Background/Objectives: Tumor mutational burden (TMB) has emerged as a potential biomarker of response to immunotherapy across multiple solid tumors. However, its role in cervical cancer remains insufficiently defined. This study aimed to evaluate the genomic landscape and TMB profile in a cohort of patients with cervical cancer treated at a tertiary gynecologic oncology center, with a focus on TMB’s associations with clinical features, HPV infection, and treatment modalities.Methods: A total of 61 patients diagnosed with cervical cancer (82.0% ca. planoepitheliale, 18.0% adenocarcinoma) were retrospectively analyzed. Tumor samples were collected during primary surgery, biopsy, or conization and subjected to targeted next-generation sequencing using the ONCOaccuPanel™ and BRCAaccuTest PLUS™ (NGeneBio). TMB was calculated as non-synonymous mutations per megabase and analyzed using NGeneAnalySys®software. Variant classification followed ACMG guidelines. Comparative analyses were conducted between TMB-high (≥10 mut/Mb) and TMB-low subgroups, and correlations with clinical and molecular variables were assessed using univariable statistics.Results: High TMB was identified in 36 patients (59.0%), while microsatellite instability was found in only 2 cases (3.3%). No significant associations were observed between TMB status and FIGO stage, histologic subtype, or HPV 16/18 infection. However, higher TMB values were observed in patients with nodal involvement, diabetes, and HPV52 infection. A diverse spectrum of mutations was detected, with PIK3CA and ARID1A being most frequently altered. Several variants of uncertain significance were identified in genes not classically associated with cervical cancer.Conclusions: TMB-high status is relatively frequent in cervical cancer and appears to be independent of FIGO stage or histological subtype. While not predictive of clinical stage, TMB correlates with specific molecular and comorbidity profiles, suggesting its potential relevance for future patient stratification in immunotherapy trials.
**背景/目的：** 肿瘤突变负荷（TMB）已成为多种实体瘤对免疫治疗反应的潜在生物标志物。然而，其在宫颈癌中的作用仍未充分明确。本研究旨在评估在一家三级妇科肿瘤中心接受治疗的宫颈癌患者队列的基因组图谱和TMB特征，重点关注TMB与临床特征、HPV感染及治疗方式之间的关联。 **方法：** 回顾性分析了61例诊断为宫颈癌的患者（82.0%为鳞状细胞癌，18.0%为腺癌）。肿瘤样本采集自初次手术、活检或锥切术，并使用ONCOaccuPanel™和BRCAaccuTest PLUS™（NGeneBio）进行靶向二代测序。TMB计算为每兆碱基的非同义突变数，并使用NGeneAnalySys®软件进行分析。变异分类遵循美国医学遗传学与基因组学学会指南。在TMB高（≥10 突变/Mb）和TMB低亚组之间进行比较分析，并使用单变量统计学方法评估其与临床及分子变量的相关性。 **结果：** 36例患者（59.0%）检测出高TMB，而仅2例（3.3%）发现微卫星不稳定性。未观察到TMB状态与FIGO分期、组织学亚型或HPV 16/18感染之间存在显著关联。然而，在淋巴结受累、患有糖尿病以及HPV52感染的患者中观察到更高的TMB值。检测到多种突变谱，其中PIK3CA和ARID1A基因改变最为常见。在通常与宫颈癌无关的基因中鉴定出数个意义未明的变异。 **结论：** 高TMB状态在宫颈癌中相对常见，且似乎与FIGO分期或组织学亚型无关。虽然TMB不能预测临床分期，但其与特定的分子特征和合并症状况相关，提示其在未来免疫治疗试验中用于患者分层的潜在相关性。
Tumor Mutational Burden in Cervical Cancer as Potential Marker for Immunotherapy Responders
肿瘤(癌症)患者之家