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

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.

Clinical applications of liquid biopsy in HPV‐negative and HPV‐positive head and neck squamous cell carcinoma: advances and challenges

“…Furthermore, no significant correlation was found with E6/E7 expression in CTCs at the end of treatment with PFS or OS. In this same context, Chang et al [ 89 ] investigated the p16 expression in CTCs from 41 cases with HNSCC (39% in stage IV). By FCM analysis, the detection rate for p16-positive CTCs was 51.2%.…”

CIP/KIP and INK4 families as hostages of oncogenic signaling

“…In head and neck squamous carcinomas p16INK4a-positive and negative circulating tumor cells (CTC) correlate with the survival of patients. Whereas CTCs with the expression of p16INK4a were associated with prolonged progression-free survival and overall survival, p16INK4a-negative CTCs correlated with rapid disease progression after primary chemoradiotherapy [ 238 ].…”

Special Issue “Cancer Biomarker Research and Personalized Medicine”

“…Prognostic biomarkers identify the likelihood of disease recurrence or progression; these factors are crucial to decision-making processes in the clinic, helping clinicians determine the most appropriate treatment for each patient. Several publications within this Special Issue explored prognostic biomarkers, focusing on the development of prognostic tissue-based biomarkers in ovarian cancer [8], prostate cancer [2,7] and renal cell carcinoma [9], in addition to prognostic liquid-based biomarkers in prostate cancer [2], bladder cancer [10] and head and neck cancer [11]. Studies published within the Special Issue also show how cancer prognosis is moving towards the use of imaging, rather than relying on tissue/liquid biomarkers alone [12].…”