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Circulating tumour HPV16 DNA quantification – A prognostic tool for progression-free survival in patients with HPV-related oropharyngeal carcinoma receiving curative chemoradiotherapy

Adrian, Gabriel LU orcid ; Forslund, Ola LU ; Pedersen, Louise LU ; Sjövall, Johanna LU and Gebre-Medhin, Maria LU (2023) In Radiotherapy and Oncology 186.
Abstract

Background and Purpose: Circulating tumour (ct) human papillomavirus (HPV) DNA is detectable in HPV-related oropharyngeal carcinoma (OPSCC) patients and has the potential to become an important clinical tool. This study aimed to evaluate the prognostic significance of ctHPV16-DNA kinetics during treatment with chemoradiotherapy in HPV-related OPSCC. Patients with p16-positive OPSCC recruited to the ARTSCAN III trial, comparing radiotherapy plus cisplatin with radiotherapy plus cetuximab, constituted the study cohort. Materials and methods: Blood samples before start and at the end of treatment of 136 patients were analysed. ctHPV16-DNA was quantified by real-time (q)PCR. The correlation between ctHPV16-DNA levels and tumour burden was... (More)

Background and Purpose: Circulating tumour (ct) human papillomavirus (HPV) DNA is detectable in HPV-related oropharyngeal carcinoma (OPSCC) patients and has the potential to become an important clinical tool. This study aimed to evaluate the prognostic significance of ctHPV16-DNA kinetics during treatment with chemoradiotherapy in HPV-related OPSCC. Patients with p16-positive OPSCC recruited to the ARTSCAN III trial, comparing radiotherapy plus cisplatin with radiotherapy plus cetuximab, constituted the study cohort. Materials and methods: Blood samples before start and at the end of treatment of 136 patients were analysed. ctHPV16-DNA was quantified by real-time (q)PCR. The correlation between ctHPV16-DNA levels and tumour burden was investigated with Pearson regression analysis. The prognostic value of ctHPV16-DNA levels at baseline and decline during treatment was evaluated by area-under-the-curve (AUC) calculations and analysed with univariable and multivariable Cox proportional hazards models. Results: ctHPV16-DNA was detectable with qPCR in 108/136 patients before start of treatment and cleared in 74% of these patients at the end of treatment. Disease burden was significantly correlated with baseline ctHPV16-DNA levels (R = 0.39, p=<0.001). Both lower baseline levels and AUC-ctHPV16DNA were associated with improved progression-free survival (p = 0.01 and p < 0.001), overall survival (p = 0.013 and p = 0.002), but not local tumour control (p = 0.12 and p = 0.2, respectively), with a stronger association for AUC-ctHPV16DNA (likelihood ratio test 10.5 vs 6.5 in Cox regression analyses of progression-free survival). In multivariable analysis including tumour volume (GTV-T) and treatment allocation (cisplatin vs cetuximab), AUC-ctHPV16DNA remained a significant prognostic marker of progression-free survival. Conclusion: ctHPV16-DNA is an independent prognostic factor in HPV-related OPSCC.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarker, Chemoradiotherapy, Head and neck squamous cell carcinoma, Human papillomavirus, Liquid biopsy
in
Radiotherapy and Oncology
volume
186
article number
109773
publisher
Elsevier
external identifiers
  • pmid:37385383
  • scopus:85164468266
ISSN
0167-8140
DOI
10.1016/j.radonc.2023.109773
language
English
LU publication?
yes
id
2c74b157-16f1-4ab2-8adc-511daed68870
date added to LUP
2023-09-04 15:13:30
date last changed
2024-04-20 02:30:25
@article{2c74b157-16f1-4ab2-8adc-511daed68870,
  abstract     = {{<p>Background and Purpose: Circulating tumour (ct) human papillomavirus (HPV) DNA is detectable in HPV-related oropharyngeal carcinoma (OPSCC) patients and has the potential to become an important clinical tool. This study aimed to evaluate the prognostic significance of ctHPV16-DNA kinetics during treatment with chemoradiotherapy in HPV-related OPSCC. Patients with p16-positive OPSCC recruited to the ARTSCAN III trial, comparing radiotherapy plus cisplatin with radiotherapy plus cetuximab, constituted the study cohort. Materials and methods: Blood samples before start and at the end of treatment of 136 patients were analysed. ctHPV16-DNA was quantified by real-time (q)PCR. The correlation between ctHPV16-DNA levels and tumour burden was investigated with Pearson regression analysis. The prognostic value of ctHPV16-DNA levels at baseline and decline during treatment was evaluated by area-under-the-curve (AUC) calculations and analysed with univariable and multivariable Cox proportional hazards models. Results: ctHPV16-DNA was detectable with qPCR in 108/136 patients before start of treatment and cleared in 74% of these patients at the end of treatment. Disease burden was significantly correlated with baseline ctHPV16-DNA levels (R = 0.39, p=&lt;0.001). Both lower baseline levels and AUC-ctHPV16DNA were associated with improved progression-free survival (p = 0.01 and p &lt; 0.001), overall survival (p = 0.013 and p = 0.002), but not local tumour control (p = 0.12 and p = 0.2, respectively), with a stronger association for AUC-ctHPV16DNA (likelihood ratio test 10.5 vs 6.5 in Cox regression analyses of progression-free survival). In multivariable analysis including tumour volume (GTV-T) and treatment allocation (cisplatin vs cetuximab), AUC-ctHPV16DNA remained a significant prognostic marker of progression-free survival. Conclusion: ctHPV16-DNA is an independent prognostic factor in HPV-related OPSCC.</p>}},
  author       = {{Adrian, Gabriel and Forslund, Ola and Pedersen, Louise and Sjövall, Johanna and Gebre-Medhin, Maria}},
  issn         = {{0167-8140}},
  keywords     = {{Biomarker; Chemoradiotherapy; Head and neck squamous cell carcinoma; Human papillomavirus; Liquid biopsy}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Radiotherapy and Oncology}},
  title        = {{Circulating tumour HPV16 DNA quantification – A prognostic tool for progression-free survival in patients with HPV-related oropharyngeal carcinoma receiving curative chemoradiotherapy}},
  url          = {{http://dx.doi.org/10.1016/j.radonc.2023.109773}},
  doi          = {{10.1016/j.radonc.2023.109773}},
  volume       = {{186}},
  year         = {{2023}},
}