Eguchi Hirotaka, Takenaka Yukinori, Tanaka Hidenori, Suzuki Motoyuki, Horie Masafumi, Kanai Haruka, Seo Yuji, Ogawa Kazuhiko, Yachida Shinichi, Inohara Hidenori
Head and Neck Surgery, Osaka University, Suita, JPN.
Basic Sciences, Osaka University, Suita, JPN.
Cureus. 2024 May 18;16(5):e60547. doi: 10.7759/cureus.60547. eCollection 2024 May.
Objectives We aimed to examine the effectiveness of platinum-based triplet induction chemotherapy in metastatic squamous cell carcinoma of the head and neck (HNSCC) at diagnosis in terms of tumor human papillomavirus (HPV) status and the clinical relevance of circulating tumor HPV DNA (ctHPVDNA) during induction chemotherapy. Methods Twenty-one patients were included. ctHPVDNA was longitudinally quantified using optimized digital PCR in a subset of patients. Results HPV-related HNSCC patients (N=7) had a significantly better response to induction chemotherapy than HPV-unrelated HNSCC patients (N=14) (complete or partial response rate, 100% vs. 36%, = 0.007). Following induction chemotherapy, more HPV-related HNSCC patients than HPV-unrelated patients received radiotherapy (86% vs. 36%, = 0.06). With a median follow-up of 26 months in surviving patients, the two-year overall survival was 86% in HPV-related HNSCC patients and 43% in HPV-unrelated HNSCC patients ( = 0.04). In two patients, ctHPVDNA levels drastically decreased after the first cycle of induction chemotherapy but turned to continuous increase after the second cycle, suggesting the acquisition of drug resistance by the end of the second cycle. Radiographic imaging after induction chemotherapy failed to identify the drug resistance. In one patient, ctHPVDNA decreased gradually but remained detectable after induction chemotherapy despite no radiographic residual disease. ctHPVDNA became undetectable during radiotherapy. Conclusion HPV-related HNSCC patients with distant metastasis at diagnosis should be treated definitively. The ctHPVDNA level reflects real-time disease activity. ctHPVDNA monitoring during induction chemotherapy could help the decision-making of the therapeutic strategy.
我们旨在根据肿瘤人乳头瘤病毒（HPV）状态，研究铂类三联诱导化疗在诊断时对转移性头颈部鳞状细胞癌（HNSCC）的有效性，以及诱导化疗期间循环肿瘤HPV DNA（ctHPVDNA）的临床相关性。方法：纳入21例患者。在部分患者中使用优化的数字PCR对ctHPVDNA进行纵向定量。结果：HPV相关的HNSCC患者（N = 7）对诱导化疗的反应明显优于HPV不相关的HNSCC患者（N = 14）（完全或部分缓解率，100%对36%，P = 0.007）。诱导化疗后，接受放疗的HPV相关HNSCC患者比HPV不相关患者更多（86%对36%，P = 0.06）。存活患者的中位随访时间为26个月，HPV相关HNSCC患者的两年总生存率为86%，HPV不相关HNSCC患者为43%（P = 0.04）。在两名患者中，ctHPVDNA水平在诱导化疗的第一个周期后急剧下降，但在第二个周期后转为持续上升，提示在第二个周期末获得了耐药性。诱导化疗后的影像学检查未能识别出耐药性。在一名患者中，ctHPVDNA逐渐下降，但诱导化疗后尽管影像学检查无残留疾病仍可检测到。ctHPVDNA在放疗期间变得不可检测。结论：诊断时伴有远处转移的HPV相关HNSCC患者应接受确定性治疗。ctHPVDNA水平反映实时疾病活动。诱导化疗期间监测ctHPVDNA有助于治疗策略的决策。
