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Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma.

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Accepted version (767.9Kb)
Date
2017-09
ICR Author
Harrington, Kevin
Turner, Nicholas
Marsden,
Garcia-Murillas, Isaac
Author
Lee, JY
Garcia-Murillas, I
Cutts, RJ
De Castro, DG
Grove, L
Hurley, T
Wang, F
Nutting, C
Newbold, K
Harrington, K
Turner, N
Bhide, S
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Type
Journal Article
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Abstract
Background Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for abnormal PET-CT, which causes significant morbidity. We assessed the role of circulating HPV DNA in identifying 'true' residual disease.Methods We prospectively recruited test (n=55) and validation (n=33) cohorts. HPV status was confirmed by E7 RT-PCR. We developed a novel amplicon-based next generation sequencing assay (HPV16-detect) to detect circulating HPV DNA. Circulating HPV DNA levels post-CCRT were correlated to disease response (PET-CT).Results In pre-CCRT plasma, HPV-detect demonstrated 100% sensitivity and 93% specificity, and 90% sensitivity and 100% specificity for the test (27 HPV+) and validation (20 HPV+) cohorts, respectively. Thirty-six out of 37 patients (test and validation cohort) with complete samples-set had negative HPV-detect at end of treatment. Six patients underwent ND (3) and repeat primary site biopsies (3) for positive PET-CT but had no viable tumour. One patient had positive HPV-detect and positive PET-CT and liver biopsy, indicating 100% agreement for HPV-detect and residual cancer.Conclusions We demonstrate that HPV16-detect is a highly sensitive and specific test for identification of HPV DNA in plasma at diagnosis. HPV DNA post-treatment correlates with clinical response.
URI
https://repository.icr.ac.uk/handle/internal/810
DOI
https://doi.org/10.1038/bjc.2017.258
Collections
  • Breast Cancer Research
  • Cancer Biology
  • Radiotherapy and Imaging
Subject
Humans
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Neoplasms
Hypopharyngeal Neoplasms
Oropharyngeal Neoplasms
Neoplasm, Residual
DNA, Viral
Treatment Outcome
Neck Dissection
Sensitivity and Specificity
Prospective Studies
Human papillomavirus 16
Chemoradiotherapy
Research team
Molecular Oncology
Targeted Therapy
Language
eng
Date accepted
2017-07-13
License start date
2017-09
Citation
British journal of cancer, 2017, 117 (6), pp. 876 - 883

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