宫颈癌中p53表达和病毒感染的研究

应用PCR对121例宫颈脱落细胞和组织分别检测HPV-16/18和HSv-2 DNA.同时应用免疫组化S-P法检测76例宫颈组织中p53过度表达.结果发现,宫颈癌组织中HPV-16/18和HSv-2阳性率分别为61.3%和32.3%,慢性宫颈炎组HPV-16/18和HSV-2阳性率分别为22.5%和20.0%,与正常宫颈组比较均有显著性差异.宫颈癌中HPV-16/18和HSV-2混合感染率为16.1%.p53过度表达率在慢性宫颈炎、宫颈上皮内瘤变(CIN)、宫颈癌组织中呈梯度递增.另外,宫颈癌组织中p53过度表达与HPV-16/18、HSv-2的感染无相关性.提示宫颈癌的发生与HPV-16/18关系密切,HSV-2可能与HPV-16/18协同作用导致宫颈癌的发生.宫颈组织中p53过度表达率与宫颈癌的进程有关,这在宫颈癌的防治方面有一定的临床意义.     

宫颈癌HPV-16感染对P53蛋白表达的影响

目的探讨宫颈癌HPV-16感染对P53蛋白表达的影响.方法采用免疫组化SP法分别检测75例宫颈癌和81例宫颈炎组织的HPV-16蛋白和P53蛋白表达情况.结果HPV-16蛋白在宫颈癌组织的表达率(73.3%,55/75)与宫颈炎组织(81.5%,66/81)差异无显著性;P53蛋白在宫颈癌组织的表达率(46.7%,33/75)高于宫颈炎组织(29.6%,24/81)(P＜0.05).宫颈癌组织HPV-16阳性组的P53蛋白阳性率(49.1%,27/55)高于HPV-16阴性组(40.0%,8/20)(P＜0.05);宫颈炎组织HPV-16阳性组的P53蛋白阳性率(36.4%,24/66)高于HPV-16阴性组(0%,0/15)(P＜0.05).宫颈癌和宫颈炎组织HPV-16蛋白与P53蛋白表达呈正相关(P＜0.05).结论HPV-16感染在宫颈癌和宫颈炎组织普遍存在,突变型P53蛋白的表达上调可作为宫颈癌发生的预警信号,HPV-16可能通过导致p53基因突变促使宫颈癌发生.     

EB病毒与子宫颈癌发病的关系

目的 分析EB病毒感染与子宫颈的关系及其对抑癌基因p53表达的影响,探讨EB病毒的致癌机制。方法 采用免疫组织化学S-P法,分别检测59例宫颈鳞癌,19例正常宫颈组织的EB病毒（Epstein-Barr virus,EBV）及抑癌基因p53蛋白的表达情况,并进一步分析宫颈癌组织EBV感染与抑癌基因p53表达的关系。结果 EBV阳性表达率在宫颈癌及正常宫颈组分别为64．4％和21．1％,2组间差异有显著性（P〈0．05）;p53在宫颈癌组织中的阳性表达率为64．4％,明显高于正常宫颈组26．3％,（P〈0．05）。EBV感染与非感染的宫颈癌组织中,p53的阳性表达率分别为78．9％与38．1％,2组间差异有显著性（P〉0．05）。结论 EBV病毒感染与宫颈癌的发病密切相关,但其机制可能是通过影响抑癌基因P53表达而致癌。     

GRP94和CD8在宫颈病变组织中的表达及意义

目的：探讨葡萄糖调节蛋白94（glucose—regulated protein94,GRP94）和CD8在宫颈病变组织中的表达及与HPV感染的关系。方法：采用免疫组化S—P法检测32例原发宫颈癌、27例宫颈上皮内瘤变（cervical intraepithelial neoplasia, CIN）及40例慢性宫颈炎组织中GRP94和CD8的表达及定位;采用western blot技术检测6例宫颈癌及6例正常宫颈组织中GRP94和CD8的表达。结果：①在宫颈癌、CIN2／3、CIN1及慢性宫颈炎组织中,GRP94的阳性表达率分别为87．5％、82．4％、40％和22．5％;CD8的阳性表达率分别为28．1％、64．7％、90％和97．5％;GRP94在宫颈癌和CIN2／3中的表达均显著高于慢性宫颈炎和CIN1组织（P均〈0．05）;CD8在宫颈癌组的表达显著低于慢性宫颈炎组、CIN1组及CIN2／3组（P均〈0．05）。②Western blot结果示GRP94在宫颈癌组织中的表达显著高于正常宫颈组织（P〈0．01）;CD8在宫颈癌组织中的表达显著低于正常宫颈组织（P〈0．01）。③GRP94的表达与宫颈癌分化程度、有无脉管侵袭有关（P〈0．05）,而与年龄、病理类型、临床分期及有无淋巴结转移无关（P〉0．05）;CD8的表达与有无脉管侵袭有关（P〈0．05）,而与年龄、病理类型、临床分期、分化程度及有无淋巴结转移无关（P〉0．05）。④宫颈病变组织中,GRP94的表达与HPV感染呈正相关（rs=0．377,P=0．000）;cD8的表达与HPV感染呈负相关（rs=-0．395,P=0．000）;GRP94与CD8的表达呈负相关（rs=-0．608,P=0．000）。结论：GRP94表达可能是宫颈CIN进展及宫颈癌预后判断的重要预测指标。     

HPV感染对P53、TGF-β1表达的影响及在子宫颈癌发病中的意义

目的检测人乳头瘤病毒HPV-16和抑癌基因P53蛋白及转化生长因子TGF-β1在宫颈癌的表达,并分析HPV-16对P53和TGF-β1表达的影响.方法应用免疫组化SP法检测56例宫颈癌和20例非宫颈癌组织中HPV-16、P53和TGF-β1蛋白的表达.结果 HPV-16蛋白在宫颈癌和非宫颈癌组的阳性表达率分别为57.1%和5.0%,宫颈癌组明显高于非宫颈癌组(P＜0.05).在宫颈癌HPV-16感染与非感染组P53蛋白的表达率分别为40.6%和8.3%(P＜0.05);TGF-β1蛋白表达率分别为21.9%和62.5%(P＜0.05).HPV-16感染组P53蛋白在病理分级Ⅰ、Ⅱ和Ⅲ级的表达分别为22.2%、45.0%和66.7%,Ⅰ级和Ⅲ级间差异有显著性(P＜0.05).TGF-β1蛋白在病理分级Ⅰ、Ⅱ和Ⅲ级的表达分别为33.3%、20.0%和33.3%,TGF-β1蛋白在病理分级的表达差异无显著性(P＞0.05)结论 HPV感染是宫颈癌发病的重要因素之一,其致癌机制可能通过变型P53蛋白表达上调,TGF-β1蛋白表达下调,引起宫颈细胞增殖失控,发生恶性转化.     

HPV-16、EB病毒对细胞增殖的影响及与子宫颈癌发病的关系

目的 了解宫颈癌患者人乳头瘤病毒16（HPV 16）、EB病毒（EBV）感染情况,探讨HPV-16、EBV对细胞核增殖性抗原（PCNA）表达的影响及在子宫颈癌发病中的意义。方法 免疫组织化学SP法检测59例宫颈癌和20例非癌性子宫颈上皮细胞中HPV-16、EBV蛋白表达和PCNA表达的情况,并分析它们的表达与病理参数的关系。结果 子宫颈癌和非癌性子宫颈上皮细胞中HPV-16、EBV及PCNA的阳性表达率依次分别为69．49％、57．63％及77．97％和30％、25％及15％;子宫颈癌和非癌性子宫颈上皮细胞中HPV-16、EBV的共同阳性表达率分别为35．59％和0％,子宫颈癌中HPV-16、EBV及PCNA的阳性表达率均高于非癌性子宫颈上皮（P〈0．05）。病理Ⅰ级、Ⅱ级和Ⅲ级子宫颈癌中HPV-16、EBV、PCNA的阳性表达率分别为65．00％、55．00％、60．00％,69．57％、60．87％、82．61％和75．OO％、56．25％、93．75％。各级子宫颈癌间HPV-16、EBV的阳性表达率差异无显著性,但PCNA的表达率随病理分级的增加显著上升（P〈0．05）。不同期别子宫颈癌问HPV-16、EBV及PCNA的阳性表达率差异无显著性。HPV-16阳性与阴性组子宫颈上皮PCNA的阳性表达率分别为82．98％（39／47）与43．75％（14／32）,两者差异有显著性（P〈0．05）。EBV阳性及阴性组子宫颈上皮PCNA的阳性表达率分别为71．79％（28／39）及42．50％（17／40）,两者差异有显著性（P〈0．05）。HPV-16和EBV共同阳性表达的21例子宫颈癌PCNA阳性表达率均为100％。结论 HPV-16、EBV通过增加PCNA表达的促细胞增生作用可能是子宫颈癌的发生机制之一。     

hMLH1、P27、P53的表达及其在宫颈癌发病中的意义

目的 了解宫颈癌中hMLH1、P27、P53表达情况及其与宫颈癌发生和发展的关系.方法 采用免疫组织化学技术SP法检测临床资料较完整的72例子宫颈鳞癌和31例慢性宫颈炎组织hMLH1、P27、P53蛋白表达.结果 （1）hMLH1在宫颈炎及宫颈癌组的表达率分别为61.3%和58.3%,差异无显著性（P＞0.05）;hM-LH1在宫颈癌各期中表达率分别为Ⅰ期60.0%,Ⅱ期52.6%,Ⅲ期33.3%,差异无显著性（P＞0.05）;hMLH1表达率与宫颈癌分级无关（P＞0.05）;（2）P27在宫颈炎及宫颈癌组的表达率分别为74.2%%和76.4%,差异无显著性（P＞0.05）;P27的表达率与宫颈癌分级和分期无关（P＞0.05）;（3）P53在宫颈炎及宫颈癌组的表达率分别为32.3%和65.3%,差异有显著性（P＜0.05）;P53在宫颈癌各级中的表达率分别为Ⅰ级36.4%,Ⅱ级73.0%,Ⅲ级67.9%,Ⅰ级与Ⅱ、Ⅲ级的表达率差异有显著性（P＜0.05）;P53表达率与宫颈癌分期无关（P＜0.05）;（4）hMLH1表达阳性与阴性的宫颈癌中P27的表达率为94.6%和60.0%,差异有显著性（P＜0.05）;P53的表达率为62.8%和62.1%,差异无显著性（P＞0.05）.结论 P53基因突变与宫颈癌的发生和组织分化程度有关;hMLH1与P27表达缺失和宫颈癌发生的关系尚不确切.hMLH1可能使宫颈癌中P27表达上调,而对p53基因突变累积无明显抑制作用.     

宫颈疾患中人乳头瘤病毒和疱疹病毒Ⅱ型DNA的检测

本文应用HPV11,16,18型和HSV-2N/BglⅡ、HSV-2L/HindⅢDNA片段等五个分子探针,通过斑点杂交技术对79例宫颈疾患(包括50例宫颈癌和29例宫颈糜烂)组织DNA进行了检测,结果发现宫颈癌组织HPV16,18和11的阳性率分别为44％,12％和4％,而宫颈糜烂组织中HPV16,18和11的阳性率分别为14％,7％和14％;且3例标本HPV16和HPV18均呈弱杂交反应;在被检的所有宫颈癌组织中各有2例分别与HSV-2N/BglⅡHSV-2L/HindⅢ弱杂交,宫颈糜烂组织无一例阳性。结果提示,HPV在宫颈癌的发生过程中可能起主要作用,HSV-2的作用尚不确定,可能与HPV起协同作用。     

湖南地区汉族人群p53基因第72位密码子多态性与宫颈鳞癌的相关性

目的：探讨宫颈组织p53基因第72位密码子的多态性及分析第72位密码子的多态性与湖南地区汉族人群宫颈鳞癌的相关性。方法：采用PCR方法扩增101例正常宫颈和150例宫颈鳞癌石蜡组织p53基因第72位密码子基因,回收目的片段进行测序。采用SPSS11．5软件分析p53基因第72位密码子的多态性。结果：p53第72位密码子基因测序结果显示,在宫颈鳞癌组织中Arg／Arg、Pro／Pro、Arg／Pro所占比例分别为40．66％、16．67％、42．67％;在正常宫颈组织中Arg／Arg、Pro／Pro、Arg／Pro所占比例分别为47．53％、7．92％、44．55％。统计学分析结果显示,Arg／Arg和Arg／Pro基因型在宫颈鳞癌和对照组中的表达差异没有统计学意义（P〉0．05）;Pro／Pro基因型在宫颈鳞癌组中所占比例显著高于正常宫颈组织（P〈0．05）。结论：p53基因第72位密码子Pro／pro基因型是湖南地区女性发生宫颈鳞癌易感因素。     

HPV-18病毒E2、E6与Brd4对宫颈癌及癌前病变的意义分析

目的:研究HPV-18病毒E2、E6与Brd4对宫颈癌及癌前病变的意义.方法:选择2009年3月至2011年3月我院接诊的17例宫颈炎患者,19例CIN Ⅰ级(轻度非典型增生)患者,14例CIN Ⅱ级(中度非典型增生)患者,15例CIN Ⅲ级(重度非典型增生及原位癌)患者,19例宫颈癌患者.分别采用RT-PCR对各组的E2 mRNA、E6mRNA阳性表达情况进行测定,采用蛋白印迹(Western Blot)法对各组患者的E2蛋白与Brd4表达情况进行测定.从而分析HPV-18病毒E2、E6与Brd4对宫颈癌及癌前病变的临床意义.结果:各项检测后,发现宫颈癌组患者的E2mRNA阳性表达率明显低于宫颈炎组、CIN组(P＜0.05);宫颈癌组患者的E6mRNA阳性表达率明显高于宫颈炎组、CIN组(P＜0.05).HPV-18病毒E2 mRNA与E6mRNA阳性表达情况呈负相关(P＜0.05).宫颈癌组患者的E2蛋白阳性率明显低于宫颈炎组、CIN组(P＜0.05);宫颈癌组患者的Brd4蛋白阳性率明显低于宫颈炎组、CIN组(P＜0.05).结论:HPV-18病毒E2、E6与Brd4对宫颈癌及癌前病变的检测有重要意义,可用于对于宫颈癌演变过程的监控.     

多聚酶链反应检测宫颈HPV感染及分型的研究

本文应用ＰＣＲ技术检测２ｌ２例临床宫颈标本的ＨＰＶ－６、ｌｌ、１６、１８型特异性核酸序列。结果发现ＨＰＶ－ＤＮＡ的阳性率：宫颈癌组为６２．５％（２５／４０）．慢性宫颈炎为５７％（８１／１４２）,正常宫颈对照组为２０％（６／３０）,Ｐ＜０．００１,提示ＨＰＶ的感染与宫颈炎、宫颈癌有关。同时分型结果显示：ＨＰＶ－６、１６、１８型与宫颈炎相关,１６型与宫颈癌密切相关,且ＨＰＶ不同型别的混合感染在宫颈中普遍存在（３１．３％）。成年女性各年龄组间ＨＰＶ的感染率并无明显差异（Ｐ＞０．０５）。     

DNA sequences of human papillomavirus types 11, 16, and 18 in lesions of the uterine cervix in the west of Scotland.

Punch biopsy specimens of the cervix were examined both histologically and for the presence of human papillomavirus (HPV) DNA sequences. The presence of HPV DNA sequences was sought with the Southern blot technique using radioactively labelled HPV-6, 11, 16, and 18 DNA probes, both together and separately. Twenty six biopsy specimens were examined. Histological examination showed cervical intraepithelial neoplasia grade 2 or 3 in 16 specimens, viral changes (koilocytosis) in four, and inflammation or a normal appearance in three. Eleven specimens were negative for HPV DNA sequences, 10 contained HPV-16 DNA, four contained HPV-18 DNA, and one contained both HPV-18 and HPV-11 DNA. Episomal HPV-16 DNA was detected in one case of cervical intraepithelial neoplasia grade 3 and in five cases of cervical intraepithelial neoplasia grade 2/3 with koilocytosis; and episomal HPV-18 DNA was found in two specimens classed as cervical intraepithelial neoplasia grade 2/3, one of which also contained HPV-11 DNA, and in one specimen that showed viral changes alone. Integrated HPV DNA was found in six specimens (four with HPV-16 DNA and two with HPV-18 DNA), including two cases of chronically inflamed cervix with no histological evidence of viral infection or cervical intraepithelial neoplasia. Detection of viral DNA in early lesions may identify patients at risk of malignant progression. This is the first report of HPV-18 DNA in cervical intraepithelial neoplasia in Scotland.     

TSHR蛋白在宫颈癌的表达及其与HPV-16感染的关系

目的研究促甲状腺激素受体（TSHR）在子宫颈癌组织的表达及其与乳头瘤病毒（HPV－16）的关系。方法应用免疫组织化学链霉菌抗生物素过氧化物酶（SP）法检测79例子宫颈癌和30例子宫颈炎组织HPV－16与TSHR蛋白表达。79例癌症患者中病理分级〈Ⅱ级33例,≥Ⅱ级46例;病理分期〈Ⅱ期56例,≥Ⅱ期23例;无淋巴结转移66例,有淋巴结转移13例;肿瘤大小〈3cm44例,肿瘤大小≥3cm35例。结果HPV－16在子宫颈癌表达率55．70％明显高于宫颈炎5％（P〈0．05）,TSHR在子宫颈癌表达率68．35％明显高于宫颈炎26．67％（P〈0．05）。HPV－16表达与肿瘤的大小、肿瘤分级、分期、淋巴结转移不相关。TSHR表达与肿瘤的大小呈正相关,P〈0．05,与肿瘤分级、分期及淋巴结转移不相关。HPV－16与TSHR在宫颈癌表达呈正相关。结论HPV感染对宫颈癌病变起到强烈的预警作用。TSHR不仅在甲状腺滤泡上皮细胞表达,在子宫颈癌细胞也表达,TSHR过表达能促进宫颈细胞的异常增殖,其异常功能可能是恶性肿瘤特定的临床表型。HPV与TSHR在子宫颈癌变过程中起协同作用。     

Presence of human papillomavirus genome in human tumor cell lines and cultured cells.

A series of 47 human carcinoma cell lines and their cultured cells were examined for human papillomavirus (HPV) genomes with the use of an HPV detection kit (DNA-RNA hybridization, mixed HPV DNA probe of types 6, 11, 16, 18, 31, 33 and 35). Four of 8 cases of mild dysplasia, 3 of 9 cases of severe dysplasia, 3 of 7 cases of carcinoma in situ, 3 of 15 cases of uterine carcinoma and 5 of 6 cases of condyloma acuminatum were shown to contain the HPV DNA genome in primary cultured cells, while HPV was not detected in the third-passage cells except for the three cases of large cell, nonkeratinizing squamous cell carcinoma. HPV was also not detected in such normal tissues as uterine cervical squamous epithelium, uterine cervical columnar epithelium and endometrium. The presence of HPV DNA genomes was detected consistently in the passages of three lines (SKG-II, HKMUS and HKTUS; large cell nonkeratinizing squamous cell carcinomas of the uterine cervix) with the use of the Southern Blot method (DNA-DNA hybridization, mixed HPV probe of types 6, 11, 16 and 18). HPV type 16 DNA was detected in HKTUS, and HPV type 18 DNA was found in SKG-II and HKMUS. The other 44 cell lines, including ovarian carcinoma, endometrial carcinoma, sarcoma, gastric cancer, pancreatic cancer and rectal cancer, were negative for the HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33 and HPV-35 genomes under stringent hybridization conditions.     

1235例妇科门诊患者高危型HPV感染状况及亚型分布调查研究

目的了解本地区妇科门诊患者宫颈高危型HPV感染状况及亚型分布,为今后的宫颈癌前病变、宫颈癌防治提供临床依据。方法采用基因芯片技术对1 235例妇科门诊患者进行HPV筛查,筛查出的阳性患者应用流式荧光杂交法进行高危型HPV亚型检测,分析比较宫颈炎、宫颈鳞癌及宫颈腺癌患者高危型HPV感染情况及亚型分布差异。结果六安市金安区妇幼保健院妇科门诊患者HPV感染率高达60%,其中高危型HPV感染率为43. 2%,主要以HPV16、HPV18为主;低危型HPV感染率为30.0%,主要以HPV11为主;单一感染阳性率为34. 1%,而混合型感染高达65. 9%,且两者均以HPV16型和HPV18型为主。宫颈炎患者HPV16型、HPV18型及HPV16 ＋ HPV18型的检出率明显低于宫颈鳞癌和宫颈腺癌患者,其中宫颈腺癌患者HPV16 ＋ HPV18型混合感染率最高。结论妇科门诊患者HPV感染率较高,宫颈癌患者HPV16及18型检出率显著高于宫颈炎患者,加强HPV高危基因型的监测有助于预警宫颈癌尤其是宫颈腺癌的发生。     

Human papillomavirus genotypes and the p53 codon 72 polymorphism in cervical cancer of Northeastern Thailand

Human papillomavirus (HPV) infection including sub-strain identification was studied in patients with squamous cell cervical cancer (SCCA) in Northeastern Thailand. Subjects were 90 cases of SCCA and 100 healthy controls. Prevalence of high-risk group of HPV infection in the controls and the SCCA patients were 13.0% and 86.7%, respectively. The HPV infection significantly increased the risk for cervical cancer 43.5-fold (95% confidential interval: 17.5-110.6; P <0.00001). Among HPV carrier patients with SCCA (n = 78), HPV-16 was also prominent (70.5%) followed by HPV-18 (23.1%). There was no statistical difference in the subtype distribution between the SCCA and the control groups. There was no significant association between genotype distribution of the p53 codon 72 polymorphism and HPV infection. HPV infection was confirmed as a critical risk factor for cervical cancer development in Northeast Thailand. Since polymorphism of the p53 itself as well as in combination with HPV infection may not be a genetic risk for cervical cancer, much attention should be paid to other risk factors such as sexual behavior and smoking.     

p53 Codon 72 Polymorphism as a Risk Factor in the Development of HPV-Associated Cervical Cancer

Human papilloma virus (HPV) has been implicated in cervical carcinoma, and the p53 gene is polymorphic at amino acid 72 of the protein that it encodes. The association between p53 polymorphisms and risk for HPV-associated cervical cancer has been examined, but the results have been conflicting. It has been reported that patients with the arginine form have a higher risk of developing cervical cancer than those with the proline form. The purpose of this study was to examine whether p53 Arg at the polymorphic position 72 could represent a risk factor for women with high-risk HPV-associated premalignant and malignant cervical lesions. The study was carried out on 60 smears from patients with high-risk HPV-related cervical lesions. Also, 74 HPV-negative normal smears and 61 normal blood samples were used as controls. HPV-18 was the most frequent type. There was a difference in the distribution of p53 genotypes between high-risk HPV-cervical lesions and the normal samples. The allele frequency of p53 Arg/Arg was much higher than the normal samples (46.5% versus 20.5% in HPV-negative normal smears and 20% in blood samples). Based on the findings of this study, it is suggested that p53 Arg homozygosity could possibly represent a potential risk factor for the tumorigenesis of the cervix. Statistically significant correlation was not observed between the presence of Arg/Pro homozygosity or Arg/Pro heterozygosity and HPV typing.     

Detection of HPV types and neutralizing antibodies in women with genital warts in Tianjin City,China

The serum samples and corresponding cervical swabs were collected from 50 women with genital warts from Tianjin city, China. The neutralizing antibodies against HPV-16, -18, -58, -45, -6 and -11 in serum samples were tested by using pseudovirus-based neutralization assays and HPV DNAs in cervical swabs were also tested by using a typing kit that can detect 21 types of HPV. The results revealed that 36% (18/50) of sera were positive for type-specific neutralizing antibodies with a titer range of 160–2560, of which 22%(11/50), 12%(6/50), 10%(5/50), 4%(2/50), 4%(2/50) and 2%(1/50) were against HPVs -6, -16, -18, -58, -45 and -11, respectively. Additionally, 60% (30/50) of samples were HPV DNA-positive, in which the most common types detected were HPV-68(18%), HPV-16(14%), HPV-58(12%), HPV-33(8%) and HPV-6, HPV-11, HPV-18 and HPV-52 (6% each). The concordance between HPV DNA and corresponding neutralizing antibodies was 56% (28/50) with a significant difference (P<0.05). The full-length sequences of five HPV types (HPV -42, -52, -53, -58 and -68) were determined and exhibited 98%–100% identities with their reported genomes. The present data may have utility for investigating the natural history of HPV infection and promote the development of HPV vaccines.     

Opportunities to improve the prevention and treatment of cervical cancer

Human papillomavirus (HPV) is a causal agent for approximately 5.3% of cancers worldwide, including cervical cancer, and subsets of genital and head and neck cancer. Persistent HPV infection is a necessary, but not sufficient, cause of cervical cancer. Of the >100 HPV genotypes, only about a dozen, termed "high-risk", are associated with cancer. HPV-16 is present in approximately 50% of all cervical cancers and HPV-16, HPV-18, HPV-31 and HPV-45 together account for approximately 80%. Most high-risk HPV infections are subclinical, and are cleared by the host's immune system. The remainder produces low or high-grade squamous intraepithelial lesions (SILs), also called cervical intraepithelial neoplasia (CIN), which also may regress spontaneously. However persistent high grade SIL represents the precursor lesion of cervical cancer and carcinogenic progression is associated with integration of the viral DNA, loss of E2 and upregulation of viral oncogene expression, and chromosomal rearrangements like 3q gain. Cytologic screening of the cervix for SIL and intervention has reduced the incidence of cervical cancer in the US by an estimated 80% and HPV viral DNA and other molecular tests may improve screening further. The licensure of a preventive HPV vaccine ushers in a new era, but issues remain, including: protection restricted to a few oncogenic HPV types, access in low resource settings and impact on current cytologic screening protocols. Importantly, preventive HPV vaccination does not help with current HPV infection or disease. Here we examine the potential of second-generation preventive HPV vaccines and therapeutic HPV vaccination to address these outstanding issues.