The role of circulating tumor DNA (ctDNA) in the treatment of human papilloma virus-positive (HPV+) oropharyngeal squamous cell carcinoma Review


Authors: Qian, J. Y.; Chen, L.; Wong, W.; Morris, L. G. T.; Yacoub, I.; Lee, N. Y.; Ma, J.
Review Title: The role of circulating tumor DNA (ctDNA) in the treatment of human papilloma virus-positive (HPV+) oropharyngeal squamous cell carcinoma
Abstract: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) presents a favorable prognosis compared with its HPV-negative counterpart, prompting interest in treatment de-escalation to reduce toxicity. However, attempts using risk factors, stage, and HPV status alone have not proven sufficient. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker to personalize treatment by detecting tumor burden, monitoring minimal residual disease (MRD), and guiding response-adaptive therapy. This review evaluates the role of ctDNA across the clinical course - from diagnosis to mid-treatment monitoring to post-treatment surveillance. It highlights ctDNA's potential to enhance diagnostic accuracy, guide treatment deintensification, and detect recurrence through a summary of recent and ongoing clinical trials. However, limitations in assay sensitivity and the need for prospective validation restrict its current clinical utility. Ongoing clinical trials will be pivotal in determining whether ctDNA can reliably support personalized de-escalation strategies in HPV+ OPSCC. © 2025 Wolters Kluwer Health, Inc.
Keywords: human tissue; genetics; disease course; review; nonhuman; diagnostic accuracy; recurrence; tumor marker; risk factor; virology; blood; minimal residual disease; tumor burden; diagnosis; surgical resection; drug therapy; isolation and purification; therapy; chemoradiotherapy; oropharyngeal neoplasms; surveillance; wart virus; papillomavirus infections; head and neck squamous cell carcinoma; complication; diagnostic test accuracy study; oropharynx tumor; papillomavirus infection; papillomaviridae; definitive chemoradiation; humans; prognosis; human; circulating tumor dna; treatment de-escalation; oropharynx squamous cell carcinoma; liquid biopsy; biomarkers, tumor; squamous cell carcinoma of head and neck; precision oncology; personalized cancer therapy; ctdna; chloroplast dna; human papillomavirus viruses; hpv-positive opscc
Journal Title: The Cancer Journal
Volume: 31
Issue: 3
ISSN: 1528-9117
Publisher: Lippincott Williams & Wilkins  
Date Published: 2025-05-01
Start Page: e0769
Language: English
DOI: 10.1097/ppo.0000000000000769
PUBMED: 40459979
PROVIDER: scopus
DOI/URL:
Notes: Review -- Source: Scopus
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MSK Authors
  1. Nancy Y. Lee
    876 Lee
  2. Luc Morris
    279 Morris
  3. Jennifer Ma
    74 Ma
  4. Winston Wong
    29 Wong
  5. Linda Chang Chen
    69 Chen
  6. Irini Yacoub
    14 Yacoub
  7. Joshua Yuan Qian
    6 Qian