冷刀宫颈锥切术在宫颈上皮内瘤变中的诊断价值及P16~（INK4A）蛋白在该病诊断中的临床意义
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摘要
目的：
1.探讨冷刀宫颈锥切术在宫颈上皮内瘤变的诊断价值。
2.探讨P16INK4A蛋白在宫颈上皮内瘤病变中的表达及临床意义。
方法：
1.在吉林市中心医院收集2007年1月至2009年11月行宫颈冷刀锥切手术(CKC)治疗的住院病人的病历,进行回顾性病历对照研究。共收集符合本研究要求且资料完整者90例,根据手术方式分为单纯CKC组(A组=60例)和CKC后再行子宫切除术组(B组=30例),对病人年龄、产次、术前阴道镜活检病理、宫颈锥切病理、子宫切除后病理及子宫标本中残留病变的相关因素进行比较分析,探讨冷刀宫颈锥切术在宫颈上皮内瘤变诊断及治疗的应用价值,并探讨宫颈冷刀锥切术后子宫标本中病变残留的危险因素。
2.收集山东省济宁医学院附属医院病理科存档的2008年3月至2009年5月于妇科行阴道镜宫颈活检、Leep刀锥切及手术切除的宫颈病变石蜡标本共60例,其中慢性宫颈炎症17例、CINⅠ13例、CINⅡ-Ⅲ18例、宫颈鳞癌12例,均由本院病理科证实。应用免疫组织化学技术(Envision法)测定宫颈鳞癌、CIN、慢性宫颈炎症、鳞状上皮组织中P16INK4A表达。
结果：
1.CKC病理与阴道镜下多点活检病理比较CKC病理与阴道镜下多点活检病理比较：总符合64例,占71.11%。其中,CKC病理较阴道镜下多点活检病理重者12例(13.33%),轻者14例(15.56%)。CINI、CINⅡ、CINⅢ的诊断符合率分别为62.50%,57.11%,和82.60%,CINⅢ组CKC与阴道镜下多点活检病理符合率明显高于CINⅠ组和CINⅡ组(P<0.05)。
2.两组病人年龄及产次和临床病理学特点比较两组病人年龄及产次的比较：A组平均年龄(42.39±8.3)岁,B组平均年龄(47.77±9.10)岁,A组平均年龄小于B组(P<0.05)。A组平均产次(1.54±0.79)(0～4次),B组平均产次(1.08±0.86)(1～6次),A组平均产次比B组少(P<0.05)。两组病人锥切病理的比较：A组锥切病理CINⅠ8例(13.33%),CINⅡ15例(24.05%),CINⅢ25例(包括CIS 3例)(41.33%),慢性子宫颈炎12例(20.00%)。B组锥切病理CINI1例(3.33%),CINⅡ6例(20.00%),CINⅢ22例(包括CIS8例)(75.61%),微小浸润癌I1例(3.33%)。A组锥切病理为低度宫颈病变(CINⅠ及慢性宫颈炎)共20例(30.00%),病理为高度宫颈病变(CINⅡ-Ⅲ及以上)共40例(70.00%)；B组病理为低度宫颈病变共1例(3.33%),高度宫颈病变共29例(96.67%)。B组病人病变级别比A组病人高(P<0.01)。
3.CKC病理与子宫切除病理比较：30例CKC后再行子宫切除,CKC常规病理与子宫病理完全符合者29例,1例CKC病理为CINⅢ累腺,子宫切除术后病理发现有微小浸润,病变级别升高。
4. CKC后再行子宫切除术后病变残留情况及危险因素分析3例CKC后病理为CIS累腺及微小浸润癌而再行全子宫切除术,子宫内发现有残留病变,总残留率为10.00%(3／30)。其中1例为微小浸润癌,1例残留病变为CINⅢ,1例残留病变为CINⅠ。27例未发现有病变残留。锥切后病变级别高者,术后病变残留显著升高,在CINⅠ-Ⅱ、CINⅢ、CIS及MIC组病变残留发生率分别为0(0／7),7.15%(1／14),12.50%(1／8)和100%(1／1)。从残留率分析,随着病变程度加重而病变残留发生率而增高。锥切病理腺体累及比腺体未累及病变残留发生率高,分别为33.30%(3／12)和0(0／18)(?2=6.344,P<0.05)。(产次)2次与1次者,病变残留率分别为12.50%(1／8)13.63%(3／22),(?2=0.689,P>0.05)。
5.不同程度宫颈病变的P16INK4A蛋白表达水平不同,P16INK4A蛋白在慢性宫颈炎与CINⅠ、CINⅠ与CINⅡ-Ⅲ表达之间均差异极显著、浸润癌分别与CINⅠ、慢性宫颈炎组相比差异均有统计学意义。
6.从慢性宫颈炎到宫颈鳞癌,随着病变程度的增加,P16 INK4A蛋白表达逐渐增多,从中度阳性～强阳性(++～+++),阳性程度可协助判定病变程度。
结论
1.宫颈锥切术在CIN治疗中不能被阴道镜下多点活检取代,它在诊断CIN具有重要价值。
2.CKC治疗CIN后,需密切随访。病变级别高、腺体累及等是病变残留的危险因素,存在的患者更应加强随访。
4.免疫组化方法标记P16INK4A蛋白,在各级别CIN及宫颈鳞癌中其阳性表达率(+～+++)均高于慢性宫颈炎,可协助鉴别宫颈良性病变与低度上皮内瘤变。
5.免疫组化方法标记P16INK4A蛋白,从慢性宫颈炎到宫颈鳞癌,随着病变程度的增加中度阳性至强阳性(++～+++)表达逐渐增多,其阳性程度可协助判定病变程度。
Objective
1. To explore the diagnostic value of the cold-knife cervical conization for cervical intraepithelial neoplasia.
2. To explore the expression and clinical significance of P16INK4A protein in cervical intraepithelial neoplasia.
Methods:
1.90 cases of patients with cervical intraepithelial neoplasia and were operated by cold-knife cervical conization were collected in the Central Hospital of Jilin City from January 2007 to November 2009, a retrospective control study of medical records was made. All patients met the criteria of study and data integrity. All patients were divided into CKC group (group A=60) and CKC+Hysterectomy group (group B=30) according to surgical methods. To compare the difference between two groups in age, parity, preoperative biopsy, conization pathology, hysterectomy pathology and the related factors of residual lesions of uterine specimens. To explore the diagnostic and therapeutic value of the cold-knife cervical conization for cervical intraepithelial neoplasia and explore the risk factors of residual lesions in Uterine specimens after CKC.
2.60 cases of patients'cervical lesions paraffin were collected in the department of pathology of the Affiliated Hospital of Jining Medical College from March 2008 to May 2009, all the patients were made cervical biopsy, or Leep knife conization, or cervical surgery.12 cases of cervical squamous cell carcinoma,13 cases of CINI,18 cases of CINⅡ-Ⅲ,17 cases of chronic cervical inflammation. All patients were confirmed by pathology. The expression P16INK4A protein in cervical squamous cell carcinoma, CIN, chronic inflammation of cervical squamous epithelial tissue with Immuno histochemistry(Envision).
Results:1. A comparison between CKC pathology and colposcopy biopsy of multi-point A comparison between CKC pathology and colposcopy biopsy of multi-point:total of 64(71.11%) cases were accord, including 12(13.33%) severe cases and 14(15.56%) mild cases of cervical lesions in CKC pathology than that of colposcopy biopsy of multi-point. The diagnose accordance rate of CINI, CINII and CINIII were 62.50%, 57.11% and 82.6% respectively. The diagnose accordance rate of CKC pathology and colposcopy biopsy of multi-point was higher in group CINIII than that of group CINI and group CINII (P<0.05).
2. A comparison on age, parity and clinical pathological features between two groupsA comparison on age and parity between two groups:the average age of group A was (42.39±8.3) years, the average age of group B was (47.77±9.10) years, group A was older than group B(P<0.05). The average parity of group A was (1.53±0.79) (0～4), the average parity of group B was (1.07±0.86) (1～6), The average parity of group A was lesser than group B(P<0.05).
A comparison on conization pathology between two groups:Group A:8(13.33%) cases of conization pathology were CINⅠ,15 (24.05%) cases were CINⅡ,25(41.33%) cases were CINⅢ,12(20.00%) cases were chronic cervicitis. Group B:1(3.33%) case of conization pathology was CINⅠ,6 (20.00%) cases were CINⅡ,22(75.61%) cases were CINⅢ,1(3.33%) case was microinvasive carcinoma. There were 20(30.00%) cases of low-grade cervical lesions(CINⅠand chronic cervicitis) and 40 (70.00%) cases of high-grade cervical lesions(CINⅡ-Ⅲ) according to conization pathology in group A. There were 1(3.33%) case of low-grade cervical lesions and 29 (96.67%) cases of high-grade cervical lesions according to conization pathology in group B. The lesions level of the patients in group B was higher than that of group A(P<0.01).
3. A comparison on CKC pathology and hysterectomy pathology between two groups 30 cases of patients were made CKC then were made hysterectomy, CKC pathology was in fOll compliance with hysterectomy pathology in 29 cases of patients. The CKC pathology was CINⅢinvolving glands in one case of patient, doctor found microinvasion in the patient's hysterectomy pathology, her lesions level bacame higher.
4. Residual status of uterine lesions and risk factors analysis after CKC then hysterectomy 3 cases of patients'CKC pathology were CIS involving glands and microinvasive carcinoma, which all were found residual uterine lesions, the total residual rate was 10.00%(3/30).In the 3 cases of patients,1 case of patient's residual lesions were microinvasive carcinoma,1 case of patient's residual lesions were CINIII,1 case of patient's residual lesions were CINI. Doctors have not found uterine lesions in 27 cases of patients.
The patients with higher lesions levels, have higher lesions residual rate. The lesions residual rate were 0(0/7),7.15%(1/14),12.50%(1/8) and 100%(1/1) respectively (?1=8.234, P<0.05). There was higher lesions residual rate with involving glands than without involving glands, The lesions residual rate were 33.30%(3/12) and 0(0/18) respectively (?2=6.344, P<0.05).
There were no differences of lesions residual rate between patients with parity 1 and parity 2, the lesions residual rate were 12.50%(1/8) and 13.63%(3/22)(?2=0.689, P>0.05).
5. There were significent differences in P16INK4A protein expression levels between patients with different cervical lesions, there were significent differences in P16INK4A protein expression levels between chronic cervicitis and CINI, CINI and CINII-Ⅲ, invasive carcinoma and CINI, invasive carcinoma and chronic cervicitis.
6. With the increase of lesions levels, from chronic cervicitis to cervical squamous cell carcinoma, P16 A protein expression levels bacame higher and higher, from moderate positive to strong positive(++-+++). The positive levels was helpful for determininmg the lesions levels.
Conclusion:
1. CKC can not be replaced by multi-point biopsy under colposcopy in the treatment of CIN. it plays a very important role in diagnosis of CIN.
2.It need to closely follow-up after CKC treatment of CIN. A high level of lesion an gland involvement are risk factors of residual lesions. The follow-up of these patients should be strengthened.
3.The positive expression rates of P16INK4A protein, marked with immunohisto chemistry, are higter at every levels of CIN and cervical squamous cell carcinoma thasn that of chronic cervicitis. The positive expression rate is helpful for distinguishing cervical benign neoplasia and Low-grade intraepithelial neoplasia.
4. With the increase of lesions levels, from chronic cervicitis to cervical squamous cell carcinoma, P16INK4A protein expression levels, marked with immunohistochemistry, bacome higher and higher, from moderate positive to strong positive(++～+++). The positive levels are helpful for determininmg the lesions levels.
1.探讨冷刀宫颈锥切术在宫颈上皮内瘤变的诊断价值。
2.探讨P16INK4A蛋白在宫颈上皮内瘤病变中的表达及临床意义。
方法：
1.在吉林市中心医院收集2007年1月至2009年11月行宫颈冷刀锥切手术(CKC)治疗的住院病人的病历,进行回顾性病历对照研究。共收集符合本研究要求且资料完整者90例,根据手术方式分为单纯CKC组(A组=60例)和CKC后再行子宫切除术组(B组=30例),对病人年龄、产次、术前阴道镜活检病理、宫颈锥切病理、子宫切除后病理及子宫标本中残留病变的相关因素进行比较分析,探讨冷刀宫颈锥切术在宫颈上皮内瘤变诊断及治疗的应用价值,并探讨宫颈冷刀锥切术后子宫标本中病变残留的危险因素。
2.收集山东省济宁医学院附属医院病理科存档的2008年3月至2009年5月于妇科行阴道镜宫颈活检、Leep刀锥切及手术切除的宫颈病变石蜡标本共60例,其中慢性宫颈炎症17例、CINⅠ13例、CINⅡ-Ⅲ18例、宫颈鳞癌12例,均由本院病理科证实。应用免疫组织化学技术(Envision法)测定宫颈鳞癌、CIN、慢性宫颈炎症、鳞状上皮组织中P16INK4A表达。
结果：
1.CKC病理与阴道镜下多点活检病理比较CKC病理与阴道镜下多点活检病理比较：总符合64例,占71.11%。其中,CKC病理较阴道镜下多点活检病理重者12例(13.33%),轻者14例(15.56%)。CINI、CINⅡ、CINⅢ的诊断符合率分别为62.50%,57.11%,和82.60%,CINⅢ组CKC与阴道镜下多点活检病理符合率明显高于CINⅠ组和CINⅡ组(P<0.05)。
2.两组病人年龄及产次和临床病理学特点比较两组病人年龄及产次的比较：A组平均年龄(42.39±8.3)岁,B组平均年龄(47.77±9.10)岁,A组平均年龄小于B组(P<0.05)。A组平均产次(1.54±0.79)(0～4次),B组平均产次(1.08±0.86)(1～6次),A组平均产次比B组少(P<0.05)。两组病人锥切病理的比较：A组锥切病理CINⅠ8例(13.33%),CINⅡ15例(24.05%),CINⅢ25例(包括CIS 3例)(41.33%),慢性子宫颈炎12例(20.00%)。B组锥切病理CINI1例(3.33%),CINⅡ6例(20.00%),CINⅢ22例(包括CIS8例)(75.61%),微小浸润癌I1例(3.33%)。A组锥切病理为低度宫颈病变(CINⅠ及慢性宫颈炎)共20例(30.00%),病理为高度宫颈病变(CINⅡ-Ⅲ及以上)共40例(70.00%)；B组病理为低度宫颈病变共1例(3.33%),高度宫颈病变共29例(96.67%)。B组病人病变级别比A组病人高(P<0.01)。
3.CKC病理与子宫切除病理比较：30例CKC后再行子宫切除,CKC常规病理与子宫病理完全符合者29例,1例CKC病理为CINⅢ累腺,子宫切除术后病理发现有微小浸润,病变级别升高。
4. CKC后再行子宫切除术后病变残留情况及危险因素分析3例CKC后病理为CIS累腺及微小浸润癌而再行全子宫切除术,子宫内发现有残留病变,总残留率为10.00%(3／30)。其中1例为微小浸润癌,1例残留病变为CINⅢ,1例残留病变为CINⅠ。27例未发现有病变残留。锥切后病变级别高者,术后病变残留显著升高,在CINⅠ-Ⅱ、CINⅢ、CIS及MIC组病变残留发生率分别为0(0／7),7.15%(1／14),12.50%(1／8)和100%(1／1)。从残留率分析,随着病变程度加重而病变残留发生率而增高。锥切病理腺体累及比腺体未累及病变残留发生率高,分别为33.30%(3／12)和0(0／18)(?2=6.344,P<0.05)。(产次)2次与1次者,病变残留率分别为12.50%(1／8)13.63%(3／22),(?2=0.689,P>0.05)。
5.不同程度宫颈病变的P16INK4A蛋白表达水平不同,P16INK4A蛋白在慢性宫颈炎与CINⅠ、CINⅠ与CINⅡ-Ⅲ表达之间均差异极显著、浸润癌分别与CINⅠ、慢性宫颈炎组相比差异均有统计学意义。
6.从慢性宫颈炎到宫颈鳞癌,随着病变程度的增加,P16 INK4A蛋白表达逐渐增多,从中度阳性～强阳性(++～+++),阳性程度可协助判定病变程度。
结论
1.宫颈锥切术在CIN治疗中不能被阴道镜下多点活检取代,它在诊断CIN具有重要价值。
2.CKC治疗CIN后,需密切随访。病变级别高、腺体累及等是病变残留的危险因素,存在的患者更应加强随访。
4.免疫组化方法标记P16INK4A蛋白,在各级别CIN及宫颈鳞癌中其阳性表达率(+～+++)均高于慢性宫颈炎,可协助鉴别宫颈良性病变与低度上皮内瘤变。
5.免疫组化方法标记P16INK4A蛋白,从慢性宫颈炎到宫颈鳞癌,随着病变程度的增加中度阳性至强阳性(++～+++)表达逐渐增多,其阳性程度可协助判定病变程度。
Objective
1. To explore the diagnostic value of the cold-knife cervical conization for cervical intraepithelial neoplasia.
2. To explore the expression and clinical significance of P16INK4A protein in cervical intraepithelial neoplasia.
Methods:
1.90 cases of patients with cervical intraepithelial neoplasia and were operated by cold-knife cervical conization were collected in the Central Hospital of Jilin City from January 2007 to November 2009, a retrospective control study of medical records was made. All patients met the criteria of study and data integrity. All patients were divided into CKC group (group A=60) and CKC+Hysterectomy group (group B=30) according to surgical methods. To compare the difference between two groups in age, parity, preoperative biopsy, conization pathology, hysterectomy pathology and the related factors of residual lesions of uterine specimens. To explore the diagnostic and therapeutic value of the cold-knife cervical conization for cervical intraepithelial neoplasia and explore the risk factors of residual lesions in Uterine specimens after CKC.
2.60 cases of patients'cervical lesions paraffin were collected in the department of pathology of the Affiliated Hospital of Jining Medical College from March 2008 to May 2009, all the patients were made cervical biopsy, or Leep knife conization, or cervical surgery.12 cases of cervical squamous cell carcinoma,13 cases of CINI,18 cases of CINⅡ-Ⅲ,17 cases of chronic cervical inflammation. All patients were confirmed by pathology. The expression P16INK4A protein in cervical squamous cell carcinoma, CIN, chronic inflammation of cervical squamous epithelial tissue with Immuno histochemistry(Envision).
Results:1. A comparison between CKC pathology and colposcopy biopsy of multi-point A comparison between CKC pathology and colposcopy biopsy of multi-point:total of 64(71.11%) cases were accord, including 12(13.33%) severe cases and 14(15.56%) mild cases of cervical lesions in CKC pathology than that of colposcopy biopsy of multi-point. The diagnose accordance rate of CINI, CINII and CINIII were 62.50%, 57.11% and 82.6% respectively. The diagnose accordance rate of CKC pathology and colposcopy biopsy of multi-point was higher in group CINIII than that of group CINI and group CINII (P<0.05).
2. A comparison on age, parity and clinical pathological features between two groupsA comparison on age and parity between two groups:the average age of group A was (42.39±8.3) years, the average age of group B was (47.77±9.10) years, group A was older than group B(P<0.05). The average parity of group A was (1.53±0.79) (0～4), the average parity of group B was (1.07±0.86) (1～6), The average parity of group A was lesser than group B(P<0.05).
A comparison on conization pathology between two groups:Group A:8(13.33%) cases of conization pathology were CINⅠ,15 (24.05%) cases were CINⅡ,25(41.33%) cases were CINⅢ,12(20.00%) cases were chronic cervicitis. Group B:1(3.33%) case of conization pathology was CINⅠ,6 (20.00%) cases were CINⅡ,22(75.61%) cases were CINⅢ,1(3.33%) case was microinvasive carcinoma. There were 20(30.00%) cases of low-grade cervical lesions(CINⅠand chronic cervicitis) and 40 (70.00%) cases of high-grade cervical lesions(CINⅡ-Ⅲ) according to conization pathology in group A. There were 1(3.33%) case of low-grade cervical lesions and 29 (96.67%) cases of high-grade cervical lesions according to conization pathology in group B. The lesions level of the patients in group B was higher than that of group A(P<0.01).
3. A comparison on CKC pathology and hysterectomy pathology between two groups 30 cases of patients were made CKC then were made hysterectomy, CKC pathology was in fOll compliance with hysterectomy pathology in 29 cases of patients. The CKC pathology was CINⅢinvolving glands in one case of patient, doctor found microinvasion in the patient's hysterectomy pathology, her lesions level bacame higher.
4. Residual status of uterine lesions and risk factors analysis after CKC then hysterectomy 3 cases of patients'CKC pathology were CIS involving glands and microinvasive carcinoma, which all were found residual uterine lesions, the total residual rate was 10.00%(3/30).In the 3 cases of patients,1 case of patient's residual lesions were microinvasive carcinoma,1 case of patient's residual lesions were CINIII,1 case of patient's residual lesions were CINI. Doctors have not found uterine lesions in 27 cases of patients.
The patients with higher lesions levels, have higher lesions residual rate. The lesions residual rate were 0(0/7),7.15%(1/14),12.50%(1/8) and 100%(1/1) respectively (?1=8.234, P<0.05). There was higher lesions residual rate with involving glands than without involving glands, The lesions residual rate were 33.30%(3/12) and 0(0/18) respectively (?2=6.344, P<0.05).
There were no differences of lesions residual rate between patients with parity 1 and parity 2, the lesions residual rate were 12.50%(1/8) and 13.63%(3/22)(?2=0.689, P>0.05).
5. There were significent differences in P16INK4A protein expression levels between patients with different cervical lesions, there were significent differences in P16INK4A protein expression levels between chronic cervicitis and CINI, CINI and CINII-Ⅲ, invasive carcinoma and CINI, invasive carcinoma and chronic cervicitis.
6. With the increase of lesions levels, from chronic cervicitis to cervical squamous cell carcinoma, P16 A protein expression levels bacame higher and higher, from moderate positive to strong positive(++-+++). The positive levels was helpful for determininmg the lesions levels.
Conclusion:
1. CKC can not be replaced by multi-point biopsy under colposcopy in the treatment of CIN. it plays a very important role in diagnosis of CIN.
2.It need to closely follow-up after CKC treatment of CIN. A high level of lesion an gland involvement are risk factors of residual lesions. The follow-up of these patients should be strengthened.
3.The positive expression rates of P16INK4A protein, marked with immunohisto chemistry, are higter at every levels of CIN and cervical squamous cell carcinoma thasn that of chronic cervicitis. The positive expression rate is helpful for distinguishing cervical benign neoplasia and Low-grade intraepithelial neoplasia.
4. With the increase of lesions levels, from chronic cervicitis to cervical squamous cell carcinoma, P16INK4A protein expression levels, marked with immunohistochemistry, bacome higher and higher, from moderate positive to strong positive(++～+++). The positive levels are helpful for determininmg the lesions levels.
引文
1.ArkinDM, BrayF, FerlayJ, etal. Estimatinthe world cancerburden:GLOBOCAN 2000[J]. Int J Cancer,2001,94:53-156
2. Lu CH, Liu FS, Tseng JJ,et al.Predictive factors for residual disease in subsequent hysterectomy following conization for CIN III[J].Gy-necol Oncol,2000,79(2):284-288
3.周慧梅,朱兰.诊断性与治疗性宫颈锥切术的临床价值[J].实用妇产科杂志,2009,25(7)：388-389
4.戴志琴,潘凌亚,黄惠芳等.宫颈上皮内瘤变手术后边缘的评价[J].中华肿瘤杂志,2007,29(2)：153-154
5.Hoffman MS,Martina,MA.2001 consensus guidelines for the managment of the women with cervical intraepithelial neoplasia.Am[J].Gynecol Oncol,2004,191:1048
6.Pilch H,Gunzel S,Schaffer U,etal.the presence of HPVDNA in cervical cancer:correlation with clinical pathologic paramenters and prognostic significance:10year perience at the Department of Obstetrics and Gynecology of the Mainz University [J].Int J Gynecolo Cancer,2001,11:39-40
7.Duensing S, Munger K. Centor some abnormalities genomieinst ability and Eareinogenie Progression[J].Bioehim Bio Phys Aeta 2001,471:81-88
8.Ni Si-ma,WANG Shi-xuan,WangWei,etal.Antisense targeting human papilloma virus type16 E6 and E7 genes contributes toapoptosis and senescencein SiHa cervical carcinoma cells[J].GynecolOncol,2007,106(2):299-304
9. Bernard HU.Gene expression of genital human papillomaviruses and considerations onpotential antiviral approaches[J].Antivir Ther 2002;7:219-237
10.Wright TC,Cox JT,Massad LS,etal.2001 Consensus guidelines for the managementof women with cervical intraepithelial neoplasia.[J].Obstet Gynecol,2003,189(1):295-304
11.高婷,赵卫东,吴大保等。宫颈冷刀锥切术在宫颈上皮内瘤变Ⅲ的诊治中的价值[J].安徽医药,2009,13(8)：907-908
12.Ferenczy A,Choukrou D,Falcone T,France E.The effect of cervical loop electrosurgical excision on subsequent pregnancy outcome:North American experience[J].Obstet Gynecol,1995,172(4Ptl):1246-1250
14.Ostor AG,Natural history of cervical intraepithelial neoplasiaia:a critical review.Int[J]. Gynecol Pathol,1993;12(2):186-192
15.Lu CH,Kuo CJ,etal.Prediction of pesrsitence or recur-rence after conization for cervical intraepithelialneoplasiaⅢ[J].ObstetGynecol,2006,107(4):830-833
16.樊庆泊.子宫颈环行电切术在宫颈上皮内瘤变治疗中的价值[J].中华妇产科杂志,2001,36：271-274
17.吴海静,张国楠.宫颈上皮内瘤变宫颈锥切术后的处理和随防[J].实用妇产科杂志.2009,25(7)391-393
18.Sandwweiss L,Thompson A,Natarajan S,etal.Cervical leep marginstatus and post-LEEP follow-up[J].International Journal of Gynecology Obstetrics,2008,100(3):284-285
19.李晨霞,吴鸣.宫颈上皮内瘤样病变冷刀锥切术后再治疗的27例临床分析[J].中国医刊,2007,42(9)：58-59
20.韩英,杜蓉,丁岩.宫颈上皮内瘤变Ⅲ级宫颈锥切术与预后相关因素分析[J].2009,39：1-4
21. Park JY,Lee SM,Yoo CW,Kang S,Park SY,Seo SS. risk factors predicting residual disease in subsequent hysterectomy following conization for cervical intraepithelial neoplasia(CIN)IIIand microinvasive cervical cancer[J].Gynecol Oncol,2007,107(1):39-44
22.Lin H,Chang HY,Huang CC,Changehien CC.Predietion of disease Persistence after conization for eroinvasive cervical carcinoma and cervilcal intraepithelial neoplasia grade3[J].IntGynecol Cancer,2004,14(2):311-316
23.Journal of Epidemiology and Biostatistics FIGO Annual Report on the Results of Treatment in Gynecological Cancer[J].2001,6(1):12
24.高志安,张世羽,杨光华.肿瘤抑制基因p16研究进展[J].肿瘤防治研究,2003,(30)70-71
25.Zhang H,Jin Y,Chen X,etal.Papillomavirus type 16E6/E7 and human telomerase rever transcriptase inesophageal cell immortalization and early transformation[J]. Cancer Lett,2007,245(1-2):184-194
26.程淑霞,赵先兰。宫颈癌及癌前病变中P16INK4A与HPV关系[J].国外医学.妇产科分册,2006,33(5)：317-318
27. Yildiz IZ,Usubutun A,Firat P,et al.Efficiency of immunohisto chemical p16 expression and HPV typing in cervical squamous intraepithelial lesion grading and review of the p16 literature[J].Pathol Res Pract,2007,203(6):445-449
28.Kalof AN,Cooper K,Dphil MBChB.p16INK4Aimmunoexpression:surro-ate marker of high-risk HPV and Highgrade cervicalin-traepithelial neopla-ia[J].AdvancedAnatomic Pathology,2006,13(4):190-194
29.何惠仪,卢丽娜,朱洪,等Ki67、 Survivin、 P16表达在宫颈癌和宫颈癌前病变诊断中的意义[J].中国妇幼保健.2006,(13)：1826-1827
30.Michael F,Elka A,David 0, etal. Immunohisto chemical Localization of Survivin in Benign Cervical Mucosa,Cervical Dysplasia,and Invasive Squamous Cell Carcinomal Am[J]. ClinPathol,2002,117(5):738.
1.ParkinDM,Bary F,FerlayJ,etal.Estamating thwor cancer burden:Globocan2000[J].IntJ Cancer,2001,94:153-156.
2.Kizacaino AP,Anderson WA,etal.International trends incidence of cervical cancer.2.Squ amous-cellcarcinoma[J].IntJcancer.2000,86:429-435.
3.章文华.318例宫颈上皮内瘤变的临床分析[J].临床肿瘤学杂志,2006,11(9)：666-669.
4.odowd MJ,philipp EE.Treatment of CIN.In:Odowdmj,philippEEds Thehistor of obstetrics and gynecology[J].NEWYork:Theparthen on publish Group,2000.533.
5.WrightVC,Davies E,Riopelle MA.Laser sugry for cervical intraepithelial neoplasia[J].Lancet 1997;349:978-980.
6.BergetA,Andereasson B,Bock JE.Laser and cryo surgery for Cerver intraepithelial neoplasma[J].Acta Obstet Gynecol Scand.1991;70:231-235.
7.Jordan JL.The treatment of cervical intraepithelial neoplasia by laser vaporization.Br J Obstet Gynecol 1985;92:394-398.
8.Prendiville W,Cullimore J,Norman S.Large Loop Excsion of The Transformation Zone(LLETZ).A new method of management For women with cervical intraepithelial neoplasi[J].BrJ ObstetGyneco1989;96:1054-1060.
9. Kitcener HC,Cruickshank M,Farmery E.The 1993 British Society for Colposcopy and Cervial pathology National Co-ordinating Network United Kingdom Colposcopy Survey[J].Br J Obstet Gynecol,1995,102:549-552.
10.BaldaufJJ,DreyfusM,RitterJ,etal.Risk of cervical stenosis after large loop excision laser conization[J].ObstetGynecol,1996,88:933-938.
11.李威,黄岩,陈荣辉.宫颈冷刀锥切术与宫颈环形电切术在宫颈上皮内瘤变治疗中疗效比较[J].现代医药卫生,2009,25(6)：846-847.
12.Machevet P,Darget D,Roy M,etal A randomized Prospective study comparmy three techniques of conization:old knife and LEEP[J].Gnynecol Oncol,1994,54:175-179.
13.刘新民主编.妇产科手术学.第三版.[M].北京：人民卫生出版社,2003.459-462.
14.高婷,赵卫东,吴大保等。宫颈冷刀锥切术在宫颈上皮内瘤变Ⅲ的诊治中的价值[J].安徽医药,2009,13(8)：907-908.
15.KolstadP,KlemV.Long-term followup of 1121 cases of carcinoma insitu[J].ObstetGynecol,1976,48(2):125-129.
16.WinterR.Conservative surgery for micro invasive Carcinoma the cervix.JObstetgy necol Res,1998,24:433-436.
17.Tseng CJ,Homg SG,SoongYK,etal. Conservative conization for Microinvasive carcinoma of the cervix[J]. AmJ Obste tGynecol,1997,176:1009-1010.
18.Chang DY,Cheng WF,Tomg PL,etal.Prediction ofresidual neoplasia based on histopathology and marginstatus of Conization Specimens[J].GynecolOncol,1996,63:53-56.
19.LivasyCA,MaygardenSJ,RajaratnamCT,etal.Predictors of recurrent Dysplasia after cervical loop eletrocautery excision procedure for CIN3[J]:astudyofmargin,endocervical gland,and Quadrant In volve me.Modpathol,1999,12:233-238.
20.杨佳欣,沈铿,郎景和等,宫颈原位癌118例临床分析[J]中华医学杂志.2006,86(5)：300-302。
21.石敏,沈铿.子宫颈锥切术的临床应用及发展[J].中华妇产科杂志.2001,36(5)：613-713.
22.杨桦.宫颈上皮内瘤变累腺深度与锥切范围的研究.[硕士学位论文].上海,上海交通大学,2008.
23.Wright TC,CoxJT,MassadLS,etal.2001 Consensus guidelines for the managent of womenwithcervicalintraepithelialneoplasia[J].AMJObstetGynecol,2003,189(1):295-304.
24.连慧之,梁德玉,熊安荣LEEP治疗宫颈高度上皮内瘤样病变临床及近期疗效观[J].中国热带医学,2007,7：731-732.
25.Lu CH,Kuo CJ,etal.Prediction of pesrsitence or recur-rence after conization for cervical intraepithelialneoplasiaIII[J].ObstetGynecol,2006,107(4):830-835.
26.杨保军,刘晖,冯力民等.CINIII和早期浸润癌冷刀锥切术后病变残存的病理分析[J].首都医科大学学报,2008,29(2)：650-652.
27.LandoniF,ParmaG,PeirettiM,etal.Chemo-conization in Early Cervical cancer [J].Gynecol Oncol,2007;107(SuppIl):125-128.
28.Kobayashi Y,Akiyama F,Hasumi K.A case of successful pregnancy after treatment of invasive cervical cancer with systemic chemotherapy and conization[J].Gyneco lOncol,2006,100(1):213-215
2. Lu CH, Liu FS, Tseng JJ,et al.Predictive factors for residual disease in subsequent hysterectomy following conization for CIN III[J].Gy-necol Oncol,2000,79(2):284-288
3.周慧梅,朱兰.诊断性与治疗性宫颈锥切术的临床价值[J].实用妇产科杂志,2009,25(7)：388-389
4.戴志琴,潘凌亚,黄惠芳等.宫颈上皮内瘤变手术后边缘的评价[J].中华肿瘤杂志,2007,29(2)：153-154
5.Hoffman MS,Martina,MA.2001 consensus guidelines for the managment of the women with cervical intraepithelial neoplasia.Am[J].Gynecol Oncol,2004,191:1048
6.Pilch H,Gunzel S,Schaffer U,etal.the presence of HPVDNA in cervical cancer:correlation with clinical pathologic paramenters and prognostic significance:10year perience at the Department of Obstetrics and Gynecology of the Mainz University [J].Int J Gynecolo Cancer,2001,11:39-40
7.Duensing S, Munger K. Centor some abnormalities genomieinst ability and Eareinogenie Progression[J].Bioehim Bio Phys Aeta 2001,471:81-88
8.Ni Si-ma,WANG Shi-xuan,WangWei,etal.Antisense targeting human papilloma virus type16 E6 and E7 genes contributes toapoptosis and senescencein SiHa cervical carcinoma cells[J].GynecolOncol,2007,106(2):299-304
9. Bernard HU.Gene expression of genital human papillomaviruses and considerations onpotential antiviral approaches[J].Antivir Ther 2002;7:219-237
10.Wright TC,Cox JT,Massad LS,etal.2001 Consensus guidelines for the managementof women with cervical intraepithelial neoplasia.[J].Obstet Gynecol,2003,189(1):295-304
11.高婷,赵卫东,吴大保等。宫颈冷刀锥切术在宫颈上皮内瘤变Ⅲ的诊治中的价值[J].安徽医药,2009,13(8)：907-908
12.Ferenczy A,Choukrou D,Falcone T,France E.The effect of cervical loop electrosurgical excision on subsequent pregnancy outcome:North American experience[J].Obstet Gynecol,1995,172(4Ptl):1246-1250
14.Ostor AG,Natural history of cervical intraepithelial neoplasiaia:a critical review.Int[J]. Gynecol Pathol,1993;12(2):186-192
15.Lu CH,Kuo CJ,etal.Prediction of pesrsitence or recur-rence after conization for cervical intraepithelialneoplasiaⅢ[J].ObstetGynecol,2006,107(4):830-833
16.樊庆泊.子宫颈环行电切术在宫颈上皮内瘤变治疗中的价值[J].中华妇产科杂志,2001,36：271-274
17.吴海静,张国楠.宫颈上皮内瘤变宫颈锥切术后的处理和随防[J].实用妇产科杂志.2009,25(7)391-393
18.Sandwweiss L,Thompson A,Natarajan S,etal.Cervical leep marginstatus and post-LEEP follow-up[J].International Journal of Gynecology Obstetrics,2008,100(3):284-285
19.李晨霞,吴鸣.宫颈上皮内瘤样病变冷刀锥切术后再治疗的27例临床分析[J].中国医刊,2007,42(9)：58-59
20.韩英,杜蓉,丁岩.宫颈上皮内瘤变Ⅲ级宫颈锥切术与预后相关因素分析[J].2009,39：1-4
21. Park JY,Lee SM,Yoo CW,Kang S,Park SY,Seo SS. risk factors predicting residual disease in subsequent hysterectomy following conization for cervical intraepithelial neoplasia(CIN)IIIand microinvasive cervical cancer[J].Gynecol Oncol,2007,107(1):39-44
22.Lin H,Chang HY,Huang CC,Changehien CC.Predietion of disease Persistence after conization for eroinvasive cervical carcinoma and cervilcal intraepithelial neoplasia grade3[J].IntGynecol Cancer,2004,14(2):311-316
23.Journal of Epidemiology and Biostatistics FIGO Annual Report on the Results of Treatment in Gynecological Cancer[J].2001,6(1):12
24.高志安,张世羽,杨光华.肿瘤抑制基因p16研究进展[J].肿瘤防治研究,2003,(30)70-71
25.Zhang H,Jin Y,Chen X,etal.Papillomavirus type 16E6/E7 and human telomerase rever transcriptase inesophageal cell immortalization and early transformation[J]. Cancer Lett,2007,245(1-2):184-194
26.程淑霞,赵先兰。宫颈癌及癌前病变中P16INK4A与HPV关系[J].国外医学.妇产科分册,2006,33(5)：317-318
27. Yildiz IZ,Usubutun A,Firat P,et al.Efficiency of immunohisto chemical p16 expression and HPV typing in cervical squamous intraepithelial lesion grading and review of the p16 literature[J].Pathol Res Pract,2007,203(6):445-449
28.Kalof AN,Cooper K,Dphil MBChB.p16INK4Aimmunoexpression:surro-ate marker of high-risk HPV and Highgrade cervicalin-traepithelial neopla-ia[J].AdvancedAnatomic Pathology,2006,13(4):190-194
29.何惠仪,卢丽娜,朱洪,等Ki67、 Survivin、 P16表达在宫颈癌和宫颈癌前病变诊断中的意义[J].中国妇幼保健.2006,(13)：1826-1827
30.Michael F,Elka A,David 0, etal. Immunohisto chemical Localization of Survivin in Benign Cervical Mucosa,Cervical Dysplasia,and Invasive Squamous Cell Carcinomal Am[J]. ClinPathol,2002,117(5):738.
1.ParkinDM,Bary F,FerlayJ,etal.Estamating thwor cancer burden:Globocan2000[J].IntJ Cancer,2001,94:153-156.
2.Kizacaino AP,Anderson WA,etal.International trends incidence of cervical cancer.2.Squ amous-cellcarcinoma[J].IntJcancer.2000,86:429-435.
3.章文华.318例宫颈上皮内瘤变的临床分析[J].临床肿瘤学杂志,2006,11(9)：666-669.
4.odowd MJ,philipp EE.Treatment of CIN.In:Odowdmj,philippEEds Thehistor of obstetrics and gynecology[J].NEWYork:Theparthen on publish Group,2000.533.
5.WrightVC,Davies E,Riopelle MA.Laser sugry for cervical intraepithelial neoplasia[J].Lancet 1997;349:978-980.
6.BergetA,Andereasson B,Bock JE.Laser and cryo surgery for Cerver intraepithelial neoplasma[J].Acta Obstet Gynecol Scand.1991;70:231-235.
7.Jordan JL.The treatment of cervical intraepithelial neoplasia by laser vaporization.Br J Obstet Gynecol 1985;92:394-398.
8.Prendiville W,Cullimore J,Norman S.Large Loop Excsion of The Transformation Zone(LLETZ).A new method of management For women with cervical intraepithelial neoplasi[J].BrJ ObstetGyneco1989;96:1054-1060.
9. Kitcener HC,Cruickshank M,Farmery E.The 1993 British Society for Colposcopy and Cervial pathology National Co-ordinating Network United Kingdom Colposcopy Survey[J].Br J Obstet Gynecol,1995,102:549-552.
10.BaldaufJJ,DreyfusM,RitterJ,etal.Risk of cervical stenosis after large loop excision laser conization[J].ObstetGynecol,1996,88:933-938.
11.李威,黄岩,陈荣辉.宫颈冷刀锥切术与宫颈环形电切术在宫颈上皮内瘤变治疗中疗效比较[J].现代医药卫生,2009,25(6)：846-847.
12.Machevet P,Darget D,Roy M,etal A randomized Prospective study comparmy three techniques of conization:old knife and LEEP[J].Gnynecol Oncol,1994,54:175-179.
13.刘新民主编.妇产科手术学.第三版.[M].北京：人民卫生出版社,2003.459-462.
14.高婷,赵卫东,吴大保等。宫颈冷刀锥切术在宫颈上皮内瘤变Ⅲ的诊治中的价值[J].安徽医药,2009,13(8)：907-908.
15.KolstadP,KlemV.Long-term followup of 1121 cases of carcinoma insitu[J].ObstetGynecol,1976,48(2):125-129.
16.WinterR.Conservative surgery for micro invasive Carcinoma the cervix.JObstetgy necol Res,1998,24:433-436.
17.Tseng CJ,Homg SG,SoongYK,etal. Conservative conization for Microinvasive carcinoma of the cervix[J]. AmJ Obste tGynecol,1997,176:1009-1010.
18.Chang DY,Cheng WF,Tomg PL,etal.Prediction ofresidual neoplasia based on histopathology and marginstatus of Conization Specimens[J].GynecolOncol,1996,63:53-56.
19.LivasyCA,MaygardenSJ,RajaratnamCT,etal.Predictors of recurrent Dysplasia after cervical loop eletrocautery excision procedure for CIN3[J]:astudyofmargin,endocervical gland,and Quadrant In volve me.Modpathol,1999,12:233-238.
20.杨佳欣,沈铿,郎景和等,宫颈原位癌118例临床分析[J]中华医学杂志.2006,86(5)：300-302。
21.石敏,沈铿.子宫颈锥切术的临床应用及发展[J].中华妇产科杂志.2001,36(5)：613-713.
22.杨桦.宫颈上皮内瘤变累腺深度与锥切范围的研究.[硕士学位论文].上海,上海交通大学,2008.
23.Wright TC,CoxJT,MassadLS,etal.2001 Consensus guidelines for the managent of womenwithcervicalintraepithelialneoplasia[J].AMJObstetGynecol,2003,189(1):295-304.
24.连慧之,梁德玉,熊安荣LEEP治疗宫颈高度上皮内瘤样病变临床及近期疗效观[J].中国热带医学,2007,7：731-732.
25.Lu CH,Kuo CJ,etal.Prediction of pesrsitence or recur-rence after conization for cervical intraepithelialneoplasiaIII[J].ObstetGynecol,2006,107(4):830-835.
26.杨保军,刘晖,冯力民等.CINIII和早期浸润癌冷刀锥切术后病变残存的病理分析[J].首都医科大学学报,2008,29(2)：650-652.
27.LandoniF,ParmaG,PeirettiM,etal.Chemo-conization in Early Cervical cancer [J].Gynecol Oncol,2007;107(SuppIl):125-128.
28.Kobayashi Y,Akiyama F,Hasumi K.A case of successful pregnancy after treatment of invasive cervical cancer with systemic chemotherapy and conization[J].Gyneco lOncol,2006,100(1):213-215