Journal
BRITISH JOURNAL OF CANCER
Volume 117, Issue 6, Pages 876-883Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2017.258
Keywords
head and neck cancer; plasma HPV DNA; response prediction
Categories
Funding
- NHS Executive
- National Institute for Health Research Royal Marsden
- Institute of Cancer Research Biomedical Research Centre
- Clinical Research Facility BRC [A67]
- Cancer Research UK [C46/A10588, C7224/A13407]
- The charity, Oracle Cancer trust
- Cancer Research UK [13407, 23275] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0515-10101] Funding Source: researchfish
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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.
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