高危型人乳头瘤状病毒基因分型与宫颈病变的相关性分析
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摘要
目的通过对高危型人乳头瘤病毒(high-risk Human Papilloma Virus,hrHPV)基因分型与宫颈病变关系的回顾性分析,为HPV感染和宫颈癌的防治提供参考依据。方法选择2015年7月~2017年3月期间在南充地区经宫颈病理组织学检查确诊为宫颈疾病的334例患者,其中宫颈炎组162例,宫颈上皮内瘤样病变CIN I组30例,CIN II组26例,CIN III组50例,宫颈癌组66例。应用实时荧光PCR方法检测15种hrHPV-DNA(16、18、31、33、35、39、45、51、52、56、58、59、68、66、82),采用SPSS 19.0对数据进行统计学分析。结果宫颈疾病患者hrHPV感染率为53.9%。其中,CIN II组、CIN III组、宫颈癌组HPV感染率分别为92.3%、92.0%和97.0%,显著高于宫颈炎组(23.5%)和CIN I组(26.7%),各级别病变中hrHPV感染率差异均有统计学意义(χ~2=163.3,P<0.01);随着宫颈病变严重程度增加,hrHPV感染率明显升高(趋势性χ~2=148.2,P<0.01)。在180例hrHPV阳性患者中,CIN组、宫颈癌组HPV单一感染率分别为74.6%和78.1%,显著高于宫颈炎组(36.8%);各级别病变中hrHPV单一感染率比较,差异均有统计学意义(χ~2=21.4,P<0.05),单一感染率随病变严重程度呈升高趋势,多重感染比例逐渐下降。HPV检出率由高到低排在前5位的型别为16型(30.9%)、58型(15.4%)、52型(11.8%)、18型(8.1%)、33型(5.1%);排在前5位的hrHPV16、58、52、18、33各型别感染率存在差异(χ~2=90.1,P<0.01);CIN组、宫颈癌组的16型、18型感染率明显高于宫颈炎组,差异均有统计学意义(P<0.05)。此外,在宫颈病变患者中,30~40、41~50和>50岁年龄段的hrHPV感染率分别为65.4%、47.3%和67.6%,显著高于<30岁年龄段的感染率(33.3%),不同年龄段hrHPV感染率差异有统计学意义(χ~2=16.8,P<0.05);30岁以上年龄段HPV感染率呈现"U"字型特点,即30~40和>50岁年龄段HPV感染率处在两个高峰,而41~50岁年龄段有一定程度地降低。结论 HPV感染率随宫颈疾病严重程度增加明显升高,宫颈癌发生、发展的主要原因可能是HPV单一感染,而并非多重感染。因此,对伴有持续性高致癌型别HPV感染的30岁以上高发年龄段女性要高度重视,做到及时诊断与治疗,以减少宫颈高级别病变和宫颈癌的发生。
Objective To investigate the relationship between High-risk HPV genotyping and cervical diseases,and provide scientific basis for prevention and treatment of cervical cancer.Methods Retrospective study was done to review 334 patients with different cervical lesions pathologically diagnosed and tested 15 subtypes(16,18,31,33,35,39,45,51,52,56,58,59,68,66,82)by PCR from July 2015 to March 2017.These patients were divided into the following groups,cervicitis(162 cases),cervical intraepithelium neoplasia grade I(CINI)(30 cases),grade II(CINII)(26 cases),grade III(CINIII)(50 cases)and cervical cancer(66 cases).The related data of the patients were analyzed by SPSS19.0.Results The total infection rate of hrHPV was 53.9%.The infection rates of CINII,III and cervical cancer were 92.3%,92.0%,97.0%respectively,higer than cervicitis 23.5% and CINI 26.7%,The infection rate of hrHPV was significantly different among varied cervical diseases(χ~2=163.3,P<0.01),and it gradually increased along with the increased disease grade(χ~2=148.2,P<0.01).180 patients infected with HPV.The single infection rates of CIN and cervical cancer were 74.6%,78.1%,which were higher than that of cervicitis(36.8%).The single infection rate of hrHPV was significantly different among varied cervical diseases.As the severity of the disease increased,the HPV single infection rate increased significantly.The five most prevalence high risk types were 16(30.9%),58(15.4%),52(11.8%),18(8.1%),33(5.1%).The infection rate of HPV 16 were higher than that of HPV 58,52,18 and 33.The infection rate of hrHPV was significantly different among 16,58,52,18 and 33.The positive rates in patients with30-40,41-50 and>50 years old were 65.4%,47.3%,67.6%,which were higher than the positive rates 33.3%in<30 years old.The infection rate of hrHPV was significantly different among varied Ages.Age-specific prevalence showed a"two-peak"pattern,with the 30-40 age group presenting the highest hrHPV infection rate(65.4%),followed by a second peak(67.6%)for the>50 years old group.Conclusion As the severity of the disease increased,the HPV infection rate increased significantly,the HPV single infection were the main ways in CIN and cervical cancer.The five most prevalence hrHPV subtypes were 16,58,52,18,33 in Nanchong,and>30 years old.Therefore,we should pay great attention to more than 30 years old women who were infected hrHPV persistently,timely diagnosis and treatment for HPV infection could reduce the occurrence of high-grade CIN and cervical cancer.
Objective To investigate the relationship between High-risk HPV genotyping and cervical diseases,and provide scientific basis for prevention and treatment of cervical cancer.Methods Retrospective study was done to review 334 patients with different cervical lesions pathologically diagnosed and tested 15 subtypes(16,18,31,33,35,39,45,51,52,56,58,59,68,66,82)by PCR from July 2015 to March 2017.These patients were divided into the following groups,cervicitis(162 cases),cervical intraepithelium neoplasia grade I(CINI)(30 cases),grade II(CINII)(26 cases),grade III(CINIII)(50 cases)and cervical cancer(66 cases).The related data of the patients were analyzed by SPSS19.0.Results The total infection rate of hrHPV was 53.9%.The infection rates of CINII,III and cervical cancer were 92.3%,92.0%,97.0%respectively,higer than cervicitis 23.5% and CINI 26.7%,The infection rate of hrHPV was significantly different among varied cervical diseases(χ~2=163.3,P<0.01),and it gradually increased along with the increased disease grade(χ~2=148.2,P<0.01).180 patients infected with HPV.The single infection rates of CIN and cervical cancer were 74.6%,78.1%,which were higher than that of cervicitis(36.8%).The single infection rate of hrHPV was significantly different among varied cervical diseases.As the severity of the disease increased,the HPV single infection rate increased significantly.The five most prevalence high risk types were 16(30.9%),58(15.4%),52(11.8%),18(8.1%),33(5.1%).The infection rate of HPV 16 were higher than that of HPV 58,52,18 and 33.The infection rate of hrHPV was significantly different among 16,58,52,18 and 33.The positive rates in patients with30-40,41-50 and>50 years old were 65.4%,47.3%,67.6%,which were higher than the positive rates 33.3%in<30 years old.The infection rate of hrHPV was significantly different among varied Ages.Age-specific prevalence showed a"two-peak"pattern,with the 30-40 age group presenting the highest hrHPV infection rate(65.4%),followed by a second peak(67.6%)for the>50 years old group.Conclusion As the severity of the disease increased,the HPV infection rate increased significantly,the HPV single infection were the main ways in CIN and cervical cancer.The five most prevalence hrHPV subtypes were 16,58,52,18,33 in Nanchong,and>30 years old.Therefore,we should pay great attention to more than 30 years old women who were infected hrHPV persistently,timely diagnosis and treatment for HPV infection could reduce the occurrence of high-grade CIN and cervical cancer.
引文
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[15] Jung Y S,Kato I,Kim HRC.A novel function of HPV16-E6/E7in epithelial mesenchymal transition[J].Bioph Resco,2013,435(3):339.
[16]李淑芹,杨靖,李蓓,等.西多福韦对HPV18阳性人宫颈癌HeLa细胞的凋亡作用及机制研究[J].西部医学,2017,29(5):598-603.
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[19] Li J,Huang R,Schmidt JE,et al.Epidemiological features of Human Papillomavirus(HPV)infection among women living in Mainland China[J].APJCP,2013,14(7):4015-4023.
[20] Bulk S,Berkhof J,Bul kmans NW,et al.Preferential risk of HPV16for squamous cell carcinoma and of HPV18for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands[J].Br J Cancer,2006,94(1):171-175.
[2] Di J,Rutherford S,Chu C.Review of the cervical cancer burden and population based cervical cancer screening in China[J].Asian Pac J Cancer Prev,2015,16(17):7401-7407.
[3] Song D,Li H,Li H,et al.Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer[J].Oncol Lett,2015,10(2):600-606.
[4]张为远.宫颈病变与宫颈癌[M].北京:人民卫生出版社,2012:79-87.
[5]李广太.HPV检测在子宫颈癌筛查中的意义[J].中华妇产科杂志,2015,50(4):241-245.
[6] Ogembo RK,Gona PN,Seymour AJ,et al.Prevalence of Human Papillomavirus Genotypes among African Women with Normal Cervical Cytology and Neoplasia:A Systematic Review and Meta-Analysis[J].PloS one,2015,10(4):e0122488.
[7] Bernard E,Pons-Salort M,Favre M,et al.Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential:a meta-analysis of observational studies[J].BMC Infect Dis,2013,13(1):373.
[8] Zhao FH,Lin MJ,Chen F,et al.Performance of high-risk human papillomavirus DNA testing as a primary screen for cervical cancer:apooled analysis of individual patient data from 17populationbased studies from China[J].Lancet Oncol,2010,11(12):1160-1171.
[9] Miranda PM,Silva NN,Pitol BC,et al.Persistence or clearance of human papillomavirus infections in women in Ouro Preto,Brazil[J].Biomed Res Int,2013,2013(5):578276.
[10]冯余宽,彭英,朱联,等.四川地区HPV亚型及多重感染与宫颈癌前病变的关系初探[J].四川大学学报(医学版),2015,46(3):422-425.
[11] Xu QX,Zhang ZY.High-risk human papillomavirus genotypes in cervical lesions and vaccination challenges in China[J].Asian Pac J Cancer Pre,2015,16(6):2193-2197.
[12]赵宇倩,赵方辉,胡尚英,等.中国女性人群宫颈人乳头瘤病毒感染及型别分布的多中心横断面研究[J].中华流行病学杂志,2015,36(12):1351-1356.
[13] Tang Y,Zheng L,Yang S,et al.Epidemiology and genotype distribution of human papillomavirus(HPV)in Southwest China:a cross-sectional five years study in non-vaccinated women[J].Virol J,2017,14(1):84.
[14] Erik Bernard,Margarita Pons-Salort.Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential:a meta-analysis of observational studies[J].BMC Infect Dis,2013,13(1):373.
[15] Jung Y S,Kato I,Kim HRC.A novel function of HPV16-E6/E7in epithelial mesenchymal transition[J].Bioph Resco,2013,435(3):339.
[16]李淑芹,杨靖,李蓓,等.西多福韦对HPV18阳性人宫颈癌HeLa细胞的凋亡作用及机制研究[J].西部医学,2017,29(5):598-603.
[17] Wang R,Guo XL,Bea G,et al.Nationwide prevalence of human papillomavirus infection and viral genotype distribution in37cities in China[J].BMC Infect Dis,2015,15(7):257.
[18] Bruni L,Diaz M,Castellsague X,et al.Cervical human papillomavirus prevalence in 5ontinents:meta-analysis of 1 million women with normal cytological findings[J].The Journal of infectious diseases,2010,202(12):1789-1799.
[19] Li J,Huang R,Schmidt JE,et al.Epidemiological features of Human Papillomavirus(HPV)infection among women living in Mainland China[J].APJCP,2013,14(7):4015-4023.
[20] Bulk S,Berkhof J,Bul kmans NW,et al.Preferential risk of HPV16for squamous cell carcinoma and of HPV18for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands[J].Br J Cancer,2006,94(1):171-175.