Background: The incidence and mortality of anal squamous cell carcinoma (ASCC) are rising, with greater than 80% of cases linked to human papillomavirus (HPV), primarily HPV16. Post-treatment surveillance can be challenging due to the limitations of anoscopy, digital anal rectal exam (DARE), and imaging. Plasma tumor tissue modified viral (TTMV)-HPV DNA has shown strong sensitivity, specificity, and predictive value in detecting the recurrence of HPV-driven oropharyngeal cancer. Here, we investigate the ability of TTMV-HPV DNA for the early recurrence detection of ASCC. Methods: This retrospective clinical case series included 117 patients with HPV-driven ASCC across 7 U.S. centers, monitored with TTMV-HPV DNA during routine clinical care between March 2020 and June 2024. Physician-reported clinical data and biomarker testing data were combined to create a comprehensive, longitudinal dataset for evaluating test performance metrics. Results: Patients had a median age of 63 years and median post-diagnosis follow-up of 19 months. HPV status was primarily confirmed by TTMV-HPV DNA (52%) or p16 immunohistochemistry (39%). Of those tested for TTMV-HPV DNA pretreatment, 85% had a positive result. TTMV-HPV DNA clearance during or within three months post-treatment was associated with significantly better recurrence-free survival. The per-patient surveillance sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 82.8%, 98.4%, 96.0%, and 92.5%. Of 24 patients with a documented recurrence and a positive TTMV-HPV DNA test, the test was the first evidence of recurrence in 14 patients (58.3%), with a median lead time of 59 days (range: 10–536). TTMV-HPV DNA accurately resolved 94.3% of cases with indeterminate clinical findings. Conclusions: TTMV-HPV DNA testing provides a sensitive and specific approach for detecting patients with recurrent ASCC and resolving the status of patients with indeterminate clinical findings.
背景：肛管鳞状细胞癌（ASCC）的发病率和死亡率持续上升，超过80%的病例与人乳头瘤病毒（HPV）相关，其中主要为HPV16型。由于肛门镜检查、肛门直肠指诊（DARE）及影像学检查存在局限性，治疗后监测面临挑战。血浆肿瘤组织修饰病毒（TTMV）-HPV DNA检测在HPV驱动型口咽癌复发监测中已显示出较高的敏感性、特异性及预测价值。本研究旨在探讨TTMV-HPV DNA检测在ASCC早期复发监测中的应用价值。 方法：本回顾性临床病例系列研究纳入2020年3月至2024年6月期间在美国7个中心接受常规临床监测的117例HPV驱动型ASCC患者，所有患者均接受TTMV-HPV DNA检测。研究整合医师报告的临床数据与生物标志物检测数据，构建用于评估检测性能指标的纵向综合数据集。 结果：患者中位年龄为63岁，中位诊断后随访时间为19个月。HPV状态主要通过TTMV-HPV DNA检测（52%）或p16免疫组化染色（39%）确认。在治疗前接受TTMV-HPV DNA检测的患者中，85%呈阳性结果。治疗期间或治疗后三个月内TTMV-HPV DNA转阴与显著改善的无复发生存期相关。基于患者个体的监测敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）分别为82.8%、98.4%、96.0%和92.5%。在24例经确诊复发且TTMV-HPV DNA检测呈阳性的患者中，该检测为14例患者（58.3%）提供了首次复发证据，中位预警时间为59天（范围：10-536天）。对于临床检查结果不确定的病例，TTMV-HPV DNA检测可准确判定94.3%的病例状态。 结论：TTMV-HPV DNA检测为ASCC复发监测提供了一种高敏感性与高特异性的方法，并能有效明确临床检查结果不确定患者的疾病状态。
肿瘤(癌症)患者之家