HPV 疫苗接种女性宫颈筛查中细胞学与 hrHPV 检测的前瞻性观察研究
本研究为前瞻性观察研究，纳入 2011—2015 年苏格兰三地常规宫颈筛查中 1991—1995 年出生、符合 HPV 免疫接种条件的女性，共 10 000 份剩余液基细胞学样本联合检测。结果显示 hrHPV 检测对 CIN2+ 的阴性预测值高但阳性预测值低，细胞学重度异常的阳性预测值较高。
要点
- hrHPV 检测对 CIN2+ 阴性预测值高，适合排除低风险人群。
- hrHPV 阳性预测值仅 14.3%，需结合细胞学分流。
- 重度细胞学异常对 CIN2+ 阳性预测值达 71.7%。
核心结论
- 在 20 岁起参加历史性苏格兰筛查项目的早期 HPV 疫苗接种队列中，hrHPV 检测对 CIN2+ 保持高阴性预测值但阳性预测值低，反映疫苗接种人群疾病低患病率。
- 结果支持细胞学分流与 hrHPV 检测联合使用，并需进一步评估高疫苗接种人群的筛查策略。
研究设计与样本
- 前瞻性观察研究，设置于 2011—2015 年苏格兰三个卫生委员会的常规宫颈筛查服务。
- 纳入 1991—1995 年出生、符合 HPV 免疫接种资格的常规筛查女性，包括补种队列。
- 共检测 10 000 份剩余液基细胞学样本，使用 Hybrid Capture 2 进行 hrHPV 检测。
主要发现
- 在临界/轻度细胞学异常的样本中 hrHPV 阳性率为 86%，细胞学阴性样本中阳性率为 27%。
- 1352 名接受阴道镜检查的女性中识别出 184 例 CIN2+。
- 在选择性转诊框架内，hrHPV 检测对 CIN2+ 的阳性预测值为 14.3%（95%CI：12.5–16.4），阴性预测值为 98.9%（95%CI：94.0–99.9）。
- 重度细胞学异常对 CIN2+ 的阳性预测值为 71.7%（95%CI：59.2–81.5），阴性预测值为 89.2%（95%CI：87.4–90.8）。
- 在 1007 名重复检测的女性中，hrHPV 持续阳性率随检测间隔延长而下降。
关键数值与推荐
- hrHPV 阳性预测值 14.3%（95%CI：12.5–16.4），阴性预测值 98.9%（95%CI：94.0–99.9），对象为转诊阴道镜框架内 CIN2+。
- 重度细胞学异常阳性预测值 71.7%（95%CI：59.2–81.5），阴性预测值 89.2%（95%CI：87.4–90.8），对象为转诊阴道镜框架内 CIN2+。
- 临界/轻度细胞学异常样本 hrHPV 阳性率 86%，细胞学阴性样本 hrHPV 阳性率 27%。
临床怎么用
- hrHPV 检测可用于排除高风险病变，阴性结果提示 CIN2+ 风险极低。
- hrHPV 阳性需结合细胞学进行分流，避免单独使用 hrHPV 作为转诊依据。
- 在 HPV 疫苗接种人群中应关注阳性预测值下降对筛查效率的影响。
局限性
- 阳性预测值和阴性预测值是在选择性阴道镜转诊框架内估计的，不应解释为人群水平的筛查准确性指标。
- 仅在一个参与地区对细胞学阴性但 hrHPV 阳性的部分女性邀请阴道镜检查，存在选择性转诊偏倚。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
ABSTRACT Objective To compare the predictive performance of cytology and high-risk HPV (hrHPV) testing in young HPV-vaccinated women participating in the cervical screening programme in Scotland. Design Prospective observational study. Setting Routine cervical screening services in three Scottish Health Boards between 2011 and 2015. Population Women born between 1991 and 1995 attending routine cervical screening who were eligible for HPV immunisation, including catch-up vaccination cohorts. Methods Residual liquid-based cytology samples were tested for hrHPV using Hybrid Capture 2. Women with high-grade cytology, hrHPV-positive and BNA/mild dyskaryosis, and a subset of hrHPV-positive women with negative cytology from one participating region were invited for colposcopy. Colposcopy and histology outcomes were obtained from the National Colposcopy Clinical Information Audit System (NCCIAS). Positive and negative predictive values (PPV, NPV) for CIN2+ were estimated within the study referral framework, and hrHPV persistence across repeat testing was examined. Main Outcome Measures PPV and NPV for CIN2+ within the colposcopy referral pathway and patterns of hrHPV persistence in a selected group who attended for colposcopy. Results From 10 000 co-tested residual samples, hrHPV positivity was 86% in borderline/mild cytology and 27% in cytology-negative samples. Among 1352 women who attended for colposcopy, 184 CIN2+ cases were identified. Within the selective referral framework, hrHPV testing demonstrated a PPV for CIN2+ of 14.3% (95% CI: 12.5–16.4) and an NPV of 98.9% (95% CI: 94.0–99.9), while high-grade cytology demonstrated a PPV of 71.7% (95% CI: 59.2–81.5) and an NPV of 89.2% (95% CI: 87.4–90.8). Among 1007 women with repeat testing, hrHPV persistence declined with increasing inter-test intervals, with greater clearance observed over longer follow-up periods. Conclusions In this early HPV-vaccinated cohort screened within the historical Scottish programme from age 20 years, hrHPV testing retained a high negative predictive value but a low positive predictive value for CIN2+, reflecting the low prevalence of disease in vaccinated populations. These estimates reflect outcomes within a selective colposcopy referral framework and should not be interpreted as population-level screening accuracy measures. The findings support the role of cytology triage alongside hrHPV testing while highlighting the need for further evaluation of screening strategies in highly v
引用
- BJOG：Cytology and hrHPV Testing in HPV‐Vaccinated Women Entering Cervical Screening: A Prospective Observational Study
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。