Clinical evaluation of the dysplasias and the early forms of cervical cancer

One hundred and forty patients, admitted to the Center of Oncology Research of the USSR Academy of Medical Sciences with a suspicion to cervical cancer, were examined by the complex method comprising in addition to routine gynecological examination also extended colposcopy, cytological investigation of smears from pathological foci surface as well as histological studies, "aimed biopsy and cervical canal curetting. It was found that the cytological picture of moderate dysplasia of cervical epithelium is more frequently recognized in patients with pseuderosions developed with unchanged in size and form uterine cervix in the background, in the presence of benign colposcopic picture. The cytological picture of marked epithelial dysplasia and dysplasia with clear-cut cell atypism is observed in patients with bleeding pseuderosions against the background of hypertrophic and deformed cervix. Histological assay in these patients revealed early cervical cancer in 67% of observations. Marked extensive leucoplakia of the cervix found in clinical examination is manifested by different forms of epithelial dysplasia, while histological assay revealed early cervical cancer in 29.4% of observations.     

宫颈上皮内瘤变与宫颈癌中DNA甲基化状态的研究

DNA甲基化与肿瘤发生发展关系的研究越来越受到重视,目前大量研究发现多种基因的异常甲基化与官颈上皮内瘤变及宫颈癌相关.     

宫颈上皮内瘤变与宫颈癌中DNA甲基化状态的研究

DNA甲基化与肿瘤发生发展关系的研究越来越受到重视,目前大量研究发现多种基因的异常甲基化与官颈上皮内瘤变及宫颈癌相关.     

Maintenance of DNA content and erbB-2 alterations in intraductal and invasive phases of mammary cancer

Summary Ductal carcinomain situ (intraductal carcinoma) of the breast is a commonly recognized and curable clinical entity. Patients with intraductal carcinoma are at risk to develop invasive breast cancer presumably due to a transition from the noninvasive to the invasive phase of growth. Primary breast malignancies commonly display bothin situ and invasive phases of growth in the same tumor. In the current study, DNA content and alterations in the erbB-2 (HER-2/neu) oncogene product were examined simultaneously in both growth phases of primary breast cancers by image analysis. DNA content in the intraductal and invasive components of primary breast cancers were virtually identical (r = 0.979, p < 0.001). Quantitative image analysis was used to measure erbB-2 expression and categories of expression were related to copy number of the erbB-2 gene. Expression of erbB-2 was similar in both growth phases and implies identity of the erbB-2 genotype. The identity of DNA content suggests that the noninvasive and invasive phases within a single breast cancer are highly related. It is likely that erbB-2 gene number remains the same during progression from intraductal to invasive disease.     

Regional distribution of human papillomavirus DNA and other risk factors for invasive cervical cancer in Panama

A population-based national cancer registry has documented strikingly different regional incidence rates of cervical cancer in the Republic of Panama. Such regional differences in disease rates could represent regional differences in the occurrence of risk factors, in particular, human genital papillomaviruses (HPV). This study enrolled newly diagnosed invasive cancer patients in the Republic of Panama over an 18-mo period. Behavioral risk factors were measured by interviewing cases and matched controls. In addition, DNA extracted from biopsies of the cancers was tested for HPV sequences. Early age at first coitus, multiple pregnancies, and nonparticipation in Pap smear screening programs were significant risk factors for cervical cancer in this population. These factors and low levels of education occurred more frequently among women residing in regions with higher cancer rates than women residing in the region with lower cancer rates. HPV DNA was detected most frequently (70%) among cases from the region with the lowest cancer rate (30 of 100,000) and least frequent (54%) among cases where the cancer rate was the highest (51 of 100,000). The observations suggest that risk factors other than HPV contribute to the differences in cervical cancer rates among women residing in various regions of Panama.     

宫颈癌前病变和早期浸润性宫颈鳞癌组织中胎盘生长因子的表达及其意义

目的:探讨胎盘生长因子(placental growth factor, PLGF)在宫颈癌前病变和早期浸润性宫颈鳞癌组织中的表达,及其与肿瘤微血管密度(microvessel density, MVD)和微淋巴管密度(lymphatic vessel density, LVD)之间的关系和临床意义.方法:采用免疫组织化学法和RT-PCR法分别检测22例宫颈癌前病变和36例早期浸润性宫颈鳞癌组织中PLGF蛋白和mRNA水平的表达,CD34和D2-40相关免疫组织化学染色法检测MVD和LVD的水平,分析PLGF的表达与MVD和LVD之间的关系及其意义.结果:宫颈癌前病变组织中PLGF蛋白表达阳性率为22.73%(5/22),早期浸润性宫颈鳞癌组织中PLGF蛋白表达阳性率为58.33%(21/36);PLGF蛋白表达水平与临床分期显著相关(P＜0.01);PLGF mRNA水平的表达与蛋白一致,且与MVD和LVD水平均呈正相关(P＜0.01,P＜0.05),尤与MVD的相关性更为密切.结论:PLGF在宫颈癌早期病变组织中的表达水平与临床分期密切相关,且与肿瘤血管新生密切相关,可能成为宫颈癌新辅助化疗的新靶点.     

Human papillomavirus and invasive cervical cancer in Brazil.

A hospital-based case-control study was undertaken to examine the role of human papillomavirus (HPV) in the development of invasive cervical cancer in Brazil. The study included 199 histologically confirmed incident cases and 225 age-frequency-matched controls selected from a wide range of diagnostic categories. A polymerase chain reaction technique was used to detect HPV DNA in cervical specimens collected with spatula and brush. HPV DNA was detected in 84% of the cases compared with 17% of controls. Grouping HPV types 16, 18, 31 and 33, 66% of the cases were positive compared with only 6% of the controls. In addition to HPV, number of sexual partners, early age at first intercourse, parity and duration of oral contraceptive use were significantly associated with an increased risk of cervical cancer. A history of previous Papanicolaou smears was significantly associated with a decreased risk. After adjustment, only presence of HPV DNA, parity and history of previous smears remained as independent risk factors. The adjusted odds ratios of cervical cancer associated with HPV 16, 18, 31, and 33 was 69.7 (95% confidence interval 28.7-169.6) and with unidentified types was 12.0 (5.1-28.5). The very high risks found in this study further implicate this virus in the aetiology of cervical cancer.     

Human papillomavirus infection and invasive cervical cancer in Paraguay

HPV types 16 and 18 have been categorized as human carcinogens based on their strong associations with cervical cancer in previous case-control studies. Recent IARC studies in the Philippines, Thailand and Morocco show strong associations between invasive cervical cancer and less common HPV types, including HPV 31, 33, 45, 51, 52 and 58. We present results of a further IARC case-control study conducted in Asunción, Paraguay, to examine the association between specific HPV types and invasive cervical cancer as well as risk factors other than HPV. One-hundred thirteen incident histologically confirmed invasive cervical cancer cases and 91 age-matched hospital controls were recruited. A standardized questionnaire was administered to investigate known and suspected risk factors for cervical cancer. For HPV status determination, cervical biopsy specimens from case subjects and exfoliated cervical cells from control subjects were obtained. HPV DNA was ascertained using a GP5+/6+ PCR-based assay capable of detecting more than 33 HPV types. Overall HPV prevalence was 97% in the cervical cancer cases and 20% in the control subjects. As a single infection, HPV 16 was the predominant type with a prevalence of 48% among case subjects and 5.5% among control subjects. Significant associations with the risk of cervical cancer were detected as follows: any HPV type (OR = 114; 95% CI: 36-361); HPV 16 (OR = 910); HPV 18 (infinite OR); HPV 31 (OR = 110); HPV 33 (OR = 261); HPV 45 (OR = 129); and HPV 58 (OR = 36). In the multivariate model, risk factors other than HPV significantly associated with cervical cancer risk were a higher number of lifetime sexual partners, lower educational status and never having had a Pap smear. Strong associations were found between invasive cervical cancer and specific HPV types 16, 18, 31, 33, 45 and 58.     

Analysis of aberrant DNA methylation and human papillomavirus DNA in cervicovaginal specimens to detect invasive cervical cancer and its precursors.

PURPOSE: Cancer of the uterine cervix is an important cause of death in women worldwide. Pap smears as a tool for screening decreased the incidence and mortality of cervical cancer dramatically. This proof of principle study aimed to develop a potential tool for cervical screening using a test that can be applied by patients without visiting a physician and to increase the coverage rate, especially of the high-risk population with low socioeconomic status. EXPERIMENTAL DESIGN: Human papillomavirus (HPV) DNA testing and methylation analysis of DNA obtained from cervicovaginal specimens of 13, 31, and 11 patients with no dysplasia/low-grade squamous intraepithelial lesion (SIL), high-grade SIL, and invasive cervical cancer, respectively, collected on a tampon, was performed using PCR-based methods to detect invasive cervical cancer and study whether these changes are already present in the precursor lesions. RESULTS: High-risk HPV DNA was present in 68 and 82% of patients with high-grade SIL and invasive cervical cancer. DNA methylation of the 11 genes tested increased with severity of the cervical lesion. Unsupervised hierarchical cluster analysis using solely information on DNA methylation of the 11 genes was able to predict the presence of invasive cervical cancers: one of the two clusters formed contained 9 of 11 invasive cervical cancers, as well as two high-grade SILs. CONCLUSIONS: HPV DNA and DNA methylation analyzed in cervicovaginal specimens are able to predict invasive cervical cancers. To detect all high-grade SILs when applying this test, genes that become methylated earlier throughout cervical carcinogenesis have to be defined.     

Serologic response in human papillomavirus-associated invasive cervical cancer

Human papillomavirus (HPV) transforming proteins E6 and E7 are uniformly expressed in HPV-associated cervical cancer. Our objective was to measure antibodies to HPV-16 E6 and E7 proteins in cervical cancer patients using an assay which would detect antibodies to conformational epitopes. Serum specimens obtained from two case-control studies of HPVs and cervical cancer were tested. The studies were performed in Cali, Colombia, South America and in 9 provinces of Spain. Cases consisted of women with invasive cervical cancer associated with HPV-16 or other HPV types and women with HPV-16-associated high-grade cervical intra-epithelial neoplasia (CIN-3). Controls for invasive cases and CIN-3 cases were women who had no cytologic abnormalities and who were matched for age and country of residence. Serum antibodies to HPV-16 E6 and E7 proteins were detected by radio-immunoprecipitation of in vitro translated proteins. Antibodies to the E6 and E7 protein were observed among 56% and 43%, respectively, of invasive cases and 1.7% and 4.1%, respectively, of controls. Antibodies to either protein were detected in 72% of sera from invasive cases and 5.8% of sera from controls. High antibody reactivity and antibodies to both proteins were found almost exclusively in invasive cases. The frequency of antibodies to the E6 protein and the E7 protein among CIN-3 cases did not differ significantly from the CIN-3 controls. Five women with HPV-18-associated invasive cervical cancer were negative for serum antibody to HPV-16 E6 and E7 proteins. Antibodies to HPV-16 E6 and E7 proteins appear to be partially virus-specific and disease state-specific markers of HPV-associated cervical cancer.     

根治性宫颈切除术在浸润性宫颈癌中的应用

根治性宫颈切除术(RT)被誉为宫颈癌治疗在21世纪手术发展的标志,给渴望保留生育能力的早期宫颈癌患者带了希望.手术范围包括RT及盆腔淋巴清扫术,手术方式包括阴式及腹式,疗效及可行性与标准的治疗方法相近,在临床上有较大的应用价值.     

122例宫颈癌患者线粒体DNA含量及10398位点突变情况分析

目的:探讨122例中国汉族女性宫颈癌患者的线粒体DNA(mtDNA)含量及10398位点的突变情况。方法:收集2002年至2012年间在武汉大学中南医院及宜昌市第二人民医院经病理确诊的中国汉族女性宫颈癌住院患者的蜡块组织，提取其mtDNA，并收集病例的临床病理资料。采用实时定量PCR方法（Real-time PCR）检测其mtDNA含量，采用聚合酶链式反应-限制性片段多态性方法(PCR-RFLP)检测mtDNA 10398位点基因型。用t检验、方差分析、卡方检验等进行统计分析。结果:本研究中共纳入122例患者。年龄从22岁至77岁，中位年龄为45岁，mtDNA含量的差异大，含量最低为14.27，最高为21 769.19，中位值为1 758.18±3 335.72。mtDNA含量与病理类型、分期等均无关（P值分别0.068、0.213），而与年龄有关，年龄大者，mtDNA含量高(P=0.019)；10398位点突变则与年龄、病理类型、分期等均无关（P值分别为0.271、0.300、0.244）。结论:mtDNA含量变化及mtDNA 10398位点突变与宫颈癌的病理、分期等无关，mtDNA含量与年龄相关。     

A case-control study of diet and invasive cervical cancer

A population-based case-control study was conducted to assess the relation of diet, especially intake of vitamins A, C and E and of folic acid, to the risk of invasive cervical cancer. Cases were 189 women diagnosed with cervical carcinoma between 1979 and 1983 in 3 counties of the Seattle area. Controls (N = 227) were selected through random digit dialling. Diet during the year preceding diagnosis was assessed by interview, using a food frequency questionnaire covering the intake of 66 food items. After adjustment for known risk factors, frequent consumption of dark green or yellow vegetables and of fruit juices was related to a reduced risk of cervical cancer. Similarly, high dietary intake of carotene was associated with a lower risk of the disease, especially of the squamous-cell type. There was an inverse relationship between vitamin C intake and the risk of cervical carcinoma. The adjusted relative risk (RR) was 0.5 (95% confidence interval: 0.2-1.0) for the highest quartile of intake compared to a RR of 1.0 for the first quartile. High vitamin E intake was also related to a reduced risk, the risk for women in the highest quartile being only one-third of the risk for those in the first quartile. Intake of pre-formed vitamin A and of folic acid was not related to the risk of cervix cancer. Thus, our study suggests that the risk of invasive cervical carcinoma might be influenced by some aspects of diet.