HPV 阳性女性 p16/Ki-67 双染分流后 5 年的宫颈癌前病变风险。
Five-Year Risk of Cervical Precancer Following p16/Ki-67 Dual-Stain Triage of HPV-Positive Women.
机构信息
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
Albert Einstein College of Medicine, Bronx, New York.
出版信息
JAMA Oncol. 2019 Feb 1;5(2):181-186. doi: 10.1001/jamaoncol.2018.4270.
IMPORTANCE
As cervical cancer screening transitions to primary human papillomavirus (HPV) testing, effective triage and management of HPV-positive women is critical to avoid unnecessary colposcopy referral and associated harms while maintaining high sensitivity for cervical precancer. Triage with p16/Ki-67 dual-stain (DS) testing has shown high sensitivity and specificity for detection of cervical precancers; however, longitudinal studies are needed to determine the long-term risk of precancer following a negative DS result.
OBJECTIVE
To evaluate the longitudinal performance of p16/Ki-67 DS triage for detection of cervical precancer in HPV-positive women over 5 years of follow-up in the context of clinical management thresholds.
DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of HPV-positive women 30 years or older undergoing routine cervical cancer screening in 2012 with HPV and Papanicolaou (hereinafter "cytology") co-testing within the Kaiser Permanente Northern California health care system. Follow-up of medical records was conducted through 2017.
EXPOSURES
All p16/Ki-67 DS testing was performed on residual SurePath material, and slides were evaluated for p16/Ki-67 positivity.
MAIN OUTCOMES AND MEASURES
Histological end points were ascertained from the clinical database through 2017. We estimated 5-year cumulative risks of cervical intraepithelial neoplasia grades of 2 or worse (≥CIN2) or grades 3 or worse (≥CIN3) by baseline DS and cytology at yearly intervals using Logistic Weibull models. Risks were compared with clinical management thresholds for colposcopy referral and a 1-year return interval.
RESULTS
Among the 1549 HPV-positive women in this study, the mean age at enrollment was 42.2 years, and the median follow-up time was 3.7 years (range, 0.2-5.4 years). Positive DS results were associated with significantly higher cumulative 5-year risks of ≥CIN2 compared with abnormal cytology (31.0%; 95% CI, 27.2%-35.3% vs 25.0%; 95% CI, 21.7%-28.7%; P = .03). Women with DS-negative findings had significantly lower 5-year risks of ≥CIN2 compared with women with normal cytology (8.5%; 95% CI, 6.5%-11.1% vs 12.3%; 95% CI, 9.8%-15.4%; P = .04). In DS-negative women, the risks of both ≥CIN2 and ≥CIN3 remained below the colposcopy referral threshold for all 5 years, crossing the 1-year return threshold at 3 years.
CONCLUSIONS AND RELEVANCE
Triage with p16/Ki-67 DS provides better long-term risk stratification than cytology over 5 years. The low risk of cervical precancer in p16/Ki-67 DS-negative women permits safe extension of follow-up intervals for 3 years.
重要性
随着宫颈癌筛查向原发性人乳头瘤病毒（HPV）检测转变，对 HPV 阳性女性进行有效的分流和管理对于避免不必要的阴道镜转诊和相关危害至关重要，同时保持对宫颈癌前病变的高敏感性。p16/Ki-67 双重染色（DS）检测的分流具有检测宫颈癌前病变的高敏感性和特异性；然而，需要进行纵向研究来确定阴性 DS 结果后癌前病变的长期风险。
目的
评估 p16/Ki-67 DS 对 HPV 阳性女性在临床管理阈值下进行 5 年以上随访时检测宫颈癌前病变的纵向表现。
设计、地点和参与者：对 2012 年在 Kaiser Permanente 北加州医疗保健系统接受常规宫颈癌筛查的 30 岁及以上 HPV 阳性女性进行前瞻性队列研究，该系统采用 HPV 和巴氏涂片（以下简称“细胞学”）联合检测。通过 2017 年对医疗记录进行随访。
暴露因素
所有 p16/Ki-67 DS 检测均在剩余的 SurePath 材料上进行，并用 p16/Ki-67 阳性对玻片进行评估。
主要结果和测量指标
通过临床数据库确定了 2017 年的组织学终点。我们使用 Logistic-Weibull 模型，在每年间隔的基础上，根据基线 DS 和细胞学评估，计算了 5 年内发生≥CIN2（≥CIN3）的累积风险。将风险与阴道镜转诊和 1 年随访间隔的临床管理阈值进行比较。
结果
在这项研究中的 1549 名 HPV 阳性女性中，平均年龄为 42.2 岁，中位随访时间为 3.7 年（范围，0.2-5.4 年）。阳性 DS 结果与异常细胞学相比，与显著更高的 5 年≥CIN2 累积风险相关（31.0%；95%CI，27.2%-35.3% vs 25.0%；95%CI，21.7%-28.7%；P=0.03）。与细胞学正常的女性相比，DS 阴性的女性 5 年内发生≥CIN2 的风险显著降低（8.5%；95%CI，6.5%-11.1% vs 12.3%；95%CI，9.8%-15.4%；P=0.04）。在 DS 阴性的女性中，≥CIN2 和≥CIN3 的风险在 5 年内均低于阴道镜转诊阈值，在 3 年内达到 1 年随访阈值。
结论和相关性
p16/Ki-67 DS 比细胞学在 5 年内提供更好的长期风险分层。p16/Ki-67 DS 阴性女性的宫颈癌前病变风险较低，允许安全延长 3 年的随访间隔。
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