Cell-free human papillomavirus DNA kinetics after surgery for human papillomavirus-associated oropharyngeal cancer.
Cell-free human papillomavirus DNA kinetics after surgery for human papillomavirus-associated oropharyngeal cancer.
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在人类乳头瘤病毒相关性口咽鳞状细胞癌(HPV+OPSCC)中，需要新的超灵敏方法来检测术后残留疾病。为探讨循环肿瘤人乳头瘤病毒DNA(CtHPVDNA)清除动力学与术后病情的关系，对33例HPV阳性的OPSCC患者进行了前瞻性观察研究。分别于手术前、术后第1天(POD 1)、第7天、第30天采血，并进行随访。12名患者在手术后24小时内进行了频繁采血，以确定早期清除动力学。血浆用定制液滴数字聚合酶链式反应(DdPCR)检测HPV基因16、18、33、35和45型。在术后无复发危险因素的患者中，术后第1天ctHPVDNA迅速下降至1拷贝/毫升(n=8/8)。在有宏观残留病危险因素的患者中，ctHPVDNA在POD 1(>；350拷贝/毫升)时显著升高，并持续升高直到辅助治疗(n=3/3)。POD1ctHPVDNA中等水平(1.2~58.4拷贝/毫升)的患者均有微小残留病的病理危险因素(n=9/9)。Pod-1ctHPVDNA水平在已知不良病理危险因素，如结外侵犯和1 mm(P=.0481)和淋巴结受累增加(P=.0453)的患者中较高(P=.0453)，并与接受辅助治疗进一步相关(P=0.0076)。33例患者中有1例复发，ctHPVDNA检测较临床提前2个月。Pod-1ctHPVDNA水平与接受治疗性手术的HPV+OPSCC患者的残留疾病风险相关，因此可以作为未来选择辅助治疗的个性化生物标志物。·人类乳头瘤病毒相关性口咽鳞状细胞癌(HPV+OPSCC)正在以流行的比例增加，通常采用手术治疗。·本报告介绍了一项研究结果，该研究检测了HPV+OPSCC手术治疗后循环肿瘤HPV DNA(循环肿瘤人乳头瘤病毒DNA[ctHPVDNA])的清除动力学。·我们发现，术后1天的ctHPVDNA水平与HPV+OPSCC患者残留疾病的风险有关，因此可以作为未来选择辅助治疗的个性化生物标志物。·这些发现首次证明了ctHPVDNA在接受手术的HPV+OPSCC患者中的潜在效用。
New ultrasensitive methods for detecting residual disease after surgery are needed in human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV+OPSCC). To determine whether the clearance kinetics of circulating tumor human papillomavirus DNA (ctHPVDNA) is associated with postoperative disease status, a prospective observational study was conducted in 33 patients with HPV+OPSCC undergoing surgery. Blood was collected before surgery, postoperative days 1 (POD 1), 7, and 30 and with follow-up. A subcohort of 12 patients underwent frequent blood collections in the first 24 hours after surgery to define early clearance kinetics. Plasma was run on custom droplet digital polymerase chain reaction (ddPCR) assays for HPV genotypes 16, 18, 33, 35, and 45. In patients without pathologic risk factors for recurrence who were observed after surgery, ctHPVDNA rapidly decreased to <1 copy/mL by POD 1 (n = 8/8). In patients with risk factors for macroscopic residual disease, ctHPVDNA was markedly elevated on POD 1 (>350 copies/mL) and remained elevated until adjuvant treatment (n = 3/3). Patients with intermediate POD 1 ctHPVDNA levels (1.2–58.4 copies/mL) all possessed pathologic risk factors for microscopic residual disease (n = 9/9). POD 1 ctHPVDNA levels were higher in patients with known adverse pathologic risk factors such as extranodal extension >1 mm (P = .0481) and with increasing lymph nodes involved (P = .0453) and were further associated with adjuvant treatment received (P = .0076). One of 33 patients had a recurrence that was detected by ctHPVDNA 2 months earlier than clinical detection. POD 1 ctHPVDNA levels are associated with the risk of residual disease in patients with HPV+OPSCC undergoing curative intent surgery and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. • Human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing at epidemic proportions and is commonly treated with surgery. • This report describes results from a study examining the clearance kinetics of circulating tumor HPV DNA (circulating tumor human papillomavirus DNA [ctHPVDNA]) following surgical treatment of HPV+OPSCC. • We found that ctHPVDNA levels 1 day after surgery are associated with the risk of residual disease in patients with HPV+OPSCC and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. • These findings are the first to demonstrate the potential utility of ctHPVDNA in patients with HPV+OPSCC undergoing surgery.
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