目的 评估配对盒基因1甲基化（paired-box gene 1 methylation,PAX1m）和病毒分型对高危型人乳头瘤病毒（high-risk human papillomavirus,hrHPV）阳性且意义不明确的非典型鳞状细胞结果（atypical squamous epithelial cell outcome of undetermined significance,ASC-US）女性的风险分层及价值。方法 横断面研究招募2024年1月至2024年7月hrHPV阳性且ASC-US的女性642名,对子宫颈脱落细胞进行甲基化检测。以活检结果为参照,剔除无病理和/或无PAX1m结果的病例,554例纳入分析,比较PAX1m和hrHPV基因分型的宫颈上皮内瘤变（cervical intraepithelial neoplasm,CIN）2级及以上（CIN2+）绝对风险,PAX1m、HPV分型及相互联合诊断CIN2+的效能。结果 PAX1m阳性和阴性结果的CIN2+绝对风险分别为13.5%（95%CI：8.9%~19.3%）和1.4%（95%CI：0.5%~3.1%）（P<0.001）。PAX1m联合HPV分型四种结果与CIN2+绝对风险呈趋势性相关（P均<0.001）,HPV16/18/31/33/45和PAX1m双阴性风险值为0.7%（95%CI：0.1%~2.5%）。HPV16/18/31/33/45及PAX1m联合检测的灵敏度和阴性预测值分别为93.3%（95%CI：77.9%~99.2%）和99.3%（95%CI：97.4%~99.8%）。结论 PAX1m和HPV分型可对ASC-US的hrHPV阳性妇女进行风险分层,降低阴道镜转诊率,具有90%的CIN2+灵敏度和99%的阴性预测值,具有分流hrHPV阳性且ASC-US女性的临床价值。
Abstract
Objective To assess the clinical value of paired-box gene 1 methylation (PAX1m) and viral genotyping for risk stratification of women with high-risk human papillomavirus (hrHPV) -positive and atypical squamous epithelial cell outcome of undetermined significance (ASC-US). Methods In a cross-sectional study, 642 women with hrHPV-positive and cytologic ASC-US were recruited from January 1, 2024, to July 30, 2024, and exfoliated cells from the uterine cervix were collected for methylation testing, and pathological results from colposcopic biopsies were used as a reference. Excluded cases with no pathological and PAX1m results, 554 cases were included in the statistical analysis, to compare PAX1m and hrHPV genotyping with different results of absolute cervical intraepithelial neoplasm (CIN) 2 grade or worse (CIN2+) risk, and to explore the performance of PAX1m, hrHPV genotyping and their combined for detecting CIN2+. Results The absolute CIN2+ risk was 13.5% (95% CI: 8.9%-19.3%) and 1.4% (95% CI: 0.5%-3.1%) for PAX1m-positive and negative results, respectively (P<0.001). The four results of PAX1m combined with hrHPV genotyping (HPV16/18 and HPV16/18/31/33/45) were trend-associated with absolute CIN2+ risk (all P<0.001), with the lowest double-negative risk for HPV16/18/31/33/45 and PAX1m of 0.7% (95% CI: 0.1%-2.5%). The sensitivity and negative predictive value of the combined HPV16/18/31/33/45 or PAX1m assay were 93.3% (95% CI: 77.9%-99.2%) and 99.3% (95% CI: 97.4%-99.8%), respectively. Conclusion PAX1m and HPV genotyping stratified the risk of hrHPV-positive women with cytological ASC-US, reduced the colposcopic referral rate while maintaining 90% CIN2+ sensitivity and 99% negative predictive value, and has the clinical value of triage hrHPV-positive women with cytological ASC-US.
关键词
配对盒基因1甲基化 /
宫颈癌 /
宫颈上皮内瘤变 /
高危型人乳头瘤病毒
Key words
paired-box gene 1 methylation /
cervical cancer /
cervical intraepithelial neoplasm /
hrHPV
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基金
长沙市2022年度软科学研究计划项目“基于深度学习针对宫颈病变建立多类特征数据预测模型的研究”（kh2302012）
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