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宫颈癌高发年龄为50~55岁。近年来,由于子宫颈细胞学筛查的普遍应用,宫颈癌和癌前病变得以早期发现和治疗[1]。宫颈癌的发生发展有明确的癌前病变期。随着宫颈癌筛查手段从细胞学检查过渡到联合人乳头瘤病毒(HPV)检测,筛查的敏感性和准确性得到提高[2],越来越多的高级别宫颈癌前病变得到诊断。宫颈锥形切除术被认为是治疗宫颈上皮内瘤变(CIN)的合适方法[3]。大多数CIN Ⅰ病变自发消退,但也可能进展为CIN Ⅱ~Ⅲ。一旦病变进展到CIN Ⅲ,浸润性癌的进展速度就会急剧增加,最高可达12%,如果观察期足够长,进展率接近100%[4]。
既往研究[5-7]发现,高级别CIN病人在宫颈锥切术后病变持续和复发的风险为4%~18%,且复发多发生在术后2年内。因此,准确预测锥切术后残余病变对于CIN病人的保守治疗和咨询至关重要。但由于没有准确预测锥切术后残留疾病的数据,医生很难向高级别CIN病人提供下一步合适的治疗方案。
本研究通过回顾性分析宫颈锥切术后再行全子宫切除的高级别CIN病人临床病例资料,了解病人锥切术后病灶残留率,并探讨可能与病灶残留发生相关的高危因素,为临床医生的治疗决策提供参考。
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患者年龄26~75岁,39例(33.9%)已绝经,产次2次及以上者48例(16.09%)。159例(8.1%)诊断为CIN Ⅲ,41例(13.9 %)诊断为CIN Ⅱ。在锥切方式上,有61例(30.50%)采用LEEP锥切,139例(69.50%)采用CKC;术前HPV-16或HPV-18检测发现阳性103例,阳性率为51.50%,200例中,98例(49.0%)子宫切除标本中有残留病变,根据2次手术后病理结果分为残留组98例和无残留组102例。
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CIN Ⅲ残留率为55.35%(88/159),CIN Ⅱ残留率为24.29%(10/41),差异有统计学意义(P < 0.01);术前HPV-16或HPV-18阳性残留率81.55%(84/103), 高于术前HPV-16或HPV-18阴性残留率14.43%(14/97), 差异有统计学意义(P < 0.01);切缘阳性病人病变残留率68.75%(55/80),均高于切缘阴性病人的35.83%(43/120),差异有统计学意义(P < 0.01);年龄、产次、绝经状态与残留无相关性,差异无统计学意义(P>0.05)(见表 1)。
分组 n 年龄/岁 绝经状态 生产次数 病变级别 HPV-16或HPV-18 锥切方式 手术切缘状态 ≥47 < 47 未绝经 已绝经 ≥2次 < 2次 CIN Ⅱ CIN Ⅲ 阴性 阳性 CKC LEEP 阴性 阳性 有残留 98 51 47 50 48 45 53 10 88 14 84 68 30 43 55 无残留 102 50 52 52 50 60 42 31 71 83 19 71 31 77 25 χ2 — 0.18 0.00 3.34 12.50 90.06 0.00 20.81 P — >0.05 >0.05 >0.05 < 0.01 < 0.01 >0.05 < 0.01 表 1 病人临床资料分析
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因变量为有无病变残留,自变量分别为CIN分级、切缘情况、HPV-16或HPV-18检测结果见表 2。进行向前逐步筛选logistic回归,发现CIN分级、切缘阳性和HPV-16或HPV-18检测结果均为病变残留的高危因素(见表 3)。
因素 变量名 赋值说明 CIN分级 X1 CIN Ⅲ=1;CIN Ⅱ=0 切缘 X2 阳性=1;阴性=0 16/18型HPV检测结果 X3 阳性=1;阴性=0 有无病变残留 Y 有=1;无=0 表 2 多因素分析变量赋值表
因素 B SE Waldχ2 P OR(95%CI) CIN分级 0.349 1.359 4.26 < 0.01 2.406(1.39~7.58) 切缘 1.633 0.246 6.79 < 0.01 0.285(0.16~11.43) 16/18型HPV检测结果 1.200 0.415 8.62 < 0.01 0.295(0.10~18.12) 表 3 病变残留发生多因素logistic回归分析
高级别宫颈上皮内瘤变宫颈锥切术后病灶残留的相关因素分析
Analysis of the related factors of residual lesions after cervical conization for high-grade cervical intraepithelial neoplasia
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摘要:
目的了解高级别宫颈上皮内瘤变(CIN)宫颈锥切术后病灶残留状况及相关影响因素,探讨宫颈锥切术后需要补充手术的必要性。 方法通过回顾性分析因高级别宫颈上皮内瘤变(CIN Ⅱ~Ⅲ)行宫颈锥切术,术后1个月即入院再次行全子宫切除手术的200例病人,通过单因素及logistic回归模型分析探讨年龄、孕产史、HR-HPV基因型、CIN分级、锥切方式、切缘状态与病灶残留之间的相关性。 结果200例病人中,98例(49.0%)子宫切除标本中有残留病变,年龄、产次、锥切方式与术后病灶残留之间无相关性;CIN分级、术前HPV-16或HPV-18阳性、切缘状态与病灶残留呈正相关,logistic回归分析发现CIN分级、切缘阳性和16/18型HPV检测结果均为病变残留的高危因素。 结论CIN分级、切缘阳性和术前HPV-16或HPV-18基因型阳性是高级别CIN行锥切术后病灶残留的可靠预测因子。 Abstract:ObjectiveTo investigate the residual status and related factors of lesions after conization of high-grade cervical intraepithelial neoplasia(CIN), and explore the necessity of supplementary surgery after conization. MethodsThe clinical data of 200 high-grade CIN(CIN Ⅱ-Ⅲ) patients treated with conization and total hysterectomy one month after surgery were retrospectively analyzed. The correlation between the age, pregnancy history, HR-HPV genotype, CIN grade, conic resection method, resection margin status and residual lesions were analyzed using univariate and logistic regression model. ResultsOf the 200 patients, the residual lesions in the hysterectomy specimens in 98 cases(49.0%) were found, and there was not correlation between the age, birth rate, coning method and postoperative residual lesions. The CIN grade, positive preoperative HPV-16 or HPV-18 and margin status were positively correlated with the residual lesions. The results of logistic regression analysis showed that the CIN grade, positive margin and HPV-16 or HPV-18 test results were the high risk factors of residual lesions. ConclusionsThe CIN grade, positive margin and preoperative HPV-16 or HPV-18 genotype are the reliable predictors of residual lesions after conization for high-grade CIN. -
表 1 病人临床资料分析
分组 n 年龄/岁 绝经状态 生产次数 病变级别 HPV-16或HPV-18 锥切方式 手术切缘状态 ≥47 < 47 未绝经 已绝经 ≥2次 < 2次 CIN Ⅱ CIN Ⅲ 阴性 阳性 CKC LEEP 阴性 阳性 有残留 98 51 47 50 48 45 53 10 88 14 84 68 30 43 55 无残留 102 50 52 52 50 60 42 31 71 83 19 71 31 77 25 χ2 — 0.18 0.00 3.34 12.50 90.06 0.00 20.81 P — >0.05 >0.05 >0.05 < 0.01 < 0.01 >0.05 < 0.01 表 2 多因素分析变量赋值表
因素 变量名 赋值说明 CIN分级 X1 CIN Ⅲ=1;CIN Ⅱ=0 切缘 X2 阳性=1;阴性=0 16/18型HPV检测结果 X3 阳性=1;阴性=0 有无病变残留 Y 有=1;无=0 表 3 病变残留发生多因素logistic回归分析
因素 B SE Waldχ2 P OR(95%CI) CIN分级 0.349 1.359 4.26 < 0.01 2.406(1.39~7.58) 切缘 1.633 0.246 6.79 < 0.01 0.285(0.16~11.43) 16/18型HPV检测结果 1.200 0.415 8.62 < 0.01 0.295(0.10~18.12) -
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