Circulating Human Papillomavirus DNA-Liquid Biopsy in Head and Neck Cancers.

Journal: Journal of medical virology

This publication reviews the current evidence on circulating tumor HPV DNA (ctHPVDNA) as a liquid biopsy tool in human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV-OPSCC).

Key points:

  • Clinical context: HPV-OPSCC differs from HPV-negative disease in biology, prognosis, failure patterns, and patient demographics. Outcomes are generally favorable, but randomized trials have not yet validated treatment de-escalation.
  • Technology: ctHPVDNA detection via droplet digital PCR and next-generation sequencing offers high sensitivity and specificity. These assays can quantify viral DNA and provide information about tumor burden and HPV integration.
  • Baseline ctHPVDNA:
    • Levels correlate with tumor volume and disease burden.
    • Associations exist between baseline levels, HPV integration status, and clinical outcomes.
  • During treatment:
    • Rapid clearance of ctHPVDNA during radiation correlates strongly with improved disease control.
    • Slow or incomplete clearance may indicate higher risk of treatment failure.
  • Postoperative and surveillance use:
    • Detectable or persistent ctHPVDNA after surgery is linked to increased recurrence risk.
    • In surveillance, ctHPVDNA can identify recurrence earlier than imaging in some studies and shows high positive and negative predictive values, in some cases outperforming conventional imaging.
  • Limitations and future directions:
    • Assay methodologies are heterogeneous and not yet standardized.
    • Larger prospective validation is needed before ctHPVDNA can be routinely integrated into risk-adapted treatment de-escalation or escalation strategies for HPV-OPSCC.

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