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

Gabriel Adrian; Ola Forslund; Louise Pedersen; Johanna Sjövall; Maria Gebre-Medhin

doi:10.1016/j.radonc.2023.109773

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

Radiother Oncol. 2023 Sep:186:109773. doi: 10.1016/j.radonc.2023.109773. Epub 2023 Jun 28.

Authors

Gabriel Adrian¹, Ola Forslund², Louise Pedersen³, Johanna Sjövall⁴, Maria Gebre-Medhin⁵

Affiliations

¹ Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden; Department of Clinical Sciences Lund, Division of Oncology, Lund University, Lund, Sweden.
² Department of Laboratory Medicine, Medical Microbiology, Lund University, Lund, Sweden; Clinical Microbiology, Infection Prevention and Control, Office for Medical Services Region Skåne, Sweden.
³ Clinical Microbiology, Infection Prevention and Control, Office for Medical Services Region Skåne, Sweden.
⁴ Department of Clinical Sciences Lund, Division of Oncology, Lund University, Lund, Sweden; Department of Otorhinolaryngology - Head and Neck Surgery, Skåne University Hospital, Lund University, Lund, Sweden.
⁵ Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden; Department of Clinical Sciences Lund, Division of Oncology, Lund University, Lund, Sweden. Electronic address: maria.gebre-medhin@med.lu.se.

PMID: 37385383
DOI: 10.1016/j.radonc.2023.109773

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 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.

Keywords: Biomarker; Chemoradiotherapy; Head and neck squamous cell carcinoma; Human papillomavirus; Liquid biopsy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell* / pathology
Cetuximab / therapeutic use
Chemoradiotherapy
Circulating Tumor DNA* / genetics
Cisplatin
Head and Neck Neoplasms*
Human papillomavirus 16 / genetics
Humans
Oropharyngeal Neoplasms* / pathology
Papillomavirus Infections* / pathology
Prognosis
Progression-Free Survival

Substances

Cetuximab
Cisplatin
Circulating Tumor DNA