Human papillomavirus types 16 and 18 in esophagus squamous cell carcinoma: a meta-analysis

PurposeA possible carcinogenic role of human papillomavirus (HPV) has been investigated in esophageal squamous cell carcinoma (ESCC) for nearly 30 years with mixed results. We performed a meta-analysis to assess the prevalence of “high-risk” HPV, HPV-16/18, in this disease. We also evaluated the association between infection with HPV-16/18 and ESCC risk by meta-analysis of case–control studies.MethodsEligible studies published up to September 30, 2012 were retrieved via both computer searches of MEDLINE and EMBASE and manual review of references. A random-effects model was used to calculate summary prevalence and odds ratios (ORs) and corresponding 95% confidence intervals (CIs).ResultsA total of 5755 cases of ESCC from 68 studies were included in this meta-analysis. Overall, 11.67% (95% CI, 7.74%–16.21%) of ESCC cases harbored HPV-16 and 1.82% (95% CI, 0.90%–2.95%) harbored HPV-18. In addition, meta-analysis of 10 case–control studies showed a significant increase in ESCC risk with HPV-16 infection (summary ORs = 3.55; 95% CIs, 2.05%–6.14%). However, this increased risk in ESCC was not made for HPV-18 infection (summary ORs = 1.25; 95% CIs, 0.46%–3.43%).ConclusionsThis meta-analysis indicated that HPV-16 and -18 can be detected in ESCC. HPV-16, but not HPV-18, is significantly associated with the risk of ESCC. However, it is early to conclude that both types of HPV are involved in esophageal carcinogenesis.     

Human papillomaviruses, herpes simplex viruses, and the risk of oral cancer in men.

A population-based case-control study was conducted in western Washington state to examine the relations between infection with human papilloma viruses (HPV), herpes simplex viruses (HSV), and risk of oral squamous cell cancer in men. Interviews were completed on 131 oral cancer cases diagnosed between January 1985 and December 1989 and 136 controls frequency matched to cases on age and date of diagnosis who were obtained by random digit dialing. The risk for oral cancer among men with 30 or more sexual partners was 2.4 times that of men with four or fewer partners (95% confidence interval (CI) 1.0-5.9). Men who ever practiced oral sex had lower risk for oral cancer relative to men who never practiced oral sex (relative risk (RR) = 0.4, 95% CI 0.2-0.8). Analyses of exfoliated oral cavity cells for the presence of HPV-6 DNA with polymerase chain reaction revealed that men with an oral HPV-6 infection had 2.9 times the risk for oral cancer of noninfected men (95% CI 1.1-7.3), whereas men with an oral HPV-16 infection had 6.2 times the risk for oral cancer of noninfected men (crude RR = 6.2, 95% CI 0.7-52.2). Relative risks associated with serologically detected HSV-1 and HSV-2 infections were 0.8 (95% CI 0.3-1.7) and 1.8 (95% CI 0.7-4.6), respectively. The authors conclude that HPV-6 is associated with oral cancer. Although men infected with HPV-16 and HSV-2 were at elevated risk, these associations may have been due to chance. The role of specific sexual practices in the transmission of viruses to the oral cavity remains unclear.     

深圳市城区育龄妇女HPV感染状况调查

目的 :了解深圳市城区育龄妇女人乳头瘤病毒 ( HPV)感染的状况 ,为宫颈癌防治提供理论依据。方法 :采用基因芯片技术对深圳市城区育龄妇女 2 2 73人进行 HPV检查 ,并对宫颈糜烂 度以上与宫颈轻度糜烂、宫颈光滑者的 HPV各个亚型感染情况进行对比分析。结果 :2 2 73名育龄妇女中共检出 HPV阳性者 5 6 8名 ,阳性率 2 4 .9% ,其中 HPV- 16型 341人 ,HPV- 18型 2 7人 ,HPV- 5 8型 2 5人。在宫颈糜烂 度以上的 5 90人中 ,HPV阳性者 2 4 7人 ,占 4 1.86 % ,其中 HPV- 16型 15 9人 ,HPV- 5 8型及 18型分别为 30人及 2 3人 ,还有 HPV- 4 5型及 33型 ,均为高危亚型 ;在 16 83例轻度宫颈糜烂及宫颈光滑者中 ,HPV阳性者 2 37例 ,占 14 .0 3% ,其中 HPV- 16型 136例、 HPV- 5 8型 5 6例 ,尚可检出 HPV- 6型及 11型等低危亚型。表明宫颈糜烂严重程度越重 ,HPV- 16高危型检出率越高。结论 :鉴于 HPV- 16型等高危型与宫颈糜烂发病关系密切 ,故积极控制HPV感染及有效治疗宫颈糜烂在宫颈癌防治中具有重要意义。基因芯片技术对 HPV检测是一种敏感和特异的方法     

人乳头瘤病毒基因型与宫颈上皮内瘤样病变的关系

目的:通过研究各级别宫颈上皮内瘤变中所感染HPV的基因型,来探讨不同基因型HPV的致病力。方法:对225例经活检证实的宫颈上皮内瘤变(CIN)患者的HPV检测结果进行分组分析,根据病变级别分为CIN I、Ⅱ、Ⅲ3组。225例CIN患者均有细胞学检查结果,HPV检测采用亚能HPV基因分型检测系统进行23种HPV-DNA亚型分析。结果:HPV-16和58亚型感染位居各级别宫颈病变的前两位,两者感染率占48·4%;本组CIN病例HPV亚型感染频度由高到低依次为HPV-16(30·2%)、58(18·2%)、33(8·6%)、18(7·1%)、56(4·9%)、31(4·4%)、11(3·2%)、35(2·2%)、45(1·6%)、6(1·6%)、52、59、68、43、39、66、73、83、42型;HPV-16(57·3%)、58(21·4%)、18(10·7%)、31(9·8%)、35(7·1%)、56(3·6%)亚型居CINⅢ组的前6位,说明这些亚型致病力强,更易导致宫颈的高级别病变;在CINI~Ⅲ级病变中HPV二重或三重感染分别占19·4%、27·9%和16·7%,提示HPV双重或多重感染与宫颈病变级别之间无正相关性。结论:本组CIN患者HPV感染的常见亚型是16、58、33、18、56、31,易导致宫颈高级别病变的亚型是16、58、18、31、35、56,HPV-DNA的分型检测对预测病变进展、评估预后、指导治疗有重要价值。     

A meta-analysis of human papillomavirus type-distribution in women from South Asia: implications for vaccination

OBJECTIVE: To determine human papillomavirus (HPV) prevalence and type-distribution in women from South Asia, with and without cervical lesions, in order to estimate the impact of an HPV 16/18 prophylactic vaccine in this region and to assess additional types that should be incorporated in new vaccines. METHODS: A meta-analysis was conducted that included studies using polymerase chain reaction to detect HPV-16, -18, -6, -11 and at least one other HPV type, with a minimum of 20 cases in each grade of lesion. Total as well as type-specific prevalence of various HPV types were estimated, stratified by cervical lesion grade, using Stata 9.0 software package. RESULTS: Nine studies from India fulfilled the inclusion criteria. A total of 558, 52, 52 and 3061 women, respectively with invasive cervical cancer (ICC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and normal cytology/histology were included. Overall HPV prevalence was 94.6%, 86.5%, 65.4% and 12.0% in women with ICC, HSIL, LSIL and normal cytology/histology, respectively. In ICC, HPV-16 was the predominant type (64.8%), followed by HPV-18, -45, -33, -35, -58, -59 and -31. The estimated HPV-16/18 positive fraction was 78.9% in women with ICC (87.7% in North and 77.2% in South India), 61.5% with HSIL, 30.8% with LSIL and 3.9% in women with normal cytology/histology. There was no difference in overall HPV prevalence in cervical cancer between North and South India (P=0.063). However, HPV-16 and -45 appeared to be more prevalent in North India (P=0.018 and 0.013, respectively), while HPV-35 appeared to be more prevalent in South India (P=0.033). CONCLUSION: It is estimated that HPV-16/18 vaccines will provide over 75% protection against ICC in South Asia. HPV-45, -33, -35 and -58 account for an additional 20% of cervical cancer in this region. The addition of these additional HPV types in a second-generation vaccine could provide optimal cervical cancer prevention in this region.     

HPV-DNA分型检测在ASC-US患者分层处理中的作用

目的:了解HPV-DNA分型检测在意义不明确的宫颈不典型鳞状上皮细胞(ASC-US)患者分层处理中的作用。方法:260例宫颈细胞学诊断为ASC-US的患者进行HPV-DNA分型检测,同时在阴道镜下多点活检。结果:260例患者中慢性炎症168例(64.62%),其中高危HPV阳性率为38.10%(64/168);宫颈上皮内瘤变(CIN)90例(34.62%),其中高危HPV阳性率为81.11%(73/90);早期浸润癌2例(0.77%),其中高危型HPV感染2例,感染率100%。慢性炎症和CIN患者两者比较高危HPV感染阳性率差异有统计学意义(P<0.05),且两型及以上HPV感染阳性率两组差异亦有统计学意义(P<0.05)。260例中高危HPV感染排在前5位的亚型分别是HPV-16、58、52、33、31。结论:HPV-DNA分型检测在ASC-US患者分层处理中有意义,对高危HPV亚型16、58、52、33、31感染的ASC-US患者需及时干预,加强随访。     

Chapter 3: HPV type-distribution in women with and without cervical neoplastic diseases

Geographical widespread data on human papillomavirus (HPV) type-distribution are essential for estimating the impact of HPV-16/18 vaccines on cervical cancer and cervical screening programmes. Epidemiological studies employing a variety of HPV typing protocols have been collated in meta-analyses. HPV-16/18 is estimated to account for 70% of all cervical cancers worldwide, although the estimated HPV-16/18 fraction is slightly higher in more developed (72-77%) than in less developed (65-72%) regions. About 41-67% of high-grade squamous intraepithelial lesion (HSIL), 16-32% of low-grade squamous intraepithelial lesion (LSIL) and 6-27% of atypical squamous cells of undetermined significance (ASCUS) are also estimated to be HPV-16/18-positive, thus highlighting the increasing relative frequency of HPV-16/18 with increasing lesion severity. After HPV-16/18, the six most common HPV types are the same in all world regions, namely 31, 33, 35, 45, 52 and 58; these account for an additional 20% of cervical cancers worldwide.     

人乳头状瘤病毒16 18、单纯疱疹病毒Ⅱ型和巨细胞病毒感染与宫颈癌发生、发展的关系

目的探讨人乳头状瘤病毒（HPV）16／18、单纯疱疹病毒Ⅱ型（HSV-Ⅱ）和巨细胞病毒（CMV）感染与宫颈癌发生、发展的关系。方法对43例宫颈癌、47例宫颈上皮瘤样病变（CIN）、56例宫颈炎和10例正常宫颈进行聚合酶链反应检测HPV16／18、HSV-Ⅱ和CMV感染情况。结果HSV-Ⅱ、HPV16／18和CMV的阳性率在宫颈癌和CIN组、CINⅢ级和CINⅠ～Ⅱ级组均有递减趋势，且差异有统计学意义。Ⅱ期宫颈癌组HPV16／18阳性显著高于Ⅰ期宫颈癌组，高分化宫颈癌组HPV16／18和HSV-Ⅱ阳性高于中分化组，与临床分期及组织类型差异均无统计学意义；CMV阳性与临床分期、组织分级及组织类型差异均无统计学意义。三种病毒感染拷贝数，HSV-Ⅱ和HPV16／18：宫颈癌〉CIN〉宫颈炎；CMV：宫颈癌〉CIN。宫颈癌中出现几种病毒混合感染，其中HPV16／18合并HSV-Ⅱ明显多于HPV16／18合并CMV者。结论HPV16／18、HSV-Ⅱ和CMV感染与宫颈癌的发生发展关系密切，且与病毒负荷量有关，可能是宫颈癌的致病因子。     

Is Smoking an Independent Risk Factor for Invasive Cervical Cancer? A Nested Case-Control Study Within Nordic Biobanks

The strong correlation between smoking and exposure to oncogenichuman papillomaviruses (HPVs) has made it difficult to verifythe independent role of smoking in cervical carcinogenesis.Thus, the authors evaluated this role. Five large Nordic serumbanks containing samples from more than 1,000,000 subjects werelinked with nationwide cancer registries (1973–2003).Serum samples were retrieved from 588 women who developed invasivecervical cancer and 2,861 matched controls. The samples wereanalyzed for cotinine (a biomarker of tobacco exposure) andantibodies to HPV types 16 and 18, herpes simplex virus type2, and Chlamydia trachomatis. Smoking was associated with therisk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositiveheavy smokers (odds ratio = 2.7, 95% confidence interval: 1.7,4.3). A similar risk of SCC (odds ratio = 3.2, 95% confidenceinterval: 2.6, 4.0) was found in heavy smokers after adjustmentfor HPV16/18 antibodies. The point estimates increased withincreasing age at diagnosis and increasing cotinine level. Thisstudy confirms that smoking is an independent risk factor forcervical cancer/SCC in women infected with oncogenic HPVs. Thesefindings emphasize the importance of cervical cancer preventionamong women exposed to tobacco smoke. carcinoma, squamous cell; risk factors; smoking; uterine cervical neoplasms     

宫颈疾病HPV亚型感染的导流杂交法检测及意义

目的:探讨导流杂交法人乳头瘤病毒(HPV)基因型检测在宫颈疾病病因学诊断中的应用价值。方法:采用导流杂交法对236例宫颈疾病筛查者(包括宫颈癌组31例、宫颈上皮内瘤变组10例、炎症组118例和正常组77例)宫颈脱落细胞进行21种HPV基因型检测,分析各组患者不同HPV亚型感染特点。结果:从236例妇女中共检出HPV(+)者72例,包括宫颈癌组29例(93.5%)、宫颈上皮内瘤变组5例(50.0%)、炎症组30例(25.4%)、正常组8例(10.4%),各组阳性率比较差异有统计学意义(χ2=76.041,P<0.001);HPV基因型检出率由高到低依次为:HPV-16(33.3%)、HPV-52(16.1%)、HPV-58(8.0%)、HPV-31(8.0%)、HPV-18(6.9%)、HPV-11(6.9%)、CP8304(3.4%)、HPV-33(3.4%)、HPV-53(2.3%)、HPV-59(2.3%)、HPV-68(2.3%)、HPV-66(2.3%)、HPV-6(1.1%)、HPV-39(1.1%)、HPV-56(1.1%)、HPV-42(1.1%)、HPV-43(1.1%)、HPV-45(1.1%);高危HPV基因型检出率随宫颈病变程度加重而明显升高(χ2=61.190,P<0.001),各疾病组检出的前3位HPV亚型均为高危型。结论:宫颈疾病与HPV感染密切相关,宫颈肿瘤主要由高危基因型HPV感染所致;导流杂交法具有操作简捷、结果清晰和比较经济等优势,值得在宫颈疾病的病因诊断中推广应用。     

HPV vaccine efficacy in preventing persistent cervical HPV infection: a systematic review and meta-analysis

INTRODUCTION: We performed a pooled analysis of randomised clinical trials (RCT) on HPV vaccine efficacy in preventing cervical persistent infection. METHODS: We carried out a bibliographic search on electronic databases and we selected RCT to perform the meta-analyses. RESULTS: We selected five studies. The first meta-analysis, including all studies, showed an important reduction of the risk of infection from HPV 16 in vaccinated cohort [RR 0.10 (95% CI: 0.07-0.15)]. The second and third meta-analyses, including only studies on bivalent and tetravalent vaccines, showed a RR of 0.13 (95% CI: 0.09-0.20) for HPV 16 infections and a RR of 0.22 (95% CI: 0.13-0.38) for HPV 18 ones. DISCUSSION: HPV vaccine efficacy in preventing persistent infection is high but there is the need for further studies on the duration of immunization and long-term vaccine efficacy.     

A meta-analysis of association of Human Leukocyte Antigens A,B, C,DR and DQ with Human Papillomavirus 16 infection

Human Papillomavirus (HPV) induced cervical cancer (CaCx) is a major health problem in women from both developing and developed regions of the world. This virus accounts for >95% of the CaCx cases with a preponderance of HPV type −16 (65%). Paradoxically HPV-16 is prevalent even in the cervix of healthier women and anti HPV-16 T-cell response is considered critical for the viral clearance. Studies on HLA association with HPV-16 infection and cervical cancer have yielded varied HLA associations in different epidemiological settings. To validate these associations, we performed a meta-analysis of HLA-A, B, C, DR and DQ association with HPV-16 infection. Of the 1409 studies retrieved, 26 qualified for meta-analysis based on stringent inclusion and exclusion criteria.HLA-B*47, B*57, DRB1*10, DRB1*15 and DQB1*0303 were significantly associated with HPV-16 infection (OR = 3.4, 1.8, 1.5, 1.1 and 1.5 respectively). HLA-B*49, B*39, A28 (serotype), C*04 and DRB1*13 were negatively associated with HPV-16 (OR = 0.5, 0.6, 0.7, 0.7, and 0.7 respectively). Certain HLA alleles such as B*07, DRB1*15, DRB1*11 and DRB1*07 showed weakly positive associations. A comprehensive analysis coupling HPV-16 antigenic diversity and the HLA variation in various global populations shall provide further insights into the immunogenetic predisposition to HPV-16 and shall help identify host-parasite co-evolution.     

HPV-16E6/E7、HIF-1α表达与宫颈癌变及微血管生成相关性研究

目的:探讨不同宫颈病变中HPV-16E6/E7、缺氧诱导因子-1α(HIF-1α)的表达及MVD的变化,分析三者与宫颈癌变及其发展的内在联系。方法:采用免疫组化EnVision法检测45例宫颈鳞癌组织(SCC)、60例宫颈上皮内瘤变组织(CINⅠ～Ⅱ30例,CINⅢ30例)及10例正常宫颈组织(NCE)中HPV-16E6/E7、HIF-1α的表达,并以CD34标记血管内皮细胞计数MVD。结果:随着宫颈病变的进展,HPV-16E6/E7与HIF-1α的阳性表达率逐渐增高,MVD逐渐增大。MVD在以上4组间相比差异均有统计学意义(P<0.05)。HPV-16E6/E7与HIF-1α在宫颈鳞癌、CINⅢ、CINⅠ～Ⅱ、正常宫颈组织中的阳性表达率分别为86.67%、66.67%、46.67%、10.00%与84.44%、63.33%、33.33%、20.00%,且两者在正常组与CINⅠ～Ⅱ组表达率差异均无统计学意义(P>0.05),在其余组间差异有统计学意义(P<0.05)。宫颈鳞癌组织中HIF-1α与HPV-16E6/E7、MVD表达呈正相关性(P<0.05),HPV-16E6/E7与MVD也呈正相关性(P<0.05)。结论:HPV-16E6/E7与HIF-1α在宫颈鳞癌的发生、发展中起着协同作用,HPV-16E6/E7增加、HIF-1α蛋白的表达和稳定性促进宫颈癌血管生成,可能在子宫颈癌变中发挥关键作用。     

Longer term efficacy of a prophylactic monovalent human papillomavirus type 16 vaccine

We conducted an extended follow-up study (March 2006–May 2008) to assess the longer term efficacy of a prophylactic monovalent human papillomavirus (HPV) type 16 L1 virus-like particle vaccine in women (n = 290) who had enrolled in a randomized controlled trial of this vaccine (October 1998–November 1999) in Seattle and remained HPV-16 DNA negative during the course of that trial. During the extended follow-up period, in the per-protocol susceptible population, none of the vaccine recipients was found to be infected with HPV-16 or developed HPV-16-related cervical lesions; among placebo recipients, 6 women were found to be infected with HPV-16 (vaccine efficacy [VE] = 100%; 95% confidence interval [CI]: 29–100%) and 3 women developed HPV-16-related cervical lesions (VE = 100%; 95% CI: <0–100%). Approximately 86% of vaccine recipients remained HPV-16 competitive Luminex immunoassay seropositive at an average of 8.5 years of follow-up. During the combined original trial and extended follow-up period, in the intention-to-treat population, 20 and 22 women developed any cervical lesion regardless of HPV type among the vaccine and placebo recipients, respectively (VE = 15%; 95% CI: <0–56%). The results suggest that this monovalent HPV-16 vaccine remains efficacious through 8.5 years after its administration.     

Epidemiology and genotype distribution of human papillomavirus (HPV) in women of Sardinia (Italy)

The human papillomavirus (HPV) infection is necessary for the development of cervical cancer. Our study aims to evaluate the rate of HPV circulation in our population, to identify the prevalent genotypes and to establish correlation with cervical abnormalities. Furthermore, the awareness of women about HPV issues was investigated.This study included 864 women attending the Oncologic Prevention Service for their routine Pap test screening or the Health Promotion Mother-Child Service for counselling about sexual activity, from July 2006 to September 2007. All the participants gave their informed consent to be enrolled in the study and were invited to fill in a questionnaire about the socio-cultural state, sexual activity and awareness about HPV. The women samples were tested for HPV-DNA and HPV genotypes: any type of HPV-DNA was detected in 31.0% of the women; single or multiple infections sustained by HPV-16 or HPV-18 represented 43.5% of all HPV infections, accounting for infections in 11.8% of the recruited women. The HPV and high-risk HPV (HR-HPV) prevalence significantly declined in women older than 46 years. The Pap test result was available in 490 women; 48.1% of the Pap test positive women had also an HPV infection and among these 22.7% were infected by HPV-16 and/or HPV-18 genotype, while 51.9% (94/181) were HPV negative. The analysis by binary logistic regression showed that genotype 16 and/or 18 is a risk factor for the Pap positive test with a odds ratio (OR) of 2.9 (95% C.I. 1.4–5.9) and 3.6 (95% C.I. 1.58–8.42) respectively, while age is a protective factor (OR 0.97, C.I. 95% 0.96–0.99); furthermore, the mean age at the first sexual intercourse and the mean number of partners since the beginning of sexual activity, were statistically associated with the risk of HPV infection. More than half of women were aware about HPV, its sexual transmission and of its correlation with cervix cancer.Our findings evidenced that HPV infection is frequent in women aged 18–46 years in Sardinia and particularly that 16 and 18 HPV genotypes are detectable in more than 40% of the infected women. The proportion of women informed about HPV issues is sufficient to guarantee an aware approach to HPV vaccination.     

持续感染状态的HPV-16及HPV-58亚型在宫颈上皮内瘤变及宫颈癌中的分布及意义

目的:研究呈持续感染状态的高危型人乳头瘤病毒(HPV-16,HPV-58)在宫颈病变患者中的分布情况及意义。方法:应用分子导流杂交技术分别检测10 477例慢性宫颈炎,3 672例宫颈上皮内瘤变,1 108例宫颈癌患者中呈持续感染状态的HPV-16和HPV-58的分布情况。结果:HPV-16持续性感染在慢性宫颈炎,CINⅠ,CINⅡ/Ⅲ中的阳性率依次为0.41%(95%CI,0.29%～0.53%),3.00%(95%CI,2.26%～3.74%),15.40%(95%CI,13.63%～17.17%),感染率呈逐渐升高趋势,差异有统计学意义(P<0.05)。HPV-58持续性感染在慢性宫颈炎,CINⅠ,CINⅡ/Ⅲ中的阳性率依次为0.56%(95%CI,0.42%～0.70%),2.66%(95%CI,2.36%～3.46%),6.92%(95%CI,5.68%～8.16%),感染率呈逐渐升高趋势,差异有统计学意义(P<0.01)。HPV-16持续性感染与宫颈癌各临床病理参数无明显联系,差异无统计学意义(P>0.05)。HPV-58持续性感染的宫颈癌患者发病年龄高于HPV-58机会性感染或未感染者,差异有统计学意义(P<0.05)。结论:HPV-16及HPV-58持续性感染在宫颈癌前病变发生、发展过程中发挥重要作用,二者有望成为预测CIN进展的风险评估指标。高危型HPV亚型的定期检测对宫颈病变的预测和防治有重要的指导意义。     

上海地区女性宫颈人乳头状瘤病毒型别分布的 Meta分析

目的：分析人乳头状瘤病毒（ HPV）在我国上海地区女性中的感染情况及型别分布,为地区宫颈癌防治提供依据。方法检索The Cochrane Library（2016年第3期）、PubMed、Ovid、EMbase、中国生物医学文献数据库、万方数据库和中国知网,查找有关上海地区女性宫颈HPV感染的文献,检索时限为2000年1月至2015年12月。由两位评价者根据纳入与排除标准独立筛选文献、提取资料和评价纳入研究后,采用Stata 12．0软件进行Meta分析。结果纳入的研究对象共165432例,总HPV感染率为32．5％（95％CI：0．289～0．361）。高危HPV感染中居前六位的是HPV 16、52、58、53、33、18,感染率分别为9．0％、4．5％、4．0％、2．1％、2．0％、1．7％;低危型HPV感染中居前三位的是HPV81、11、6,感染率分别为2．0％、1．8％、1．5％。有明确宫颈组织病理学结果的研究对象共21587例,总HPV感染率为41．9％（95％CI：0．276～0．562）,宫颈HPV的感染率在低级别宫颈病变组居前五位的是HPV16、58、52、18、33;在高级别宫颈病变组感染率居前五位的是HPV16、58、33、18、52。其中HPV16、18、31、33、58在高级别宫颈病变组的感染率高于低级别宫颈病变组。结论 HPV16、52、58、53、33、18是上海地区女性宫颈HPV感染的优势型别,HPV型别分布在不同级别宫颈病变组之间存在差异。     

高危型HPV在宫颈癌发生中的作用

本文利用PCR技术检测了44例宫颈癌患者和15例慢性宫颈炎患者病变组织中高危型HPV（16，18，31，33）的感染率，发现44例宫颈癌患者高危型HPV的阳性率高达91％（40／44），其中HPV16型感染率54．55％（24／44），HPV18型感染率18．2％（8／44），HPV31型感染率13．6％（6／44），HPV33型感染率4．55％（2／44）；15例慢性宫颈炎患者有2例感染HPV16型。结果提示HPV16型是宫颈癌发生最常见的基因型，其次为HPV18型和HPV31型，故对育龄妇女定期进行高危型HPV感染的普查，在早期预防宫颈癌的发生具有十分重要的意义；联合采用分子生物学和宫颈脱落细胞学技术进行即定期普查，既能提高阳性率，又能对感染高危型HPV的慢性宫颈炎患者进行早期的有效预防。     

Infection and integration of human papillomavirus in esophageal carcinoma

Infection with human papillomavirus (HPV) could be a suspected or potential modifiable risk factor in esophageal carcinoma (EC) but findings have not been consistent. We therefore investigated the epidemiology of HPV infection and integration in the pathogenesis of esophageal carcinoma (EC) in the Shantou region, China. This was a retrospective study involving nested PCR to evaluate HPV presence, HPV genotyping, and analyzing HPV-16 integration status in esophageal tumor tissues (n=106) and paired tumor-adjacent normal tissues, as well as normal esophagus tissue from control subjects (n=100). The detection rates of HPV DNA in EC and tumor-adjacent tissue were significantly higher than that in normal controls (77.4% and 80.2% vs. 33.0%). HPV infection was mainly found in adults, ages 35-47 years old, and the infection rate was negatively associated with the age of EC patients (P-trend<0.05). In addition, the HPV infection rates in patients who smoked was 3.27 times higher than in non-smoking patients (84.9% vs. 67.4%, P<0.05) but was not associated with gender, alcohol consumption, tumor grade or lymph-node metastasis of EC patients. The distribution of HPV genotypes in patients from high to low proportion was HPV-16, -58, -18, -33, -31 and -11. Infection with multiple HPV genotypes mainly included HPV-16/-18 and HPV-16/-33. The integration rate of HPV-16 in EC tissue was higher than that in tumor-adjacent and control tissues (93.4% vs. 50.9% and 45.5%). Our findings indicate that infection with HPV, especially the high-risk HPV, and their integration suggest an association in malignant transformation of EC in the high-incidence EC region in Shantou, China.     

端粒酶活性、HPV 16/18感染及致癌基因与宫颈癌的关系

目的:探讨端粒酶活性、HPV 16/18感染及致癌基因与宫颈癌的相关性。方法:对40例浸润型宫颈癌,110例宫颈上皮内瘤变(C INⅢ32例、C INⅡ40例、C INⅠ38例)及30例正常者的宫颈新鲜组织,用TRAP—PCR检测端粒酶活性、用FQ—PCR检测HPV l6/18DNA、用PCR方法对HPV 16/18 DNA阳性组织作HPV 16型致癌基因E 6、E 7检测。结果:宫颈癌组中端粒酶阳性38例(95.00%)(HPV 16/18+39例,17例有E 6、E 7表达),端粒酶阴性2例(HPV 16/18+1例,无E 6、E 7表达):C INⅢ级中端粒酶阳性28例(87.5%)(HPV 16/18+30例,22例有E 6、E 7表达),端粒酶阴性4例(2例HPV16/18+);C INⅡ级中端粒酶阳性12例(30%)(HPV 16/18+16例,4例有E 6、E 7表达),端粒酶阴性28例(4例HPV 16/18+);C INⅠ级中端粒酶阳性3例(7.89%)(HPV 16/18+5例,无E 6、E 7表达):而30例正常宫颈组织仅有2例(6.67%)端粒酶活性表达,1例HPV也为阳性而无E 6、E 7表达。宫颈癌和癌前病变(C INⅢ)组织端粒酶活性表达频率(P<0.01)和HPV 16/18感染率(P<0.01)及其致癌基因表达(P<0.01)显著高于良性病变(C INⅠ和C INⅡ)和正常对照。结论:端粒酶活性在宫颈癌发生中可能起到重要作用,在子宫颈损伤中端粒酶激活与HPV感染及其致癌基因的表达密切相关;对于探讨宫颈病变的进展和宫颈癌的发生发展具有重要意义。