宫颈癌石蜡标本中HPV检测分型与HWAPL基因表达之间的关系
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摘要
宫颈癌是最常见的妇科恶性肿瘤之一，性传播疾病和HPV感染使其发病年龄逐渐趋向于年轻化，由于广泛开展宫颈癌预防普查，子宫颈癌的早期诊断率大大提高，子宫颈癌患者生存率得到提高。
文献报告宫颈癌中HPV的检出率可以达到90％以上。HPV是一种环状双链结构的DNA病毒，由8000左右碱基对组成。高危型HPV E6、E7基因编码的原癌蛋白是导致宫颈癌的重要原因。它们均为小分子蛋白，分别含有158个和98个氨基酸，具有锌指结构。这种锌指结构与细胞的恶性转化密切相关。表达了E6、E7原癌蛋白的体外培养细胞能继续增殖到永生化，这种永生化可能是肿瘤发生的前奏。转基因研究还发现高危型HPV E6、E7能直接导致肿瘤形成。目前已经有学者研制成功了HPV疫苗，宫颈癌的发病率可能将会明显下降。基因治疗是以后肿瘤治疗的一个趋势，但有关宫颈癌特异性基因的研究的报道很少，影响了宫颈癌基因治疗进展。WAPL基因是在果蝇体内发现的一个基因，在人体内的同源序列称为HWAPL基因，其具体作用可能与染色体的稳定有关。Oikawa等发现宫颈癌相对于卵巢癌、乳腺癌、肺癌、肾癌、结肠癌及其相应的正常组织，HWAPL基因的mRNA表达升高更明显，相对于其他细胞系，宫颈癌细胞系中HWAPL有更高程度的表达。初步推测HWAPL基因可能是一种宫颈癌特异性高表达基因，推动了宫颈癌基因治疗的研究进展。
本试验研究目的在于检测出宫颈癌石蜡标本中HPV并进行分型，为用石蜡标本对HPV研究提供理论依据；同时结合HWAPL蛋白免疫组化的结果，从临
床角度找出高危型HPV与HWAPL基因之间的关系，为以后宫颈癌的预防和基因治疗的研究提供理论依据。
材料和方法
收集2004年2月到2006年2月郑州大学第二附属医院75例宫颈石蜡标本。30例宫颈鳞癌，患者术前均未进行放疗或化疗，年龄29～57岁，平均年龄43岁。45例宫颈上皮内瘤变(CIN)，包括CINⅠ级15例、CINⅡ级15例、CINⅢ级15例，年龄24～50岁，平均年龄37岁。
采用普通PCR技术和基因芯片检测技术，检测出标本中的HPV并对之进行分型。结合HPV分型结果和HWAPL蛋白免疫组化研究结果，找出HPV分型与HWAPL基因之间的关系。用SPSS10.0软件系统对数据进行分析，以α=0.05作为判断显著差异的标准。
结果
(1)30例宫颈鳞癌石蜡标本中28例(93.3％)普通PCR扩增后显示HPVDNA阳性，基因芯片检测显示27例(90％)显示HPV16/18阳性，1(3.3％)例显示HPV6阳性；15例CINⅢ石蜡标本中14例(93.3％)普通PCR扩增后显示HPVDNA阳性，基因芯片检测显示10例(66.7％)HPV16/18阳性，1例(6.7％)58型阳性，3(20％)例HPV6/11阳性；15例CINⅡ石蜡标本中14例(93.3％)普通PCR扩增后显示HPV DNA阳性，基因芯片检测显示11(73.3％)例HPV 6/11阳性，3例(20％)HPV16/18阳性；15例CINⅠ石蜡标本中12例(80％)普通PCR扩增后显示HPV DNA阳性，基因芯片检测显示10例(66.7％)HPV6/11阳性，2例(13.3％)HPV16/18阳性。与CINⅠ、CINⅡ比较，宫颈癌和CINⅢ中高危HPV感染所占比率较大，差异有统计学意义(χ~2=32.248，P=0.001)；
(2)30例宫颈癌标本中HWAPL蛋白表达强度5例(16.7％)为弱阳性(+)，8例(26.7％)为阳性(++)，17例(56.7％)为强阳性(+++)；15例CINⅢ标本中HWAPL蛋白表达强度4例(26.7％)为+，4例(26.7％)为++，7例(46.7％)为+++；15例CINⅡ标本中6例(40％)为+，5例(33.3％)为++，4例(26.7％)为+++；15例CINⅠ标本中HWAPL蛋白表达强度7例(46.7％)为+，6例(40％)为++，2例(13.3％)为+++。宫颈癌和CINⅢ中HWAPL蛋白表达强度远远高于CINⅠ和CINⅡ中，差异有统
计学意义(χ~2=8.928，P=0.012)；
(3)HPV阴性的7例标本中4例(57.1％)HWAPL蛋白表达为+，2例(28.6％)为++，1例(14.3％)为+++；低危HPV感染的26例标本中12例(46.2％)HWAPL蛋白表达为+，9例(34.6％)为H，5例(19.2％)为+++；检测出高危HPV的42例标本中6例(14.3％)HWAPL蛋白表达为弱阳性+，12例(28.6％)为++，24例(57.1％)为强阳性+++。高危HPV感染的标本与低危HPV感染的标本及HPV阴性标本相比较HWAPL蛋白表达强度差异有统计学意义(χ~2=14.844，P=0.005)。Spearmen相关性分析显示高危HPV感染与HWAPL基因表呈正相关(r=0.440，P=0.000)。
结论
(1)宫颈癌石蜡标本中可以检测出93.3％HPV DNA,可用作宫颈癌HPV感染的研究手段；
(2)基因芯片技术有自动化、通量大、准确率高、特异性强等优点可以作为临床HPV检测和分型的常用手段；
(3)宫颈癌中HWAPL基因呈高表达，高危HPV感染可增强HWAPL基因的复制表达，HWAPL基因异常表达可能是HPV致宫颈癌发病机制的重要环节。
Background and objective
Cervical cancer was one maligant tumor of female. For sexual transmitted diseases and HPV infection, the patients with cervical cancer were becoming younger and younger. For the wide-ranging general survey used in cervical cancer, the rate of earlier diagnose of cervical cancer was improved. And the patients' survival rate have been increased.
As the literature reported the detection rate of HPV in cervical cancer was over 90 percentage. HPV is a double-stranded circular structure DNA virus and it is made up of about 8000 base pairs. The major cause of cervical cancer was the original cancer protein encoded by E6 gene and E7 gene of high risk HPV. They are small protein molecules, which contain 158 and 98 amino acids. They have zinc finger structure, which related to the malignant transformation of cells closely. Cells in vitro, which expressed original cancer protein of E6 gene and E7 gene, would reach eternal life. And the eternal life would be a prelude of tumor. Transgenic study also founded that in high-risk HPV E6 gene and E7 gene could directly lead to tumor. For the reasons above, some scholars have already successfully developed the HPV vaccine. With clinical application of HPV vaccine, the incidence of cervical cancer would be significantly decreased. Gene therapy would be a trend in clinical in the future. For the research about specific gene of cervical cancer was few, the progress of gene therapy in cervical cancer was inhibited. WAPL gene was found in Drosophila. And in human the homology sequence was HWAPL gene. The specific role of HWAPL gene may be keeping the stability of chromosome. Oikawa and so on found that compared to ovarian cancer, breast cancer, lung cancer, kidney cancer, colon cancer and the corresponding normal tissues the expression of HWAPL mRNA in cervical cancer increased more obviously. They also found that compared to other cell lines, HWAPL gene in cervical cancer cell lines expressed a higher level. So they guessed that HWAPL gene may be a cervical cancer-specific gene and this promoted the research progress of gene therapy in cervical cancer.
In this test, HPV would be detected and typed from paraffin-embedded specimens of cervical cancer, then provided a theoretical basis for studying HPV. At the same time, immunohistochemical results of HWAPL protein would be compined to find out the relationship between HPV and HWAPL gene expression. This study will provide a theoretical basis for the prevention and gene therapy of cervical cancer in the future.
Materials and methods
75 cases of cervical paraffin-embedded specimens were collected in Zhengzhou University 2nd affiliated hospital from February 2004 to February 2006. The age of 30 cases of cervical squamous cell carcinoma was from 29 years old to 57 years old and the average age was 43 years old. In 45 cases of cervical intraepthelial neoplasia , there were 15 cases of CIN I,15 cases of CIN II and 15 cases of CINIII. The age of 45 cases of CIN was from 24 years old to 50 years old and the average age was 37 years old. All women hadn't been treated with chemotherapy or radiotherapy.
PCR and gene chip technology were used to detect and type HPV from paraffin-embedded cervical specimens. According to typing results and immunohistochemical results of HWAPL protein, we would find the relationship between HPV with HWAPL gene expression. SPSS10.0 was used to analyze the datum.
Results
(1) After amplifying with PCR, the results showed that there were 28 cases of HPV DNA positive in 30 cases of cervical cancer and the positive rate was 93.3%. In 15 cases of CIN III, there were 14 cases of HPV DNA positive and the positive rate was 93.3%. In 15 cases of CIN II, there were 14 cases of HPV DNA positive and the positive rate was 93.3%. In 15 cases of CIN I , there were 12 cases of HPV DNA positive and the positive rate was 80%. Detected by gene chip, the results showed that in 30 cases of cervical cancer there were 27 cases of HPV16/18 positive and 1 case of HPV6 positive. The positive rate was 90% and 6.7% respectively. In 15 cases of CIN III, there were 10 cases of HPV16 /18 positive, 1 case of HPV58 positive and 3 cases of HPV6/11 positive. The positive rate was 66.7%, 6.7% and 20% respectively. In 15 cases of CIN II, there were 11 cases of HPV6/11 positive and 3 cases of HPV16/18 positive. The positive rate was 73.3% and 20% respectively. In 15 cases of CIN I , there were 10 cases of HPV6/11 positive and 2 cases of HPV 16/18 positive. The positive rate was 66.7% and 13.3% respectively. In cervical cancer and CIN III the detection rate of high-risk HPV was significant higher than in CIN II and CIN I (x~2 = 32.248, P=0.000).
(2) The immunohistochemical results of HWAPL protein showed that in 30 cases of cervical cancer there were 5 cases with weak positive staining intensity (+), 8 cases with middle positive staining intensity (++) and 17 cases with strong positive staining intensity(+++). In 15 cases of CIN III, there were 4 cases with +, 4 cases with ++ and 7 cases with +++. In 15 cases of CIN II, there were 6 cases with +, 5 cases with ++ and 4 cases with +++. In 15 cases of CIN I , there were 7 cases with +, 6 cases with ++ and 2 cases with +++. There were significant difference between the expression of HWAPL protein in CIN III and cervical with the expression of HWAPL protein in CIN II and CIN I (x~2 = 8.928, P=0.012).
(3) There were 7 cases of HPV negative specimens, in which 4 cases with HWAPL protein +, 2 cases with ++ and 1 case with +++. There were 26 cases of low risk HPV positive specimens, in which 12 cases with HWAPL protein +, 5 cases with ++ and 9 cases with +++. There were 42 cases of high risk HPV positive specimens, in which 6 cases with HWAPL protein +, 12 cases with ++ and 24 cases with +++. Specimens with high-risk HPV positive expressed HWAPL protein significant higher than specimens without high risk HPV positive (x~2=14.844, P=0.005). Correlation analysis showed that high risk HPV and the expression of HWAPL gene correlated (r =0.440, P= 0.000).
Conclusions
(1) 90% HPV DNA could be detected from Paraffin-embedded specimens of cervical cancer. And these specimens could be used as cervical HPV infection research.
(2) For automation throughput high accuracy and specificity advantages, gene chip technology could be used as an important method for clinical HPV testing and classification.
(3) In cervical cancer HWAPL gene expression was high. High risk HPV infection may increased the replication and expression of HWAPL gene. The abnormal expression of HWAPL gene may play an important role in the pathogenesis of cervical cancer.
文献报告宫颈癌中HPV的检出率可以达到90％以上。HPV是一种环状双链结构的DNA病毒，由8000左右碱基对组成。高危型HPV E6、E7基因编码的原癌蛋白是导致宫颈癌的重要原因。它们均为小分子蛋白，分别含有158个和98个氨基酸，具有锌指结构。这种锌指结构与细胞的恶性转化密切相关。表达了E6、E7原癌蛋白的体外培养细胞能继续增殖到永生化，这种永生化可能是肿瘤发生的前奏。转基因研究还发现高危型HPV E6、E7能直接导致肿瘤形成。目前已经有学者研制成功了HPV疫苗，宫颈癌的发病率可能将会明显下降。基因治疗是以后肿瘤治疗的一个趋势，但有关宫颈癌特异性基因的研究的报道很少，影响了宫颈癌基因治疗进展。WAPL基因是在果蝇体内发现的一个基因，在人体内的同源序列称为HWAPL基因，其具体作用可能与染色体的稳定有关。Oikawa等发现宫颈癌相对于卵巢癌、乳腺癌、肺癌、肾癌、结肠癌及其相应的正常组织，HWAPL基因的mRNA表达升高更明显，相对于其他细胞系，宫颈癌细胞系中HWAPL有更高程度的表达。初步推测HWAPL基因可能是一种宫颈癌特异性高表达基因，推动了宫颈癌基因治疗的研究进展。
本试验研究目的在于检测出宫颈癌石蜡标本中HPV并进行分型，为用石蜡标本对HPV研究提供理论依据；同时结合HWAPL蛋白免疫组化的结果，从临
床角度找出高危型HPV与HWAPL基因之间的关系，为以后宫颈癌的预防和基因治疗的研究提供理论依据。
材料和方法
收集2004年2月到2006年2月郑州大学第二附属医院75例宫颈石蜡标本。30例宫颈鳞癌，患者术前均未进行放疗或化疗，年龄29～57岁，平均年龄43岁。45例宫颈上皮内瘤变(CIN)，包括CINⅠ级15例、CINⅡ级15例、CINⅢ级15例，年龄24～50岁，平均年龄37岁。
采用普通PCR技术和基因芯片检测技术，检测出标本中的HPV并对之进行分型。结合HPV分型结果和HWAPL蛋白免疫组化研究结果，找出HPV分型与HWAPL基因之间的关系。用SPSS10.0软件系统对数据进行分析，以α=0.05作为判断显著差异的标准。
结果
(1)30例宫颈鳞癌石蜡标本中28例(93.3％)普通PCR扩增后显示HPVDNA阳性，基因芯片检测显示27例(90％)显示HPV16/18阳性，1(3.3％)例显示HPV6阳性；15例CINⅢ石蜡标本中14例(93.3％)普通PCR扩增后显示HPVDNA阳性，基因芯片检测显示10例(66.7％)HPV16/18阳性，1例(6.7％)58型阳性，3(20％)例HPV6/11阳性；15例CINⅡ石蜡标本中14例(93.3％)普通PCR扩增后显示HPV DNA阳性，基因芯片检测显示11(73.3％)例HPV 6/11阳性，3例(20％)HPV16/18阳性；15例CINⅠ石蜡标本中12例(80％)普通PCR扩增后显示HPV DNA阳性，基因芯片检测显示10例(66.7％)HPV6/11阳性，2例(13.3％)HPV16/18阳性。与CINⅠ、CINⅡ比较，宫颈癌和CINⅢ中高危HPV感染所占比率较大，差异有统计学意义(χ~2=32.248，P=0.001)；
(2)30例宫颈癌标本中HWAPL蛋白表达强度5例(16.7％)为弱阳性(+)，8例(26.7％)为阳性(++)，17例(56.7％)为强阳性(+++)；15例CINⅢ标本中HWAPL蛋白表达强度4例(26.7％)为+，4例(26.7％)为++，7例(46.7％)为+++；15例CINⅡ标本中6例(40％)为+，5例(33.3％)为++，4例(26.7％)为+++；15例CINⅠ标本中HWAPL蛋白表达强度7例(46.7％)为+，6例(40％)为++，2例(13.3％)为+++。宫颈癌和CINⅢ中HWAPL蛋白表达强度远远高于CINⅠ和CINⅡ中，差异有统
计学意义(χ~2=8.928，P=0.012)；
(3)HPV阴性的7例标本中4例(57.1％)HWAPL蛋白表达为+，2例(28.6％)为++，1例(14.3％)为+++；低危HPV感染的26例标本中12例(46.2％)HWAPL蛋白表达为+，9例(34.6％)为H，5例(19.2％)为+++；检测出高危HPV的42例标本中6例(14.3％)HWAPL蛋白表达为弱阳性+，12例(28.6％)为++，24例(57.1％)为强阳性+++。高危HPV感染的标本与低危HPV感染的标本及HPV阴性标本相比较HWAPL蛋白表达强度差异有统计学意义(χ~2=14.844，P=0.005)。Spearmen相关性分析显示高危HPV感染与HWAPL基因表呈正相关(r=0.440，P=0.000)。
结论
(1)宫颈癌石蜡标本中可以检测出93.3％HPV DNA,可用作宫颈癌HPV感染的研究手段；
(2)基因芯片技术有自动化、通量大、准确率高、特异性强等优点可以作为临床HPV检测和分型的常用手段；
(3)宫颈癌中HWAPL基因呈高表达，高危HPV感染可增强HWAPL基因的复制表达，HWAPL基因异常表达可能是HPV致宫颈癌发病机制的重要环节。
Background and objective
Cervical cancer was one maligant tumor of female. For sexual transmitted diseases and HPV infection, the patients with cervical cancer were becoming younger and younger. For the wide-ranging general survey used in cervical cancer, the rate of earlier diagnose of cervical cancer was improved. And the patients' survival rate have been increased.
As the literature reported the detection rate of HPV in cervical cancer was over 90 percentage. HPV is a double-stranded circular structure DNA virus and it is made up of about 8000 base pairs. The major cause of cervical cancer was the original cancer protein encoded by E6 gene and E7 gene of high risk HPV. They are small protein molecules, which contain 158 and 98 amino acids. They have zinc finger structure, which related to the malignant transformation of cells closely. Cells in vitro, which expressed original cancer protein of E6 gene and E7 gene, would reach eternal life. And the eternal life would be a prelude of tumor. Transgenic study also founded that in high-risk HPV E6 gene and E7 gene could directly lead to tumor. For the reasons above, some scholars have already successfully developed the HPV vaccine. With clinical application of HPV vaccine, the incidence of cervical cancer would be significantly decreased. Gene therapy would be a trend in clinical in the future. For the research about specific gene of cervical cancer was few, the progress of gene therapy in cervical cancer was inhibited. WAPL gene was found in Drosophila. And in human the homology sequence was HWAPL gene. The specific role of HWAPL gene may be keeping the stability of chromosome. Oikawa and so on found that compared to ovarian cancer, breast cancer, lung cancer, kidney cancer, colon cancer and the corresponding normal tissues the expression of HWAPL mRNA in cervical cancer increased more obviously. They also found that compared to other cell lines, HWAPL gene in cervical cancer cell lines expressed a higher level. So they guessed that HWAPL gene may be a cervical cancer-specific gene and this promoted the research progress of gene therapy in cervical cancer.
In this test, HPV would be detected and typed from paraffin-embedded specimens of cervical cancer, then provided a theoretical basis for studying HPV. At the same time, immunohistochemical results of HWAPL protein would be compined to find out the relationship between HPV and HWAPL gene expression. This study will provide a theoretical basis for the prevention and gene therapy of cervical cancer in the future.
Materials and methods
75 cases of cervical paraffin-embedded specimens were collected in Zhengzhou University 2nd affiliated hospital from February 2004 to February 2006. The age of 30 cases of cervical squamous cell carcinoma was from 29 years old to 57 years old and the average age was 43 years old. In 45 cases of cervical intraepthelial neoplasia , there were 15 cases of CIN I,15 cases of CIN II and 15 cases of CINIII. The age of 45 cases of CIN was from 24 years old to 50 years old and the average age was 37 years old. All women hadn't been treated with chemotherapy or radiotherapy.
PCR and gene chip technology were used to detect and type HPV from paraffin-embedded cervical specimens. According to typing results and immunohistochemical results of HWAPL protein, we would find the relationship between HPV with HWAPL gene expression. SPSS10.0 was used to analyze the datum.
Results
(1) After amplifying with PCR, the results showed that there were 28 cases of HPV DNA positive in 30 cases of cervical cancer and the positive rate was 93.3%. In 15 cases of CIN III, there were 14 cases of HPV DNA positive and the positive rate was 93.3%. In 15 cases of CIN II, there were 14 cases of HPV DNA positive and the positive rate was 93.3%. In 15 cases of CIN I , there were 12 cases of HPV DNA positive and the positive rate was 80%. Detected by gene chip, the results showed that in 30 cases of cervical cancer there were 27 cases of HPV16/18 positive and 1 case of HPV6 positive. The positive rate was 90% and 6.7% respectively. In 15 cases of CIN III, there were 10 cases of HPV16 /18 positive, 1 case of HPV58 positive and 3 cases of HPV6/11 positive. The positive rate was 66.7%, 6.7% and 20% respectively. In 15 cases of CIN II, there were 11 cases of HPV6/11 positive and 3 cases of HPV16/18 positive. The positive rate was 73.3% and 20% respectively. In 15 cases of CIN I , there were 10 cases of HPV6/11 positive and 2 cases of HPV 16/18 positive. The positive rate was 66.7% and 13.3% respectively. In cervical cancer and CIN III the detection rate of high-risk HPV was significant higher than in CIN II and CIN I (x~2 = 32.248, P=0.000).
(2) The immunohistochemical results of HWAPL protein showed that in 30 cases of cervical cancer there were 5 cases with weak positive staining intensity (+), 8 cases with middle positive staining intensity (++) and 17 cases with strong positive staining intensity(+++). In 15 cases of CIN III, there were 4 cases with +, 4 cases with ++ and 7 cases with +++. In 15 cases of CIN II, there were 6 cases with +, 5 cases with ++ and 4 cases with +++. In 15 cases of CIN I , there were 7 cases with +, 6 cases with ++ and 2 cases with +++. There were significant difference between the expression of HWAPL protein in CIN III and cervical with the expression of HWAPL protein in CIN II and CIN I (x~2 = 8.928, P=0.012).
(3) There were 7 cases of HPV negative specimens, in which 4 cases with HWAPL protein +, 2 cases with ++ and 1 case with +++. There were 26 cases of low risk HPV positive specimens, in which 12 cases with HWAPL protein +, 5 cases with ++ and 9 cases with +++. There were 42 cases of high risk HPV positive specimens, in which 6 cases with HWAPL protein +, 12 cases with ++ and 24 cases with +++. Specimens with high-risk HPV positive expressed HWAPL protein significant higher than specimens without high risk HPV positive (x~2=14.844, P=0.005). Correlation analysis showed that high risk HPV and the expression of HWAPL gene correlated (r =0.440, P= 0.000).
Conclusions
(1) 90% HPV DNA could be detected from Paraffin-embedded specimens of cervical cancer. And these specimens could be used as cervical HPV infection research.
(2) For automation throughput high accuracy and specificity advantages, gene chip technology could be used as an important method for clinical HPV testing and classification.
(3) In cervical cancer HWAPL gene expression was high. High risk HPV infection may increased the replication and expression of HWAPL gene. The abnormal expression of HWAPL gene may play an important role in the pathogenesis of cervical cancer.
引文
1. Bosch F X, Lorincz A, Munoz N, et al. The causal relation between human papillomavirus and cervical cancer [J]. J Clin Pathol, 2002, 55:244-265.
2. Bosch FX, Manos MM, Munoz N, et al. Prevalence of human papillomavirus in cervical cancer: a world-wide perspective[J]. Natl Cancer Inst, 1995, 87:796-802.
3. Turan T; Kalantari M; Calleja Macias IE; Cubie HA; Cuschieri K; Villa LL;SkomedaI H; Barrera Saldana HA; Bernard HU. Methylation of the human papillomavirus-18 L1 gene: a biomarker of neoplasticprogression. Virology, 2006, 349(1). 175-183.
4. Walboomrs JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer world-wide [J]. Pathol, 1999, 189:12-19.
5. Chhieng DC; Chen J; Connolly K; Roberson J; Eltoum I. High-risk HPV DNA detection rate in patients with atypical squamous cells andits relationship to the atypical squamous cell: squamous intraepithelial lesion ratio. Acta Cytologica, 2006, 50(3).-291-294.
6. Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide:a systematic review. Cancer Epidemiol Biomarkers Prev, 2005 Feb; 14(2):467-75.
7. Rajeevan MS; Swan DC; Nisenbaum R; Lee DR; Vernon SD; Ruffin MT; Horowitz IR; Flowers LC; Kmak D; Tadros T; Birdsong G; Husain M; Srivastava S; Unger ER. Epidemiologic and viral factors associated with cervical neoplasia inHPV-16-positive women. International Journal of Cancer, 2005, 115(1). 114-120.
8. Kuroda M; Ohbayashi T; Yamada K; Matsuda Y; Mukai K. A dioxin sensitive gene, mammalian WAPL, is implicated in spermatogenesis. FEBS Letters, 2005, 579(1). 167-172.
9. Oikawa K; Ohbayashi T; Kiyono T; Nishi H; Isaka K; Umezawa A; Kuroda M; MukaiK. Expression of a novel human gene, human wings apart-like (hWAPL), isassociated with cervical carcinogenesis and tumor progression. Cancer research, 2004, 64(10).-3545-3549.
10.Kuroda M; Oikawa K; Yoshida K; Takeuchi A; Takeuchi M; Usui M; Umezawa A; Mukai K. Effects of 3-methylcholanthrene on the transcriptional activity and mRNA accumulation of the oncogene hWAPL. Cancer letters, 2005, 221(1). 21-28.
11.Kuroda M; Kiyono T; Oikawa K; Yoshida K; Mukai K. The human papillomavirus E6 and E7 inducible oncogene, hWAPL, exhibitspotential as a therapeutic target. The British Journal of Cancer, 2005, 92(2). 290-293.
12.Hubbard RA.Human papillomavirus testing methods. Arch Pathol Lab Med, 2003 Aug, 127(8):940-5.
13.Chew K, Rooney PH, Cruickshank ME, Murray GI. Laser capture microdissection and PCR for analysis of human papilloma virus infection. Methods. Mol Biol, 2005, 293:295-30.
14.Roberts CC; Tadesse AS; Sands J; Halvorsen T; Schofield TL; Dalen A; Skjeldestad FE; Jansen KU. Detection of HPV in Norwegian cervical biopsy specimens with type-specific PCR and reverse line blot assays. Journal of clinical virology, 2006,36(4). 277-282.
15.Yoshikawa H, Kawana T, Kitagawa K, Mizuno M, Yoshikura H, Iwamoto A. Detection and typing of multipe genital human papillomavirus by DNA amplification with consensus primers. Jpn J Cancer Res, 1991, 82:524-531.
16.Kim KH; Yoon MS; Na YJ; Park CS; Oh MR; Moon WC. Development and evaluation of a highly sensitive human papillomavirus genotyping DNA chip. Gynecologic Oncology, 2006, 100(1). 38-43.
17．冷彦宁．基因芯片技术与检验医学[J]．国外医学临床生物化学与检验学分册，2002，23(1)：12-16．
18.Lont AP; Kroon BK; Horenblas S; Gallee MP; Berkhof J; Meijer CJ; Snijders PJ. Presence of high-risk human papillomavirus DNA in penile carcinoma predictsfavorable outcome in survival. International Journal of Cancer, 2006, 119(5). 1078-1081.
19.Kraus I; Molden T; Holm R; Lie AK; Karlsen F; Kristensen GB; Skomedal H. Presence of E6 and E7 mRNA from human papillomavirus types 16, 18, 31, 33, and 45 in the majority of cervical carcinomas. Journal of Clinical Microbiology, 2006, 44(4). 1310-1317.
20.Chhieng DC; Chen J; Connolly K; Roberson J; Eltoum I. High-risk HPV DNA detection rate in patients with atypical squamous cells andits relationship to the atypical squamous cell: squamous intraepithelial lesion ratio. Acta Cytologica, 2006,50(3). 291-294.
21.Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide:a systematic review. Cancer Epidemiol Biomarkers Prev, 2005 Feb; 14(2):467-75.
22.Yang YC, Chang CL, Chen ML. Effect of p53 polymorphism on the susceptibility of cervical cancer [J]. Gynecol Obstet Invest, 2001, 51 (3): 197-201.
23.Cheung TH, Lo KW, Yu MM, et al. Aberranl expression of p21 (WAFI/CIPI) in cervical cancer, 2002, 79(3): 135-147.
24.Roh JW, Kim MH, Kim JW, et al.Polvmorphism in codon 31 of p21 and cervical cancer serciptibility in Korean women [J]. Cancer Letter, 2001, 165:59-62.
25.Borges HL, Bird J, Wasson K, CardiffRD, Varki N, Eckmann L, Wang JY. Tumor promotion by caspase-resistant retinoblastoma protein. Proc Natl Acad Sci USA, 2005; 102: 15587-15592.
26.Huang LW, Chao SL, Hwang JL, et al.Down regulation of P27 is associated with maligment transformation and aggressive phenotype of cervical neoplasm [J] .Int cervical carcinoma [J]. Cancer Lett, 2001, 172:93-98.
27．吕亚莉，钟梅，赵坡．应用基因芯片诊断宫颈石蜡组织样本中人乳头状瘤病毒感染及其临床意义．中华病理学杂志，2006，35：719—721．
28.Franco EL. Primary screening of cervical cancer with human papillomavirus tests. J Natl Cancer Inst Monogr, 2003; (31):89-96.
29.Wright TC; Bosch FX; Franco EL; Cuzick J; Schiller JT; Garnett GP; Meheus A. HPV vaccines and screening in the prevention of cervical cancer;conclusions from a 2006 workshop of international experts. Vaccine, 2006, 24(Sup3). s251-s261.
30.Mao C; Koutsky LA; Ault KA; Wheeler CM; Brown DR; Wiley DJ; Alvarez FB; Bautista OM; Jansen KU; Barr E. Efficacy of human papillomavirus-16 vaccine to prevent cervicalintraepithelial neoplasia: a randomized controlled trial. Obstetrics & Gynecology, 2006, 107(1). 18-27.
31.Carcia-Carranca A.Vaccines against human papillomavirus and perspectives for the prevention and control of cervical cancer. Salud Publica Mex, 2004 Jul-Auq; 46(4):284-5.
32.Smith JR, Boyle DC, Corless DJ, et al. Abdominal radical trachelectomy:anew surgical technique foe the conservative management of cervical carcinoma.Br J Obstet Gynaecol, 1997, 104(10):1196.
33．李爱玲，孙建衡．子宫颈癌放射治疗512例临床报道．中华妇产科杂志，2000，25，(5)：303．
34.Shinada M, Kigawa J, Takahashi M, et al. Stromal invasion of the cervix can be excluded from the criteria using adjuvant radiotherapy follow radical surgery for patients with cervical cancer[J]. G YNECOL Oncol, 2004, 93(3):628-631.
1．沈铿，郎景和．妇科肿瘤面临的问题和挑战[M]．北京：人民卫生出版社，2002．20—21．
2.Walboomrs JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer world-wide[J]. Pathol, 1999, 189:12-19.
3.Bosch F X, Lorincz A, Munoz N, et al. The causal relation between human papillomavirus and cervical cancer[J]. J Clin Pathol, 2002, 55:244-265.
4.Bosch FX, Manos MM, Munoz N, et al. Prevalence of human papillomavirus in cervical cancer: a world-wide perspective[J]. Natl Cancer Inst, 1995, 87:796-802.
5.Turan T; Kalantari M; Calleja Macias IE; Cubie HA; Cuschieri K; Villa LL; Skomedal H; Barrera Saldana HA; Bernard HU. Methylation of the human papillomavirus- 18 L1 gene: a biomarker of neoplasticprogression. Virology, 2006, 349(1). 175-183.
6．洪少林，王家壁，刘跃华，等．尖锐湿疣患者皮损中人乳头状瘤病毒的检测和分型[J]．中国医学科学院报，2002，24(4)：397-400．
7.Clifford GM,Rana RK,Franceschi S, Smith JS, Gough G, Pimenta JM. Human papillomavirus genotype distribution in low-grade cervical lesions:comparison by geographic region and with cervical cancer. Cancer Epidemiol Biomarkers Prev, 2005 May; 14(5): 1157-64.
8.Fule T; Csapo Z; Mathe M; Tatrai P; Laszlo V; Papp Z; Kovalszky I. Prognostic significance of high-risk HPV status in advanced cervical cancersand pelvic lymph nodes. Gynecologic Oncology, 2006, 100(3). 570-578.
9.Chhieng DC; Chen J; Connolly K; Roberson J; Eltoum I. High-risk HPV DNA detection rate in patients with atypical squamous cells andits relationship to the atypical squamous cell: squamous intraepithelial lesion ratio. Acta Cytologica, 2006, 50(3). 291-294.
10.Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide:a systematic review. Cancer Epidemiol Biomarkers Prev, 2005 Feb; 14(2):467-75.
11.Rajeevan MS; Swan DC; Nisenbaum R; Lee DR; Vernon SD; Ruffin MT; Horowitz IR; Flowers LC; Kmak D; Tadros T; Birdsong G; Husain M; Srivastava S; Unger ER. Epidemiologic and viral factors associated with cervical neoplasia inHPV-16-positive women. International Journal of Cancer, 2005, 115(1). 114-120.
12. Brestovac B; Harnett GB; Smith DW; Shellam GR; Frost FA. Human papillomavirus genotypes and their association with cervical neoplasiain a cohort of Western Australian women. Journal of Medical Virology, 2005,76(1).-106-110.
13. Hammouda D; Munoz N; Herrero R; Arslan A; Bouhadef A; Oublil M; Djedeat B;Fontaniere B; Snijders P; Meijer C; Franceschi S. Cervical carcinoma in Algiers, Algeria: human papillomavirus and lifestylerisk factors. International Journal of Cancer, 2005,113(3).-483-489.
14. Wu, YP; Chen, YL; Li, LY; Yu, GF; He, Y; Zhang, YF. Analysis of mutations in the E6/E7 oncogenes and L1 gene of human papillomavirus 16 cervical cancer isolates from China. The Journal of General Virology, 2006, 87(5). 1181-1188.
15. Si Mohamed A; Ndjoyi Mbiguino A; Cuschieri K; Onas IN; Colombet I; Ozouaki F;Goff JL; Cubie H; Belec L. High prevalence of high-risk oncogenic human papillomaviruses harboringatypical distribution in women of childbearing age living in Libreville, Gabon. Journal of Medical Virology, 2005, 77(3). 430-438.
16. Einstein MH, Goldberg GL. Human papillomavirus and cervical neoplasia. Cancer Invest, 2002; 20(7-8): 1080-5.
17. Lu DW. Prevalence of High-Risk Human Papillomavirus DNA in Nonkeratinizing(Cylindrical Cell) Carcinoma of the Sinonasal Tract: A Distinct Clinicopathologic and MolecularDisease Entity. American Journal of Surgical Pathology, 2005,29(10). 1367-1372.
18. Hillemanns P; Wang X. Integration of HPV-16 and HPV-18 DNA in vulvar intraepithelial neoplasia. Gynecologic Oncology, 2006, 100(2).-276-282.
19. Lont AP; Kroon BK; Horenblas S; Gallee MP; Berkhof J; Meijer CJ; Snijders PJ. Presence of high-risk human papillomavirus DNA in penile carcinoma predictsfavorable outcome in survival. International Journal of Cancer, 2006, 119(5). 1078-1081.
20.Kraus I; Molden T; Holm R; Lie AK; Karlsen F; Kristensen GB; Skomedal H. Presence of E6 and E7 mRNA from human papillomavirus types 16, 18, 31, 33,and 45 in the majority of cervical carcinomas. Journal of Clinical Microbiology, 2006, 44(4). 1310-1317.
21.Molden T; Kraus I; Karlsen F; Skomedal H; Hagmar B. Human papillomavirus E6/E7 mRNA expression in women younger than 30 years age. Gynecologic Oncology, 2006, 100(1). 95-100.
22.Menges CW; Baglia LA; Lapoint R; McCance DJ. Human papillomavirus type 16 E7 up-regulates AKT activity through theretinoblastoma protein. Cancer research, 2006, 66(11). 5555-5559.
23.Dang C; Koehler A; Forschner T; Sehr P; Michael K; Pawlita M; Stockfleth E; Nindl I. E6/E7 expression of human papillomavirus types in cutaneous squamous celldysplasia and carcinoma in immunosuppressed organ transplant recipients. British Journal of Dermatology, 2006, 155(1). 129-136.
24．刘红．构建来自宫颈癌并带有突变及缺失LCR的HPV16重组体[J]．中国病毒学，1996，11(3)：242．
25.Haensen G, Krause U, Becker A, et al. Tumor hypoxia, p53 and prognosis in cervical cancers[J]. Int J Radiation Oncology Biol Phys, 2001, 50(4):865-872.
26.Yang YC, Chang CL, Chen ML.Effect of p53 polymorphism on the susceptibility of cervical cancer[J]. Gynecol Obstet Invest, 2001, 51 (3): 197-201.
27.Cheung TH, Lo KW, Yu MM, et al. Aberranl expression of p21 (WAFI/CIPI) in cervical cancer, 2002, 79(3): 135-147.
28.Borges HL, Bird J, Wasson K, Cardiff RD, Varki N, Eckmann L, Wang JY. Tumor promotion by caspase-resistant retinoblastoma protein. Proc Natl Acad Sci, USA 2005, 102: 15587-15592.
29.Roh JW, Kim MH, Kim JW, et al. Polvmorphism in codon 31 of p21 and cervical cancer serciptibility in Korean women[J]. Cancer Letter, 2001, 165:59-62.
30. Huang LW, Chao SL, Hwang JL, et al. Down regulation of P27 is associated with maligment transformation and aggressive phenotype of cervical neoplasm[J] .Int cervical carcinoma[J]. Cancer Lett, 2001, 172:93-98.
31. Roberts CC; Tadesse AS; Sands J; Halvorsen T; Schofield TL; Dalen A; Skjeldestad FE; Jansen KU. Detection of HPV in Norwegian cervical biopsy specimens with type-specific PCR and reverse line blot assays. Journal of clinical virology, 2006, 36(4). 277-282.
32. Hubbard RA. Human papillomavirus testing methods.Arch Pathol Lab Med, 2003 Aug; 127(8):940-5.
33. Chew K, Rooney PH, Cruickshank ME, Murray GI. Laser capture microdissection and PCR for analysis of human papilloma virus infection. Methods Mol Biol, 2005; 293:295-300.
34. Chang HK; Park J; Kim W; Kim K; Lee M; Park U; Choi B. The expression of MAGE and GAGE genes in uterine cervical carcinoma of Koreaby RT-PCR with common primers. Gynecologic Oncology, 2005, 97(2). 342-347.
35. Lin H; Moh JS; Ou YC; Shen SY; Tsai YM; Changchien CC; Liu JM; Ma YY. A simple method for the detection and genotyping of high-risk humanpapillomavirus using seminested polymerase chain reaction and reverse hybridization. Gynecologic Oncology, 2005, 96(1).-84-91.
36. Soderlund Strand A; Rymark P; Andersson P; Dillner J; Dillner L. Comparison between the Hybrid Capture II Test and a PCR-Based Human Papillomavirus Detection Method for Diagnosis and Posttreatment Follow-Up of Cervical Intraepithelial Neoplasia. Journal of Clinical Microbiology, 2005, 43(7). 3260-3266.
37. Brestovac B; Harnett GB; Smith DW; Shellam GR; Frost FA. Human papillomavirus genotypes and their association with cervical neoplasiain a cohort of Western Australian women. Journal of Medical Virology, 2005,76(1).-106-110.
38. Kim KH; Yoon MS; Na YJ; Park CS; Oh MR; Moon WC. Development and evaluation of a highly sensitive human papillomavirus genotyping DNA chip. Gynecologic Oncology, 2006, 100(1).-38-43.
39．冷彦宁．基因芯片技术与检验医学[J]．国外医学临床生物化学与检验学分册，2002，23(1)：12-16．
40. Wright TC; Bosch FX; Franco EL; Cuzick J; Schiller JT; Garnett GP; Meheus A. HPV vaccines and screening in the prevention of cervical cancer; conclusions from a 2006 workshop of international experts. Vaccine,2006,24(Sup3).-s251-s261
41. Mao C; Koutsky LA; Ault KA; Wheeler CM; Brown DR; Wiley DJ; Alvarez FB; Bautista OM; Jansen KU; Barr E. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstetrics & Gynecology,2006,107(1).-18-27
42. Carcia-Carranca A. Vaccines against human papillomavirus and perspectives for the prevention and control of cervical cancer. Salud Publica Mex, 2004 Jul-Auq;46(4):284-5.
43. Lorincz AT.Screening for cervical cancer: new alternatives and research. Salud Publica Mex, 2003;45 Suppl 3:S376-87.
44. Kuroda M; Ohbayashi T; Yamada K; Matsuda Y; Mukai K. A dioxin sensitive gene, mammalian WAPL, is implicated in spermatogenesis. FEBS Letters, 2005,579(1). 167-172.
45. Oikawa K; Ohbayashi T; Kiyono T; Nishi H; Isaka K; Umezawa A; Kuroda M; MukaiK. Expression of a novel human gene, human wings apart-like (hWAPL), isassociated with cervical carcinogenesis and tumor progression. Cancer research, 2004, 64(10). 3545-3549.
46. Kuroda M; Oikawa K; Yoshida K; Takeuchi A; Takeuchi M; Usui M; Umezawa A; Mukai K. Effects of 3-methylcholanthrene on the transcriptional activity and mRNA accumulation Of the oncogene hWAPL. Cancer letters, 2005, 221(1). 21-28.
47. Kuroda M; Kiyono T; Oikawa K; Yoshida K; Mukai K. The human papillomavirus E6 and E7 inducible oncogene, hWAPL, exhibitspotential as a therapeutic target. The British Journal of Cancer, 2005, 92(2). 290-293.
2. Bosch FX, Manos MM, Munoz N, et al. Prevalence of human papillomavirus in cervical cancer: a world-wide perspective[J]. Natl Cancer Inst, 1995, 87:796-802.
3. Turan T; Kalantari M; Calleja Macias IE; Cubie HA; Cuschieri K; Villa LL;SkomedaI H; Barrera Saldana HA; Bernard HU. Methylation of the human papillomavirus-18 L1 gene: a biomarker of neoplasticprogression. Virology, 2006, 349(1). 175-183.
4. Walboomrs JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer world-wide [J]. Pathol, 1999, 189:12-19.
5. Chhieng DC; Chen J; Connolly K; Roberson J; Eltoum I. High-risk HPV DNA detection rate in patients with atypical squamous cells andits relationship to the atypical squamous cell: squamous intraepithelial lesion ratio. Acta Cytologica, 2006, 50(3).-291-294.
6. Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide:a systematic review. Cancer Epidemiol Biomarkers Prev, 2005 Feb; 14(2):467-75.
7. Rajeevan MS; Swan DC; Nisenbaum R; Lee DR; Vernon SD; Ruffin MT; Horowitz IR; Flowers LC; Kmak D; Tadros T; Birdsong G; Husain M; Srivastava S; Unger ER. Epidemiologic and viral factors associated with cervical neoplasia inHPV-16-positive women. International Journal of Cancer, 2005, 115(1). 114-120.
8. Kuroda M; Ohbayashi T; Yamada K; Matsuda Y; Mukai K. A dioxin sensitive gene, mammalian WAPL, is implicated in spermatogenesis. FEBS Letters, 2005, 579(1). 167-172.
9. Oikawa K; Ohbayashi T; Kiyono T; Nishi H; Isaka K; Umezawa A; Kuroda M; MukaiK. Expression of a novel human gene, human wings apart-like (hWAPL), isassociated with cervical carcinogenesis and tumor progression. Cancer research, 2004, 64(10).-3545-3549.
10.Kuroda M; Oikawa K; Yoshida K; Takeuchi A; Takeuchi M; Usui M; Umezawa A; Mukai K. Effects of 3-methylcholanthrene on the transcriptional activity and mRNA accumulation of the oncogene hWAPL. Cancer letters, 2005, 221(1). 21-28.
11.Kuroda M; Kiyono T; Oikawa K; Yoshida K; Mukai K. The human papillomavirus E6 and E7 inducible oncogene, hWAPL, exhibitspotential as a therapeutic target. The British Journal of Cancer, 2005, 92(2). 290-293.
12.Hubbard RA.Human papillomavirus testing methods. Arch Pathol Lab Med, 2003 Aug, 127(8):940-5.
13.Chew K, Rooney PH, Cruickshank ME, Murray GI. Laser capture microdissection and PCR for analysis of human papilloma virus infection. Methods. Mol Biol, 2005, 293:295-30.
14.Roberts CC; Tadesse AS; Sands J; Halvorsen T; Schofield TL; Dalen A; Skjeldestad FE; Jansen KU. Detection of HPV in Norwegian cervical biopsy specimens with type-specific PCR and reverse line blot assays. Journal of clinical virology, 2006,36(4). 277-282.
15.Yoshikawa H, Kawana T, Kitagawa K, Mizuno M, Yoshikura H, Iwamoto A. Detection and typing of multipe genital human papillomavirus by DNA amplification with consensus primers. Jpn J Cancer Res, 1991, 82:524-531.
16.Kim KH; Yoon MS; Na YJ; Park CS; Oh MR; Moon WC. Development and evaluation of a highly sensitive human papillomavirus genotyping DNA chip. Gynecologic Oncology, 2006, 100(1). 38-43.
17．冷彦宁．基因芯片技术与检验医学[J]．国外医学临床生物化学与检验学分册，2002，23(1)：12-16．
18.Lont AP; Kroon BK; Horenblas S; Gallee MP; Berkhof J; Meijer CJ; Snijders PJ. Presence of high-risk human papillomavirus DNA in penile carcinoma predictsfavorable outcome in survival. International Journal of Cancer, 2006, 119(5). 1078-1081.
19.Kraus I; Molden T; Holm R; Lie AK; Karlsen F; Kristensen GB; Skomedal H. Presence of E6 and E7 mRNA from human papillomavirus types 16, 18, 31, 33, and 45 in the majority of cervical carcinomas. Journal of Clinical Microbiology, 2006, 44(4). 1310-1317.
20.Chhieng DC; Chen J; Connolly K; Roberson J; Eltoum I. High-risk HPV DNA detection rate in patients with atypical squamous cells andits relationship to the atypical squamous cell: squamous intraepithelial lesion ratio. Acta Cytologica, 2006,50(3). 291-294.
21.Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide:a systematic review. Cancer Epidemiol Biomarkers Prev, 2005 Feb; 14(2):467-75.
22.Yang YC, Chang CL, Chen ML. Effect of p53 polymorphism on the susceptibility of cervical cancer [J]. Gynecol Obstet Invest, 2001, 51 (3): 197-201.
23.Cheung TH, Lo KW, Yu MM, et al. Aberranl expression of p21 (WAFI/CIPI) in cervical cancer, 2002, 79(3): 135-147.
24.Roh JW, Kim MH, Kim JW, et al.Polvmorphism in codon 31 of p21 and cervical cancer serciptibility in Korean women [J]. Cancer Letter, 2001, 165:59-62.
25.Borges HL, Bird J, Wasson K, CardiffRD, Varki N, Eckmann L, Wang JY. Tumor promotion by caspase-resistant retinoblastoma protein. Proc Natl Acad Sci USA, 2005; 102: 15587-15592.
26.Huang LW, Chao SL, Hwang JL, et al.Down regulation of P27 is associated with maligment transformation and aggressive phenotype of cervical neoplasm [J] .Int cervical carcinoma [J]. Cancer Lett, 2001, 172:93-98.
27．吕亚莉，钟梅，赵坡．应用基因芯片诊断宫颈石蜡组织样本中人乳头状瘤病毒感染及其临床意义．中华病理学杂志，2006，35：719—721．
28.Franco EL. Primary screening of cervical cancer with human papillomavirus tests. J Natl Cancer Inst Monogr, 2003; (31):89-96.
29.Wright TC; Bosch FX; Franco EL; Cuzick J; Schiller JT; Garnett GP; Meheus A. HPV vaccines and screening in the prevention of cervical cancer;conclusions from a 2006 workshop of international experts. Vaccine, 2006, 24(Sup3). s251-s261.
30.Mao C; Koutsky LA; Ault KA; Wheeler CM; Brown DR; Wiley DJ; Alvarez FB; Bautista OM; Jansen KU; Barr E. Efficacy of human papillomavirus-16 vaccine to prevent cervicalintraepithelial neoplasia: a randomized controlled trial. Obstetrics & Gynecology, 2006, 107(1). 18-27.
31.Carcia-Carranca A.Vaccines against human papillomavirus and perspectives for the prevention and control of cervical cancer. Salud Publica Mex, 2004 Jul-Auq; 46(4):284-5.
32.Smith JR, Boyle DC, Corless DJ, et al. Abdominal radical trachelectomy:anew surgical technique foe the conservative management of cervical carcinoma.Br J Obstet Gynaecol, 1997, 104(10):1196.
33．李爱玲，孙建衡．子宫颈癌放射治疗512例临床报道．中华妇产科杂志，2000，25，(5)：303．
34.Shinada M, Kigawa J, Takahashi M, et al. Stromal invasion of the cervix can be excluded from the criteria using adjuvant radiotherapy follow radical surgery for patients with cervical cancer[J]. G YNECOL Oncol, 2004, 93(3):628-631.
1．沈铿，郎景和．妇科肿瘤面临的问题和挑战[M]．北京：人民卫生出版社，2002．20—21．
2.Walboomrs JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer world-wide[J]. Pathol, 1999, 189:12-19.
3.Bosch F X, Lorincz A, Munoz N, et al. The causal relation between human papillomavirus and cervical cancer[J]. J Clin Pathol, 2002, 55:244-265.
4.Bosch FX, Manos MM, Munoz N, et al. Prevalence of human papillomavirus in cervical cancer: a world-wide perspective[J]. Natl Cancer Inst, 1995, 87:796-802.
5.Turan T; Kalantari M; Calleja Macias IE; Cubie HA; Cuschieri K; Villa LL; Skomedal H; Barrera Saldana HA; Bernard HU. Methylation of the human papillomavirus- 18 L1 gene: a biomarker of neoplasticprogression. Virology, 2006, 349(1). 175-183.
6．洪少林，王家壁，刘跃华，等．尖锐湿疣患者皮损中人乳头状瘤病毒的检测和分型[J]．中国医学科学院报，2002，24(4)：397-400．
7.Clifford GM,Rana RK,Franceschi S, Smith JS, Gough G, Pimenta JM. Human papillomavirus genotype distribution in low-grade cervical lesions:comparison by geographic region and with cervical cancer. Cancer Epidemiol Biomarkers Prev, 2005 May; 14(5): 1157-64.
8.Fule T; Csapo Z; Mathe M; Tatrai P; Laszlo V; Papp Z; Kovalszky I. Prognostic significance of high-risk HPV status in advanced cervical cancersand pelvic lymph nodes. Gynecologic Oncology, 2006, 100(3). 570-578.
9.Chhieng DC; Chen J; Connolly K; Roberson J; Eltoum I. High-risk HPV DNA detection rate in patients with atypical squamous cells andits relationship to the atypical squamous cell: squamous intraepithelial lesion ratio. Acta Cytologica, 2006, 50(3). 291-294.
10.Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide:a systematic review. Cancer Epidemiol Biomarkers Prev, 2005 Feb; 14(2):467-75.
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