Bello-Perez Melissa, Mascarell Paula, Fernández-González Marta, García Jose Alberto, de la Tabla Ana Gutiérrez-Ortiz, Ledesma Christian, De la Rica Alba, Galiana Antonio, López Leo, Ocete Maria Dolores, Salvador Carme, Gimeno Concepción, García-Abellán Javier, Padilla Sergio, Gutiérrez Félix, Masiá Mar
Infectious Diseases Unit, Hospital General Universitario de Elche, Elche, Spain.
FISABIO, Hospital General Universitario de Elche, Elche, Spain.
Int J Cancer. 2025 Nov 1;157(9):1939-1947. doi: 10.1002/ijc.70050. Epub 2025 Jul 24.
Anal squamous cell carcinoma is a significant concern among people with HIV (PWH), with high-grade squamous intraepithelial lesions (HSIL) as its precursor. Current screening, primarily based on abnormal anal cytology, often results in unnecessary high-resolution anoscopies (HRA) due to limited specificity. This study evaluates whether quantifying Adenosine Deaminase Acting on RNA-1 (ADAR1) mRNA in anal swabs improves HSIL prediction and optimizes HRA selection. In this prospective cohort, HIV-positive adults with abnormal anal cytology underwent HRA. ADAR1 mRNA levels were quantified from anal swabs, and human papillomavirus (HPV) genotyping was performed. The diagnostic performance of ADAR1 mRNA was assessed using receiver operating characteristic (ROC) curve analysis and compared with E6/E7 mRNA detection for high-risk HPV (HR-HPV). HSIL was confirmed by biopsy in 40 of 171 participants (23.4%). HSIL cases had significantly higher ADAR1 mRNA levels (median: 49.4 vs. 4.1 relative units [RU], p < .001) and a greater median number of HPV genotypes (5 vs. 3, p < .001). ROC analysis for ADAR1 mRNA yielded an area under the curve (AUC) of 0.83 (95% CI: 0.75-0.92). At a cut-off of ≥24.8 RU, it demonstrated 73% sensitivity, 92% specificity, 74% positive predictive value, and 92% negative predictive value. Compared to E6/E7 mRNA, ADAR1 mRNA improved screening accuracy (64%-88%) and reduced HRA referrals (77.2%-48.8%). ADAR1 mRNA quantification reliably predicts HSIL in PWH with abnormal anal cytology. Integrating ADAR1 mRNA measurement into anal cancer screening protocols may enhance diagnostic accuracy, reduce unnecessary invasive procedures, and alleviate the burden on limited HRA resources.
肛管鳞状细胞癌是艾滋病毒感染者（PWH）中的一个重要问题，高级别鳞状上皮内病变（HSIL）是其前驱病变。目前的筛查主要基于异常的肛管细胞学检查，由于特异性有限，常常导致不必要的高分辨率肛门镜检查（HRA）。本研究评估在肛管拭子中定量RNA特异性腺苷脱氨酶1（ADAR1）mRNA是否能改善HSIL预测并优化HRA选择。在这个前瞻性队列中，肛管细胞学异常的HIV阳性成年人接受了HRA。从肛管拭子中定量ADAR1 mRNA水平，并进行人乳头瘤病毒（HPV）基因分型。使用受试者操作特征（ROC）曲线分析评估ADAR1 mRNA的诊断性能，并与高危HPV（HR-HPV）的E6/E7 mRNA检测进行比较。171名参与者中有40名（23.4%）经活检确诊为HSIL。HSIL病例的ADAR1 mRNA水平显著更高（中位数：49.4对4.1相对单位[RU]，p<0.001），HPV基因型的中位数更多（5对3，p<0.001）。ADAR1 mRNA的ROC分析得出曲线下面积（AUC）为0.83（95%CI：0.75-0.92）。在≥24.8 RU的临界值时，其敏感性为73%，特异性为92%，阳性预测值为74%，阴性预测值为92%。与E6/E7 mRNA相比，ADAR1 mRNA提高了筛查准确性（64%-88%），并减少了HRA转诊（77.2%-48.8%）。ADAR1 mRNA定量可可靠地预测肛管细胞学异常的PWH中的HSIL。将ADAR1 mRNA检测纳入肛管癌筛查方案可能会提高诊断准确性，减少不必要的侵入性检查，并减轻有限的HRA资源负担。
