Bhamidipati Deepak, Johnson Jay R, Lin Kangyu, Pelicano Helene, Eng Cathy, Huey Ryan, Wolff Robert A, Halperin Daniel M, Frumovitz Michael F, Wistuba Ignacio I, Duose Dzifa Y, Mallampati Saradhi, Luthra Rajyalakshmi, Morris Van K
Department of Cancer Medicine Fellowship Program, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sarah Cannon Research Institute, Nashville, TN 37203, USA.
Cancers (Basel). 2025 Jan 19;17(2):308. doi: 10.3390/cancers17020308.
To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).
ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types. The HPV type, copy number (CN), and integration sites were determined using a bioinformatic pipeline.
A total of 77 plasma samples from 28 patients with HPV-related SCCA were retrospectively analyzed. HPV ctDNA was detected in 26 cases (93%) (including uncommon subtypes). The median HPV CN was higher in metastatic versus locally recurrent/unresectable SCCA ( = 0.043). Changes in the HPV CN were concordant with the radiographic response ( = 0.027). An integration event was detected in 23 patients (82%), with presumed episomal HPV DNA present in the remaining patients. Higher HPV integration (a mean of ≥1 integration across samples) was associated with a worse overall survival from the start of immunotherapy (13.6 months versus 36.0 months; = 0.003).
Using HPV-informed next-generation sequencing of the ctDNA, we found changes in the HPV CN correlated with the treatment response and that HPV integration detected in the ctDNA is an unfavorable prognostic biomarker.
为了将液体活检的实用性扩展到传统人乳头瘤病毒循环肿瘤DNA（ctDNA）检测之外，我们评估了一种新型的下一代测序HPV ctDNA检测方法在局部晚期和转移性肛管鳞状细胞癌（mSCCA）患者中的临床相关性。
从mSCCA患者血浆中分离的ctDNA使用一个覆盖所有193种HPV类型全基因组序列的1.4 Mb杂交捕获目标富集panel进行测序。使用生物信息学流程确定HPV类型、拷贝数（CN）和整合位点。
对28例HPV相关SCCA患者的77份血浆样本进行回顾性分析。26例（93%）检测到HPV ctDNA（包括不常见亚型）。转移性SCCA与局部复发/不可切除SCCA相比，HPV CN中位数更高（P = 0.043）。HPV CN的变化与影像学反应一致（P = 0.027）。23例（82%）检测到整合事件，其余患者推测存在游离型HPV DNA。从免疫治疗开始，较高的HPV整合（样本平均≥1次整合）与较差的总生存期相关（13.6个月对36.0个月；P = 0.003）。
通过对ctDNA进行HPV信息指导的下一代测序，我们发现HPV CN的变化与治疗反应相关，并且在ctDNA中检测到的HPV整合是一种不良预后生物标志物。
