人类乳头瘤病毒（HPV）是宫颈癌的主要诱因。虽然在其他恶性肿瘤中的研究表明，外周血DNA清除与良好的疗效有关，但使用肿瘤内HPV清零的前瞻性研究在妇科肿瘤的预后价值方面研究较少。我们旨在量化接受化学放射治疗（CRT）的患者中的肿瘤内HPV病毒组和临床特征和预后之间的联系。这项前瞻性研究招募了79例接受决定性CRT的IB-IVB期宫颈癌患者。在基线和第5周（强度调制放疗结束时）采集了宫颈肿瘤拭子进行短枪药物组成测序（SMS），并通过VirMAP进行处理，这是一个用于所有已知HPV类型的病毒基因组测序和鉴定工具。将数据分为HPV组（16、18、高危组和低危组）。我们使用独立t检验和Wilcoxon符号秩检验比较连续性变量，使用卡方和Fisher确切检验比较分类变量。对采用对数秩检验进行Kaplan-Meier生存建模。使用qPCR验证了HPV基因型，以验证使用接收器操作特征曲线和Cohen的Kappa验证VirMAP结果。在基线时，42％、12％、25％和16％的患者分别为HPV 16、HPV18、HPV高危、HPV低危阳性，8％为HPV阴性。 HPV类型与保险状态和CRT反应有关。 HPV 16阳性和其他HPV高危肿瘤的患者与HPV 18和HPV LR / HPV阴性肿瘤的患者相比，CRT完全反应的可能性显着增加。总体而言，HPV病毒载量主要在CRT过程中降低，除了HPV LR病毒载量外。宫颈肿瘤中较少研究的、不常见的HPV类型具有临床意义。 HPV 18和HPV LR / 阴性肿瘤与CRT反应差有关。这项可行性研究为进一步研究肿瘤内HPV谱系提供了框架，以预测宫颈癌患者的预后。版权所有©2023 Elsevier Inc.发表。

Human papillomavirus (HPV) is the primary driver of cervical cancer. Though studies in other malignancies correlated peripheral blood DNA clearance with favorable outcomes, research on the prognostic value of HPV clearance in gynecological cancers using intratumoral HPV is scarce. We aimed to quantify the intratumoral HPV virome in patients undergoing chemoradiation therapy (CRT) and associate this with clinical characteristics and outcomes.This prospective study enrolled 79 patients with stage IB-IVB cervical cancer undergoing definitive CRT. Cervical tumor swabs collected at baseline and week 5 (end of intensity modulated radiation therapy) were sent for shotgun metagenome sequencing (SMS) and processed via VirMAP, a viral genome sequencing and identification tool for all known HPV types. The data were categorized into HPV groups (16, 18, high-risk [HR], and low-risk [LR]). We used independent t-tests and Wilcoxon Signed-Rank to compare continuous variables and Chi-square and Fisher's exact test to compare categorical variables. Kaplan-Meier survival modeling was performed with log-rank testing. HPV genotyping was verified using qPCR to validate VirMAP results using Receiver Operating Characteristic Curve and Cohen's Kappa.At baseline, 42%, 12%, 25%, and 16% of patients were positive for HPV 16, HPV18, HPV HR, and HPV LR, respectively, and 8% were HPV negative. HPV type was associated with insurance status and CRT response. Patients with HPV 16+ and other HPV HR+ tumors were significantly more likely to have a complete response to CRT versus patients with HPV 18 and HPV LR/HPV negative tumors. Overall HPV viral loads predominantly decreased throughout CRT, except for HPV LR viral load.Rarer, less well-studied HPV types in cervical tumors are clinically significant. HPV 18 and HPV LR/negative tumors are associated with poor CRT response. This feasibility study provides a framework for a larger study of intratumoral HPV profiling to predict outcomes in cervical cancer patients.Copyright © 2023. Published by Elsevier Inc.