中国部分地区宫颈癌及相关组织中人乳头瘤病毒分子流行病学调查
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摘要
宫颈癌(Cervical Cancer, CC)是最常见的女性恶性肿瘤之一。高危型人乳头瘤病毒(Human Papillomavirus, HPV)已被证实为是引发宫颈癌的主要病原体。明确某一地区HPV主要流行型别对指导HPV疫苗的应用推广和新一代疫苗的设计优化有着重要意义。同时,了解宫颈癌中HPV的物理状态和基因突变情况对深入研究HPV生活史和致癌机理也有着重要意义。
本实验从我国四川省,内蒙古通辽市和吉林省长春市收集宫颈癌及其相关组织,考察HPV整体感染和各型别分布情况,根据HPV型别调查结果,对在各地区流行最广泛的HPV16的E6基因的突变情况进行了分析。此外,本实验还对在东亚地区有着广泛流行的HPV58在宫颈癌组织内的物理状态和基因突变进行了考察。
对来自四川,通辽和长春的样品进行的HPV检测结果表明,在我国一些地区,一些人群中,除了HPV16,18之外,HPV45、52、58、59等型别也有着广泛的流行,在针对我国人群的下一代宫颈癌疫苗的研发工作中应当充分考虑这些型别的流行特点。对109例HPV16的E6基因序列分析中,共检测出20处点突变;系统进化分析结果表明分离自我国的所有HPV16突变体均属于欧洲原型突变组。对宫颈癌组织中HPV58的基因突变及物理状态的分析表明,78.4%的样品中的HPV58以完全整合形态存在,其中近一半的HPV58有多点断裂现象。在HPV58基因组中有118个位点发生了突变;系统进化分析结果表明,分离自我国的所有HPV58突变体均与HPV58原型处于同一分支,而另一分支主要由分离自非洲的突变株组成。这一结果提示,与HPV16一样,HPV58不同的突变株在世界各地的分布也有着明显的地域性特征。
Cervical cancer (CC) is the second most common cancer affecting women worldwide, and it is generally accepted that HPV is the primary causal agent of cervical carcinoma. The distribution of HPV types, subtypes and the variants varies greatly worldwide, which is closely related to the corresponding risk of cervical cancer. The determination of the prevalence of HPV types is important to the evaluation of the potential impact of current HPV vaccines and can assist in the identification of those additional HPV types, which should be considered for the development of future generation HPV prophylactic vaccines. Besides, the detailed delineation of the HPV gene variants and the pattern of viral integration could provide useful insights into understanding of mechanism of HPV-linked carcinogenesis and the natural history of HPV infections.
At present study, we have evaluated the prevalence and distribution of HPV types in cervical specimens collected from Sichuan province, Tongliao city of Inner Mongolia and Changchun city of Jilin province by combination of nested PCR and sequencing method. And also, we sequenced the E6 gene of HPV16, which is predominant HPV type in all of those three areas, and determined the subtype of the HPV16 based on the sequence of the E6 gene. In addition, we investigated the physical status and the gene variants of HPV58, which was reported to have a relatively high frequency in CC patients from East Asia.
Of the 190 CC specimens isolated from Sichuan province, HPV16 was found to be the most prevalent HPV genotypes. HPV 58, 52 and 59, detected in more than 10% of specimens, respectively, were quite prevalent in cervical cancer specimens from Sichuan province. HPV18, the second most prevalent HPV type worldwide, was found in 8.4% of specimens, which is lower than the rate reported in worldwide (12.8%). It is interesting that many HPV16, 52, 58 and 59 infections detected in this study existed with lower viral load, and was only detected by nested PCR methods. The role of such high prevalence of these types with low viral load in development of cervical cancer needs further investigation.
In the result of HPV detection in 175 archival cervical lesions collected from Tongliao, HPV16 was found to be the most predominant HPV type in all cervical lesions, and HPV 45 was found as the second most predominant HPV type in CC and HSIL (High-grade Squamous Intraepithelial Lesion). The prevalence of HPV 45 in Tongliao area is significantly higher than those previous studies on other region of China, and the infection rate of HPV 45 was found to increase as the severity of cervical lesions increased, which indicate that HPV 45 may play a more significant role in the etiology of cervical cancer in Tongliao area than other region of China. Comparing the HPV detection rates in Han Chinese and Mongolian, the prevalence of HPV 18 in Mongolian CC patient was found to be significantly higher than that in Han Chinese patients.
In Changchun area, HPV16 was found to be the most predominant HPV type in both CC and normal cervical swab specimens. The infection rates of other high risk HPV types, such as HPV 18, 45, 52, 58 and 59, which were reported to have high frequency in CC from different region of China, were quite low in CC specimens from Changchun. However, the prevalence of HPV58, which is prevalent in Southern China, and HPV 62, which is prevalent in Korea, were found to be quite prevalent in normal cervical samples from this area. The uncommon higher prevalence of HPV58 and 62 in normal cervical samples than that of cervical cancer in Changchun area may have some association with the change of population flow during recent decades since the open-door policy; and because the development of cervical cancer is usually slow, and occurs over a period of years, the changes of prevalence of HPV types may has not been reflected in the HPV infection rates in cervical cancer.
Comparing the HPV detection rates in cervical cancer from Sichuan, Tongliao and Changchun, no significant differences were observed in the overall prevalence of HPV infection, while the distribution of some certain HPV types varies greatly across populations. Combining with the results of previous studies in China, our result further confirmed that the distribution of HPV types in China is different from other region of the world, and there is also some difference in prevalence of HPV types among different region and different ethic group in China. Besides HPV16 and 18, which were most prevalent high-risk types worldwide, HPV 45, 52, 58 and 59 is prevalent in different region of China, and for optimal population coverage, these HPV carcinogenic types should be considered for second-generation HPV prophylactic vaccines.
By sequencing 109 cases of HPV16 E6 gene, 20 nucleotide positions in E6 gene found to be variable, and among them, the nucleotide changes A121G、C158G、T377G、t429c、C434G have not been reported previously. The nucleotide change T96G was found to be the most common variant in present study, 27 samples contained this nucleotide change, and the nucleotide change T268G was found to be the second most common variant, 22 samples contained this nucleotide change. Of the 20 nucleotide changes, 17 lead to amino acid changes. Among them amino acid change R10G、T22S、H24Y、D25K、D25E、E29Q、K34E、A46G、R55K、N58S、L64E、S71C、H78Y、L83V、L119R、K121E、S138C were located in the HPV E6 epitope regions, suggests that these changes may alter their epitope specificity. The amino acid change D113E was located in the HPV E6 P53 binding and degeneration regions; indicate that this change may affect the binding affinity of E6 to p53.
Phylogenetic analysis based on sequences of 33 variants isolated from in present study and 5 main HPV 16 subtypes show that 27 of 33 variants were classified as As (East-Asia) subtype, and 6 of variants were classified as E (European, prototype) subtype; all variants isolated in present studies were included in the Prototype-prototype like group. Both As subtype and E subtype were found in both Han Chinese and Mongolian from Sichuan, Inner Mongolia and Changchun, and. the As subtype seems to be more prevalent in Sichuan, which located at southern china, while the E subtype seems to be more prevalent in Changchun and Tongliao, where located at northern China.
By investigating the physical status and the gene variants of 37 cases of HPV58, a pure integrated genome was found in 78.4 % ( 29/37) specimens, which is much higher than those in previous studies. In the 29 completely integrated HPV 58 isolates, 15 cases were found to have multiple disruptions in the HPV 58. There is, to our knowledge, no previous report on phenomena of the multiple disruptions found in the integrated HPV genome. The mechanism of action and biological activity of the multiple disruptions of HPV genome remain unclear and require further investigation. The sequence between nucleotides 7557 and 970 is conserved in all completely integrated HPV 58 genome, indicates that detection of this sequence might be an ideal marker for PCR-based determination of HPV 58 infections. Besides, all completely integrated HPV 58 genome isolated in this study have disrupted or lost at least part of nucleotide sequence between nucleotides 1883 and 3184, indicating that detection of the loss of this sequence might be an ideal marker for PCR-based determination of HPV 58 integration.
In the entire HPV 58 genome, 119 (1.52 %) nucleotide changes were found; of these, 45 lead to amino acid changes when compared with the reference sequence. Among each region or ORF of the HPV58 genomes, the unncoding region between nt 4123-4244 had the highest proportion of variable nucleotide positions 3.31% (4/121); among each ORF of the HPV 58, the amino acid changes frequency in E7 was the highest 7.14% (7/98), followed by E4, E1, E6, E5, L2, L1 and E2. Phylogenetic analyses based on partial L1 sequences of 14 variants isolated in previous studies and this study shows that two main groups were observed in HPV 58 variants, the prototype or prototype-like group and non-prototype-like group. All variants identified in this study were included in the prototype/prototype-like group. No African specimens were included in the prototype/prototype-like group, and no Asian specimens in the non-prototype-like group, while European and American specimens were included in both groups.
本实验从我国四川省,内蒙古通辽市和吉林省长春市收集宫颈癌及其相关组织,考察HPV整体感染和各型别分布情况,根据HPV型别调查结果,对在各地区流行最广泛的HPV16的E6基因的突变情况进行了分析。此外,本实验还对在东亚地区有着广泛流行的HPV58在宫颈癌组织内的物理状态和基因突变进行了考察。
对来自四川,通辽和长春的样品进行的HPV检测结果表明,在我国一些地区,一些人群中,除了HPV16,18之外,HPV45、52、58、59等型别也有着广泛的流行,在针对我国人群的下一代宫颈癌疫苗的研发工作中应当充分考虑这些型别的流行特点。对109例HPV16的E6基因序列分析中,共检测出20处点突变;系统进化分析结果表明分离自我国的所有HPV16突变体均属于欧洲原型突变组。对宫颈癌组织中HPV58的基因突变及物理状态的分析表明,78.4%的样品中的HPV58以完全整合形态存在,其中近一半的HPV58有多点断裂现象。在HPV58基因组中有118个位点发生了突变;系统进化分析结果表明,分离自我国的所有HPV58突变体均与HPV58原型处于同一分支,而另一分支主要由分离自非洲的突变株组成。这一结果提示,与HPV16一样,HPV58不同的突变株在世界各地的分布也有着明显的地域性特征。
Cervical cancer (CC) is the second most common cancer affecting women worldwide, and it is generally accepted that HPV is the primary causal agent of cervical carcinoma. The distribution of HPV types, subtypes and the variants varies greatly worldwide, which is closely related to the corresponding risk of cervical cancer. The determination of the prevalence of HPV types is important to the evaluation of the potential impact of current HPV vaccines and can assist in the identification of those additional HPV types, which should be considered for the development of future generation HPV prophylactic vaccines. Besides, the detailed delineation of the HPV gene variants and the pattern of viral integration could provide useful insights into understanding of mechanism of HPV-linked carcinogenesis and the natural history of HPV infections.
At present study, we have evaluated the prevalence and distribution of HPV types in cervical specimens collected from Sichuan province, Tongliao city of Inner Mongolia and Changchun city of Jilin province by combination of nested PCR and sequencing method. And also, we sequenced the E6 gene of HPV16, which is predominant HPV type in all of those three areas, and determined the subtype of the HPV16 based on the sequence of the E6 gene. In addition, we investigated the physical status and the gene variants of HPV58, which was reported to have a relatively high frequency in CC patients from East Asia.
Of the 190 CC specimens isolated from Sichuan province, HPV16 was found to be the most prevalent HPV genotypes. HPV 58, 52 and 59, detected in more than 10% of specimens, respectively, were quite prevalent in cervical cancer specimens from Sichuan province. HPV18, the second most prevalent HPV type worldwide, was found in 8.4% of specimens, which is lower than the rate reported in worldwide (12.8%). It is interesting that many HPV16, 52, 58 and 59 infections detected in this study existed with lower viral load, and was only detected by nested PCR methods. The role of such high prevalence of these types with low viral load in development of cervical cancer needs further investigation.
In the result of HPV detection in 175 archival cervical lesions collected from Tongliao, HPV16 was found to be the most predominant HPV type in all cervical lesions, and HPV 45 was found as the second most predominant HPV type in CC and HSIL (High-grade Squamous Intraepithelial Lesion). The prevalence of HPV 45 in Tongliao area is significantly higher than those previous studies on other region of China, and the infection rate of HPV 45 was found to increase as the severity of cervical lesions increased, which indicate that HPV 45 may play a more significant role in the etiology of cervical cancer in Tongliao area than other region of China. Comparing the HPV detection rates in Han Chinese and Mongolian, the prevalence of HPV 18 in Mongolian CC patient was found to be significantly higher than that in Han Chinese patients.
In Changchun area, HPV16 was found to be the most predominant HPV type in both CC and normal cervical swab specimens. The infection rates of other high risk HPV types, such as HPV 18, 45, 52, 58 and 59, which were reported to have high frequency in CC from different region of China, were quite low in CC specimens from Changchun. However, the prevalence of HPV58, which is prevalent in Southern China, and HPV 62, which is prevalent in Korea, were found to be quite prevalent in normal cervical samples from this area. The uncommon higher prevalence of HPV58 and 62 in normal cervical samples than that of cervical cancer in Changchun area may have some association with the change of population flow during recent decades since the open-door policy; and because the development of cervical cancer is usually slow, and occurs over a period of years, the changes of prevalence of HPV types may has not been reflected in the HPV infection rates in cervical cancer.
Comparing the HPV detection rates in cervical cancer from Sichuan, Tongliao and Changchun, no significant differences were observed in the overall prevalence of HPV infection, while the distribution of some certain HPV types varies greatly across populations. Combining with the results of previous studies in China, our result further confirmed that the distribution of HPV types in China is different from other region of the world, and there is also some difference in prevalence of HPV types among different region and different ethic group in China. Besides HPV16 and 18, which were most prevalent high-risk types worldwide, HPV 45, 52, 58 and 59 is prevalent in different region of China, and for optimal population coverage, these HPV carcinogenic types should be considered for second-generation HPV prophylactic vaccines.
By sequencing 109 cases of HPV16 E6 gene, 20 nucleotide positions in E6 gene found to be variable, and among them, the nucleotide changes A121G、C158G、T377G、t429c、C434G have not been reported previously. The nucleotide change T96G was found to be the most common variant in present study, 27 samples contained this nucleotide change, and the nucleotide change T268G was found to be the second most common variant, 22 samples contained this nucleotide change. Of the 20 nucleotide changes, 17 lead to amino acid changes. Among them amino acid change R10G、T22S、H24Y、D25K、D25E、E29Q、K34E、A46G、R55K、N58S、L64E、S71C、H78Y、L83V、L119R、K121E、S138C were located in the HPV E6 epitope regions, suggests that these changes may alter their epitope specificity. The amino acid change D113E was located in the HPV E6 P53 binding and degeneration regions; indicate that this change may affect the binding affinity of E6 to p53.
Phylogenetic analysis based on sequences of 33 variants isolated from in present study and 5 main HPV 16 subtypes show that 27 of 33 variants were classified as As (East-Asia) subtype, and 6 of variants were classified as E (European, prototype) subtype; all variants isolated in present studies were included in the Prototype-prototype like group. Both As subtype and E subtype were found in both Han Chinese and Mongolian from Sichuan, Inner Mongolia and Changchun, and. the As subtype seems to be more prevalent in Sichuan, which located at southern china, while the E subtype seems to be more prevalent in Changchun and Tongliao, where located at northern China.
By investigating the physical status and the gene variants of 37 cases of HPV58, a pure integrated genome was found in 78.4 % ( 29/37) specimens, which is much higher than those in previous studies. In the 29 completely integrated HPV 58 isolates, 15 cases were found to have multiple disruptions in the HPV 58. There is, to our knowledge, no previous report on phenomena of the multiple disruptions found in the integrated HPV genome. The mechanism of action and biological activity of the multiple disruptions of HPV genome remain unclear and require further investigation. The sequence between nucleotides 7557 and 970 is conserved in all completely integrated HPV 58 genome, indicates that detection of this sequence might be an ideal marker for PCR-based determination of HPV 58 infections. Besides, all completely integrated HPV 58 genome isolated in this study have disrupted or lost at least part of nucleotide sequence between nucleotides 1883 and 3184, indicating that detection of the loss of this sequence might be an ideal marker for PCR-based determination of HPV 58 integration.
In the entire HPV 58 genome, 119 (1.52 %) nucleotide changes were found; of these, 45 lead to amino acid changes when compared with the reference sequence. Among each region or ORF of the HPV58 genomes, the unncoding region between nt 4123-4244 had the highest proportion of variable nucleotide positions 3.31% (4/121); among each ORF of the HPV 58, the amino acid changes frequency in E7 was the highest 7.14% (7/98), followed by E4, E1, E6, E5, L2, L1 and E2. Phylogenetic analyses based on partial L1 sequences of 14 variants isolated in previous studies and this study shows that two main groups were observed in HPV 58 variants, the prototype or prototype-like group and non-prototype-like group. All variants identified in this study were included in the prototype/prototype-like group. No African specimens were included in the prototype/prototype-like group, and no Asian specimens in the non-prototype-like group, while European and American specimens were included in both groups.
引文
1. Ferlay, J. and D.M. Parkin, GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC Cancer Base No. 5, version 2.0. IARC Press. 2004.
2. Vernon, S.D., E.R. Unger, and W.C. Reeves, Human papillomavirus and cervical cancer. Curr Probl Obstet Gynecol Fertil, 1998. 2(4): p. 104.
3. Zur Hausen, H., Virus and cancer: the concept of the masked causative agent. Immun Infekt, 1973(1): p. 5-9.
4. zur Hausen, H., Human papillomaviruses and their possible role in squamous cell carcinomas. Curr Top Microbiol Immunol, 1977. 78: p. 1-30.
5. Bekkers, R.L., et al., Epidemiological and clinical aspects of human papillomavirus detection in the prevention of cervical cancer. Rev Med Virol, 2004. 14(2): p. 95-105.
6. Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum, 1995. 64: p. 1-378.
7. Modis, Y., B.L. Trus, and S.C. Harrison, Atomic model of the papillomavirus capsid. Embo J, 2002. 21(18): p. 4754-62.
8. de Villiers, E.M., et al., Classification of papillomaviruses. Virology, 2004. 324(1): p. 17-27.
9. Munoz, N., et al., Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med, 2003. 348(6): p. 518-27.
10. Jacobs, M.V., et al., Group-specific differentiation between high- and low-risk human papillomavirus genotypes by general primer-mediated PCR and two cocktails of oligonucleotide probes. J Clin Microbiol, 1995. 33(4): p. 901-5.
11. Gravitt, P.E., et al., Genotyping of 27 human papillomavirus types by using L1 consensus PCR products by a single-hybridization, reverse line blot detection method. J Clin Microbiol, 1998. 36(10): p. 3020-7.
12. Davies, P., J. Kornegay, and T. Iftner, Current methods of testing for human papillomavirus. Best Pract Res Clin Obstet Gynaecol, 2001. 15(5): p. 677-700.
13. van den Brule, A.J.C., et al., GP5+/6+PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. Journal of Clinical Microbiology, 2002. 40(3): p. 779-787.
14. Scheffner, M., et al., Functions of human papillomavirus proteins. Curr Top Microbiol Immunol, 1994. 186: p. 83-99.
15. Stoler, M.H., Human papillomaviruses and cervical neoplasia: a model for carcinogenesis. Int J Gynecol Pathol, 2000. 19(1): p. 16-28.
16. Stoler, M.H., The virology of cervical neoplasia: an HPV-associated malignancy. Cancer J, 2003. 9(5): p. 360-7.
17. Kalantari, M., et al., Disruption of the E1 and E2 reading frames of HPV 16 in cervical carcinoma is associated with poor prognosis. Int J Gynecol Pathol, 1998. 17(2): p.146-53.
18. Cripe, T.P., et al., Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. Embo J, 1987. 6(12): p. 3745-53.
19. Thierry, F. and M. Yaniv, The BPV1-E2 trans-acting protein can be either an activator or a repressor of the HPV18 regulatory region. Embo J, 1987. 6(11): p. 3391-7.
20. Wilson, V.G., et al., Papillomavirus E1 proteins: form, function, and features. Virus Genes, 2002. 24(3): p. 275-90.
21. Doorbar, J., et al., Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature, 1991. 352(6338): p. 824-7.
22. Wang, Q., et al., Functional analysis of the human papillomavirus type 16 E1=E4 protein provides a mechanism for in vivo and in vitro keratin filament reorganization. J Virol, 2004. 78(2): p. 821-33.
23. Peh, W.L., et al., Life cycle heterogeneity in animal models of human papillomavirus-associated disease. J Virol, 2002. 76(20): p. 10401-16.
24. Hwang, E.S., T. Nottoli, and D. Dimaio, The HPV16 E5 protein: expression, detection, and stable complex formation with transmembrane proteins in COS cells. Virology, 1995. 211(1): p. 227-33.
25. Liu, Y.M., A. McKalip, and B. Herman, Human papillomavirus type 16 E6 and HPV-16 E6/E7 sensitize human keratinocytes to apoptosis induced by chemotherapeutic agents: Roles of p53 and caspase activation. Journal of Cellular Biochemistry, 2000. 78(2): p. 334-349.
26. Crish, J.F., et al., Suprabasal expression of the human papillomavirus type 16 oncoproteins in mouse epidermis alters expression of cell cycle regulatory proteins. Carcinogenesis, 2000. 21(5): p. 1031-7.
27. Xu, X.M., Human Papillomaviruses and Cervical Cancer Vaccines: To Decode 2008 Nobel Prize in Physiology or Medicine. Progress in Biochemistry and Biophysics, 2008. 35(10): p. 1095-1103.
28. Doorbar, J., Papillomavirus life cycle organization and biomarker selection. Dis Markers, 2007. 23(4): p. 297-313.
29. Feoli-Fonseca, J.C., et al., Human papillomavirus (HPV) study of 691 pathological specimens from Quebec by PCR-direct sequencing approach. J Med Virol, 2001. 63(4): p. 284-92.
30. Gharizadeh, B., et al., Typing of human papillomavirus by pyrosequencing. Lab Invest, 2001. 81(5): p. 673-9.
31.陈汶, et al.,人乳头状瘤病毒DNA检测进展.中华检验医学杂志, 2005. 28(5): p. 552-554.
32. Baseman, J.G. and L.A. Koutsky, The epidemiology of human papillomavirus infections. JClin Virol, 2005. 32 Suppl 1: p. S16-24.
33. Sanchez-Perez, A.M., et al., Disruption of the human papillomavirus type 16 E2 gene protects cervical carcinoma cells from E2F-induced apoptosis. J Gen Virol, 1997. 78 ( Pt 11): p. 3009-18.
34. Alvarez-Salas, L.M., et al., Inhibition of HPV-16 E6/E7 immortalization of normal keratinocytes by hairpin ribozymes. Proc Natl Acad Sci U S A, 1998. 95(3): p. 1189-94.
35. Schoell, W.M., M.F. Janicek, and R. Mirhashemi, Epidemiology and biology of cervical cancer. Semin Surg Oncol, 1999. 16(3): p. 203-11.
36. Magal, S.S., et al., Induction of apoptosis in human keratinocytes containing mutated p53 alleles and its inhibition by both the E6 and E7 oncoproteins. Int J Cancer, 1998. 75(1): p. 96-104.
37. Brown, J., et al., Human papillomavirus (HPV) 16 E6 sensitizes cells to atractyloside-induced apoptosis: role of p53, ICE-like proteases and the mitochondrial permeability transition. J Cell Biochem, 1997. 66(2): p. 245-55.
38. Pillai, M.R., et al., High-risk human papillomavirus infection and E6 protein expression in lesions of the uterine cervix. Pathobiology, 1998. 66(5): p. 240-6.
39. Morris, J.D., et al., Human papillomavirus type 16 E7 regulates E2F and contributes to mitogenic signalling. Oncogene, 1993. 8(4): p. 893-8.
40. Schiffman, M.H., Recent progress in defining the epidemiology of human papillomavirus infection and cervical neoplasia. J Natl Cancer Inst, 1992. 84(6): p. 394-8.
41. Kjaer, S.K., et al., High-risk human papillomavirus is sexually transmitted: Evidence from a follow-up study of virgins starting sexual activity (intercourse). Cancer Epidemiology Biomarkers & Prevention, 2001. 10(2): p. 101-106.
42. Koutsky, L.A., et al., A controlled trial of a human papillomavirus type 16 vaccine. New England Journal of Medicine, 2002. 347(21): p. 1645-1651.
43. Clifford, G.M., et al., Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br J Cancer, 2003. 89(1): p. 101-5.
44. Farjadian, S., et al., High risk HPV types in southern Iranian patients with cervical cancer. Pathol Oncol Res, 2003. 9(2): p. 121-5.
45. Smith, J.S., et al., Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer, 2007. 121(3): p. 621-32.
46. Yamada, T., et al., Human papillomavirus type 16 variant lineages in United States populations characterized by nucleotide sequence analysis of the E6, L2, and L1 coding segments. J Virol, 1995. 69(12): p. 7743-53.
47. Yamada, T., et al., Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective. J Virol, 1997. 71(3): p. 2463-72.
48. Xi, L.F., et al., Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia. J Natl Cancer Inst, 1997. 89(11): p. 796-802.
49. Wheeler, C.M., et al., Human papillomavirus type 16 sequence variants: identification byE6 and L1 lineage-specific hybridization. J Clin Microbiol, 1997. 35(1): p. 11-9.
50. Xi, L.F., et al., Analysis of human papillomavirus type 16 variants indicates establishment of persistent infection. J Infect Dis, 1995. 172(3): p. 747-55.
51. Villa, L.L., et al., Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia. J Gen Virol, 2000. 81(Pt 12): p. 2959-68.
52. Matsumoto, K., et al., Enhanced oncogenicity of human papillomavirus type 16 (HPV16) variants in Japanese population. Cancer Lett, 2000. 156(2): p. 159-65.
53. Berumen, J., et al., Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study. J Natl Cancer Inst, 2001. 93(17): p. 1325-30.
54. Hildesheim, A., et al., Human papillomavirus type 16 variants and risk of cervical cancer. J Natl Cancer Inst, 2001. 93(4): p. 315-8.
55. Zehbe, I., et al., Human papillomavirus 16 E6 variants are more prevalent in invasive cervical carcinoma than the prototype. Cancer Res, 1998. 58(4): p. 829-33.
56. Woodman, C.B., S.I. Collins, and L.S. Young, The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer, 2007. 7(1): p. 11-22.
57. Jeon, S. and P.F. Lambert, Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci U S A, 1995. 92(5): p. 1654-8.
58. Romanczuk, H., F. Thierry, and P.M. Howley, Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. J Virol, 1990. 64(6): p. 2849-59.
59. Thierry, F. and P.M. Howley, Functional analysis of E2-mediated repression of the HPV18 P105 promoter. New Biol, 1991. 3(1): p. 90-100.
60. Jeon, S., B.L. Allen-Hoffmann, and P.F. Lambert, Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol, 1995. 69(5): p. 2989-97.
61. Hall, S., et al., Human papillomavirus DNA detection in cervical specimens by hybrid capture: correlation with cytologic and histologic diagnoses of squamous intraepithelial lesions of the cervix. Gynecol Oncol, 1996. 62(3): p. 353-9.
62. Lillo, F.B., et al., Determination of human papillomavirus (HPV) load and type in high-grade cervical lesions surgically resected from HIV-infected women during follow-up of HPV infection. Clin Infect Dis, 2005. 40(3): p. 451-7.
63. Swan, D.C., et al., Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type. J Clin Microbiol, 1999. 37(4): p. 1030-4.
64. Kataja, V., et al., Prospective follow-up of genital HPV infections: survival analysis of the HPV typing data. Eur J Epidemiol, 1990. 6(1): p. 9-14.
65. Burk, R.D., et al., Sexual behavior and partner characteristics are the predominant risk factors for genital human papillomavirus infection in young women. J Infect Dis, 1996. 174(4): p. 679-89.
66. Franco, E.L., et al., Transmission of cervical human papillomavirus infection by sexual activity: differences between low and high oncogenic risk types. J Infect Dis, 1995. 172(3): p. 756-63.
67. Moreno, V., et al., Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet, 2002. 359(9312): p. 1085-1092.
68. Shields, T.S., et al., A case-control study of risk factors for invasive cervical cancer among U.S. women exposed to oncogenic types of human papillomavirus. Cancer Epidemiol Biomarkers Prev, 2004. 13(10): p. 1574-82.
69. Gram, I.T., et al., Cigarette smoking and risk of borderline and invasive epithelial ovarian cancer. Int J Cancer, 2008. 122(3): p. 647-652.
70. Brinton, L.A. and J.F. Fraumeni, Jr., Epidemiology of uterine cervical cancer. J Chronic Dis, 1986. 39(12): p. 1051-65.
71. Ngan, H.Y., V.W. Liu, and S.S. Liu, Risk of cervical cancer is not increased in Chinese carrying homozygous arginine at codon 72 of p53. Br J Cancer, 1999. 80(11): p. 1828-9.
72. Abba, M.C., et al., The p53 codon 72 genotypes in HPV infection and cervical disease. Eur J Obstet Gynecol Reprod Biol, 2003. 109(1): p. 63-6.
73. Palker, T.J., et al., Antibody, cytokine and cytotoxic T lymphocyte responses in chimpanzees immunized with human papillomavirus virus-like particles. Vaccine, 2001. 19(27): p. 3733-43.
74. Koutsky, L.A., et al., A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med, 2002. 347(21): p. 1645-51.
75. Govan, V.A., A novel vaccine for cervical cancer: quadrivalent human papillomavirus (types 6, 11, 16 and 18) recombinant vaccine (Gardasil). Ther Clin Risk Manag, 2008. 4(1): p. 65-70.
76. Keam, S.J. and D.M. Harper, Human papillomavirus types 16 and 18 vaccine (Recombinant, AS04 adjuvanted, adsorbed) [Cervarix (TM)]. Biodrugs, 2008. 22(3): p. 205-208.
77. Castellsague, X., et al., HPV and Cervical Cancer in the World 2007 Report. Vaccine, 2007. 25: p. Iv-+.
78. China national cause-of-death surveys China Cancer Database Web site [cited 2008. November 2].
79.郝敏and王静芳,宫颈癌流行病学研究与调查.国外医学妇幼保健分册, 2005. 16(6).
80.李洁,刘宝印, and Z. Hausen.,中国妇女宫颈癌组织中人乳头瘤病毒感染及地理分布的调查.中国实验和临床病毒学, 1996(10): p. 50-55.
81. Bao, Y.P., et al., Human papillomavirus type-distribution in the cervix of Chinese women: a meta-analysis. Int J STD AIDS, 2008. 19(2): p. 106-11.
82. Stephen, A.L., et al., Analysis of mutations in the URR and E6/E7oncogenes of HPV cervical cancer isolates from central China. International Journal of Cancer, 2000. 86(5):p. 695-701.
83. Manos, M. and D.K. Wright, The use of polymerase chain reaction amplification for the detection of genital human papillomaviruses. Cancer Cells, 1989(7): p. 209-214.
84. Sotlar, K., et al., Detection and typing of human papillomavirus by e6 nested multiplex PCR. J Clin Microbiol, 2004. 42(7): p. 3176-84.
85. Hong, D., et al., Distribution of human papillomavirus genotypes in the patients with cervical carcinoma and its precursors in Zhejiang Province, China. International Journal of Gynecological Cancer, 2008. 18(1): p. 104-109.
86. Huang, S., et al., Human papillomavirus types 52 and 58 are prevalent in cervical cancers from Chinese women. Int J Cancer, 1997. 70(4): p. 408-11.
87. Liu, J., et al., Comparative analysis of characteristics of women with cervical cancer in high- versus low-incidence regions. Gynecol Oncol, 2004. 94(3): p. 803-10.
88. Bao, Y.P., et al., Human papillomavirus type distribution in women from Asia: a meta-analysis. International Journal of Gynecological Cancer, 2008. 18(1): p. 71-79.
89. Lin, M., et al., Genital human papillomavirus screening by gene chip in Chinese women of Guangdong province. Aust N Z J Obstet Gynaecol, 2008. 48(2): p. 189-94.
90. Dai, M., et al., Human papillomavirus infection in Shanxi Province, People's Republic of China: a population-based study. Br J Cancer, 2006. 95(1): p. 96-101.
91. Dai, Y., et al., Distribution and clinical significance of human papillomavirus subtypes in Shenzhen city, People's Republic of China. Int J Gynecol Cancer, 2008. 18(2): p. 295-9.
92. Li, X.L., et al., [Human papillomaviruses infections among village women in Henan province]. Zhonghua Yu Fang Yi Xue Za Zhi, 2007. 41 Suppl: p. 77-80.
93. Li, L.K., et al., Human papillomavirus infection in Shenyang City, People's Republic of China: A population-based study. Br J Cancer, 2006. 95(11): p. 1593-7.
94. Zhang, W.Y., et al., Prevalence of high-risk human papillomavirus infection in different cervical lesion among organized health-examination women in Shanghai, China. Chin Med J (Engl), 2008. 121(16): p. 1578-82.
95. Choi, Y.D., et al., Detection of HPV genotypes in cervical lesions by the HPV DNA Chip and sequencing. Gynecol Oncol, 2005. 98(3): p. 369-75.
96. Kast, W.M., et al., Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. J Immunol, 1994. 152(8): p. 3904-12.
97. Crook, T., J.A. Tidy, and K.H. Vousden, Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation. Cell, 1991. 67(3): p. 547-56.
98. Foster, S.A., et al., The ability of human papillomavirus E6 proteins to target p53 for degradation in vivo correlates with their ability to abrogate actinomycin D-induced growth arrest. J Virol, 1994. 68(9): p. 5698-705.
99. Chen, Z., et al., Diversifying selection in human papillomavirus type 16 lineages based on complete genome analyses. J Virol, 2005. 79(11): p. 7014-23.
100. Arias-Pulido, H., et al., Human papillomavirus type 16 integration in cervical carcinomain situ and in invasive cervical cancer. J Clin Microbiol, 2006. 44(5): p. 1755-62.
101. Chan, P.K., et al., Profile of viral load, integration, and E2 gene disruption of HPV58 in normal cervix and cervical neoplasia. J Infect Dis, 2007. 196(6): p. 868-75.
102. Ho, C.M., et al., Integrated human papillomavirus types 52 and 58 are infrequently found in cervical cancer, and high viral loads predict risk of cervical cancer. Gynecol Oncol, 2006. 102(1): p. 54-60.
103. Qiu, A.D., et al., HPV prevalence, E6 sequence variation and physical state of HPV16 isolates from patients with cervical cancer in Sichuan, China. Gynecol Oncol, 2007. 104(1): p. 77-85.
104. Chan, P.K., et al., Association of human papillomavirus type 58 variant with the risk of cervical cancer. J Natl Cancer Inst, 2002. 94(16): p. 1249-53.
105. Xin, C.Y., et al., Analysis of E6 variants of human papillomavirus type 33, 52 and 58 in Japanese women with cervical intraepithelial neoplasia/cervical cancer in relation to their oncogenic potential. Cancer Lett, 2001. 170(1): p. 19-24.
106. Androphy, E.J., D.R. Lowy, and J.T. Schiller, Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA. Nature, 1987. 325(6099): p. 70-3.
107. Lewis, H., et al., Cellular transcription factors regulate human papillomavirus type 16 gene expression by binding to a subset of the DNA sequences recognized by the viral E2 protein. J Gen Virol, 1999. 80 ( Pt 8): p. 2087-96.
108. Storey, A., et al., Mutations in the human papillomavirus type 16 E2 protein identify a region of the protein involved in binding to E1 protein. J Gen Virol, 1995. 76 ( Pt 4): p.
819-26.
109. Hegde, R.S., et al., Crystal structure at 1.7 A of the bovine papillomavirus-1 E2 DNA-binding domain bound to its DNA target. Nature, 1992. 359(6395): p. 505-12.
110. Kurvinen, K., et al., Variants of the long control region of human papillomavirus type 16. Eur J Cancer, 2000. 36(11): p. 1402-10.
111. Chan, S.Y., et al., Analysis of genomic sequences of 95 papillomavirus types: uniting typing, phylogeny, and taxonomy. J Virol, 1995. 69(5): p. 3074-83.
112. Calleja-Macias, I.E., et al., Worldwide genomic diversity of the high-risk human papillomavirus types 31, 35, 52, and 58, four close relatives of human papillomavirus type 16. J Virol, 2005. 79(21): p. 13630-40.
113. Stewart, A.C., et al., Intratype variation in 12 human papillomavirus types: a worldwide perspective. J Virol, 1996. 70(5): p. 3127-36.
114. Tornesello, M.L., et al., Prevalence of human papillomavirus genotypes and their variants in high risk West Africa women immigrants in South Italy. Infect Agent Cancer, 2007. 2: p. 1.
2. Vernon, S.D., E.R. Unger, and W.C. Reeves, Human papillomavirus and cervical cancer. Curr Probl Obstet Gynecol Fertil, 1998. 2(4): p. 104.
3. Zur Hausen, H., Virus and cancer: the concept of the masked causative agent. Immun Infekt, 1973(1): p. 5-9.
4. zur Hausen, H., Human papillomaviruses and their possible role in squamous cell carcinomas. Curr Top Microbiol Immunol, 1977. 78: p. 1-30.
5. Bekkers, R.L., et al., Epidemiological and clinical aspects of human papillomavirus detection in the prevention of cervical cancer. Rev Med Virol, 2004. 14(2): p. 95-105.
6. Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum, 1995. 64: p. 1-378.
7. Modis, Y., B.L. Trus, and S.C. Harrison, Atomic model of the papillomavirus capsid. Embo J, 2002. 21(18): p. 4754-62.
8. de Villiers, E.M., et al., Classification of papillomaviruses. Virology, 2004. 324(1): p. 17-27.
9. Munoz, N., et al., Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med, 2003. 348(6): p. 518-27.
10. Jacobs, M.V., et al., Group-specific differentiation between high- and low-risk human papillomavirus genotypes by general primer-mediated PCR and two cocktails of oligonucleotide probes. J Clin Microbiol, 1995. 33(4): p. 901-5.
11. Gravitt, P.E., et al., Genotyping of 27 human papillomavirus types by using L1 consensus PCR products by a single-hybridization, reverse line blot detection method. J Clin Microbiol, 1998. 36(10): p. 3020-7.
12. Davies, P., J. Kornegay, and T. Iftner, Current methods of testing for human papillomavirus. Best Pract Res Clin Obstet Gynaecol, 2001. 15(5): p. 677-700.
13. van den Brule, A.J.C., et al., GP5+/6+PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. Journal of Clinical Microbiology, 2002. 40(3): p. 779-787.
14. Scheffner, M., et al., Functions of human papillomavirus proteins. Curr Top Microbiol Immunol, 1994. 186: p. 83-99.
15. Stoler, M.H., Human papillomaviruses and cervical neoplasia: a model for carcinogenesis. Int J Gynecol Pathol, 2000. 19(1): p. 16-28.
16. Stoler, M.H., The virology of cervical neoplasia: an HPV-associated malignancy. Cancer J, 2003. 9(5): p. 360-7.
17. Kalantari, M., et al., Disruption of the E1 and E2 reading frames of HPV 16 in cervical carcinoma is associated with poor prognosis. Int J Gynecol Pathol, 1998. 17(2): p.146-53.
18. Cripe, T.P., et al., Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. Embo J, 1987. 6(12): p. 3745-53.
19. Thierry, F. and M. Yaniv, The BPV1-E2 trans-acting protein can be either an activator or a repressor of the HPV18 regulatory region. Embo J, 1987. 6(11): p. 3391-7.
20. Wilson, V.G., et al., Papillomavirus E1 proteins: form, function, and features. Virus Genes, 2002. 24(3): p. 275-90.
21. Doorbar, J., et al., Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature, 1991. 352(6338): p. 824-7.
22. Wang, Q., et al., Functional analysis of the human papillomavirus type 16 E1=E4 protein provides a mechanism for in vivo and in vitro keratin filament reorganization. J Virol, 2004. 78(2): p. 821-33.
23. Peh, W.L., et al., Life cycle heterogeneity in animal models of human papillomavirus-associated disease. J Virol, 2002. 76(20): p. 10401-16.
24. Hwang, E.S., T. Nottoli, and D. Dimaio, The HPV16 E5 protein: expression, detection, and stable complex formation with transmembrane proteins in COS cells. Virology, 1995. 211(1): p. 227-33.
25. Liu, Y.M., A. McKalip, and B. Herman, Human papillomavirus type 16 E6 and HPV-16 E6/E7 sensitize human keratinocytes to apoptosis induced by chemotherapeutic agents: Roles of p53 and caspase activation. Journal of Cellular Biochemistry, 2000. 78(2): p. 334-349.
26. Crish, J.F., et al., Suprabasal expression of the human papillomavirus type 16 oncoproteins in mouse epidermis alters expression of cell cycle regulatory proteins. Carcinogenesis, 2000. 21(5): p. 1031-7.
27. Xu, X.M., Human Papillomaviruses and Cervical Cancer Vaccines: To Decode 2008 Nobel Prize in Physiology or Medicine. Progress in Biochemistry and Biophysics, 2008. 35(10): p. 1095-1103.
28. Doorbar, J., Papillomavirus life cycle organization and biomarker selection. Dis Markers, 2007. 23(4): p. 297-313.
29. Feoli-Fonseca, J.C., et al., Human papillomavirus (HPV) study of 691 pathological specimens from Quebec by PCR-direct sequencing approach. J Med Virol, 2001. 63(4): p. 284-92.
30. Gharizadeh, B., et al., Typing of human papillomavirus by pyrosequencing. Lab Invest, 2001. 81(5): p. 673-9.
31.陈汶, et al.,人乳头状瘤病毒DNA检测进展.中华检验医学杂志, 2005. 28(5): p. 552-554.
32. Baseman, J.G. and L.A. Koutsky, The epidemiology of human papillomavirus infections. JClin Virol, 2005. 32 Suppl 1: p. S16-24.
33. Sanchez-Perez, A.M., et al., Disruption of the human papillomavirus type 16 E2 gene protects cervical carcinoma cells from E2F-induced apoptosis. J Gen Virol, 1997. 78 ( Pt 11): p. 3009-18.
34. Alvarez-Salas, L.M., et al., Inhibition of HPV-16 E6/E7 immortalization of normal keratinocytes by hairpin ribozymes. Proc Natl Acad Sci U S A, 1998. 95(3): p. 1189-94.
35. Schoell, W.M., M.F. Janicek, and R. Mirhashemi, Epidemiology and biology of cervical cancer. Semin Surg Oncol, 1999. 16(3): p. 203-11.
36. Magal, S.S., et al., Induction of apoptosis in human keratinocytes containing mutated p53 alleles and its inhibition by both the E6 and E7 oncoproteins. Int J Cancer, 1998. 75(1): p. 96-104.
37. Brown, J., et al., Human papillomavirus (HPV) 16 E6 sensitizes cells to atractyloside-induced apoptosis: role of p53, ICE-like proteases and the mitochondrial permeability transition. J Cell Biochem, 1997. 66(2): p. 245-55.
38. Pillai, M.R., et al., High-risk human papillomavirus infection and E6 protein expression in lesions of the uterine cervix. Pathobiology, 1998. 66(5): p. 240-6.
39. Morris, J.D., et al., Human papillomavirus type 16 E7 regulates E2F and contributes to mitogenic signalling. Oncogene, 1993. 8(4): p. 893-8.
40. Schiffman, M.H., Recent progress in defining the epidemiology of human papillomavirus infection and cervical neoplasia. J Natl Cancer Inst, 1992. 84(6): p. 394-8.
41. Kjaer, S.K., et al., High-risk human papillomavirus is sexually transmitted: Evidence from a follow-up study of virgins starting sexual activity (intercourse). Cancer Epidemiology Biomarkers & Prevention, 2001. 10(2): p. 101-106.
42. Koutsky, L.A., et al., A controlled trial of a human papillomavirus type 16 vaccine. New England Journal of Medicine, 2002. 347(21): p. 1645-1651.
43. Clifford, G.M., et al., Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br J Cancer, 2003. 89(1): p. 101-5.
44. Farjadian, S., et al., High risk HPV types in southern Iranian patients with cervical cancer. Pathol Oncol Res, 2003. 9(2): p. 121-5.
45. Smith, J.S., et al., Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer, 2007. 121(3): p. 621-32.
46. Yamada, T., et al., Human papillomavirus type 16 variant lineages in United States populations characterized by nucleotide sequence analysis of the E6, L2, and L1 coding segments. J Virol, 1995. 69(12): p. 7743-53.
47. Yamada, T., et al., Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective. J Virol, 1997. 71(3): p. 2463-72.
48. Xi, L.F., et al., Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia. J Natl Cancer Inst, 1997. 89(11): p. 796-802.
49. Wheeler, C.M., et al., Human papillomavirus type 16 sequence variants: identification byE6 and L1 lineage-specific hybridization. J Clin Microbiol, 1997. 35(1): p. 11-9.
50. Xi, L.F., et al., Analysis of human papillomavirus type 16 variants indicates establishment of persistent infection. J Infect Dis, 1995. 172(3): p. 747-55.
51. Villa, L.L., et al., Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia. J Gen Virol, 2000. 81(Pt 12): p. 2959-68.
52. Matsumoto, K., et al., Enhanced oncogenicity of human papillomavirus type 16 (HPV16) variants in Japanese population. Cancer Lett, 2000. 156(2): p. 159-65.
53. Berumen, J., et al., Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study. J Natl Cancer Inst, 2001. 93(17): p. 1325-30.
54. Hildesheim, A., et al., Human papillomavirus type 16 variants and risk of cervical cancer. J Natl Cancer Inst, 2001. 93(4): p. 315-8.
55. Zehbe, I., et al., Human papillomavirus 16 E6 variants are more prevalent in invasive cervical carcinoma than the prototype. Cancer Res, 1998. 58(4): p. 829-33.
56. Woodman, C.B., S.I. Collins, and L.S. Young, The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer, 2007. 7(1): p. 11-22.
57. Jeon, S. and P.F. Lambert, Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci U S A, 1995. 92(5): p. 1654-8.
58. Romanczuk, H., F. Thierry, and P.M. Howley, Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. J Virol, 1990. 64(6): p. 2849-59.
59. Thierry, F. and P.M. Howley, Functional analysis of E2-mediated repression of the HPV18 P105 promoter. New Biol, 1991. 3(1): p. 90-100.
60. Jeon, S., B.L. Allen-Hoffmann, and P.F. Lambert, Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol, 1995. 69(5): p. 2989-97.
61. Hall, S., et al., Human papillomavirus DNA detection in cervical specimens by hybrid capture: correlation with cytologic and histologic diagnoses of squamous intraepithelial lesions of the cervix. Gynecol Oncol, 1996. 62(3): p. 353-9.
62. Lillo, F.B., et al., Determination of human papillomavirus (HPV) load and type in high-grade cervical lesions surgically resected from HIV-infected women during follow-up of HPV infection. Clin Infect Dis, 2005. 40(3): p. 451-7.
63. Swan, D.C., et al., Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type. J Clin Microbiol, 1999. 37(4): p. 1030-4.
64. Kataja, V., et al., Prospective follow-up of genital HPV infections: survival analysis of the HPV typing data. Eur J Epidemiol, 1990. 6(1): p. 9-14.
65. Burk, R.D., et al., Sexual behavior and partner characteristics are the predominant risk factors for genital human papillomavirus infection in young women. J Infect Dis, 1996. 174(4): p. 679-89.
66. Franco, E.L., et al., Transmission of cervical human papillomavirus infection by sexual activity: differences between low and high oncogenic risk types. J Infect Dis, 1995. 172(3): p. 756-63.
67. Moreno, V., et al., Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. Lancet, 2002. 359(9312): p. 1085-1092.
68. Shields, T.S., et al., A case-control study of risk factors for invasive cervical cancer among U.S. women exposed to oncogenic types of human papillomavirus. Cancer Epidemiol Biomarkers Prev, 2004. 13(10): p. 1574-82.
69. Gram, I.T., et al., Cigarette smoking and risk of borderline and invasive epithelial ovarian cancer. Int J Cancer, 2008. 122(3): p. 647-652.
70. Brinton, L.A. and J.F. Fraumeni, Jr., Epidemiology of uterine cervical cancer. J Chronic Dis, 1986. 39(12): p. 1051-65.
71. Ngan, H.Y., V.W. Liu, and S.S. Liu, Risk of cervical cancer is not increased in Chinese carrying homozygous arginine at codon 72 of p53. Br J Cancer, 1999. 80(11): p. 1828-9.
72. Abba, M.C., et al., The p53 codon 72 genotypes in HPV infection and cervical disease. Eur J Obstet Gynecol Reprod Biol, 2003. 109(1): p. 63-6.
73. Palker, T.J., et al., Antibody, cytokine and cytotoxic T lymphocyte responses in chimpanzees immunized with human papillomavirus virus-like particles. Vaccine, 2001. 19(27): p. 3733-43.
74. Koutsky, L.A., et al., A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med, 2002. 347(21): p. 1645-51.
75. Govan, V.A., A novel vaccine for cervical cancer: quadrivalent human papillomavirus (types 6, 11, 16 and 18) recombinant vaccine (Gardasil). Ther Clin Risk Manag, 2008. 4(1): p. 65-70.
76. Keam, S.J. and D.M. Harper, Human papillomavirus types 16 and 18 vaccine (Recombinant, AS04 adjuvanted, adsorbed) [Cervarix (TM)]. Biodrugs, 2008. 22(3): p. 205-208.
77. Castellsague, X., et al., HPV and Cervical Cancer in the World 2007 Report. Vaccine, 2007. 25: p. Iv-+.
78. China national cause-of-death surveys
79.郝敏and王静芳,宫颈癌流行病学研究与调查.国外医学妇幼保健分册, 2005. 16(6).
80.李洁,刘宝印, and Z. Hausen.,中国妇女宫颈癌组织中人乳头瘤病毒感染及地理分布的调查.中国实验和临床病毒学, 1996(10): p. 50-55.
81. Bao, Y.P., et al., Human papillomavirus type-distribution in the cervix of Chinese women: a meta-analysis. Int J STD AIDS, 2008. 19(2): p. 106-11.
82. Stephen, A.L., et al., Analysis of mutations in the URR and E6/E7oncogenes of HPV cervical cancer isolates from central China. International Journal of Cancer, 2000. 86(5):p. 695-701.
83. Manos, M. and D.K. Wright, The use of polymerase chain reaction amplification for the detection of genital human papillomaviruses. Cancer Cells, 1989(7): p. 209-214.
84. Sotlar, K., et al., Detection and typing of human papillomavirus by e6 nested multiplex PCR. J Clin Microbiol, 2004. 42(7): p. 3176-84.
85. Hong, D., et al., Distribution of human papillomavirus genotypes in the patients with cervical carcinoma and its precursors in Zhejiang Province, China. International Journal of Gynecological Cancer, 2008. 18(1): p. 104-109.
86. Huang, S., et al., Human papillomavirus types 52 and 58 are prevalent in cervical cancers from Chinese women. Int J Cancer, 1997. 70(4): p. 408-11.
87. Liu, J., et al., Comparative analysis of characteristics of women with cervical cancer in high- versus low-incidence regions. Gynecol Oncol, 2004. 94(3): p. 803-10.
88. Bao, Y.P., et al., Human papillomavirus type distribution in women from Asia: a meta-analysis. International Journal of Gynecological Cancer, 2008. 18(1): p. 71-79.
89. Lin, M., et al., Genital human papillomavirus screening by gene chip in Chinese women of Guangdong province. Aust N Z J Obstet Gynaecol, 2008. 48(2): p. 189-94.
90. Dai, M., et al., Human papillomavirus infection in Shanxi Province, People's Republic of China: a population-based study. Br J Cancer, 2006. 95(1): p. 96-101.
91. Dai, Y., et al., Distribution and clinical significance of human papillomavirus subtypes in Shenzhen city, People's Republic of China. Int J Gynecol Cancer, 2008. 18(2): p. 295-9.
92. Li, X.L., et al., [Human papillomaviruses infections among village women in Henan province]. Zhonghua Yu Fang Yi Xue Za Zhi, 2007. 41 Suppl: p. 77-80.
93. Li, L.K., et al., Human papillomavirus infection in Shenyang City, People's Republic of China: A population-based study. Br J Cancer, 2006. 95(11): p. 1593-7.
94. Zhang, W.Y., et al., Prevalence of high-risk human papillomavirus infection in different cervical lesion among organized health-examination women in Shanghai, China. Chin Med J (Engl), 2008. 121(16): p. 1578-82.
95. Choi, Y.D., et al., Detection of HPV genotypes in cervical lesions by the HPV DNA Chip and sequencing. Gynecol Oncol, 2005. 98(3): p. 369-75.
96. Kast, W.M., et al., Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. J Immunol, 1994. 152(8): p. 3904-12.
97. Crook, T., J.A. Tidy, and K.H. Vousden, Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation. Cell, 1991. 67(3): p. 547-56.
98. Foster, S.A., et al., The ability of human papillomavirus E6 proteins to target p53 for degradation in vivo correlates with their ability to abrogate actinomycin D-induced growth arrest. J Virol, 1994. 68(9): p. 5698-705.
99. Chen, Z., et al., Diversifying selection in human papillomavirus type 16 lineages based on complete genome analyses. J Virol, 2005. 79(11): p. 7014-23.
100. Arias-Pulido, H., et al., Human papillomavirus type 16 integration in cervical carcinomain situ and in invasive cervical cancer. J Clin Microbiol, 2006. 44(5): p. 1755-62.
101. Chan, P.K., et al., Profile of viral load, integration, and E2 gene disruption of HPV58 in normal cervix and cervical neoplasia. J Infect Dis, 2007. 196(6): p. 868-75.
102. Ho, C.M., et al., Integrated human papillomavirus types 52 and 58 are infrequently found in cervical cancer, and high viral loads predict risk of cervical cancer. Gynecol Oncol, 2006. 102(1): p. 54-60.
103. Qiu, A.D., et al., HPV prevalence, E6 sequence variation and physical state of HPV16 isolates from patients with cervical cancer in Sichuan, China. Gynecol Oncol, 2007. 104(1): p. 77-85.
104. Chan, P.K., et al., Association of human papillomavirus type 58 variant with the risk of cervical cancer. J Natl Cancer Inst, 2002. 94(16): p. 1249-53.
105. Xin, C.Y., et al., Analysis of E6 variants of human papillomavirus type 33, 52 and 58 in Japanese women with cervical intraepithelial neoplasia/cervical cancer in relation to their oncogenic potential. Cancer Lett, 2001. 170(1): p. 19-24.
106. Androphy, E.J., D.R. Lowy, and J.T. Schiller, Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA. Nature, 1987. 325(6099): p. 70-3.
107. Lewis, H., et al., Cellular transcription factors regulate human papillomavirus type 16 gene expression by binding to a subset of the DNA sequences recognized by the viral E2 protein. J Gen Virol, 1999. 80 ( Pt 8): p. 2087-96.
108. Storey, A., et al., Mutations in the human papillomavirus type 16 E2 protein identify a region of the protein involved in binding to E1 protein. J Gen Virol, 1995. 76 ( Pt 4): p.
819-26.
109. Hegde, R.S., et al., Crystal structure at 1.7 A of the bovine papillomavirus-1 E2 DNA-binding domain bound to its DNA target. Nature, 1992. 359(6395): p. 505-12.
110. Kurvinen, K., et al., Variants of the long control region of human papillomavirus type 16. Eur J Cancer, 2000. 36(11): p. 1402-10.
111. Chan, S.Y., et al., Analysis of genomic sequences of 95 papillomavirus types: uniting typing, phylogeny, and taxonomy. J Virol, 1995. 69(5): p. 3074-83.
112. Calleja-Macias, I.E., et al., Worldwide genomic diversity of the high-risk human papillomavirus types 31, 35, 52, and 58, four close relatives of human papillomavirus type 16. J Virol, 2005. 79(21): p. 13630-40.
113. Stewart, A.C., et al., Intratype variation in 12 human papillomavirus types: a worldwide perspective. J Virol, 1996. 70(5): p. 3127-36.
114. Tornesello, M.L., et al., Prevalence of human papillomavirus genotypes and their variants in high risk West Africa women immigrants in South Italy. Infect Agent Cancer, 2007. 2: p. 1.
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