T cell fraction impacts oncologic outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma

Kathryn M. Van Abel, David M. Routman, Eric J. Moore, Daniel J. Ma, Linda X. Yin, Paul A. Fields, Matt Schofield, Kathleen R. Bartemes, Kyriakos Chatzopoulos, Daniel L. Price, Jeffrey R. Janus, Jan L. Kasperbauer, Katharine A. Price, Ashish V. Chintakuntlawar, Michelle A. Neben-Wittich, Robert L. Foote, Joaquin J. Garcia

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: We investigated T cell clonality (TCC) and T cell fraction (TCF) in human papilloma virus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) progressors [cases] vs. non-progressors [controls]. Methods: This nested case-control study included patients undergoing intent-to-cure surgery ± adjuvant therapy from 6/1/2007–10/3/2016. Patients experiencing local/regional/distant disease (progressors), and a consecutive sample of non-progressors were matched (2 controls: 1 case) on tumor subsite, T-stage and number of metastatic lymph nodes. We performed imunosequencing of the CDR3 regions of human TCRβ chains. Results: 34 progressors and 65 non-progressors were included. There was no statistically significant difference in baseline TCF (range: 0.039–1.084) and TCC (range: 0.007–0.240) (p > 0.05). Female sex was associated with higher TCF (p = 0.03), while extranodal extension (ENE) was associated with lower TCF (p = 0.01). There was a positive correlation between tumor size and clonality (R = 0.34, p < 0.01). The strongest predictor of progression-free survival (PFS) was TCF (HR 0.80, 95%CI 0.66–0.96, p = 0.02). The strongest predictors of cancer specific survival (CSS) were TCF (HR0.69, 95%CI 0.47–1.00, p < 0.05) and Adult Comorbidity Evaluation-27 (ACE-27) score (p < 0.05). Similarly, the strongest predictors of overall survival (OS) were TCF (HR 0.62, 95%CI 0.43–0.91, p = 0.01) and ACE-27 score (p = 0.03). On multivariable modeling, TCF ≥ 0.4 was independently associated with PFS (HR 0.34, 95%CI 0.14–0.85, p = 0.02) while an ACE-27 score of ≥ 2 independently predicted CSS (HR 3.85, 95%CI 1.07–13.85, p = 0.04) and OS (HR 3.51, 95%CI 1.10–11.20, p = 0.03). Conclusions: In patients with HPV(+)OPSCC, TCF was higher in female patients and those without ENE, suggesting differential immune responses. Lower TCF was significantly and independently associated with disease progression. Better ACE-27 scores appear to predict improved oncologic control.

Original languageEnglish (US)
Article number104894
JournalOral Oncology
StatePublished - Dec 2020


  • ACE-27
  • Comorbidities
  • HPV
  • Human papillomavirus
  • Immune
  • Immunoseq
  • Oropharyngeal
  • Oropharynx
  • Squamous cell carcinoma
  • T cell clonality
  • T cell repertoire
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research


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