Background/Objectives: Surveillance for anal squamous cell carcinoma (ASCC) recurrence relies on clinical examination and imaging. Post-treatment edema, fibrosis, and inflammation can result in clinically indeterminate findings (CIFs) that delay diagnosis and increase patient and system burden. Circulating tumor tissue-modified viral (TTMV)-HPV DNA offers a biologically specific, noninvasive biomarker that may clarify equivocal assessments. Methods: In this multi-center retrospective study, 233 patients with HPV-associated ASCC were evaluated, including 185 with ≥1 post-treatment TTMV-HPV DNA test. CIFs were defined as exams or imaging results not definitively positive or negative for disease, and were paired with subsequent TTMV-HPV DNA tests. Concordance was defined by prespecified follow-up windows comparing TTMV-HPV DNA results with subsequent clinical outcomes. Results: Ninety patients (39%) experienced 214 CIFs, arising from exams (46%, 98) or imaging (54%, 116). Indeterminate rates by assessment were 7% for exams, 17% for imaging, and 1.3% for TTMV-HPV DNA testing. Overall, 52 CIF/TTMV-HPV DNA pairs were eligible for analysis, and TTMV-HPV DNA resolved disease status accurately for 48/52 (92%, 95% CI: 81.5–97.9). Negative tests predicted cancer-free status for 37/41 CIFs (90%), while 100% of positive tests (11/11) were concordant with clinically confirmed recurrence. In 73% of positive cases (8/11), TTMV-HPV DNA was the first indication of recurrence (median lead-time 29 days; IQR 25–147). Conclusions: TTMV-HPV DNA testing reliably clarifies clinically indeterminate findings during ASCC surveillance, demonstrating high accuracy (92%) and earlier detection of recurrence. These data support integration into post-treatment management to reduce diagnostic uncertainty and guide timely care.
**背景/目的：** 肛门鳞状细胞癌（ASCC）复发监测主要依赖临床检查和影像学检查。治疗后的水肿、纤维化和炎症可导致临床不确定发现（CIFs），从而延误诊断并增加患者和医疗系统的负担。循环肿瘤组织修饰病毒（TTMV）-HPV DNA 提供了一种具有生物学特异性、非侵入性的生物标志物，可能有助于明确模棱两可的评估结果。 **方法：** 在这项多中心回顾性研究中，评估了 233 例 HPV 相关 ASCC 患者，其中 185 例接受了至少一次治疗后 TTMV-HPV DNA 检测。CIFs 定义为检查或影像学结果无法明确判定疾病为阳性或阴性，并与随后的 TTMV-HPV DNA 检测结果进行配对分析。一致性定义为在预设的随访窗口内，将 TTMV-HPV DNA 结果与后续临床结局进行比较。 **结果：** 90 名患者（39%）出现了 214 次 CIFs，来源于临床检查（46%，98 次）或影像学检查（54%，116 次）。按评估方式划分的不确定率分别为：临床检查 7%，影像学检查 17%，TTMV-HPV DNA 检测 1.3%。总体而言，52 对 CIF/TTMV-HPV DNA 配对符合分析条件，其中 TTMV-HPV DNA 准确判定了 48/52 例（92%，95% CI: 81.5–97.9）的疾病状态。阴性检测结果预测了 37/41 例 CIFs（90%）无癌状态，而阳性检测结果（11/11）100% 与临床证实的复发一致。在 73% 的阳性病例（8/11）中，TTMV-HPV DNA 是复发的首个指征（中位提前时间 29 天；IQR 25–147）。 **结论：** TTMV-HPV DNA 检测在 ASCC 监测期间能够可靠地澄清临床不确定发现，显示出高准确性（92%）并能更早地检测复发。这些数据支持将其整合到治疗后管理中，以减少诊断不确定性并指导及时治疗。
Resolving Clinically Indeterminate Findings During Anal Cancer Surveillance with TTMV-HPV DNA
肿瘤(癌症)患者之家