人乳头瘤病毒16型E5序列进化分析

目的 通过HPV 16 E5序列进化分析,初步研究中日友好医院妇产科宫颈病变诊治中心无宫颈病变的汉族妇女HPV 16型内变异株类型.方法 用PCR法扩增HPV 16 E5基因片段,并进行比对分析测序.比对后的结果结合临床资料进行分析.结果 本研究第一次利用只有236 bp碱基的E5序列进行HPV 16变异株的进化分析,发现单独使用E5序列进行HPV 16变异株进化分析的准确率很高,并且,本研究第一次发现以4075T即可将亚洲株(As)变异株和其他变异株区分开来.结论 从E5基因序列出发进行进化分析,准确率高.单独以4075T即可将As变异株和其他变异株区分开来.     

新疆汉族、维吾尔族HPV16E6基因变异与子宫颈癌及宫颈病变的关系

目的探讨新疆地区汉族、维吾尔族宫颈癌及宫颈病变中HPV16型E6基因变异分布及频率,比较两个民族之间的差异。方法对140例HPV16阳性标本,设计E6基因特异性引物,通过PCR扩增HPV16E6全长基因,PCR产物直接测序,进行序列分析并与德国标准株对比,筛选突变位点。结果 123例汉族、维吾尔族妇女宫颈癌及宫颈病变标本中均存在HPV16E6变异株,其中突变率分别为:47.37%(27/57)和50%(33/66),E6突变位点主要是L83V、D25E、D64E、I73V、H78Y、D113E,其中L83V变异株在两个民族突变中占的比例均最高,汉族L83V突变频率为29.82%(17/57)显著低于维吾尔族的40.90%(27/66)(P0.05)。而汉族D25E突变频率为19.30%(11/57)显著高于维吾尔族的7.58%(5/66)(P0.05),D64E变异株在维族突变株中占的比例为6.1%,而汉族标本中未检出。结论两个民族HPV16 E6基因变异发生的位置和变异发生的频率存在差异,维吾尔族人群中HPV16E6基因D64E变异株可能与该地区维吾尔族宫颈癌高发存在一定的关系。     

宫颈瘤变程度与其相对应的HPV基因型分布规律的研究

目的研究不同级别宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）与人乳头瘤病毒（Human papil-lomavirus,HPV）基因型分布之间的关系。方法收集321例经组织病理学诊断确定为CIN2及以上（CIN2＋）病人的宫颈分泌物标本,其中CIN2 67例,CIN3/ACIS 247例,浸润性宫颈癌7例。采用深圳亚能生物技术有限公司的人乳头瘤病毒（HPV）基因分型检测试剂盒对所选标本进行HPV检测及基因分型。结果在所有321例标本中,HPV阳性300例,阳性率93.5%,两型及两型以上感染138例,占比43.0%。HPV16最常见,检出率为41.1%（132/321）,其次为HPV31,33,52,18和51。HPV16和33的单型感染在CIN3＋中比CIN2更常见,具有统计学差异（P〈0.05）。在包含有HPV16或HPV33的多型感染中,含有HPV16或HPV33的多型感染在CIN3＋中比CIN2更常见,具有统计学意义（P〈0.05）。结论 HPV16和HPV33比其他型别HPV具有更强的潜在致癌性。     

人类乳头状瘤病毒分型检测在宫颈癌筛查中的临床研究

目的 探讨人类乳头状瘤病毒（human papillomavirus,HPV）基因分型检测在宫颈病变诊断中的临床应用价值.方法 选取2010年1月至2012年12月在北京大学第一医院妇产科就诊的1715例患者作为研究对象,所有患者均行宫颈脱落细胞学检查、HPV分型检测及阴道镜检查下行多点活检,并最终经组织病理学检查诊断为宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）.分析HPV分型检查在宫颈癌筛查诊断中临床应用价值.结果 1715例CIN患者HPV检出率排名前五位的依次是HPV16、58、52、33、31;CIN2＋（包括CIN2/CIN3/原位腺癌/宫颈癌,以下简称CIN2＋）患者中前五位依次是HPVI6、58、33、52、31;其中CIN2＋中细胞学未见上皮内病变细胞和恶性细胞（negative for intraepithelial lesion or malignancy,NILM）患者中,Logistic回归分析结果显示HPV16、33和18型阳性致CIN2＋风险性较大,回归系数OR分别为5.031（P=0.000）、2.375 （P=0.000）和1.598（P =0.027）.宫颈脱落细胞学为非典型鳞状上皮细胞（atypical squamous cells of undetermined significance,ASCUS）,伴随HPV16、58型阳性,发生CIN2＋风险性较大,回归系数OR分别为5.139（P=0.000）和2.096（P=0.025）.宫颈脱落细胞学为低度鳞状上皮内病变（low squamous intraepithelial lesion,LSIL）,伴随HPV16、33、52型CIN2＋风险性较大,回归系数OR分别为5.774（P =0.000）、3.368（P =0.000）和1.747（P=0.034）.结论 HPV分型检测在宫颈癌筛查中具有重要作用,是指导细胞学阴性、ASCUS和LSIL患者临床处理时的重要参考指标,尤其是当HPV16型阳性时.     

实时荧光定量PCR法检测人乳头状瘤病毒的实验研究

目的 通过研究病变宫颈中人乳头状瘤病毒(HPV)16/18型的表达,探讨HPV16/18型病毒感染与宫颈病变发生发展之间的关系.方法 结合病理切片诊断,以免疫组化作对照.运用实时荧光定量PCR技术检测病变宫颈中HPV16/18型DNA拷贝数,以及HPV16/18型E7基因mRNA表达量.结果 慢性宫颈炎患者中HPV16/18型感染率低(7.4%).宫颈管上皮内瘤样变(CIN)组HPV16型感染率较高为69.6%,宫颈癌患者巾为72.7%.HPV16型DNA的拷贝数在宫颈上皮内瘤样变患者中与病理分级没有明显的相关性.但在宫颈癌患者中,病毒DNA的拷贝数明显升高,二者差异明显.CIN轻度(I)、中度(Ⅱ)、高度(Ⅲ)组和宫颈癌患者中,HPV16 E7基冈的表达率分别为0、37.5%、42.9%、63.6%.统计学分析表明,HPV16 E7 mRNA的拷贝数与病情呈明显的正相关性.结论 感染者中主要以HPV16型为主,HPV18型较少.宫颈癌患者中HPV16 DNA拷贝数明显高于CIN Ⅱ、Ⅲ组,HPV16型E7 mRNA在宫颈癌中表达率及表达量明显增加并与宫颈癌变呈正相关.实时荧光定量PCR适合临床宫颈病变病毒的筛查与检测.     

宫颈上皮内瘤样病变135例三年随访分析

目的 探讨宫颈薄层细胞学检查（TCT）和HPV检测联合筛查在宫颈上皮内瘤样病变（CIN）诊治和随访中的作用.方法 对2006年进行细胞学检查异常,且组织病理学诊断为宫颈上皮内瘤样病变的患者共135人进行病例回顾性总结,并在2006年至2009年进行连续随访,对其进行TCT和HPV检测.结果 （1）73例高危型HPV阳性的患者中,15例为ASCUS,3例为ASCUS-H,28例为LSIL,27例为HSIL;17例为CINⅠ,24例为CINⅡ,30例为CINⅢ,2例为CINⅢ可疑早侵.（2）3次随访中未出现CIN复发或病理升级情况.结论 HPV检测联合宫颈细胞学检查法在宫颈上皮内瘤样病变的诊治和随访中具有重要的意义.     

人乳头瘤病毒检测在宫颈病变中的应用价值

目的了解宫颈细胞学异常患者中人乳头瘤“毒（HPV）的感染状况,评估HPV检测在宫颈病变筛查中的价值。方法随机选取宫颈薄层液基细胞学检测异常的101例患者进行了HPV检测,同时行组织病理学检查。结果（1）101例宫颈细胞学异常患者中,细胞学为ASCUS、LSIL、HSIL、鳞状细胞癌时高危型HPV阳性率分别为84．2％、88．6％、100．0％和2／2;（2）10l例细胞学异常患者中20例为CINI,81例为CINⅡ及以上级别,高危型HPV阳性率存CINI、CINⅡ及以上级别分别为60％、97．5％;（3）ASCUS组中,高危型HPV阳性患者中CINⅡ及以上病变的发生率为87．5％,HPV阴性患者中CINⅡ及以上病变的发生率为16．7％;（4）高危型HPV型别分布由高到低分别为HPVl6型39．6％（40／101）,HPV58型17．8％（18／101）,HPV52型16．8％（17／101）,HPVl8型9．9％（10／101）以及HPV33型9．9％（10／101）。结论高危型HPV感染率与宫颈病变级别呈正相关;HPV检测可作为ASCUS患者的有效分流手段。宫颈病变患者中高危型HPV感染以16、58、52、18、33型为主。     

新疆妇女子宫颈病变组织中HPV16E6基因突变分析

目的通过检测HPV16E6基因突变在新疆维吾尔族和汉族妇女宫颈癌组织中的分布规律,以探讨该突变与宫颈癌发生的关系。方法取汉族宫颈炎(含石蜡包埋组织及宫颈刷液基标本)125例,维吾尔族宫颈炎(含石蜡包埋组织及宫颈刷液基标本)124例;汉族石蜡包埋宫颈癌35例,维吾尔族石蜡包埋宫颈癌共109例。用以上HPV16阳性DNA模板PCR扩增HPV16E6全长基因,PCR产物直接测序,分析新疆女宫颈癌组织HPV16E6基因的突变。结果PCR检测结果显示汉族族宫颈炎组织中HPV16E6阳性率为35.71%(15/42);维吾尔族宫颈炎组织中HPV16E6阳性率为30.46%(14/46);汉族族宫颈癌组织中HPV16E6阳性率为33.33%(2/6),维吾尔族宫颈癌组织中HPV16E6阳性率为22.22%(12/54);宫颈炎与宫颈癌中HPV16E6阳性表达无统计学意义(P>0.05),对21份(上皮内低度病变1例,原位癌1例,低分化宫颈癌4例,中分化宫颈癌4例,高分化1例,轻度炎症4例,中度炎症3例,重度炎症1例,正常宫颈2例)HPV16E6扩增片段的双向测序,其中5例成功测序得到一级结构,并且序列分析表明,2例(维吾尔...     

人乳头瘤病毒16型E6和E7基因特征分析

目的 对北京15例宫颈癌病变组织中的人乳头瘤病毒(HPV)16型E6和E7基因进行扩增及序列测定,分析E6和E7基因突变特征,并探讨宫颈癌病变中HPV16的感染情况.方法 自行设计HPVl6型E6和E7基因扩增引物,采用PCR法扩增15例宫颈癌组织中HPV16 E6和E7片段,将PCR产物克隆到TA载体,进行序列测定.通过Sequencer、Bioedit、Mega等生物学软件对E6和E7基因进行核苷酸和氨基酸序列分析.结果 15例宫颈癌中8例鳞癌检出E6和E7基因,检出率为8/15.2例腺癌、1例腺鳞癌和其他4例鳞癌中均未检出HPV16 E6E7 DNA.8例鳞癌中的4例检出的HPVl6为亚洲类似株,在E6基因178位(T→G,D25E)和E7基因647位(A→G,N29S)发生突变;另外4例为欧洲类似株,其中1例(BJ16)的HPV16在E6基因335位点发生突变(C→T,H78Y).结论 HPV16是致宫颈癌的重要因素;宫颈鳞状细胞癌HPV16感染的发生频率较腺癌和腺鳞癌高;E6基因178位点可能是区分亚洲株和欧洲株的重要位点;E6基因178位点和E7基因647位点是突变频率较高的位点,可能导致HPV16致癌能力发生改变.     

宫颈鳞癌和癌前病变中eIF-4E表达及其与HPV16/18感染的关系

目的探讨真核翻译启始因子eIF-4E在宫颈鳞癌和癌前病变中的表达规律及其与人乳头瘤病毒（HPV）感染之间的关系。方法采用免疫组化ABC法和原位杂交技术检测eIF-4E蛋白和HPV16／18DNA在10例正常宫颈鳞状上皮,29例低级别上皮内瘤变（CIN1级）,31例高级别上皮内瘤变（CIN2、3级）和31例宫颈鳞癌中的表达。结果eIF4E在正常宫颈鳞状上皮中呈阴性表达,随着上皮病变级别升高,表达逐渐增强：低级别〈高级别上皮内瘤变〈宫颈鳞癌（P〈0．05）,且在宫颈鳞癌中表达更强;HPV16／18DNA在四组中的阳性表达率,除高级别上皮内瘤变和宫颈鳞癌两组之间没有差别（均为96．8％）以外,其余各组之间差异均有显著性（P〈0．01）;在低级别、高级别上皮内瘤变和宫颈鳞癌三组中eIF-4E蛋白表达和HPV感染均呈明显正相关（P〈0．01）。结论宫颈鳞癌的发生与eIF-4E蛋白表达及HPV16／18感染密切相关;二者在宫颈鳞癌的发病机制中可能起着协同作用。     

Human papillomavirus 16 variants from Zambian women with normal pap smears

Human papillomavirus (HPV) type 16 is the most prevalent high-risk viral genotype associated with cervical cancer. Six distinct phylogenetic clusters of HPVs have been identified and are distributed differently across five continents. HPV16 DNA was extracted from cervicolavage samples from women with normal pap smears. The LCR regions were amplified in triplicate, cloned, sequenced, and analyzed from a total of 11 recovered HPV16 positive samples [Ng'andwe et al. (2007): BMC Infect Dis 7:77] were analyzed for sequence variation. The HPV16 LCR variants were assessed for promoter activity by use of a luciferase reporter gene. Six novel HPV16 variants with nucleotide exchanges in the LCR region were identified. Five clones were classified as European group HPV16 variants and one as an African group variant. Two of these variants had relatively lower promoter activity, 30% of that of the wild-type strain. The decreased promoter activity of some HPV16 variants may decrease expression of viral oncogenes and may be linked with the development, phenotype and severity of the cervical lesions in women infected with these across HPV16 variants.     

A novel real-time genotyping assay for detection of the E6-350G HPV 16 variant

It has been suggested that some E6 human papillomavirus (HPV) type 16 variants could be involved in viral persistence and progression of HPV infection. A novel one-step allelic discrimination real-time PCR was evaluated for E6-350G variant detection in 102 endocervical HPV 16 positive samples. This assay was also used to assess the distribution of this variant in Spanish women with cervical cancer related to HPV 16.The detection limit for the allelic discrimination assay was 50 copies per reaction, even where the E6-350G variant represents only 20% of the variants in the sample. Complete concordance was observed between DNA sequencing and the novel AD RT-PCR assay. Fourteen E6-350T reference strains and 18 E6-350G variants were detected out of 32 endocervical samples from women with cervical cancer. The average age of women who were infected by the E6-350G HPV 16 variant was 10 years lower in these samples than in women who were infected by the reference strain.This novel allelic discrimination assay is a fast, sensitive and specific method for detection of the E6-350G HPV 16 variant.     

Molecular variants of human papillomavirus type 16 and 18 and risk for cervical neoplasia in Portugal

Persistent high-risk human papillomavirus (HPV) infection is considered as the central cause of invasive cervical cancer. Specific HPV 16 and 18 sequence variations were associated with an increased risk for progression. The purpose of this study was to analyze intratypic variations of HPV 16 and 18 within the E6 gene, MY09/11 and LCR regions, and to evaluate the risk of these variants for cervical neoplasia among Portuguese women. Cervical samples from 187 HPV 16-positive and 41 HPV 18-positive women with normal epithelium, cervical intraepithelial neoplasia, or invasive cervical cancer were amplified by type-specific PCR, followed by sequence and phylogenetic analysis. Sixteen new HPV 16 and 18 patterns are described in this paper. European HPV 16 variants were the most frequent (74.3%), particularly Ep-T350 (44.4%), followed by African (16.1%), and Asian-American (9.6%). Non-European HPV 16 variants were more frequent in pre-invasive lesions than in normal tissue and low-grade lesions. However, when analyzed separately, only African variants were associated significantly with an increased risk for cervical cancer. For HPV 18, the AsAi variant showed a trend, which was not statistically significant to an enhanced oncogenicity. European variants seemed to be significantly associated with a lower risk for cervical cancer development. The distribution of HPV 16 and 18 variants was not related to age or race among women living in the same geographical region. Knowledge of variants will be important for risk determination as well as for designing primers or probes for HPV detection methods, and for appropriate cervical cancer prevention strategies.     

宁波市妇女宫颈癌和人乳头瘤病毒感染的流行病学调查

目的 分析宁波市女性宫颈癌和感染人乳头瘤病毒(HPV)的流行病学特征.方法 收集2002-2014年宁波市女性宫颈癌发病和死亡资料,调查社区已婚妇女和妇科就诊妇女HPV感染情况,对社区妇女感染HPV相关危险因素进行分析,对检出的HPV16型病毒进行序列分析.结果 2006-2014年宁波市宫颈癌粗发病率、中标发病率、世标发病率分别为15.74/105、11.29/105和10.05/105,高发年龄为45-50岁;2002-2014年粗死亡率、中标死亡率和世标死亡率分别为3.09/105、2.26/105和2.08/105.778例社区妇女和387例妇科就诊妇女高危型HPV感染率分别为16.2％和18.3％,居前3位的亚型分别为HPV52(4.2％)、HPV16(3.0％)、HPV58(2.1％)与HPV16(4.9％)、HPV52(3.6％)和HPV58(2.6％).HPV16型病毒E6基因序列分析显示当地流行株均为lineage A组的亚洲变异株及欧洲变异株.结论 宁波市女性宫颈癌标化发病和死亡率均接近全国平均水平,社区妇女HPV感染率处于较高水平,研究结果为将来开展HPV疫苗人群预防提供基线资料.     

Nucleotide polymorphisms of the human papillomavirus 16 E1 gene

The E1 ORF is one of the most conserved regions in the human papillomavirus (HPV) genome. The complete E1 gene of the HPV16 genome was amplified with four overlapping primer sets in 16 high-grade (CIN II, III) and 13 low-grade cervical (CIN I) intraepithelial neoplasias as well as in one cervical cancer case. Sequence analysis of the E6 and E7 genes was also carried out in the same cervical samples in order to confirm the association between nucleotide sequence variations in the HPV16 E1 ORF and HPV16 variant lineages. Analysis of the E1 ORF revealed 27 nucleotide changes, and these changes were correlated with those found in HPV16 Asian American and African type II variants. Of these nucleotide variations, A1668G, G2073A, T2169C, T2189C, A2453T, C2454T, A2587T and G2650A were identified only in high-grade dysplasia cases. A phylogenetic tree of the E1 ORF and nucleotide sequence analysis of the E1, E6 and E7 genes revealed that intratypic nucleotide sequence polymorphisms located in the E1 ORF can be used to identify the major phylogenetic branch to which a HPV16 genome belongs. Moreover, amplification of the E1 ORF revealed a disruption between nucleotides 878 and 1523 in five high- and two low-grade cervical cases, indicating that integration of HPV DNA occurs at an early stage of viral infection.     

Human papillomavirus type 16 variant analysis of E6, E7, and L1 [corrected] genes and long control region in [corrected] cervical carcinomas in patients in northeast China

Human papillomavirus type 16 (HPV 16) plays a cardinal role in the pathogenesis of cervical cancer. HPV 16 has intratypic variants which show different geographical distributions and different oncogenic potentials. To analyze the presence of sequence variations of HPV 16 variants in northeast China, 71 cervical carcinomas were identified by HPV typing. HPV 16-positive specimens were analyzed by PCR-directed sequencing in the E6, E7, and L1 genes and the LCR (long control region). The variation data were compared with those of neighboring districts. In this hospital-based study, HPV 16 was the most common type (73.24%). In HPV 16-positive specimens, 67.31% belonged to the European (E) lineage, while 32.69% were Asian (As) variants. The Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and northern American (NA) lineages were not detected. The most frequently observed variation sites were T178G (32.69%) in E6; A647G (34.62%), G666A (38.46%), and T846C (32.69%) in E7; C6826T (36.17%) and G7060A (61.70%) in L1; and G7521A (98.08%) in the LCR. The most prevalent amino acid variations were D25E in E6 and N29S in E7. In addition, 28 novel variations of HPV 16 were reported. Some covariations between different genes were obtained. In this study, HPV 16 variants belonged to the European lineage and the Asian lineage. Compared with neighboring districts, the distribution of HPV 16 variants in northeast China had a typical pattern. As the first report on HPV 16 variants in northeast China, it should be helpful for designing a HPV vaccine and HPV vaccination program in China.     

Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women

Human papillomavirus (HPV)16 gene mutation is usually associated with persistent HPV infection and cervical intraepithelial neoplasia (CIN). However, the functional implications of HPV16 mutations remain poorly understood.145 LCR/E6/E7 of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the LCR, 13 in E6, 8 in E7) were discovered, 11 of which were nonsynonymous mutations (8 in E6, 3 in E7). The H85Y and E120D variants in E6 were significantly reduced in the high-grade squamous intraepithelial lesion (HSIL) group compared to the <HSIL group (P = .046 and .005), conversely the N29S in E7(P = .01). Amino acid substitutions (D32N/E, E36Q, H85Y, and E120D in E6 and N29H/S and R77C in E7) were predicted to have an effect on conserved structural and functional residues, and five amino acid substitutions (H85Y, E36Q, I34L, and D32E in E6; R77C in E7) would potentially change the secondary structure. “6329G>T,” a potential binding site for TATA-binding protein, is the most common in LCR variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1–3(P = .009). The H85/E120 in E6 and N29 in HPV16 E7 might play a critical role in carcinogenesis by disrupting p53 and Rb degradation due to affecting their interaction, respectively. In a word, the findings in this study provide preventative and therapeutic interventions of HPV16 -related cervical lesions/cancer.     

HPV16 E6 oncogene variants in women with cervical intraepithelial neoplasia

Human papillomaviruses (HPVs) are strongly associated with the development of high grade cervical intraepithelial neoplasia (CIN) and cervical carcinoma, with between 40-80% of patients with cervical carcinoma being attributed to a single HPV type, HPV16 depending on the methods used and geographical location of the particular study [van den Brule et al., 1996]. An HPV16 E6 variant has been described which is strongly associated with high grade CIN [Ellis et al., 1997] and with the human leukocyte antigen (HLA)-B7 genotype in women with cervical carcinoma where HLA-B7 positive patients were demonstrated to have a significantly poorer clinical outcome [Ellis et al., 1995]. To determine whether this HPV16 E6 variant might play a significant role in the pathogenesis of cervical disease, 174 HPV16 positive women were selected from those attending the colposcopy clinics of Guy's and St Thomas' Hospital Trust following polymerase chain reaction (PCR) amplification of HPV16 L1 or E5 DNAs from cervical brush swabs or fixed biopsy tissue. HPV16 E6 DNA was amplified by PCR and the variant sequence was identified by Msp 1 restriction enzyme digestion, as the nucleotide substitution creates an additional unique Msp 1 site. The study group comprised 29 normal controls, 7 women with borderline cytology, 123 women with cervical dysplasia and 12 women with cervical cancer. 101/174 (58%) of these women had amplifiable E6 DNA and restriction enzyme digestion was performed on 95 of these. The variant E6 sequence was identified in 3/95 (3%) individuals, two of whom had normal histology and one had a CIN II lesion. Wild type E6 sequence was identified in the remaining 92/95 (97%) individuals. These data suggest that this particular E6 variant does not play a major role in the pathogenesis of HPV16 related cervical disease in women living in the South London area.     

Human papillomavirus type-16 variants in Quechua aboriginals from Argentina

Cervical carcinoma is the leading cause of cancer death in Quechua indians from Jujuy (northwestern Argentina). To determine the prevalence of HPV-16 variants, 106 HPV-16 positive cervical samples were studied, including 33 low-grade squamous intraepithelial lesions (LSIL), 28 high-grade squamous intraepithelial lesions (HSIL), 9 invasive cervical cancer (ICC), and 36 samples from women with normal colposcopy and cytology. HPV genome variability was examined in the L1 and E6 genes by PCR-hybridization. In a subset of 20 samples, a LCR fragment was also analyzed by PCR-sequencing. Most variants belonged to the European branch with subtle differences that depended on the viral gene fragment studied. Only about 10% of the specimens had non-European variants, including eight Asian-American, two Asian, and one North-American-1. E6 gene analysis revealed that 43% of the samples were identical to HPV-16 prototype, while 57% corresponded to variants. Interestingly, the majority (87%) of normal smears had HPV-16 prototype, whereas variants were detected mainly in SIL and ICC. LCR sequencing yielded 80% of variants, including 69% of European, 19% Asian-American, and 12% Asian. We identified a new variant, the Argentine Quechua-51 (AQ-51), similar to B-14 plus two additional changes: G7842-->A and A7837-->C; phylogenetic inference allocated it in the Asian-American branch. The high proportion of European variants may reflect Spanish colonial influence on these native Inca descendants. The predominance of HPV-16 variants in pathologic samples when compared to normal controls could have implications for the natural history of cervical lesions.