Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma.
De Castro, DG
MetadataShow full item record
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.
The Institute of Cancer Research (Grant ID: Unspecified)
Version of record
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Human papillomavirus 16
Sensitivity and Specificity
License start date
Br J Cancer, 2017, 117 (6), pp. 876 - 883
Showing items related by title, author, creator and subject.
Viski, C; König, C; Kijewska, M; Mogler, C; Isacke, CM; Augustin, HGMetastasis is a multistep process that is critically dependent on the interaction of metastasizing tumor cells with cells in the local microenvironment. Within this tumor stroma, vessel-associated pericytes and myofibroblasts ...
Frentzas, S; Simoneau, E; Bridgeman, VL; Vermeulen, PB; Foo, S; Kostaras, E; Nathan, M; Wotherspoon, A; Gao, Z-H; Shi, Y; Van den Eynden, G; Daley, F; Peckitt, C; Tan, X; Salman, A; Lazaris, A; Gazinska, P; Berg, TJ; Eltahir, Z; Ritsma, L; Van Rheenen, J; Khashper, A; Brown, G; Nystrom, H; Sund, M; Van Laere, S; Loyer, E; Dirix, L; Cunningham, D; Metrakos, P; Reynolds, ARThe efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the ...
Sud, A; Thomsen, H; Sundquist, K; Houlston, RS; Hemminki, K (2017-05-10)Purpose Although advances in Hodgkin lymphoma (HL) treatment have led to improved disease-free survival, this has been accompanied by an increased risk of second cancers. We sought to quantify the second cancer risks and ...