Background:The relationship between detectable circulating tumor DNA levels and clinical outcome following definitive therapy in patients with human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma has not been well established.Methods:In this retrospective analysis of patients with HPV-positive oropharyngeal squamous cell carcinoma seen from 2016 to 2024 at a single institution, 88 patients met inclusion criteria with baseline-positive tumor tissue-modified viral HPV DNA (TTMV-HPV DNA) testing and post-treatment testing performed.Results:Of the 88 patients included in the survival analysis, 77 had undetectable tumor tissue-modified viral human papillomavirus DNA after treatment, while 11 had positive (detectable) tumor tissue-modified viral human papillomavirus DNA. TTMV-HPV DNA positivity after treatment was associated with worse 1-year and 2-year overall survival outcomes, at 63.5% (37.7–100,p= 0.022) and 50.8% (25.7–100,p= 0.017) compared to 100% and 96.4% (91.6–100,p= 0.017) in patients with undetectable TTMV-HPV DNA. Inability to clear TTMV-HPV DNA after treatment was associated with worse progression-free survival, at 45.0% (95% CI 21.8–92.7,p= 0.009) at 1 year and 11.3% (95% CI 1.8–71.2,p= <0.001) at 2 years compared to 93% (95% CI 87.3–99.1) and 84.7% (95% CI, 76.3–94.0) in patients with cleared TTMV-HPV DNA after treatment.Conclusion:Tumor tissue-modified viral human papillomavirus DNA positivity after definitive treatment was associated with worse survival and disease recurrence outcomes compared to that in patients with undetectable post-treatment TTMV-HPV DNA. Prospective studies are warranted to further establish the clinical utility of TTMV-HPV DNA testing and its use in surveillance, treatment intensification, or de-intensification.
背景：人乳头瘤病毒（HPV）介导的口咽鳞状细胞癌患者在根治性治疗后，可检测到的循环肿瘤DNA水平与临床结局之间的关系尚未明确。方法：本研究对2016年至2024年间在同一机构就诊的HPV阳性口咽鳞状细胞癌患者进行回顾性分析，共纳入88例符合标准的患者，这些患者均接受了基线肿瘤组织修饰病毒HPV DNA（TTMV-HPV DNA）检测阳性且完成治疗后检测。结果：在纳入生存分析的88例患者中，77例治疗后TTMV-HPV DNA检测为阴性（不可检测），11例为阳性（可检测）。治疗后TTMV-HPV DNA阳性与较差的1年和2年总生存率相关，分别为63.5%（37.7–100，p=0.022）和50.8%（25.7–100，p=0.017），而治疗后TTMV-HPV DNA阴性患者的1年和2年总生存率分别为100%和96.4%（91.6–100，p=0.017）。治疗后未能清除TTMV-HPV DNA与较差的无进展生存率相关，其1年和2年无进展生存率分别为45.0%（95% CI 21.8–92.7，p=0.009）和11.3%（95% CI 1.8–71.2，p<0.001），而治疗后清除TTMV-HPV DNA患者的1年和2年无进展生存率分别为93%（95% CI 87.3–99.1）和84.7%（95% CI 76.3–94.0）。结论：与治疗后TTMV-HPV DNA阴性患者相比，根治性治疗后TTMV-HPV DNA阳性与较差的生存率和疾病复发结局相关。有必要开展前瞻性研究，进一步确立TTMV-HPV DNA检测的临床应用价值，及其在疾病监测、强化治疗或降级治疗中的应用潜力。
肿瘤(癌症)患者之家