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Peer-reviewedCC BYClinical and Translational Discovery

Longitudinal liquid biopsy alongside positron emission tomography‐computed tomography surveillance in p16‐positive oropharyngeal squamous cell carcinoma: A translational case study

  1. 1Saliva and Liquid Biopsy Translational Laboratory Institute for Biomedicine and Glycomics Griffith University Brisbane Australia
  2. 2School of Medicine The University of Queensland Brisbane Australia
  3. 3Translational Research Institute Brisbane Australia

Abstract

Background Post‐treatment surveillance of p16‐positive oropharyngeal squamous cell carcinoma (OPSCC) relies on clinical assessment and fluorodeoxyglucose positron emission tomographycomputed tomography (FDG PET‐CT). Longitudinal liquid biopsy may provide complementary biological information, but the relationship between oral‐rinse human papillomavirus (HPV) DNA, circulating tumour cells (CTCs), and imaging findings remains incompletely defined. Methods A 77‐year‐old man with p16‐positive OPSCC underwent serial liquid‐biopsy sampling within an ongoing prospective cohort. Peripheral blood and oral‐rinse specimens were collected before treatment, at week 4 of chemoradiotherapy, and approximately 13 weeks after treatment completion. CTCs were enriched from 15 mL peripheral blood using marker‐independent spiral microfluidics and characterised by immunofluorescence. Oral‐rinse high‐risk HPV DNA was assessed by multiplex quantitative polymerase chain reaction and reported qualitatively. Results Baseline PET‐CT demonstrated a base‐of‐tongue primary tumour and cervical nodal disease without distant metastases. Oral‐rinse HPV16 DNA was detected, and CTCs were identified at 3 CTCs/mL, predominantly with cytokeratin‐positive phenotypes. During chemoradiotherapy, HPV16 DNA remained detectable and CTCs persisted at 1 CTC/mL, with a shift towards cell‐surface‐vimentin‐positive phenotypes. At post‐treatment assessment, PET‐CT showed complete locoregional metabolic response but identified a new right iliac crest lesion subsequently confirmed as metastatic p16‐positive squamous cell carcinoma. Oral‐rinse HPV16 DNA was no longer detected, whereas CTCs persisted at 4 CTCs/mL, including cell‐surface‐vimentin‐positive and CD44‐positive cells and a CTC‐white‐blood‐cell cluster. The patient subsequently developed widespread osseous progression and died approximately eight months after chemoradiotherapy. Conclusions Oral‐rinse HPV16 DNA clearance coincided with locoregional metabolic response, whereas persistent CTCs coincided with biopsy‐confirmed distant metastasis. This hypothesis‐generating observation supports prospective evaluation of complementary imaging and liquid‐biopsy surveillance but does not establish earlier metastatic detection or discrimination between locoregional and distant recurrence.

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BibTeX
@article{damodaran2026longitudinal,
  title = {{Longitudinal liquid biopsy alongside positron emission tomography‐computed tomography surveillance in p16‐positive oropharyngeal squamous cell carcinoma: A translational case study}},
  author = {Sreedevi Damodaran and Chameera Ekanayake Weeramange and Lizbeth Kenny and Sarju Vasani and Omar Breik and Touraj Taheri and Paul Leo and Brett G. M. Hughes and Chamindie Punyadeera},
  journal = {Clinical and Translational Discovery},
  year = {2026},
  month = oct,
  doi = {10.1002/ctd2.70220},
  url = {https://doi.org/10.1002/ctd2.70220},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Longitudinal liquid biopsy alongside positron emission tomography‐computed tomography surveillance in p16‐positive oropharyngeal squamous cell carcinoma: A translational case study
AU  - Sreedevi Damodaran
AU  - Chameera Ekanayake Weeramange
AU  - Lizbeth Kenny
AU  - Sarju Vasani
AU  - Omar Breik
AU  - Touraj Taheri
AU  - Paul Leo
AU  - Brett G. M. Hughes
AU  - Chamindie Punyadeera
PY  - 2026
DA  - 2026/10/26
JO  - Clinical and Translational Discovery
DO  - 10.1002/ctd2.70220
UR  - https://doi.org/10.1002/ctd2.70220
AB  - Background Post‐treatment surveillance of p16‐positive oropharyngeal squamous cell carcinoma (OPSCC) relies on clinical assessment and fluorodeoxyglucose positron emission tomographycomputed tomography (FDG PET‐CT). Longitudinal liquid biopsy may provide complementary biological information, but the relationship between oral‐rinse human papillomavirus (HPV) DNA, circulating tumour cells (CTCs), and imaging findings remains incompletely defined. Methods A 77‐year‐old man with p16‐positive OPSCC underwent serial liquid‐biopsy sampling within an ongoing prospective cohort. Peripheral blood and oral‐rinse specimens were collected before treatment, at week 4 of chemoradiotherapy, and approximately 13 weeks after treatment completion. CTCs were enriched from 15 mL peripheral blood using marker‐independent spiral microfluidics and characterised by immunofluorescence. Oral‐rinse high‐risk HPV DNA was assessed by multiplex quantitative polymerase chain reaction and reported qualitatively. Results Baseline PET‐CT demonstrated a base‐of‐tongue primary tumour and cervical nodal disease without distant metastases. Oral‐rinse HPV16 DNA was detected, and CTCs were identified at 3 CTCs/mL, predominantly with cytokeratin‐positive phenotypes. During chemoradiotherapy, HPV16 DNA remained detectable and CTCs persisted at 1 CTC/mL, with a shift towards cell‐surface‐vimentin‐positive phenotypes. At post‐treatment assessment, PET‐CT showed complete locoregional metabolic response but identified a new right iliac crest lesion subsequently confirmed as metastatic p16‐positive squamous cell carcinoma. Oral‐rinse HPV16 DNA was no longer detected, whereas CTCs persisted at 4 CTCs/mL, including cell‐surface‐vimentin‐positive and CD44‐positive cells and a CTC‐white‐blood‐cell cluster. The patient subsequently developed widespread osseous progression and died approximately eight months after chemoradiotherapy. Conclusions Oral‐rinse HPV16 DNA clearance coincided with locoregional metabolic response, whereas persistent CTCs coincided with biopsy‐confirmed distant metastasis. This hypothesis‐generating observation supports prospective evaluation of complementary imaging and liquid‐biopsy surveillance but does not establish earlier metastatic detection or discrimination between locoregional and distant recurrence.
SN  - 2768-0622
ER  -