改良三阶梯技术在宫颈病变诊治中的临床应用研究
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摘要
目的：探讨改良三阶梯技术(‘'improved three-step" technique)在宫颈病变诊治过程中的临床应用价值。
方法：本研究收集2010年8月-2012年5月在山东大学齐鲁医院就诊的1098例患者,受检者年龄20-66岁。平均年龄35.48岁,患者无子宫手术史,均非妊娠期。所有受检者均接受TCT及HR-HPV DNA检查,对发现TCT异常即发现ASCUS及以上病变和/或HPV阳性者采取阴道镜检查,并根据阴道镜下表现行宫颈活检和/或ECC,或LEEP。阴道镜检查满意,镜下可见病灶者,则直接行病灶活检；若TCT结果为ASC-H、AGC、HSIL且阴道镜检查不满意,则行多点活检(选择宫颈3、6、9、12点)和ECC。部分HSIL且HPV阳性的患者,阴道镜检查可见病灶者,无宫颈锥切禁忌者,则直接行LEEP诊断性宫颈锥切手术。分析细胞学和HR-HPV DNA结果、阴道镜活检病理结果、锥切手术病理结果,比较三项检查结果的符合率与特异性,从而评价改良三阶梯技术在宫颈病变诊治过程中的临床作用。
结果：1.1098例受检者中经TCT检查,炎症或正常者882例(80.32%),异常病例216例(19.68%),其中ASCUS51例(4.70%),ASC-H53例(4.81%),LSIL77例(6.97%),HSIL35例(3.20%)。2.经HC2检查,高危型HPV阳性者395例,人群中总的感染率为35.97%,平均年龄为(35.87±10.68)岁；HPV阴性者703例,年龄平均(39.95±11.76)岁,HPV阳性组的年龄明显小于HPV阴性组,差异有统计学意义,P<0.01。3.TCT结果各组别的HR-HPV DNA感染情况：炎症或正常者中HR-HPV DNA阳性率为28.91%,ASCUS组中阳性率为50.98%,ASC-H组中阳性率为58.49%,LSII组中阳性率为76.62%,HSIL组中阳性率为94.29%,可见随着TCT诊断结果级别的升高,HPV阳性率明显升高,经统计学检验差异有统计学意义(P<0.01)。4.TCT异常或高危型HPV DNA阳性的患者中有198例行阴道镜检查并行镜下多点活组织检查,病理结果炎症者84例(42.42%),CINⅠ29例(14.65%),CINⅡ39例(19.70%),CINⅢ32例(16.16%),浸润癌2例(1.01%),湿疣6例(3.03%)。5.不同病理组HPV感染情况为：炎症34.52%,CINⅠ58.62%,CINⅡ84.61%。 CINIII96.87%,浸润癌100%,湿疣50.00%。6.经阴道镜引导下多点活检结果与TCT及HR-HPV DNA(?)日性预测值之间的关联：TCT结果为ASCUS的48例患者接受阴道镜检查及活检,HR-HPV DNA(?)日性组中发现高级别病变者占37.50%,阴性组只有8.33%发生高级别病变。TCT结果为ASC-H组的53例患者接受阴道镜检查及活检,其中HR-HPV DNA阳性组中发现58.06%高级别病变者,阴性组只有9.09%发生高级别病变。TCT结果为LSIL的74例患者行阴道镜引导下活检,其中HR-HPV DNAP阳性组中发现35.09%高级别病变者,阴性组只有5.88%发生高级别病变。TCT结果为HSIL者23例行阴道镜引导下活检,HR-HPV DNA阳性者21例,17例高级别病变,2例SCC,高级别以上病变发现率为90.47%,2例(?)HR-HPV DNA活检病理结果均为高级别病变(病变发现率为100%)。7.12例TCT为HSIL、HR-HPV阳性,阴道镜检查可见明显病变的患者直接行LEEP诊断性宫颈锥切术,病理结果均为高级别宫颈上皮内瘤变。8.阴道镜下活检病理结果与宫颈锥切术后病理结果对比,接受LEEP手术的70例患者中,术前术后病理结果完全符合率为81.69%(58／71),术后病理结果高1-2个级别者9.86%(7／71),下降1-2个级别者8.45%(6／71)；应用卡方检验,两者病理诊断结果的差别具显著性x2=9.81,p<0.005。
结论：1.宫颈液基细胞学(TCT)结合HP-HPV DNA联合检测明显提高了宫颈病变的检出率和准确性,有利于早期发现宫颈病变。
2.阴道镜检查指导下活检病理检查可进一步提高宫颈上皮内瘤变的检出率对指导临床进一步处理有重要意义。
3.对于部分TCT为HISL, HR-HPV DNA阳性者,阴道镜可见病变时,可直接行LEEP诊断性宫颈锥切手术。
4.改良三阶梯技术不仅提高了宫颈病变诊断的准确性,而且在很大程度上避免了诊断不足和治疗不足、过度诊断和过度治疗。
Objectives:To investigate the clinical value of improved "three-step" technique (improved "three-step" technique) in the diagnosis and treatment of cervical lesions.
Methods:The study in Qilu Hospital treatment of1098patients were collected in August2010-May2012subjects aged20-66years old. The average age of these patients was35.48years old. They have not history of uterine surgery, non-pregnancy. All subjects caught accept the TCT and HR-HPV DNA check, the discovery of TCT abnormal ASCUS and above lesions and/or HPV-positive taken colposcopy and cervical biopsy and/or ECC performance according to the colposcopy, or LEEP surgery. Satisfactory colposcopy, microscope lesions, the direct line of the biopsy of the lesion; TCT results for ASC-H, AGC, HSIL and colposcopy are not satisfied, the line multiple biopsies (cervical select3,6,9,12points) and the ECC. HSIL patients without cervical conization contraindications, direct line LEEP diagnostic conization surgery. Analysis of cytology and HR-HPV DNA results, colposcopy biopsy results, conization surgical and pathological findings, to take self-control laws, Analysed line with the rate and specificity of the test results, to evaluate the improvement of the three-tiered technology in the diagnosis and treatment of cervical lesions in the clinical role
Results:1.1098cases subjects TCT examination, inflammation or normal in882cases (80.32%), abnormal cases.216cases (19.68%), ASCUS51cases (4.70%), ASC-H53cases (4.81%). LSIL77cases (6.97%), HSIL35cases (3.20%).2. HC2 examination, the overall infection rate in the population of35.97%,395cases of high-risk HPV-positive, the average age of (35.87±10.68) years,703cases of HPV-negative, the average age (39.95±11.76) years of age.The age of the HPV-positive group was significantly less than the HPV-negative group.The difference was statistically significant, P<0.01.3. TCT results of each category of HR-HPV DNA infection:Inflammation or normal HR-HPV DNA positive rate was28.91%.The positive rate of ASCUS group was50.98%.The positive rate of ASC-H group was58.49%.The positive rate was76.62%in LSIL group. The positive rate of HSIL group was94.29%. We found in pace with the elevated levels of TCT diagnostic results, HPV positive rate was significantly increased. The statistical test difference is statistically significant.(P<0.01).4. The TCT198cases of unusual or high-risk HPV DNA positive patients had done colposcopically directed biopsy. Pathological findings of inflammation, there are84cases (42.42%)%,CINI29cases (14.65%), CIN Ⅱ39cases (19.70%), CIN Ⅲ32cases(16.16%), invasive carcinoma2cases (1.01%), warts6cases(3.03%).5Different pathological Group HPV infection: Inflammation of34.52%of the people are positive, CINI58.62%, CIN Ⅱ84.61%. CIN Ⅲ96.87%,100%of invasive cervical cancer, genital warts50.00%.6.Colposcopy association between the guide and multiple biopsies results with TCT and HR-HPV DNA positive predictive value:48cases TCT results for ASCUS patients received colposcopy-guided biopsy. HR-HPV DNA positive group found Level lesions accounted for37.50%, negative group, only8.33%of the high-level lesions. TCT results for ASC-H group of53patients received colposcopy and biopsy, which HR-HPV DNA positive group found that58.06%of high-level lesions, negative group, only9.09%of the high-level lesions. TCT LSIL74patients underwent colposcopy-guided biopsy,35.09%high-level lesions, including HR-HPV DNA positive group found negative group, only5.88%of the high-level lesions. TCT results for HSIL23cases colposcopy-guided biopsy, HR-HPV DNA positive by21cases,17cases of high-level lesions, two cases of SCC, high-level lesions found was90.47%,2cases of HR-HPV DNA biopsy pathological findings are high-level lesions (lesion detection rate was100%). The712cases TCT HSIL, HR-HPV positive patients directly cervical LEEP circumcision, pathology results are high-level cervical intraepithelial neoplasia.8Colposcopic biopsy results with cervical cone resection of pathological findings contrast LEEP surgery in70patients, preoperative and postoperative pathological findings in full compliance with the rate of81.69%(58/71), the postoperative pathological findings.1-2levels by9.86%(7/71), down1-2levels by8.45%(6/71); application of chi-square test, significant differences in the results of both pathological diagnosis with x2=9.81, p<0.005.
Conclusion:1. Liquid-based cervical cytology (TCT) combined with HP-HPV DNA detection could significantly increase the detection rate and accuracy of cervical lesions. It is conducive to the early detection of cervical lesions
2. Colposcopically directed biopsy can further improve the detection rate of cervical intraepithelial neoplasia (CIN), further processing to guide clinical significance.
3.For HSIL, HR-HPV DNA-positive patients, no cervical cone cut contraindications, direct line conization surgery.
4.Improved three-step technique in the diagnosis of cervical lesions, can not only improve the accuracy of diagnosis but also avoid the over-diagnosis and over-treatment.
方法：本研究收集2010年8月-2012年5月在山东大学齐鲁医院就诊的1098例患者,受检者年龄20-66岁。平均年龄35.48岁,患者无子宫手术史,均非妊娠期。所有受检者均接受TCT及HR-HPV DNA检查,对发现TCT异常即发现ASCUS及以上病变和/或HPV阳性者采取阴道镜检查,并根据阴道镜下表现行宫颈活检和/或ECC,或LEEP。阴道镜检查满意,镜下可见病灶者,则直接行病灶活检；若TCT结果为ASC-H、AGC、HSIL且阴道镜检查不满意,则行多点活检(选择宫颈3、6、9、12点)和ECC。部分HSIL且HPV阳性的患者,阴道镜检查可见病灶者,无宫颈锥切禁忌者,则直接行LEEP诊断性宫颈锥切手术。分析细胞学和HR-HPV DNA结果、阴道镜活检病理结果、锥切手术病理结果,比较三项检查结果的符合率与特异性,从而评价改良三阶梯技术在宫颈病变诊治过程中的临床作用。
结果：1.1098例受检者中经TCT检查,炎症或正常者882例(80.32%),异常病例216例(19.68%),其中ASCUS51例(4.70%),ASC-H53例(4.81%),LSIL77例(6.97%),HSIL35例(3.20%)。2.经HC2检查,高危型HPV阳性者395例,人群中总的感染率为35.97%,平均年龄为(35.87±10.68)岁；HPV阴性者703例,年龄平均(39.95±11.76)岁,HPV阳性组的年龄明显小于HPV阴性组,差异有统计学意义,P<0.01。3.TCT结果各组别的HR-HPV DNA感染情况：炎症或正常者中HR-HPV DNA阳性率为28.91%,ASCUS组中阳性率为50.98%,ASC-H组中阳性率为58.49%,LSII组中阳性率为76.62%,HSIL组中阳性率为94.29%,可见随着TCT诊断结果级别的升高,HPV阳性率明显升高,经统计学检验差异有统计学意义(P<0.01)。4.TCT异常或高危型HPV DNA阳性的患者中有198例行阴道镜检查并行镜下多点活组织检查,病理结果炎症者84例(42.42%),CINⅠ29例(14.65%),CINⅡ39例(19.70%),CINⅢ32例(16.16%),浸润癌2例(1.01%),湿疣6例(3.03%)。5.不同病理组HPV感染情况为：炎症34.52%,CINⅠ58.62%,CINⅡ84.61%。 CINIII96.87%,浸润癌100%,湿疣50.00%。6.经阴道镜引导下多点活检结果与TCT及HR-HPV DNA(?)日性预测值之间的关联：TCT结果为ASCUS的48例患者接受阴道镜检查及活检,HR-HPV DNA(?)日性组中发现高级别病变者占37.50%,阴性组只有8.33%发生高级别病变。TCT结果为ASC-H组的53例患者接受阴道镜检查及活检,其中HR-HPV DNA阳性组中发现58.06%高级别病变者,阴性组只有9.09%发生高级别病变。TCT结果为LSIL的74例患者行阴道镜引导下活检,其中HR-HPV DNAP阳性组中发现35.09%高级别病变者,阴性组只有5.88%发生高级别病变。TCT结果为HSIL者23例行阴道镜引导下活检,HR-HPV DNA阳性者21例,17例高级别病变,2例SCC,高级别以上病变发现率为90.47%,2例(?)HR-HPV DNA活检病理结果均为高级别病变(病变发现率为100%)。7.12例TCT为HSIL、HR-HPV阳性,阴道镜检查可见明显病变的患者直接行LEEP诊断性宫颈锥切术,病理结果均为高级别宫颈上皮内瘤变。8.阴道镜下活检病理结果与宫颈锥切术后病理结果对比,接受LEEP手术的70例患者中,术前术后病理结果完全符合率为81.69%(58／71),术后病理结果高1-2个级别者9.86%(7／71),下降1-2个级别者8.45%(6／71)；应用卡方检验,两者病理诊断结果的差别具显著性x2=9.81,p<0.005。
结论：1.宫颈液基细胞学(TCT)结合HP-HPV DNA联合检测明显提高了宫颈病变的检出率和准确性,有利于早期发现宫颈病变。
2.阴道镜检查指导下活检病理检查可进一步提高宫颈上皮内瘤变的检出率对指导临床进一步处理有重要意义。
3.对于部分TCT为HISL, HR-HPV DNA阳性者,阴道镜可见病变时,可直接行LEEP诊断性宫颈锥切手术。
4.改良三阶梯技术不仅提高了宫颈病变诊断的准确性,而且在很大程度上避免了诊断不足和治疗不足、过度诊断和过度治疗。
Objectives:To investigate the clinical value of improved "three-step" technique (improved "three-step" technique) in the diagnosis and treatment of cervical lesions.
Methods:The study in Qilu Hospital treatment of1098patients were collected in August2010-May2012subjects aged20-66years old. The average age of these patients was35.48years old. They have not history of uterine surgery, non-pregnancy. All subjects caught accept the TCT and HR-HPV DNA check, the discovery of TCT abnormal ASCUS and above lesions and/or HPV-positive taken colposcopy and cervical biopsy and/or ECC performance according to the colposcopy, or LEEP surgery. Satisfactory colposcopy, microscope lesions, the direct line of the biopsy of the lesion; TCT results for ASC-H, AGC, HSIL and colposcopy are not satisfied, the line multiple biopsies (cervical select3,6,9,12points) and the ECC. HSIL patients without cervical conization contraindications, direct line LEEP diagnostic conization surgery. Analysis of cytology and HR-HPV DNA results, colposcopy biopsy results, conization surgical and pathological findings, to take self-control laws, Analysed line with the rate and specificity of the test results, to evaluate the improvement of the three-tiered technology in the diagnosis and treatment of cervical lesions in the clinical role
Results:1.1098cases subjects TCT examination, inflammation or normal in882cases (80.32%), abnormal cases.216cases (19.68%), ASCUS51cases (4.70%), ASC-H53cases (4.81%). LSIL77cases (6.97%), HSIL35cases (3.20%).2. HC2 examination, the overall infection rate in the population of35.97%,395cases of high-risk HPV-positive, the average age of (35.87±10.68) years,703cases of HPV-negative, the average age (39.95±11.76) years of age.The age of the HPV-positive group was significantly less than the HPV-negative group.The difference was statistically significant, P<0.01.3. TCT results of each category of HR-HPV DNA infection:Inflammation or normal HR-HPV DNA positive rate was28.91%.The positive rate of ASCUS group was50.98%.The positive rate of ASC-H group was58.49%.The positive rate was76.62%in LSIL group. The positive rate of HSIL group was94.29%. We found in pace with the elevated levels of TCT diagnostic results, HPV positive rate was significantly increased. The statistical test difference is statistically significant.(P<0.01).4. The TCT198cases of unusual or high-risk HPV DNA positive patients had done colposcopically directed biopsy. Pathological findings of inflammation, there are84cases (42.42%)%,CINI29cases (14.65%), CIN Ⅱ39cases (19.70%), CIN Ⅲ32cases(16.16%), invasive carcinoma2cases (1.01%), warts6cases(3.03%).5Different pathological Group HPV infection: Inflammation of34.52%of the people are positive, CINI58.62%, CIN Ⅱ84.61%. CIN Ⅲ96.87%,100%of invasive cervical cancer, genital warts50.00%.6.Colposcopy association between the guide and multiple biopsies results with TCT and HR-HPV DNA positive predictive value:48cases TCT results for ASCUS patients received colposcopy-guided biopsy. HR-HPV DNA positive group found Level lesions accounted for37.50%, negative group, only8.33%of the high-level lesions. TCT results for ASC-H group of53patients received colposcopy and biopsy, which HR-HPV DNA positive group found that58.06%of high-level lesions, negative group, only9.09%of the high-level lesions. TCT LSIL74patients underwent colposcopy-guided biopsy,35.09%high-level lesions, including HR-HPV DNA positive group found negative group, only5.88%of the high-level lesions. TCT results for HSIL23cases colposcopy-guided biopsy, HR-HPV DNA positive by21cases,17cases of high-level lesions, two cases of SCC, high-level lesions found was90.47%,2cases of HR-HPV DNA biopsy pathological findings are high-level lesions (lesion detection rate was100%). The712cases TCT HSIL, HR-HPV positive patients directly cervical LEEP circumcision, pathology results are high-level cervical intraepithelial neoplasia.8Colposcopic biopsy results with cervical cone resection of pathological findings contrast LEEP surgery in70patients, preoperative and postoperative pathological findings in full compliance with the rate of81.69%(58/71), the postoperative pathological findings.1-2levels by9.86%(7/71), down1-2levels by8.45%(6/71); application of chi-square test, significant differences in the results of both pathological diagnosis with x2=9.81, p<0.005.
Conclusion:1. Liquid-based cervical cytology (TCT) combined with HP-HPV DNA detection could significantly increase the detection rate and accuracy of cervical lesions. It is conducive to the early detection of cervical lesions
2. Colposcopically directed biopsy can further improve the detection rate of cervical intraepithelial neoplasia (CIN), further processing to guide clinical significance.
3.For HSIL, HR-HPV DNA-positive patients, no cervical cone cut contraindications, direct line conization surgery.
4.Improved three-step technique in the diagnosis of cervical lesions, can not only improve the accuracy of diagnosis but also avoid the over-diagnosis and over-treatment.
引文
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[26]Charoenkwan K, Srisomboon J, Siriaunkgul S, et al. A "See and Treat" approach for high grade squamous intraepithelial lesion on cervical cytology. J Med Assoc Thai, 2004,87:865-868
[27]沈铿,郎景和,黄惠芳等。子宫颈锥切术在宫颈上皮内瘤变诊断和治疗中的价值.中华妇产科杂志,2001,36：264-266
[1]D.M. Parkin, F. Bray, J. Ferlay and P. Pisani, Global cancer statistics,2002, CA:A Cancer Journal for Clinicians 55 (2005), pp.74-108.
[2]Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC Cancer Base No.5 Version 2.0. Lyon: IARC Press; 2004.
[3]卞美璐.宫颈上皮内瘤样病变的诊断与处理[J].中国实用妇科与产科杂志,2003,19(3)：139.
[4]Holowaty P, Miller AB, Rohan T,et al. Natrural history of dysplasia of the uterine cervix. Journal of the National Cancer Institute,1999,91:252-258.
[5]乔友林,章文华,李凌等,子宫颈癌筛查方法的横断面比较。中国医学科学院院报,2002,24：50-54.
[6]潘秦镜,李凌,乔友林等,液基细胞学筛查宫颈癌的研究。中华肿瘤学杂志,2001,23：309-311
[7]Belinson J,Pretorius R,Zhang WH,er al. Cervical Cancer Screening by simple visual inspection after acetic Acid. Obstet Gynecology,2001,98:441-444
[8]Sankaranarayanan, Wesley R,Thara S,et al.Test characteristics of visual inspection with 4% acetic acid (VIA) and lugol's Iodine(VILI) in cervical cancer screening in kerala,India. Int. Ⅰ. Cancer,2003,106:404-408.
[9]李楠,章文华.宫颈上皮内瘤病变150例临床分析.实用癌症杂志,2001,16：140-143.
[10]Bosch FX. Prevalence of human papillomavirus in cervical cancer:a worldwide perspective. J Natl Cancer Inst,1995,87:79
[11]曹泽毅.中华妇产科学.临床版.第1版.北京：人民卫生出版社,2010.
[12]Andersen EA,et al.Cryosurgery for cervical intraepithelial neoplasia:10-year follow-up.Gynecol Oncol,1992,45:240.
[13]卞美璐.宫颈上皮内瘤变的治疗.医师进修杂志,2002,25：14.
[14]王世阆,子宫颈上皮内瘤变[J],实用妇产科志,2001,17：63-65
[15]Barker B, Garcia F, Lozevski J, et al.The corelation between colposcopically directed cervical biopsy and loop electrosurgical excision procedure pathology and the effect of time on that agreement.Gynecol Oncol,2001,82:22-26
[16]Fambrini M, Penna MG, et al. Management of cervical intraepithe lial neoplasia: the role of biopsy. Inter J Gynecol Obster,2003,82:219-210
[17]Charoenkwan K, Srisomboon J, Siriaunkgul S, et al. A "See and Treat" approach for high grade squamous intraepithelial lesion on cervical cytology. J Med Assoc Thai, 2004,87:865-868
[18]Costa S,Nuzzo MD Rubino A,et al.Independent determinants of inaccuraclly directed punch biopsy of the cervix. Gynecol Oncol,2003,90:57-63
[19]Cecchini S, Visioli CB,Zappa M,et al.Recurrence after treatment by loop electrosurgical excision procedure (LEEP) of high-grade cervical intraepithelial neoplasia. Tumori,2002,88:478-480
[20]沈铿,郎景和,黄惠芳等。子宫颈锥切术在宫颈上皮内瘤变诊断和治疗中的价值.中华妇产科杂志,2001,36：264-266
[21]郝敏,宫颈癌流行病学研究与调查.中华医学会第一次全国宫颈病学术会议,2002.1：P.13-16.
[22]顾晓梅,张玉泉,宫颈癌的流行病学高危因素研究进展.中国妇幼保健,2007.22(35)：P.5073——5075.
[23]McKenzie, N. D., etal., Women with HIV are more commonly infected with non-16 and-18 high-risk HPV types. Gynecol Oncol,2010.116(3):P.572-577.
[2]Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC Cancer Base No.5 Version 2.0. Lyon: IARC Press; 2004.
[3]D.M. Parkin, F. Bray, J. Ferlay and P. Pisani, Global cancer statistics,2002, CA:A Cancer Journal for Clinicians 55 (2005), pp.74-108.
[4]郎景和.子宫颈癌预防的现代策略.中国医学科学院学报.Acta Acad M ed S in,2007,29(5)：575-578
[5]常莹,HPV检测、TCT检查及阴道镜活检在宫颈病变诊断中的作用(综述),中国城乡企业卫生2009.6
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[10]RL Bekkers,LF Massuger,J Bulten, et al.Epidemiological and clinical aspects of human papillomavirus detection in the prevention of cervical cancer. Rev Med Virol,2004,14:95-105
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[14]ACOG PUBLICATIONS. Clinical Management Guidelines for Obstetrician-Gynecologists. Number 45, August 2003 (Replaces Committee Opinion Number 152, March 1995):Cercical cytology Screening.Obstet gynecol,2003,102:417-412
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[16]M Arbyn, F Buntinx, M Van Ranst,et al. Vrilogic Versus Cytologic Triage of Women With Equivocal Pap Smears:A Meta-analysis of the Accuracy To Detect High-Grade Intraepithelial Neoplasia. J Natl Cancer Inst,2004,96:280-293
[17]E Paraskevaidis, G Koliopoulos, Y Alamanos, et al.Human Papillomavirus Testing and the Outcome of Treatment for Cervical Intraepithelial Neopplasia. Obstet Gynecol,2001,98:833-836
[18]吴令英,李楠,章文华等.醋酸肉眼观察在宫颈啊普查中的应用.癌症,2003,22：1096
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[20]章文华,阴道镜检查.见连利娟主编.林巧稚妇科肿瘤学.第三版.北京：人民卫生出版社,2000,96-97
[21]李楠,章文华.宫颈上皮内瘤病变150例临床分析.实用癌症杂志,2001,16：140-143
[22]Fambrini M, Penna MG, et al. Management of cervical intraepithe lial neoplasia: the role of biopsy. Inter J Gynecol Obster,2003,82:219-210
[23]Barker B, Garcia F, Lozevski J, et al.The corelation between colposcopically directed cervical biopsy and loop electrosurgical excision procedure pathology and the effect of time on that agreement.Gynecol Oncol,2001,82:22-26
[24]Costa S,Nuzzo MD Rubino A,et al.Independent determinants of inaccuraclly directed punch biopsy of the cervix. Gynecol Oncol,2003,90:57-63
[25]Cecchini S, Visioli CB,Zappa M,et al.Recurrence after treatment by loop electrosurgical excision procedure (LEEP) of high-grade cervical intraepithelial neoplasia. Tumori,2002,88:478-480
[26]Charoenkwan K, Srisomboon J, Siriaunkgul S, et al. A "See and Treat" approach for high grade squamous intraepithelial lesion on cervical cytology. J Med Assoc Thai, 2004,87:865-868
[27]沈铿,郎景和,黄惠芳等。子宫颈锥切术在宫颈上皮内瘤变诊断和治疗中的价值.中华妇产科杂志,2001,36：264-266
[1]D.M. Parkin, F. Bray, J. Ferlay and P. Pisani, Global cancer statistics,2002, CA:A Cancer Journal for Clinicians 55 (2005), pp.74-108.
[2]Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC Cancer Base No.5 Version 2.0. Lyon: IARC Press; 2004.
[3]卞美璐.宫颈上皮内瘤样病变的诊断与处理[J].中国实用妇科与产科杂志,2003,19(3)：139.
[4]Holowaty P, Miller AB, Rohan T,et al. Natrural history of dysplasia of the uterine cervix. Journal of the National Cancer Institute,1999,91:252-258.
[5]乔友林,章文华,李凌等,子宫颈癌筛查方法的横断面比较。中国医学科学院院报,2002,24：50-54.
[6]潘秦镜,李凌,乔友林等,液基细胞学筛查宫颈癌的研究。中华肿瘤学杂志,2001,23：309-311
[7]Belinson J,Pretorius R,Zhang WH,er al. Cervical Cancer Screening by simple visual inspection after acetic Acid. Obstet Gynecology,2001,98:441-444
[8]Sankaranarayanan, Wesley R,Thara S,et al.Test characteristics of visual inspection with 4% acetic acid (VIA) and lugol's Iodine(VILI) in cervical cancer screening in kerala,India. Int. Ⅰ. Cancer,2003,106:404-408.
[9]李楠,章文华.宫颈上皮内瘤病变150例临床分析.实用癌症杂志,2001,16：140-143.
[10]Bosch FX. Prevalence of human papillomavirus in cervical cancer:a worldwide perspective. J Natl Cancer Inst,1995,87:79
[11]曹泽毅.中华妇产科学.临床版.第1版.北京：人民卫生出版社,2010.
[12]Andersen EA,et al.Cryosurgery for cervical intraepithelial neoplasia:10-year follow-up.Gynecol Oncol,1992,45:240.
[13]卞美璐.宫颈上皮内瘤变的治疗.医师进修杂志,2002,25：14.
[14]王世阆,子宫颈上皮内瘤变[J],实用妇产科志,2001,17：63-65
[15]Barker B, Garcia F, Lozevski J, et al.The corelation between colposcopically directed cervical biopsy and loop electrosurgical excision procedure pathology and the effect of time on that agreement.Gynecol Oncol,2001,82:22-26
[16]Fambrini M, Penna MG, et al. Management of cervical intraepithe lial neoplasia: the role of biopsy. Inter J Gynecol Obster,2003,82:219-210
[17]Charoenkwan K, Srisomboon J, Siriaunkgul S, et al. A "See and Treat" approach for high grade squamous intraepithelial lesion on cervical cytology. J Med Assoc Thai, 2004,87:865-868
[18]Costa S,Nuzzo MD Rubino A,et al.Independent determinants of inaccuraclly directed punch biopsy of the cervix. Gynecol Oncol,2003,90:57-63
[19]Cecchini S, Visioli CB,Zappa M,et al.Recurrence after treatment by loop electrosurgical excision procedure (LEEP) of high-grade cervical intraepithelial neoplasia. Tumori,2002,88:478-480
[20]沈铿,郎景和,黄惠芳等。子宫颈锥切术在宫颈上皮内瘤变诊断和治疗中的价值.中华妇产科杂志,2001,36：264-266
[21]郝敏,宫颈癌流行病学研究与调查.中华医学会第一次全国宫颈病学术会议,2002.1：P.13-16.
[22]顾晓梅,张玉泉,宫颈癌的流行病学高危因素研究进展.中国妇幼保健,2007.22(35)：P.5073——5075.
[23]McKenzie, N. D., etal., Women with HIV are more commonly infected with non-16 and-18 high-risk HPV types. Gynecol Oncol,2010.116(3):P.572-577.
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