Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma.
Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma.
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DOI：
10.1038/bjc.2017.258
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发表时间：
2017-09-05
影响因子：
8.8
通讯作者：
Bhide S
中科院分区：
文献类型：
--
作者：
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
人乳头瘤病毒阳性（HPV+）局部晚期头颈部癌的化疗放疗（CCRT）后，患者经常进行不必要的颈部清扫（ND）和/或重复的PET-CT异常活检，这导致了显著的发病率。我们评估了循环HPV DNA在识别“真正的”残留疾病中的作用。我们前瞻性地招募了检验组（n=55）和验证组（n=33）。E7 RT-PCR检测HPV感染。我们开发了一种新的基于扩增子的下一代测序测定（HPV16-detect）来检测循环HPV DNA。ccrt后循环HPV DNA水平与疾病反应（PET-CT）相关。在ccrt前的血浆中，HPV检测显示出100%的敏感性和93%的特异性，检测（27个HPV+）和验证（20个HPV+）队列分别显示出90%的敏感性和100%的特异性。37例样本集完整的患者（试验和验证队列）中有36例在治疗结束时hpv检测阴性。6例患者因PET-CT阳性接受ND(3)和重复原发部位活检(3)，但未发现活肿瘤。1例患者hpv检测阳性，PET-CT和肝活检阳性，表明hpv检测和残留癌100%一致。我们证明HPV16-detect在诊断时是一种高度敏感和特异性的检测血浆中HPV DNA的方法。HPV DNA治疗后与临床反应相关。
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. 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). 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. 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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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
DOI：
10.1158/1078-0432.ccr-11-0388
发表时间：
2011-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Schache AG;Liloglou T;Risk JM;Filia A;Jones TM;Sheard J;Woolgar JA;Helliwell TR;Triantafyllou A;Robinson M;Sloan P;Harvey-Woodworth C;Sisson D;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
28.4
作者：
Rettig EM;Wentz A;Posner MR;Gross ND;Haddad RI;Gillison ML;Fakhry C;Quon H;Sikora AG;Stott WJ;Lorch JH;Gourin CG;Guo Y;Xiao W;Miles BA;Richmon JD;Andersen PE;Misiukiewicz KJ;Chung CH;Gerber JE;Rajan SD;D'Souza G
通讯作者：
D'Souza G
影响因子：
1.2
作者：
Bhide, Shreerang;Clark, Catherine;Nutting, Christopher M.
通讯作者：
Nutting, Christopher M.
影响因子：
45.3
作者：
Blanchard, Pierre;Bourhis, Jean;Pignon, Jean-Pierre
通讯作者：
Pignon, Jean-Pierre