CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:HPV-specific innovations and controversies in therapeutic strategies for HPV-associated oropharyngeal carcinoma.
HPV-specific innovations and controversies in therapeutic strategies for HPV-associated oropharyngeal carcinoma.
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全球人乳头瘤病毒(HPV)相关口咽鳞状细胞癌(OPSCC)发病率的激增,迫使临床管理发生根本性转变。尽管与HPV阴性患者相比,此类患者预后较好,但如何在肿瘤治愈率与降低毒性之间取得平衡仍是一项关键挑战。本综述阐明了由致癌蛋白E6和E7驱动的病毒学机制,并评估了新型诊断生物标志物,重点强调了液体活检(循环肿瘤HPV DNA,ctHPV DNA)和人工智能在动态风险分层中的应用价值。我们批判性地审视了当前的治疗争议,特别是无指导的治疗降阶梯所伴随的复发风险。此外,本文重点介绍了精准医学的创新,包括利用病毒抗原的免疫再激活策略(治疗性疫苗、过继细胞疗法)以及针对代谢脆弱性(PI3K/Akt/mTOR通路)和DNA损伤修复缺陷的靶向干预。最终,我们倡导从静态TNM分期转向整合基因组学和免疫学的多维适应性治疗模式,以实现对HPV相关OPSCC的精准个体化诊疗。
The global surge in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has necessitated a fundamental shift in clinical management. While patients exhibit favorable prognoses compared to HPV-negative counterparts, balancing oncological cure rates with toxicity reduction remains a critical challenge.
This review elucidates the virological mechanisms driven by oncoproteins E6 and E7 and evaluates novel diagnostic biomarkers, emphasizing the utility of liquid biopsy (circulating tumor HPV DNA,ctHPV DNA) and artificial intelligence for dynamic risk stratification.
We critically examine current therapeutic controversies, particularly the risks of recurrence associated with unguided treatment de-escalation.
Furthermore, the article highlights innovations in precision medicine, including immune reactivation strategies leveraging viral antigens (therapeutic vaccines, adoptive cell therapy) and targeted interventions exploiting metabolic vulnerabilities (PI3K/Akt/mTOR pathway) and DNA damage repair defects. Ultimately, we advocate transitioning from static TNM staging to a multidimensional, adaptive treatment model integrating genomics and immunology to achieve precise, individualized care for HPV-associated OPSCC.
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