Abstract：
OBJECTIVE: Investigate the association between p16/Ki-67 dual stain cytology test (DST) results, obtained prior to- and 6 months after LLETZ surgery for treatment of CIN, and the follow-up regimen three years after treatment.
METHODS: Secondary analysis of a prospective cohort study. Cervical cytology samples were obtained just prior to- and 6 months after LLETZ and underwent conventional liquid-based cytology (LBC) and p16/Ki-67 dual staining, as well as high-risk HPV genotyping. Clinical management after the LLETZ was according to Belgian national guidelines, with clinicians being blinded to DST results at both time points. Case records were reviewed in 01/2023 to document the follow-up regimen on average three years afterwards: women had either been advised to return to routine screening (i.e., three-annual LBC testing according to the Belgian guideline at that time), or were still subject to more frequent posttreatment surveillance (i.e., more frequent visits because of persistent hrHPV infection or absence of cytological regression).
RESULTS: The follow-up regimen was recorded in 79/110 women originally recruited (72%). The need for continued intense posttreatment surveillance was associated with hrHPV infection 6 months after treatment (79.3% vs. 18.0%, p < 0.001), a positive DST result at baseline and follow-up (41.4% vs. 84.0%, p < 0.001-55.2% vs. 16.0%, p < 0.001), and persistent cytological anomalies at 6 months (at an ASCUS or worse threshold, 37.9% vs. 16.0%, p = 0.028). In multivariable logistic regression analysis, a positive DST at baseline (aOR 20.1, 95%CI 2.03-199.1) was independently associated with the need for intense post-treatment surveillance multiple years after treatment.
CONCLUSIONS: This exploratory study suggests a possible role of dual-stain cytology in predicting treatment outcome multiple years after LLETZ surgery.
METHODS: Secondary analysis of a prospective cohort study. Cervical cytology samples were obtained just prior to- and 6 months after LLETZ and underwent conventional liquid-based cytology (LBC) and p16/Ki-67 dual staining, as well as high-risk HPV genotyping. Clinical management after the LLETZ was according to Belgian national guidelines, with clinicians being blinded to DST results at both time points. Case records were reviewed in 01/2023 to document the follow-up regimen on average three years afterwards: women had either been advised to return to routine screening (i.e., three-annual LBC testing according to the Belgian guideline at that time), or were still subject to more frequent posttreatment surveillance (i.e., more frequent visits because of persistent hrHPV infection or absence of cytological regression).
RESULTS: The follow-up regimen was recorded in 79/110 women originally recruited (72%). The need for continued intense posttreatment surveillance was associated with hrHPV infection 6 months after treatment (79.3% vs. 18.0%, p < 0.001), a positive DST result at baseline and follow-up (41.4% vs. 84.0%, p < 0.001-55.2% vs. 16.0%, p < 0.001), and persistent cytological anomalies at 6 months (at an ASCUS or worse threshold, 37.9% vs. 16.0%, p = 0.028). In multivariable logistic regression analysis, a positive DST at baseline (aOR 20.1, 95%CI 2.03-199.1) was independently associated with the need for intense post-treatment surveillance multiple years after treatment.
CONCLUSIONS: This exploratory study suggests a possible role of dual-stain cytology in predicting treatment outcome multiple years after LLETZ surgery.
摘要：
目的：研究p16/Ki-67双重染色细胞学检查（DST）结果之间的关系，在LLETZ手术治疗CIN之前和之后6个月获得，以及治疗后3年的随访方案。
方法：前瞻性队列研究的次要分析。在LLETZ之前和之后6个月获得宫颈细胞学样本，并进行常规液基细胞学（LBC）和p16/Ki-67双重染色，以及高危HPV基因分型。LLETZ后的临床管理是根据比利时国家指南，临床医生在两个时间点都不知道DST结果。在2023年1月1日审查了病例记录，以记录平均三年后的随访方案：建议女性恢复常规筛查（即，根据当时的比利时指南进行三年一次的LBC测试)，或仍受到更频繁的治疗后监测(即，由于持续的hrHPV感染或不存在细胞学消退，因此就诊频率更高）。
结果：在最初招募的79/110名女性中记录了随访方案（72％）。需要持续的强化治疗后监测与治疗后6个月的hrHPV感染相关(79.3%vs.18.0%,p<0.001)，基线和随访时DST结果呈阳性(41.4%vs.84.0%,p<0.001-55.2%vs.16.0%,p<0.001)，和6个月时持续的细胞学异常（在ASCUS或更差的阈值，37.9%与16.0%,p=0.028)。在多变量逻辑回归分析中，基线时的DST阳性(aOR20.1,95CI2.03-199.1)与治疗多年后需要强化治疗后监测独立相关.
结论：这项探索性研究表明，双染色细胞学在预测LLETZ手术后多年的治疗结果方面可能发挥着作用。
方法：前瞻性队列研究的次要分析。在LLETZ之前和之后6个月获得宫颈细胞学样本，并进行常规液基细胞学（LBC）和p16/Ki-67双重染色，以及高危HPV基因分型。LLETZ后的临床管理是根据比利时国家指南，临床医生在两个时间点都不知道DST结果。在2023年1月1日审查了病例记录，以记录平均三年后的随访方案：建议女性恢复常规筛查（即，根据当时的比利时指南进行三年一次的LBC测试)，或仍受到更频繁的治疗后监测(即，由于持续的hrHPV感染或不存在细胞学消退，因此就诊频率更高）。
结果：在最初招募的79/110名女性中记录了随访方案（72％）。需要持续的强化治疗后监测与治疗后6个月的hrHPV感染相关(79.3%vs.18.0%,p<0.001)，基线和随访时DST结果呈阳性(41.4%vs.84.0%,p<0.001-55.2%vs.16.0%,p<0.001)，和6个月时持续的细胞学异常（在ASCUS或更差的阈值，37.9%与16.0%,p=0.028)。在多变量逻辑回归分析中，基线时的DST阳性(aOR20.1,95CI2.03-199.1)与治疗多年后需要强化治疗后监测独立相关.
结论：这项探索性研究表明，双染色细胞学在预测LLETZ手术后多年的治疗结果方面可能发挥着作用。
