HPV-relatedness definitions for classifying HPV-related oropharyngeal cancer patient do impact on TNM classification and patients' survival

• Published in: PloS one Vol. 13; no. 4; p. e0194107
• Main Authors: Taberna, Miren, Mena, Marisa, Tous, Sara, Pavón, Miquel Angel, Oliva, Marc, León, Xavier, Garcia, Jacinto, Guix, Marta, Hijano, Rafael, Bonfill, Teresa, Aguilà, Antón, Alemany, Laia, Mesía, Ricard
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2018; Public Library of Science (PLoS)
• Subjects: Biology and life sciences; Biomarkers; Cancer; Cancer therapies; Carcinoma; Classification; Clinical trials; Collaboration; Càncer; Deoxyribonucleic acid; Diagnostic systems; DNA; Epidemiology; Faringe; Head & neck cancer; Human papillomavirus; INK4a protein; Medical prognosis; Medical research; Medicine and Health Sciences; mRNA; Oncology; Oropharyngeal cancer; Otolaryngology; p16 Protein; Patients; Proposals; Research and Analysis Methods; Survival; Systematic review; Throat cancer; Tumors; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0194107

Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value.
The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests.
A total of 788 consecutive OPC cases diagnosed from 1991 to 2013 were considered eligible for the analysis. Of these samples, 66 (8.4%) were positive for HPV-DNA and (p16INK4a or HPV-mRNA), 83 (10.5%) were p16INK4a positive and 58 (7.4%) were double positive for HPV-DNA/p16INK4a. ICON-S model was the staging system, which performed better in our series when using at least two biomarkers to define HPV-causality. When the same analysis was performed considering only p16INK4a-positivity, RPA stage with non-anatomic factors (Princess Margaret) has the best classification based on AIC criteria.
HPV-relatedness definition for classifying HPV-related OPC patient do impact on TNM classification and patients' survival. Further studies assessing HPV-relatedness definitions are warranted to better classify HPV-related OPC patients in the era of de-escalation clinical trials.