Circulating p16-Positive and p16-Negative Tumor Cells Serve as Independent Prognostic Indicators of Survival in Patients with Head and Neck Squamous Cell Carcinomas.

Pei-Hung Chang,Chun-Ta Liao,Pei-Wei Huang,Li-Yu Lee,Cheng-Lung Hsu,Chia-Jung Liao,Hsuan-Chih Kuo,Jason Chia-Hsun Hsieh,Sanger Hung-Chi Lin,Hung-Ming Wang,Tyler Min-Hsien Wu,Yung-Chia Kuo

doi:10.3390/jpm11111156

Abstract

Background: Decisions regarding the staging, prognosis, and treatment of patients with head and neck squamous cell carcinomas (HNSCCs) are made after determining their p16 expression levels and human papillomavirus (HPV) infection status. Methods: We investigated the prognostic roles of p16-positive and p16-negative circulating tumor cells (CTCs) and their cell counts in HNSCC patients. We enrolled patients with locally advanced HNSCCs who received definitive concurrent chemoradiotherapy for final analysis. We performed CTC testing and p16 expression analysis before chemoradiotherapy. We analyzed the correlation between p16-positive and p16-negative CTCs and HPV genotyping, tissue p16 expression status, response to chemoradiotherapy, disease-free survival, and overall survival. Results: Forty-one patients who fulfilled the study criteria were prospectively enrolled for final analysis. The detection rates of p16-positive (>0 cells/mL blood) and p16-negative (≥3 cells/mL blood) CTCs were 51.2% (n = 21/41) and 70.7%, respectively. The best responses of chemoradiotherapy and the p16 positivity of CTCs are independent prognostic factors of disease progression, with hazard ratios of 1.738 (95% confidence interval (CI): 1.031–2.927), 5.497 (95% CI: 1.818–16.615), and 0.176 (95% CI: 0.056–0.554), respectively. The p16 positivity of CTCs was a prognostic factor for cancer death, with a hazard ratio of 0.294 (95% CI: 0.102–0.852). Conclusions: The p16-positive and p16-negative CTCs could predict outcomes in HNSCC patients receiving definitive chemoradiotherapy. This non-invasive CTC test could help stratify the risk and prognosis before chemoradiotherapy in clinical practice and enable us to perform de-intensifying therapies.

Highlights

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has been widely investigated and thought of as a critical biomarker in head and neck squamous cell carcinomas (HNSCCs) [1,2]
A total of 28 (68.3%) patients had oropharyngeal cancer, while 13 (31.7%) patients had non-oropharyngeal cancer. These 13 patients were enrolled because they had initially presented with an unknown primary cancer or a huge confluent mass in the hypopharynx and
These 13 patients were enrolled because they had initially presented with an unknown primary cancer or a huge confluent mass in the hypopharynx and oropharynx area

Summary

Introduction

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has been widely investigated and thought of as a critical biomarker in HNSCC [1,2]. Given the positive prognostic impact of HPV infection, the p16 expression or HPV genotyping status at cancer staging have been strongly suggested for patients presenting with neck squamous cell carcinoma, without identified primary sites [14,15]. Prognosis, and treatment of patients with head and neck squamous cell carcinomas (HNSCCs) are made after determining their p16 expression levels and human papillomavirus (HPV) infection status. Conclusions: The p16-positive and p16-negative CTCs could predict outcomes in HNSCC patients receiving definitive chemoradiotherapy. This non-invasive CTC test could help stratify the risk and prognosis before chemoradiotherapy in clinical practice and enable us to perform de-intensifying therapies

Methods

Results

Conclusion