Giunco Silvia, Del Mistro Annarosa, Morello Marzia, Lidonnici Jacopo, Frayle Helena, Gori Silvia, De Rossi Anita, Boscolo-Rizzo Paolo
Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, 35128 Padova, Italy; Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, 35128 Padova, Italy.
Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, 35128 Padova, Italy.
Oral Oncol. 2025 Feb;161:107169. doi: 10.1016/j.oraloncology.2024.107169. Epub 2025 Jan 3.
Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of malignancies with multifactorial aetiologies. High-risk human papillomavirus (hrHPV) infections, particularly HPV16, and the dysregulation of telomerase activity, specifically through its catalytic subunit, telomerase reverse transcriptase (TERT) are among the key contributors to HNSCC development and progression. HPV promotes oncogenesis via the E6 and E7 oncoproteins, which inactivate tumour suppressors TP53 and RB1, leading to unchecked cellular proliferation. Concurrently, telomerase activation plays a critical role in HNSCC by maintaining telomere length, thus enabling cellular immortality, and facilitating tumour development and progression. The interplay between HPV and telomerase is significant; HPV oncoprotein E6 enhances telomerase activity through multiple regulatory mechanisms, including upregulating TERT expression. Beyond telomere maintenance, TERT influences signalling pathways, cellular metabolism, and the tumour microenvironment, contributing to aggressive tumour behaviour and poor prognosis. This review integrates the roles of HPV and telomerase in HNSCC, focusing on their molecular mechanisms and interactions that drive carcinogenesis and influence disease progression. Understanding the synergistic effects of HPV and TERT in HNSCC may be crucial for risk stratification, prognostic assessment, and the development of novel therapeutic strategies targeting these specific molecular pathways.
头颈部鳞状细胞癌（HNSCC）是一组具有多因素病因的异质性恶性肿瘤。高危型人乳头瘤病毒（hrHPV）感染，尤其是HPV16感染，以及端粒酶活性失调，特别是通过其催化亚基端粒酶逆转录酶（TERT）的失调，是HNSCC发生和发展的关键因素。HPV通过E6和E7癌蛋白促进肿瘤发生，这两种癌蛋白会使肿瘤抑制因子TP53和RB1失活，导致细胞不受控制地增殖。同时，端粒酶激活在HNSCC中起着关键作用，它通过维持端粒长度来实现细胞永生化，并促进肿瘤的发生和发展。HPV与端粒酶之间的相互作用非常重要；HPV癌蛋白E6通过多种调节机制增强端粒酶活性，包括上调TERT表达。除了维持端粒外，TERT还影响信号通路、细胞代谢和肿瘤微环境，导致肿瘤侵袭性增加和预后不良。本综述整合了HPV和端粒酶在HNSCC中的作用，重点关注它们驱动癌变和影响疾病进展的分子机制及相互作用。了解HPV和TERT在HNSCC中的协同作用对于风险分层、预后评估以及针对这些特定分子途径的新型治疗策略的开发可能至关重要。
