阴道镜直视下宫颈活检诊断CINII中漏诊CINII以上病变的研究及意义

目的:评价阴道镜直视下活检诊断CINII的准确性,分析影响漏诊CINII以上病变(简称CINII~+)的相关因素,并探讨P16~(INK4a)蛋白表达在预测漏诊CINII~+中的价值。方法:回顾分析2013年12月至2015年7月在南京医科大学第一附属医院宫颈病中心阴道镜直视下宫颈活检诊断为CINII,且在短期内行LEEP的148例患者。研究患者手术前后病理诊断,同时对患者年龄、初次TCT结果、高危型HPV负荷量、阴道镜下病变累及宫颈象限数、转化区类型、阴道镜图像表现以及CINII组织中P16~(INK4a)蛋白表达等与漏诊CINII~+的关系进行单因素及多因素分析。结果:(1)阴道镜直视下活检诊断的148例CINII中,71例(49.97%)漏诊CINII~+,其中1例宫颈鳞癌IA1期,1例宫颈鳞癌IB1期。单因素分析显示,患者年龄、初次TCT结果、高危型HPV负荷量、阴道镜下病变累及象限数、转化区类型、阴道镜图像特征与CINII~+病变漏诊无明显相关性(P0.05),CINII组织中P16~(INK4a)蛋白表达与CINII~+病变漏诊明显相关(P0.05)。多因素分析显示,P16~(INK4a)蛋白阳性表达是影响阴道镜直视下活检诊断CINII漏诊CINII~+的危险因素(OR=9.846,95%CI为2.165~44.787;P=0.003)。(2)21例(14.19%)P16~(INK4a)蛋白呈阴性表达,127例(85.81%)呈阳性表达。P16~(INK4a)蛋白表达阴性组中漏诊CINII~+3例(14.29%),P16~(INK4a)蛋白表达阳性组中漏诊CINII~+68例(53.54%),两组比较差异有统计学意义(P0.05)。P16~(INK4a)阳性表达预测漏诊CINII~+的敏感性95.77%,特异性为23.38%,阴性预测值为85.71%,阳性预测值为53.54%。结论:阴道镜直视下活检诊断的CINII中存在CINII~+的漏诊,而CINII并P16~(INK4a)蛋白阳性表达是影响CINII~+漏诊的危险因素,对P16~(INK4a)蛋白表达阳性的CINII患者的临床干预存在其合理性。针对CINII的个体化管理,需综合考虑患者的年龄、P16~(INK4a)蛋白表达、对生育功能保护的需求及随访的依从性。

Analysis of missed CINII+ in CINII diagnosed by colposcopy-guided biopsy

Objective:To evaluate the accuracy of colposcopy-guided biopsy in diagno-sis of CINII and the factors of missed CINII+ and to analyze the predictive values of P16 INK4a protein for the missed CINII+. Methods:A retrospective study was performed on 148 cases with diagnosis of CINII in the colposcopy guided biopsy and treated by LEEP later at the Department of Obstetrics and Gynecology, the First Affiliated Hospital of Nanjing Medical University, be-tween Dec. 2013 and July 2015. In order to analyze the relationship between missing diagnosis of CINII+ with clinical biologic factors,including age of the patient,cervical cytology before col-poscopy,loads of HR-HPV,the quadrants of the cervical surface at the colposcopy evaluation, different types of cervical transformation zone,the feature of colposcopic impression and P16INK4a protein testing result in biopsy,by comparing the histopathologic diagnosis between colposcopy-guided biopsy and cone specimen. Patients were separated according to LEEP pathology (≤CI-NII vs >CINII) .χ2 tests was used to compare the different frequencies of factors in two groups, then 7 factors with the missed CINII+were processed into binary logistic regression analysis. Re-sult:(1) Among the 148 cases with CINII diagnosed by colposcopy-directed biopsy,71 cases ( 49 . 97%) were missed diagnosis of CINII+. One patient was diagnosed cervical squamous car-cinoma(IA1),another one was diagnosed cervical squamous carcinoma(IB1) in cone speci-men. Univariate analysis showed that age of the patient, cervical cytology before colposcopy, loads of HR-HPV,the quadrants of the cervical surface at the colposcopy evaluation,different types of cervical transformation zone and the feature of colposcopic impression were not risk fac-tors of missed diagnosis of CINII+(all P>0. 05) except for the expression of P16INK4a protein in biopsy (P<0. 05). Multivariable analysis found that P16INK4a protein positive was associated with missed diagnosis of CINII+(OR=9. 846,95%CI:2. 165~44. 787;P=0. 003). (2)All the colposcopically direated biopsy were accepted immunohistochemical detection the expression of P16INK4a protein. The result showed that 21 cases (15. 32%) were negative and 127 cases (84. 68%) were positive. Among the 21 cases with P16INK4a protein negative,3 case(14. 29%) were missed diagnosis of CINII+,while 68 case(53. 54%) with P16INK4a protein positive were missed. In which there were significant difference (P<0. 05). The sensitivity was 95. 77%,the specificity was 23. 38%,the positive predictive value was 83. 71% and the negative predictive value was 53. 54% for missed CINII+ of P16INK4a protein staining. Conclusions:There were missed diagnosis of CINII+in CINII diagnosed by colposcopically directed biopsy. Immunostain-ing of P16 INK4a protein as the risk factors of missed diagnosis of CINII+,It is reasonable to take immediate treatment for patients who diagnosed CINII in biopsy with P16INK4a protein positive. The decision of treatment or observation for CINII will require individualization by considering patients' age,P16INK4a protein expression in biopsy,protection of fertility and follow-up compli-ance.