Objective: To evaluate the screening efficiency of gene DNA methylation testing, p16 staining, human papillomavirus (HPV) genotyping, and liquid-based cytology (LBC), and their combined strategies in self-collected high-risk HPV (HR-HPV) positive individuals. Methods: This study analyzed a subset of data from a free self-sampling cervical cancer screening program conducted in Baise, Guangxi Zhuang Autonomous Region (from May 2023 to April 2024). HR-HPV positive self-collected cases with complete data and quality control were included. Using the triage strategy recommended by the 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) risk-based management guideline and the Chinese cervical cancer screening guideline [ie, HPV16/18 positivity and (or) LBC of atypical squamous cell of undetermined significance (ASCUS) or worse] as reference standard, the sensitivity, specificity, colposcopy referral rate, and the number needed to colposcopy (NNC) of various secondary triage approaches were assessed. Results: (1) A total of 777 HR-HPV positive women with complete data were analyzed. (2) Methylation positivity was significantly higher in high-risk group HPV16/18 (20.5%, 25/122) and high-intermediate-risk group HPV31/33/35/45/52/58 (17.2%, 66/381) than that in the low-risk group HPV39/51/56/59/66/68 (9.6%, 26/371; χ²=8.85 and χ²=7.59, P=0.003 and P=0.006). (3) Methylation positivity of cervical intraepithelial neoplasia (CIN)Ⅲ and cervical cancer cases (67.5%, 27/40) was significantly higher than CINⅠ cases (12.9%, 31/240), and CINⅡ cases (16.4%, 12/73), with statistically significant differences (P<0.05). The p16 positivity increased with lesion severity in all pairwise comparisons (P≤0.005 after correction). (4) When the guideline-recommended triage strategy [HPV16/18 positivity and (or) LBC≥ASCUS] was applied to this study population, using colposcopy-directed biopsy pathology as the reference standard, the sensitivity and specificity for detecting CINⅡ+ and CINⅢ+ were 69.03%, 65.21%, and 95.00%, 63.23%, respectively; the colposcopy referral rate was 39.77% (309/777), and NNC was 3.96 for CINⅡ+ and 8.13 for CINⅢ+. (5) Methylation performance: for CINⅡ+, sensitivity was 34.51% and specificity was 88.25%; for CINⅢ+, sensitivity was 67.50% and specificity was 87.79%. (6) p16 performance: the sensitivity for detecting CINⅡ+ and CINⅢ+ were 72.57% and 92.50%, respectively, which did not differ significantly from the guideline-recommended strategy (all P>0.05), whereas the specificity for CINⅡ+ and CINⅢ+ were 68.67% and 65.60%, respectively, similar to the guideline-recommended strategy (all P>0.05). The colposcopy referral rate was lower with p16 testing alone compared with the guideline-recommended strategy [37.32% (290/777) vs 39.77%; P>0.05]. (7) Combined strategy 3a achieved a sensitivity of 63.72% for detecting CINⅡ+, which was similar to the guideline-recommended strategy (P=0.109), and a sensitivity of 95.00% for detecting CINⅢ+, identical to that of the guideline-recommended strategy. The specificity of strategy 3a for CINⅡ+and CINⅢ+ were 70.18% and 68.52%, respectively, both significantly higher than those of the guideline-recommended strategy (χ²=9.75 and 12.56, all P<0.01). The colposcopy referral rate for strategy 3a was significantly lower than that of the guideline-recommended strategy [34.75% (270/777) vs 39.77%; P<0.001], with corresponding NNC of 3.75 for CINⅡ+ and 7.11 for CINⅢ+. Strategy 5a showed a sensitivity of 64.60% for detecting CINⅡ+, which was not significantly different from that of the guideline-recommended strategy (64.60% vs 69.03%; χ²=3.20, P=0.074), and a sensitivity of 95.00% for CINⅢ+, identical to that of the guideline-recommended strategy. The specificity of strategy 5a for CINⅡ+ and CINⅢ+ were 75.30% and 73.00%, respectively, both significantly higher than the guideline-recommended strategy (both P<0.001). NNC for strategy 5a was 3.25 for CINⅡ+ and 6.24 for CINⅢ+, both lower than those of the guideline-recommended strategy (3.96 and 8.13, respectively). The colposcopy referral rate for strategy 5a was also significantly lower than that of the guideline-recommended strategy [30.50% (237/777) vs 39.77%; χ²=70.01, P<0.001]. Conclusions: Among self-collected, high-risk HPV-positive individuals, combined triage strategies that integrate HPV genotyping with cytology, p16 staining and methylation testing, specifically strategy 3a and 5a, offer comparable sensitivity with superior specificity and lower referral rates versus co-testing for detecting CINⅡ+ and CINⅢ+. 目的： 评价基因甲基化检测、p16染色、人乳头状瘤病毒（HPV）分型检测、子宫颈液基细胞学检查及其联合方案，对阴道自取样高危型HPV（HR-HPV）阳性人群的分流效率。 方法： 前瞻性选取2023年5月至2024年4月北京大学深圳医院在广西壮族自治区百色地区开展的自取样子宫颈癌免费筛查项目的部分数据，纳入结果齐全并通过质控的自取样HR-HPV阳性妇女共777例，以2019年美国阴道镜和子宫颈病理学会（ASCCP）基于风险的子宫颈癌筛查结果异常和癌前病变的管理指南及中国子宫颈筛查指南推荐的HPV16/18阳性和（或）细胞学检查结果≥未明确诊断意义的不典型鳞状上皮细胞（ASCUS）分流方案（简称：指南推荐方案）应用在本研究人群中的敏感度、特异度、阴道镜转诊率及需行阴道镜数量（NNC）为参照，比较基因甲基化检测、p16染色、HPV分型检测、子宫颈液基细胞学检查及其联合方案在自取样HR-HPV阳性人群中的分流效能。 结果： 高风险的HPV16/18阳性受试者的基因甲基化阳性率高于低风险的HPV39/51/56/59/66/68阳性者［分别为20.5%（25/122）、9.6%（26/271）；χ²=8.85，P=0.003］，高~中风险的HPV31/33/35/45/52/58阳性受试者的基因甲基化阳性率高于低风险的HPV39/51/56/59/66/68阳性者［分别为17.2%（66/381）、9.6%；χ²=7.59，P=0.006］；子宫颈上皮内瘤变（CIN）Ⅲ和子宫颈癌受试者的甲基化阳性率（67.5%，27/40）显著高于CINⅠ（12.9%，31/240）和CINⅡ（16.4%，12/73），差异有统计学意义（P<0.05）。p16阳性率随子宫颈病变级别升高而显著增加（校正P≤0.005）。以子宫颈活检病理检查结果作为标准，应用指南推荐方案作为分流方案时，诊断CINⅡ+、CINⅢ+的敏感度及特异度分别为69.03%、65.21%和95.00%、63.23%，阴道镜转诊率为39.77%（309/777），NNC分别为3.96、8.13例；基因甲基化检测分流方案诊断CINⅡ+、CINⅢ+的敏感度和特异度分别为34.51%、88.25%和67.50%、87.79%；p16分流方案诊断CINⅡ+、CINⅢ+的敏感度分别为72.57%、92.50%，与指南推荐方案相近（P均>0.05），特异度分别为68.67%、65.60%，与指南推荐方案相当（P均>0.05），且阴道镜转诊率低［分别为37.32%（290/777）、39.77%；P>0.05］。在联合分流方案中，3a方案诊断CINⅡ+的敏感度为63.72%，与指南推荐方案（69.03%）相近（P=0.109），诊断CINⅢ+的敏感度与指南推荐方案一致，均为95.00%，特异度分别为70.18%和68.52%，均高于指南推荐方案（χ2值分别为9.75、12.56，P均<0.01），阴道镜转诊率低于指南推荐方案［分别为34.75%（270/777）、39.77%；P<0.001］，NNC分别为3.75和7.11例；5a方案诊断CINⅡ+的敏感度为64.60%，低于指南推荐方案（χ2=3.20，P=0.074），诊断CINⅢ+的敏感度为95.00%，与指南推荐方案一致，特异度分别为75.30%和73.00%，均高于指南推荐方案（P均<0.001），NNC分别为3.25和6.24例，低于指南推荐方案（分别为3.96和8.13例），阴道镜转诊率低于指南推荐方案［分别为30.50%（237/777）、39.77%；χ2=70.01，P<0.001］。 结论： 在自取样HR-HPV阳性人群中，HPV分型检测结合细胞学检查、p16染色、基因甲基化检测的联合分流方案——3a方案及5a方案，在诊断CINⅡ+、CINⅢ+时可获得与指南推荐方案相近的敏感度、显著更高的特异度及更低的阴道镜转诊率。.
使用 AI 将内容摘要翻译为中文，便于快速阅读
使用 AI 分析这篇文章的核心发现、关键要点和深度见解
由 DeepSeek AI 提供分析 · 首次使用需配置 API Key
PubMed · 2026-04-25