F. Ghiringhelli
, D. Vansteene
, C. Gomez-Roca
, S. Cousin
, A. Lambert
, E. Saada-Bouzid

X. Durando, C. Abdeddaim, C. Borel, R. Chaltiel, E. Borcoman, F. Legrand, S. Bernhart, M. Jimenez, I. Bièche, T. Filleron, C. Le Tourneau, M. Kamal, E. Jeannot^*

^*Corresponding author for this work

Clinical Research Project Management 1

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

Abstract

BACKGROUND: Limited data are available on the role of human papillomavirus circulating tumor DNA (HPV-ctDNA) as a pharmacodynamic marker to monitor the response to treatment in the recurrent/metastatic (R/M) setting. Our study aimed to investigate the sensitivity and pharmacodynamic value of HPV-ctDNA levels during treatment in patients with R/M HPV-related squamous cell carcinoma (SCC) treated with pembrolizumab in combination with vorinostat (PEVO trial, NCT04357873).

MATERIALS AND METHODS: Plasma samples were prospectively collected from 57 patients with HPV-related SCC before treatment initiation and every 6 weeks until disease progression. HPV-ctDNA was quantified by droplet digital PCR. The levels before treatment were analyzed according to the patient and tumor characteristics. Landmark analyses were carried out to study the association between dynamic changes in HPV-ctDNA and progression-free survival (PFS), overall survival (OS), and overall response rate (ORR).

RESULTS: HPV-ctDNA was detected before treatment in all patients (n = 57) with HPV-related SCC. HPV-ctDNA levels correlated with the number of HPV copies in tumor tissue (P < 0.001). Higher levels of HPV-ctDNA in plasma samples were observed in anal cancer than in other tumor types (P < 0.001), and in patients with distant metastases with or without locoregional recurrence than in patients with locoregional recurrence alone (P = 0.02). The increase in HPV-ctDNA levels during treatment was associated with a lower ORR (P = 0.01) and shorter PFS and OS (both P = 0.01).

CONCLUSION: These findings reveal that dynamic HPV-ctDNA variation levels during treatment have a pharmacodynamic value and may help monitor treatment response in patients with advanced HPV-related SCC from different locations.

Original language	English
Article number	106024
Number of pages	10
Journal	ESMO Open
Volume	11
Issue number	1
Early online date	29 Dec 2025
DOIs	https://doi.org/10.1016/j.esmoop.2025.106024
Publication status	Published - Jan 2026

Keywords

HPV
biomarker
circulating tumor DNA
immunotherapy
pharmacodynamic
squamous cell carcinoma

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Filippini, D. M., Cabarrou, B., Dupain, C., Halladjian, M., Coquan, E., Sablin, M. P., Mazzarella, L., Francisco, M., Servant, N., Tonini, M. M., Hundt, A. F., Castel-Ajgal, Z., You, B., Bigot, F., Ghiringhelli, F., Vansteene, D., Gomez-Roca, C., Cousin, S., Lambert, A., ... Jeannot, E. (2026). HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas. ESMO Open, 11(1), Article 106024. https://doi.org/10.1016/j.esmoop.2025.106024

@article{687fe59468fd442cbbe3798906024abc,

title = "HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas",

abstract = "BACKGROUND: Limited data are available on the role of human papillomavirus circulating tumor DNA (HPV-ctDNA) as a pharmacodynamic marker to monitor the response to treatment in the recurrent/metastatic (R/M) setting. Our study aimed to investigate the sensitivity and pharmacodynamic value of HPV-ctDNA levels during treatment in patients with R/M HPV-related squamous cell carcinoma (SCC) treated with pembrolizumab in combination with vorinostat (PEVO trial, NCT04357873).MATERIALS AND METHODS: Plasma samples were prospectively collected from 57 patients with HPV-related SCC before treatment initiation and every 6 weeks until disease progression. HPV-ctDNA was quantified by droplet digital PCR. The levels before treatment were analyzed according to the patient and tumor characteristics. Landmark analyses were carried out to study the association between dynamic changes in HPV-ctDNA and progression-free survival (PFS), overall survival (OS), and overall response rate (ORR).RESULTS: HPV-ctDNA was detected before treatment in all patients (n = 57) with HPV-related SCC. HPV-ctDNA levels correlated with the number of HPV copies in tumor tissue (P < 0.001). Higher levels of HPV-ctDNA in plasma samples were observed in anal cancer than in other tumor types (P < 0.001), and in patients with distant metastases with or without locoregional recurrence than in patients with locoregional recurrence alone (P = 0.02). The increase in HPV-ctDNA levels during treatment was associated with a lower ORR (P = 0.01) and shorter PFS and OS (both P = 0.01).CONCLUSION: These findings reveal that dynamic HPV-ctDNA variation levels during treatment have a pharmacodynamic value and may help monitor treatment response in patients with advanced HPV-related SCC from different locations.",

keywords = "HPV, biomarker, circulating tumor DNA, immunotherapy, pharmacodynamic, squamous cell carcinoma",

author = "Filippini, \{D. M.\} and B. Cabarrou and C. Dupain and M. Halladjian and E. Coquan and Sablin, \{M. P.\} and L. Mazzarella and M. Francisco and N. Servant and Tonini, \{M. M.\} and Hundt, \{A. F.\} and Z. Castel-Ajgal and B. You and F. Bigot and F. Ghiringhelli and D. Vansteene and C. Gomez-Roca and S. Cousin and A. Lambert and E. Saada-Bouzid and X. Durando and C. Abdeddaim and C. Borel and R. Chaltiel and E. Borcoman and F. Legrand and S. Bernhart and M. Jimenez and I. Bi{\`e}che and T. Filleron and \{Le Tourneau\}, C. and M. Kamal and E. Jeannot",

year = "2026",

month = jan,

doi = "10.1016/j.esmoop.2025.106024",

language = "English",

volume = "11",

journal = "ESMO Open",

issn = "2059-7029",

publisher = "Elsevier B.V.",

number = "1",

}

Filippini, DM, Cabarrou, B, Dupain, C, Halladjian, M, Coquan, E, Sablin, MP, Mazzarella, L, Francisco, M, Servant, N, Tonini, MM, Hundt, AF, Castel-Ajgal, Z, You, B, Bigot, F, Ghiringhelli, F, Vansteene, D, Gomez-Roca, C, Cousin, S, Lambert, A, Saada-Bouzid, E, Durando, X, Abdeddaim, C, Borel, C, Chaltiel, R, Borcoman, E, Legrand, F, Bernhart, S, Jimenez, M, Bièche, I, Filleron, T, Le Tourneau, C, Kamal, M & Jeannot, E 2026, 'HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas', ESMO Open, vol. 11, no. 1, 106024. https://doi.org/10.1016/j.esmoop.2025.106024

TY - JOUR

T1 - HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas

AU - Filippini, D. M.

AU - Cabarrou, B.

AU - Dupain, C.

AU - Halladjian, M.

AU - Coquan, E.

AU - Sablin, M. P.

AU - Mazzarella, L.

AU - Francisco, M.

AU - Servant, N.

AU - Tonini, M. M.

AU - Hundt, A. F.

AU - Castel-Ajgal, Z.

AU - You, B.

AU - Bigot, F.

AU - Ghiringhelli, F.

AU - Vansteene, D.

AU - Gomez-Roca, C.

AU - Cousin, S.

AU - Lambert, A.

AU - Saada-Bouzid, E.

AU - Durando, X.

AU - Abdeddaim, C.

AU - Borel, C.

AU - Chaltiel, R.

AU - Borcoman, E.

AU - Legrand, F.

AU - Bernhart, S.

AU - Jimenez, M.

AU - Bièche, I.

AU - Filleron, T.

AU - Le Tourneau, C.

AU - Kamal, M.

AU - Jeannot, E.

PY - 2026/1

Y1 - 2026/1

N2 - BACKGROUND: Limited data are available on the role of human papillomavirus circulating tumor DNA (HPV-ctDNA) as a pharmacodynamic marker to monitor the response to treatment in the recurrent/metastatic (R/M) setting. Our study aimed to investigate the sensitivity and pharmacodynamic value of HPV-ctDNA levels during treatment in patients with R/M HPV-related squamous cell carcinoma (SCC) treated with pembrolizumab in combination with vorinostat (PEVO trial, NCT04357873).MATERIALS AND METHODS: Plasma samples were prospectively collected from 57 patients with HPV-related SCC before treatment initiation and every 6 weeks until disease progression. HPV-ctDNA was quantified by droplet digital PCR. The levels before treatment were analyzed according to the patient and tumor characteristics. Landmark analyses were carried out to study the association between dynamic changes in HPV-ctDNA and progression-free survival (PFS), overall survival (OS), and overall response rate (ORR).RESULTS: HPV-ctDNA was detected before treatment in all patients (n = 57) with HPV-related SCC. HPV-ctDNA levels correlated with the number of HPV copies in tumor tissue (P < 0.001). Higher levels of HPV-ctDNA in plasma samples were observed in anal cancer than in other tumor types (P < 0.001), and in patients with distant metastases with or without locoregional recurrence than in patients with locoregional recurrence alone (P = 0.02). The increase in HPV-ctDNA levels during treatment was associated with a lower ORR (P = 0.01) and shorter PFS and OS (both P = 0.01).CONCLUSION: These findings reveal that dynamic HPV-ctDNA variation levels during treatment have a pharmacodynamic value and may help monitor treatment response in patients with advanced HPV-related SCC from different locations.

AB - BACKGROUND: Limited data are available on the role of human papillomavirus circulating tumor DNA (HPV-ctDNA) as a pharmacodynamic marker to monitor the response to treatment in the recurrent/metastatic (R/M) setting. Our study aimed to investigate the sensitivity and pharmacodynamic value of HPV-ctDNA levels during treatment in patients with R/M HPV-related squamous cell carcinoma (SCC) treated with pembrolizumab in combination with vorinostat (PEVO trial, NCT04357873).MATERIALS AND METHODS: Plasma samples were prospectively collected from 57 patients with HPV-related SCC before treatment initiation and every 6 weeks until disease progression. HPV-ctDNA was quantified by droplet digital PCR. The levels before treatment were analyzed according to the patient and tumor characteristics. Landmark analyses were carried out to study the association between dynamic changes in HPV-ctDNA and progression-free survival (PFS), overall survival (OS), and overall response rate (ORR).RESULTS: HPV-ctDNA was detected before treatment in all patients (n = 57) with HPV-related SCC. HPV-ctDNA levels correlated with the number of HPV copies in tumor tissue (P < 0.001). Higher levels of HPV-ctDNA in plasma samples were observed in anal cancer than in other tumor types (P < 0.001), and in patients with distant metastases with or without locoregional recurrence than in patients with locoregional recurrence alone (P = 0.02). The increase in HPV-ctDNA levels during treatment was associated with a lower ORR (P = 0.01) and shorter PFS and OS (both P = 0.01).CONCLUSION: These findings reveal that dynamic HPV-ctDNA variation levels during treatment have a pharmacodynamic value and may help monitor treatment response in patients with advanced HPV-related SCC from different locations.

KW - HPV

KW - biomarker

KW - circulating tumor DNA

KW - immunotherapy

KW - pharmacodynamic

KW - squamous cell carcinoma

UR - https://www.scopus.com/pages/publications/105025815684

UR - https://pubmed.ncbi.nlm.nih.gov/41468684/

U2 - 10.1016/j.esmoop.2025.106024

DO - 10.1016/j.esmoop.2025.106024

M3 - Article

C2 - 41468684

AN - SCOPUS:105025815684

SN - 2059-7029

VL - 11

JO - ESMO Open

JF - ESMO Open

IS - 1

M1 - 106024

ER -

HPV circulating tumor DNA to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous-cell carcinomas

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