Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer
Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer
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DOI：
10.1158/1078-0432.ccr-19-0211
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发表时间：
2019-08-01
影响因子：
11.5
通讯作者：
Gupta, Gaorav P.
中科院分区：
文献类型：
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作者：
Chera, Bhishamjit S.;Kumar, Sunil;Gupta, Gaorav P.
目的：为了确定循环肿瘤人乳头状瘤病毒（HPV）DNA（ctHPVDNA）清除动力学的概况，这与HPV相关口咽鳞状细胞癌（OPSCC.Experimental Design）的放化疗（CRT）后的疾病控制相关：在103例（i）p16阳性OPSCC，（ii）M0疾病和（iii）接受最终CRT的患者中进行了多机构前瞻性生物标志物试验。在基线、CRT期间每周和随访访视时采集血液标本。使用优化的多分析物数字PCR检测来定量血浆中的ctHPVDNA（16/18/31/33/35型）。55名健康志愿者和60例非HPV相关恶性肿瘤患者的对照队列也analysed.Results：基线血浆ctHPVDNA检测新诊断的HPV相关OPSCC具有高特异性（97%）和高敏感性（89%）。治疗前ctHPV 16 DNA拷贝数与疾病负荷、肿瘤HPV拷贝数和HPV整合状态相关。我们将ctHPV 16 DNA有利的清除概况定义为具有高基线拷贝数（> 200拷贝/mL）和在CRT的第28天ctHPV 16 DNA的> 95%清除。67例可评估患者中有19例ctHPV 16 DNA清除率良好，CRT后无持续性或复发性局部疾病。相反，具有不良临床风险因素的患者（T4或> 10包年）和不利的ctHPV 16 DNA清除情况，CRT后持续或复发性局部疾病的精算率为35（P = 0.0049）。ctHPVDNA的快速清除特征可以预测HPV相关OPSCC患者接受确定性CRT治疗后疾病控制的可能性，选择患者进行去强化治疗。
Purpose: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).Experimental Design: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16-positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non-HPV-associated malignancy was also analyzed.Results: Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diag-nosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (> 200 copies/mL) and > 95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or > 10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049).Conclusions: A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPVassociated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy.