Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment

BMC Cancer. 2022 Jan 3;22(1):17. doi: 10.1186/s12885-021-09146-z.


Background: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC.

Methods: Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, [Formula: see text] 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response.

Discussion: A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC.

Trial registration: This trial is registered with on October 1st, 2020 with Identifier: NCT04572100 .

Keywords: Chemotherapy; Head and neck cancer; Human papillomavirus; Radiotherapy; Treatment de-escalation.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Biomarkers, Tumor / blood
  • Carboplatin / administration & dosage
  • Cell-Free Nucleic Acids / blood*
  • Chemoradiotherapy
  • Cisplatin / administration & dosage
  • DNA, Viral / blood*
  • Drug Monitoring / methods*
  • Feasibility Studies
  • Female
  • Humans
  • Induction Chemotherapy
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / blood
  • Oropharyngeal Neoplasms / drug therapy*
  • Oropharyngeal Neoplasms / virology
  • Paclitaxel / administration & dosage
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / blood*
  • Papillomavirus Infections / virology
  • Prognosis
  • Prospective Studies
  • Treatment Outcome
  • Young Adult


  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • DNA, Viral
  • Carboplatin
  • Paclitaxel
  • Cisplatin

Associated data