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The role of liquid biopsy in management of the neck with indeterminate response on post-treatment imaging following non-surgical management of oropharyngeal cancer

  • Author Footnotes
    1 Contributed equally.
    ,
    Author Footnotes
    2 Present address: Department of Otolaryngology and Head and Neck Surgery, NHS Greater Glasgow and Clyde.
    Lucy Q. Li
    Footnotes
    1 Contributed equally.
    2 Present address: Department of Otolaryngology and Head and Neck Surgery, NHS Greater Glasgow and Clyde.
    Affiliations
    Department of Otolaryngology and Head and Neck Surgery, NHS Lothian, Lauriston Place, Edinburgh, EH3 9HX, UK
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  • Author Footnotes
    1 Contributed equally.
    Martyna Adamowicz
    Footnotes
    1 Contributed equally.
    Affiliations
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK
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  • Author Footnotes
    1 Contributed equally.
    Robert A. Wescott
    Footnotes
    1 Contributed equally.
    Affiliations
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK

    NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK
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  • Sophie J. Warlow
    Affiliations
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK

    NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK
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  • John P. Thomson
    Affiliations
    Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Cancer, University of Edinburgh, UK
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  • Christelle Robert
    Affiliations
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK
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  • Lara M. Carey
    Affiliations
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK
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  • Helen Thain
    Affiliations
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK

    NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK
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  • Kate Cuschieri
    Affiliations
    Scottish HPV Reference Laboratory, Department of Laboratory Medicine, NHS Lothian, Royal Infirmary of Edinburgh, EH16 4SA, UK
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  • Brendan Conn
    Affiliations
    Department of Pathology, NHS Lothian, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh, EH16 4SA, UK
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  • Ashley Hay
    Affiliations
    Department of Otolaryngology and Head and Neck Surgery, NHS Lothian, Lauriston Place, Edinburgh, EH3 9HX, UK
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  • Timothy J. Aitman
    Affiliations
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK

    NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK
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  • Iain J. Nixon
    Correspondence
    Corresponding author. Department of Otorhinolaryngology Head and Neck Surgery, NHS Lothian, Lauriston Building, 41 Lauriston Place, Edinburgh, EH3 9HB, United Kingdom.
    Affiliations
    Department of Otolaryngology and Head and Neck Surgery, NHS Lothian, Lauriston Place, Edinburgh, EH3 9HX, UK

    NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally.
    2 Present address: Department of Otolaryngology and Head and Neck Surgery, NHS Greater Glasgow and Clyde.
Published:September 29, 2022DOI:https://doi.org/10.1016/j.ejso.2022.09.016

      Highlights

      • A partial response in the neck post OPSCC treatment represents a significant management challenge
      • HPV cell-free DNA (cfDNA) is a promising biomarker of disease recurrence in HPV + ve cancers
      • HPV cfDNA detection may help target salvage therapy in this group of patients

      Abstract

      Introduction

      This study aimed to determine if post-treatment HPV cell-free DNA (cfDNA) can assist in the decision-making process for salvage neck dissection in patients following non-surgical treatment of oropharyngeal squamous cell carcinoma (OPSCC) with a partial response in the neck on imaging at 12 weeks post-treatment.

      Methods

      86 patients who completed treatment were prospectively recruited through the regional multidisciplinary team (MDT). Treatment response was categorised as complete response (CR), partial response (PR) or progressive disease on 12-week post-treatment imaging. Pre- and post-treatment blood samples were assessed for HPV cfDNA through droplet digital PCR (ddPCR).

      Results

      Eight patients had an isolated partial response in the neck. One (12.5%) had detectable HPV cfDNA (22.96 copies/ml) at ∼12 weeks post-treatment with positive disease on subsequent neck dissection (positive predictive value; PPV = 100%). Of the seven patients with undetectable HPV cfDNA, two patients had evidence of regional disease recurrence at 23.9 and 27.4 months respectively (negative predictive value; NPV = 71%).

      Conclusion

      The detection of HPV cfDNA may help target salvage therapy in patients with a partial response in the neck. Follow-up studies in larger cohorts would be required to further validate the use of post-treatment HPV cfDNA in the management of OPSCC.

      Keywords

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