Tarle Marko, Raguž Marina, Lukšić Ivica
Department of Maxillofacial Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia.
School of Dental Medicine, University of Zagreb, Gundulićeva 5, 10000 Zagreb, Croatia.
Int J Mol Sci. 2025 Sep 15;26(18):8969. doi: 10.3390/ijms26188969.
Autoimmune polyendocrine syndrome type 1 (APS-1, APECED) is a rare monogenic disorder caused by biallelic AIRE mutations and is classically associated with chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency. Apart from the autoimmune manifestations, APS-1 is associated with an increased risk of squamous cell carcinoma (SCC), particularly in the oral cavity and esophagus. However, the evidence is patchy and has not yet been systematically reviewed. We conducted a scoping review according to the PRISMA-ScR guidelines. Pub-Med, Scopus, and Web of Science were searched using the terms APS-1/APECED and malignancy until July 2025. Eligible studies reported on APS-1 patients with histologically confirmed head, neck or esophageal cancer. Clinical, pathological, genetic and outcome data were summarized narratively. Nine publications described 19 APS-1 patients with 26 tumors. The mean age at cancer diagnosis was 35 years, with a latency period of ~24 years from the onset of APS-1. Tumors occurred most frequently in the oral cavity (65%), followed by the lip (19%) and esophagus (15%). In 96% of cases, the tumors were SCC. The grade of the tumor varied, and almost half of the cases were diagnosed at an advanced stage. As far as reported, the usual risk factors were not particularly pronounced; many patients did not smoke or drink alcohol. The main treatment consisted of surgery, often in combination with radiotherapy or chemoradiotherapy, alongside long-term antifungal therapy. Despite the multimodal treatment, outcomes were poor: the overall survival rate was ~50%, with recurrence occurring in 38% of cases and a second primary tumor in 26%. A further 14 cases were reported from another Italian cohort, which together with the national cohort dana suggest a risk of approximately ~10% with APS-1; however, the true lifetime risk remains uncertain. Head and neck malignancies in APS-1 occur early, often without classic risk factors, and have a high recurrence and mortality rate. Lifelong surveillance, antifungal stewardship and increased clinical awareness, ideally as part of multidisciplinary treatment pathways, are critical to improving outcomes in this rare but high-risk population.
1型自身免疫性多内分泌腺综合征（APS-1，自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良）是一种由双等位基因AIRE突变引起的罕见单基因疾病，典型表现为慢性黏膜皮肤念珠菌病（CMC）、甲状旁腺功能减退和肾上腺功能不全。除自身免疫表现外，APS-1还与鳞状细胞癌（SCC）风险增加有关，尤其是口腔和食管的鳞状细胞癌。然而，证据并不充分，尚未进行系统综述。我们根据PRISMA-ScR指南进行了一项范围综述。截至2025年7月，在PubMed、Scopus和Web of Science数据库中使用“APS-1/APECED”和“恶性肿瘤”等关键词进行检索。纳入的研究报告了组织学确诊为头颈部或食管癌的APS-1患者。对临床、病理、基因和结局数据进行了叙述性总结。9篇文献描述了19例患有26种肿瘤的APS-1患者。癌症诊断时的平均年龄为35岁，从APS-1发病到癌症诊断的潜伏期约为24年。肿瘤最常发生在口腔（65%），其次是嘴唇（19%）和食管（15%）。96%的病例为鳞状细胞癌。肿瘤分级各异，近一半病例在晚期确诊。据报道，常见的风险因素并不特别突出；许多患者不吸烟或饮酒。主要治疗方法包括手术，通常联合放疗或放化疗，同时进行长期抗真菌治疗。尽管采用了多模式治疗，但结局不佳：总生存率约为50%，38%的病例复发，26%的病例出现第二原发性肿瘤。另一个意大利队列报告了另外14例病例，与全国队列dana的数据一起表明APS-1患者患癌风险约为10%；然而，真实的终生风险仍不确定。APS-1患者的头颈部恶性肿瘤发病早，通常没有典型风险因素，复发率和死亡率高。终身监测、抗真菌管理以及提高临床意识，理想情况下作为多学科治疗途径的一部分，对于改善这一罕见但高危人群的结局至关重要。
