Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma.
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Authors
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
Garcia-Murillas, I
Cutts, RJ
De Castro, DG
Grove, L
Hurley, T
Wang, F
Nutting, C
Newbold, K
Harrington, K
Turner, N
Bhide, S
Document Type
Journal Article
Date
2017-09-05
Date Accepted
2017-07-13
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.
Citation
British journal of cancer, 2017, 117 (6), pp. 876 - 883
Source Title
Publisher
SPRINGERNATURE
ISSN
0007-0920
eISSN
1532-1827
Research Team
Molecular Oncology
Targeted Therapy
Targeted Therapy