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Radiother Oncol. 2018 Jan;126(1):107-115. doi: 10.1016/j.radonc.2017.10.018.

Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: The MARCH-HPV project.

Author information

1
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
2
Gustave-Roussy, Paris-Saclay University, Biostatistics and Epidemiology Department, Villejuif, France; INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
3
Moffitt Cancer Center, Department of Radiation Oncology, Tampa, USA.
4
Department of Radiation Sciences - Oncology, Umeå University, Umeå, Sweden.
5
NRG Oncology Statistics and Data Management Center (formerly RTOG), Philadelphia, USA.
6
Gustave-Roussy, Paris-Saclay University, Radiotherapy Department, Villejuif, France; INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. Electronic address: pierre.blanchard@gustaveroussy.fr.

Abstract

BACKGROUND AND PURPOSE:

Evaluate the prognostic and predictive impact of HPV-associated p16-expression and assess the combined prognostic impact of p16 and smoking on altered fractionated radiotherapy (AFRT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH).

MATERIALS AND METHODS:

Patients with OPC, known tumor p16-status and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of radiotherapy fractionation, p16, smoking. Primary endpoint was progression-free survival (PFS).

RESULTS:

In total, 465 patients (57%) had p16-positive tumors and 350 (43%) p16-negative. Compared to p16-negative, p16-positive patients had significantly better PFS (HR = 0.42 [95% CI: 0.34-0.51], 28.9% absolute increase at 10 years) and OS (HR = 0.40 [0.32-0.49], 32.1% absolute increase at 10 years). No interaction between p16-status and fractionation schedule was detected. Smoking negatively impacted outcome; in the p16-positive subgroup, never smokers had significantly better PFS than former/current smokers (HR = 0.49 [0.33-0.75], 24.2% survival benefit at 10 years).

CONCLUSIONS:

No predictive impact of p16-status on response to AFRT could be detected but the strong prognostic impact of p16-status was confirmed and especially p16-positive never smoking patients have superior outcome after RT.

KEYWORDS:

Altered fractionation; HPV; Oropharynx carcinoma; Prognostic; Radiotherapy; Smoking

PMID:
29100700
DOI:
10.1016/j.radonc.2017.10.018
[Indexed for MEDLINE]

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