Yin Linda X, Hidalgo Cecelia M, Bogan Aaron W, Hunter Danielle E, Bartemes Kathleen R, Tasche Kendall K, Moore Eric J, Price Daniel L, Ma Daniel J, Neben-Wittich Michelle A, Lester Scott C, Price Katharine A, McGarrah Patrick W, Fuentes Bayne Harry E, Routman David M, Van Abel Kathryn M
Department of Otolaryngology-Head & Neck Surgery, Mayo Clinic, Rochester, Minnesota.
Division of Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, Arizona.
JAMA Otolaryngol Head Neck Surg. 2025 May 14. doi: 10.1001/jamaoto.2025.1606.
Circulating tumor human papillomavirus DNA (ctHPVDNA) is an important biomarker for the presence of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but little is known about early postoperative kinetics of ctHPVDNA clearance.
To investigate early postoperative kinetics of ctHPVDNA in patients with HPV-associated OPSCC.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted at a single tertiary care center from January 4, 2020, to January 26, 2023. Patients with newly diagnosed HPV-associated OPSCC undergoing surgical management were enrolled. HPV status was defined as positive if findings of p16 immunohistochemistry and/or HPV DNA in situ hybridization and/or E6/E7 RNA in situ hybridization were positive. Exclusion criteria included history of prior head and neck cancer and metastatic disease at presentation. Data were analyzed from September 1, 2024, to April 25, 2025.
Transoral robotic surgery with concurrent neck dissection.
Blood was drawn prior to surgery (pretreatment), 1 to 2 days after surgery (postoperative days 1 to 2), and approximately 2 weeks after surgery (postoperative week 2; range, 8 to 20 days). ctHPVDNA was quantified by a tumor tissue-modified viral (TTMV) HPV DNA test. Correlations were tested between the pretreatment and postoperative day 1 to 2 TTMV HPV DNA levels using Gaussian regression. Concordance between detectability at postoperative day 1 to 2 and postoperative week 2 was explored using negative predictive value and positive predictive value.
Of 57 included patients with detectable pretreatment TTMV HPV DNA, 51 (89%) were male, and the median (IQR) age was 59 (54-66) years. A total of 35 patients (61%) had blood draws at all 3 time points; 16 (28%) had detectable TTMV HPV DNA on postoperative day 1 to 2. Pretreatment and postoperative day 1 to 2 TTMV HPV DNA levels had a medium positive linear correlation (r = 0.31; 95% CI, 0.04-0.54). Undetectable TTMV HPV DNA on postoperative day 1 to 2 blood draw had a negative predictive value of 0.95 (95% CI, 0.74-1.00) for an undetectable level on postoperative week 2 blood draw, but a detectable level on postoperative day 1 to 2 blood draw only had a positive predictive value of 0.19 (95% CI, 0.04-0.46). Of the 16 patients with detectable TTMV HPV DNA pretreatment and at postoperative day 1 to 2, only 3 (19%) continued to have detectable TTMV HPV DNA at postoperative week 2. One patient had undetectable levels at postoperative day 1 to 2 and detectable levels at postoperative week 2.
In this study, ctHPVDNA detectability early after surgery did not predict detectability at 2 weeks after surgery. ctHPVDNA clearance early after surgery could predict a negative test at 2 weeks. A negative blood draw finding on postoperative day 1 may be used to omit a postoperative blood draw at 2 weeks for minimal residual disease detection in future clinical trials.
循环肿瘤人乳头瘤病毒DNA（ctHPVDNA）是HPV相关口咽鳞状细胞癌（OPSCC）存在的重要生物标志物，但关于术后早期ctHPVDNA清除动力学知之甚少。
研究HPV相关OPSCC患者术后早期ctHPVDNA的动力学。
设计、设置和参与者：这项前瞻性队列研究于2020年1月4日至2023年1月26日在一家三级医疗中心进行。纳入了接受手术治疗的新诊断HPV相关OPSCC患者。如果p16免疫组化和/或HPV DNA原位杂交和/或E6/E7 RNA原位杂交结果为阳性，则HPV状态定义为阳性。排除标准包括既往有头颈癌病史和就诊时存在转移性疾病。数据于2024年9月1日至2025年4月25日进行分析。
经口机器人手术联合颈部淋巴结清扫术。
在手术前（预处理）、手术后1至2天（术后第1至2天）以及手术后约2周（术后第2周；范围为8至20天）采集血液。通过肿瘤组织改良病毒（TTMV）HPV DNA检测对ctHPVDNA进行定量。使用高斯回归检验预处理和术后第1至2天TTMV HPV DNA水平之间的相关性。使用阴性预测值和阳性预测值探讨术后第1至2天和术后第2周检测性之间的一致性。
在57例术前可检测到TTMV HPV DNA的纳入患者中，51例（89%）为男性，中位（IQR）年龄为59（54 - 66）岁。共有35例患者（61%）在所有3个时间点采集了血液；16例（28%）在术后第1至2天可检测到TTMV HPV DNA。预处理和术后第1至2天TTMV HPV DNA水平呈中度正线性相关（r = 0.31；95% CI，0.04 - 0.54）。术后第1至2天血液检测未检测到TTMV HPV DNA，对于术后第2周血液检测未检测到TTMV HPV DNA水平的阴性预测值为0.95（95% CI，0.74 - 1.00），但术后第1至2天血液检测可检测到TTMV HPV DNA水平，其阳性预测值仅为0.19（95% CI，0.04 - 0.46）。在16例术前和术后第1至2天可检测到TTMV HPV DNA的患者中，仅3例（19%）在术后第2周仍可检测到TTMV HPV DNA。1例患者术后第1至2天检测不到，术后第2周检测到。
在本研究中，术后早期ctHPVDNA的可检测性不能预测术后2周的可检测性。术后早期ctHPVDNA清除可预测2周时检测结果为阴性。术后第天血液检测结果为阴性，可用于在未来临床试验中省略术后2周用于最小残留疾病检测的血液检测。
