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PubMed2005

TNF-alpha promoter polymorphisms and susceptibility to human papillomavirus 16-associated cervical cancer.

BACKGROUND: Polymorphisms in the TNF-alpha promoter region have recently been shown to be associated with susceptibility to cervical cancer. Some polymorphisms have been reported to influence transcription for this cytokine. Altered local levels in the cervix may influence an individual's immune response, thereby affecting persistence of human papillomavirus (HPV) 16 infection, a primary etiological factor for cervical cancer. METHODS AND RESULTS: The association of 11 TNF-alpha single-nucleotide polymorphisms (SNPs) with susceptibility to HPV16-associated cervical cancer was investigated. Sequencing of the TNF-alpha promoter region confirmed 10 SNPs, and 1 previously unreported SNP (161 bp upstream of the transcriptional start site) was discovered. Microsphere-array flow cytometry-based genotyping was performed on 787 samples from Hispanic and non-Hispanic white women (241 from randomly selected control subjects, 205 from HPV16-positive control subjects, and 341 from HPV16-positive subjects with cervical cancer). The genotype distribution of 3 SNPs (-572, -857, and -863) was significantly different between case subjects and control subjects. Analysis of haplotypes, which were computationally inferred from genotype data, also revealed statistically significant differences in haplotype distribution between case subjects and control subjects. CONCLUSIONS: We report new associations between several TNF-alpha SNPs and susceptibility to cervical cancer that support the involvement of the TNF- alpha promoter region in development of cervical cancer.

Adolescent↗
PubMed2003

Knowledge of cervical cancer risk factors among Chinese immigrants in Seattle.

Chinese American immigrants are a growing part of the United States population. Cervical cancer is a significant cause of morbidity and mortality among Chinese Americans. Pap smear testing is less common in Chinese American immigrants than in the general population. During 1999, we conducted a community-based survey of Chinese American women living in Seattle. We assessed knowledge of cervical cancer risk factors and history of Pap smear testing along with socioeconomic and acculturation characteristics. The overall estimated response rate was 64%, and the cooperation rate was 72%. Our study sample included 472 women. Most cervical cancer risk factors were recognized by less than half of our participants. Factors independently associated with knowledge of cervical cancer risk factors included marital status, employment, and education. Respondents with the highest knowledge had greater odds of ever receiving a Pap smear, compared to those respondents with the lowest knowledge (OR 2.5; 95% CI: 1.1,5.8). Our findings suggest a need for increased recognition of cervical cancer risk factors among Chinese American immigrants. Culturally and linguistically appropriate educational interventions for cervical cancer risk factors should be developed, implemented and evaluated.

Adult↗
PubMed2004

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.

DNA↗
PubMed2003

The combined treatment of aspirin and radiation induces apoptosis by the regulation of bcl-2 and caspase-3 in human cervical cancer cell.

The antitumor mechanisms mediated by combined treatment of aspirin and radiation on human cervical cancer cells are unclear. In this paper, we studied whether aspirin and radiation induced apoptosis and whether the sensitivity to radiation was enhanced in aspirin-pretreated HeLa TG, human cervical cancer cells. We identified the regulation of apoptosis-responsive genes, bcl-2, caspase-3 and p53 after combined treatment. To investigate the growth inhibitory effect on HeLa TG cells after treatment of various nonsteroidal anti-inflammatory drugs (NSAIDs), we performed cell proliferation assay and colony-forming assay. In the presence of aspirin, sulindac and indomethacin, cell proliferation and colony formation were decreased in a time- and dose-dependent manner. According to flow cytometry analysis and Hoechst 33342 staining, we found that aspirin increased sub-G1 population and nuclear condensation of cervical cancer cells. Remarkably, the combined treatment decreased cell proliferation compared with treatment of 1 mM aspirin or 6 Gy radiation alone. Pretreatment of aspirin followed by irradiation also elevated the population of apoptotic cells. These results revealed that sensitivity to radiation was enhanced in aspirin-pretreated HeLa TG cells, and aspirin has the additive role for amplifying the radiotherapeutic effect in cervical cancer cells. Finally, combined treatment revealed bcl-2 repression and caspase-3 induction did not detect any change but p53 expression did. We have demonstrated that combined treatment of aspirin and radiation induces the antitumor effect mediated by bcl-2 and caspase-3 pathway in cervical cancer cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

HPV presence precedes abnormal cytology in women developing cervical cancer and signals false negative smears.

In a retrospective case-control study, we investigated high-risk HPV DNA presence by general primer GP5+/6+ PCR in the last normal cervical smear in the patient archives (i.e. baseline smear) of 57 women who later developed cervical cancer. Also, normal cervical smears of 114 age-matched control women were analysed. High-risk HPV DNA was detected in 37 of the 57 (65%) baseline smears of the case women, and 7 (6%) of 114 smears of the control women (OR 28, 95% Cl 11-72). The HPV positive subsequent smears and cervical cancer biopsies of the case women contained the same HPV type as was detected in the baseline smear. After cytological revision, the baseline smears of 48 case women (84%) were reclassified as abnormal, 33 (69%) of which scored high-risk HPV DNA positive. Ultimately, an undisputable normal baseline smear was found in only 10 case women. In 7 (70%) of them this smear was HPV positive, whereas only 7 (7%) of 104 revised, undisputable normal smears of control women were high-risk HPV positive (OR 32, 95% Cl 6.8-153). The results showed that (1) high-risk HPV presence precedes abnormal cytology in women who develop cervical cancer, and (2) high-risk HPV testing signals false-negative smears of women at risk of cervical cancer.

Adenocarcinoma↗
PubMed2000

PIK3CA as an oncogene in cervical cancer.

Amplification of chromosome arm 3q is the most consistent aberration in cervical cancer, and is implicated in the progression of dysplastic uterine cervical cells into invasive cancer. The present study employed the 'positional candidate gene' strategy to determine the contribution of PIK3CA, which is located in 3q26.3, in cervical tumorigenesis. PIK3CA is known to be involved in the PI 3-kinase/AKT signaling pathway, which plays an important role in regulating cell growth and apoptosis. The results of comparative genomic hybridization show that the 3q26.3 amplification was the most consistent chromosomal aberration in primary tissues of cervical carcinoma, and a positive correlation between an increased copy number of PIK3CA (detected by competitive PCR) and 3q26.3 amplification was found in tumor tissues and in cervical cancer cell lines. In cervical cancer cell lines harboring amplified PIK3CA, the expression of gene product (p110alpha) of PIK3CA was increased, and was subsequently associated with high kinase activity. In addition, transformation phenotypes in these lines, including increased cell growth and decreased apoptosis, were found to be significantly affected by the treatment of specific PI 3-kinase inhibitor, suggesting that increased expression of PIK3CA in cervical cancer may result in promoting cell proliferation and reducing apoptosis. These evidences support that PIK3CA is an oncogene in cervical cancer and PIK3CA amplification may be linked to cervical tumorigenesis. Oncogene (2000).

Apoptosis↗
PubMed1993

Increasing cervical cancer screening among minority elderly. Education and on-site services increase screening.

Older women participate in cervical cancer screening less regularly than do younger women. As a consequence, more lesions are found in more advanced and less curable stages in older women. Elderly black and Hispanic women have had lower rates of participation in cervical cancer screening than white women. There is a marked, inverse relationship between the stage of cervical cancer at diagnosis and the 5-year survival rate. The rate of cervical cancer screening among older women can be increased by offering education about Pap tests and onsite cervical cancer screening in housing for the elderly.

Adult↗
PubMed1996

PCR-based high-risk HPV test in cervical cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears.

Cervical-cancer screening programmes using cytomorphological criteria could be more efficient if the screening included objective individual risk factors for women with normal cytology, such as a test for high-risk human papillomavirus (HPV). The value of a PCR-based test for high-risk HPV types was studied in a cohort of 1622 women presenting in a routine triannual population-based screening programme. Women were included in the study when they had no previous history of cervical dysplasia; and their initial Pap smear was read as normal (Pap 1 or 2). The mean age of the women was 42 years (range 34-54 years) and mean follow-up time was 40 months (range 5-73 months). Women were referred for colposcopically directed biopsies if they had had 2 successive cervical smears read as Pap 3a (mild to moderate dyskaryosis) or one read as > or = Pap 3b (severe dyskaryosis). Women with histologically confirmed cervical intraepithelial neoplasia grade III (CIN III) were considered positive cases. All women were tested for 14 high-risk HPV genotypes. Of the 86 high-risk HPV-positive women, 6 developed CIN III, whereas only 1 of the 1536 HPV-negative women did. The women with normal Pap smears containing high-risk HPV genotypes were 116 times (95% CI, 13-990) more at risk of developing CIN III, in contrast to women without high-risk HPV. These results support the view that the interval between successive smears in cervical-cancer screening can be increased considerably for women with cytomorphologically normal and high-risk HPV-negative cervical smears as determined by PCR.

Adult↗
PubMed2004

Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus.

Although gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers, few studies have explored this possibility for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 protein is highly expressed in uterine cervical cancer tissues, but not in normal cervix, we constructed a tumor-specific replication-competent adenoviral vector utilizing MN/CA9 promoter (Ad-MN/CA9-E1a), which can replicate only in MN/CA9-expressing cells. Infection of Ad-MN/CA9-E1a to MN/CA9-positive uterine cervical cancer cells (HeLa, C-33 A and SiHa) resulted in much stronger Ad5 E1a protein expressions compared with MN/CA9-negative cells (SK-RC-29), suggesting a tissue-specific replication of this recombinant adenovirus. In vitro cytotoxicity assay revealed that the growth of MN/CA9-positive cells was significantly inhibited with 0.01-1 MOI of Ad-MN/CA9-E1a, but the growth of MN/CA9-negative cells (SK-RC-29) could only be inhibited by as many as 100 MOI. Intratumoral injection of Ad-MN/CA9-E1a effectively induced growth delay of HeLa tumors in nude mice. These results suggest that a novel replication-competent adenoviral vector mediated by MN/CA9 promoter, Ad-MN/CA9-E1a, can selectively replicate in MN/CA9-expressing tumors with cytotoxic effects and may be utilized for the treatment of uterine cervical cancer.

Adenoviridae↗
PubMed1996

Knowledge of cervical cancer in teenage school children in Trinidad.

Students from five secondary schools in Trinidad were randomly selected to enter into a survey determining their knowledge of cervical cancer. Four hundred and seventy four (95%) students aged between 14-19, participated. The majority of the students were boys. Twenty-nine per cent of the students had never heard of either cervical cancer or a cervical smear. Among those who had some knowledge of the disease, 11% had accurate knowledge of the location of the cervix and approximately 85%, composed largely of boys were unable to identify the cervix on a diagram of the female reproductive tract. More girls than boys knew that a smear test involved an "internal examination. Trinidad has a high incidence of cervical cancer, and this study was designed to provide an infrastructure for planning health education workshops on cervical cancer, in the young generation of Trinidad and Tobago. The study revealed a lack of information on cervical cancer in teenage school children and the need for introduction of effective sex education programmes.

Adolescent↗
PubMed1991

Cervical cancer: women aged 35 and younger compared to women aged 36 and older.

One hundred fifty-three patients with invasive cervical cancer were evaluated and treated at one of the two teaching hospitals of the Intergrated Ob-Gyn Residency Program of Wright State University, Dayton, Ohio, from 1 July 1983 to 30 June 1989. Sixteen patients with recurrent cervical cancer who initially had received their treatment elsewhere were excluded. Forty-one of the 137 newly diagnosed patients with cervical cancer were aged 35 years or less. This review was undertaken because of frequent reports of the increasing incidence of cervical cancer in women aged 35 and under. Some reports also reveal a worse prognosis for the younger age group. This investigation provided the opportunity to evaluate cervical cancer patients aged 35 and under and compare the results to the evaluations of women aged 36 and over. Evaluation of age, stage, presenting symptoms, number of positive lymph nodes, pap smear history, pregnancy within 1 year of diagnosis, treatment, and survival was carried out in patients aged 35 years and less and compared to their older counterparts aged 36 and over with cervical cancer.

Adult↗
PubMed2002

Nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer.

High risk human papillomaviruses (HPVs) are central to the development of cervical cancer and the deregulated expression of high risk HPV oncogenes is a critical event in this process. Here, we find that the cell protein nucleolin binds in a sequence-specific manner to the HPV18 enhancer. The DNA binding activity of nucleolin is primarily S phase specific, much like the transcription of the E6 and E7 oncoproteins of HPV18 in cervical cancer cells. Antisense inactivation of nucleolin blocks E6 and E7 oncogene transcription and selectively decreases HPV18(+) cervical cancer cell growth. Furthermore, nucleolin controls the chromatin structure of the HPV18 enhancer. In contrast, HPV16 oncogene transcription and proliferation rates of HPV16(+) SiHa cervical cancer cells are independent of nucleolin activity. Moreover, nucleolin expression is altered in HPV18(+) precancerous and cancerous tissue from the cervix uteri. Whereas nucleolin was homogeneously distributed in the nuclei of normal epithelial cells, it showed a speckled nuclear phenotype in HPV18(+) carcinomas. Thus, the host cell protein nucleolin is directly linked to HPV18-induced cervical carcinogenesis.

Base Sequence↗
PubMed2001

[Study of the association between human papillomavirus infection and cervical cancer in Xianguan county, Shanxi province].

OBJECTIVE: To investigate human papillomavirus (HPV) prevalence in the high incidence areas of cervical cancer in Shanxi and to study the association between HPV infection and cervical cancer. METHODS: Cells exfoliated from cervix (collected by clinician) and from vagina (collected by subject herself) of 1997 women aged 35-45 from Xiangyuan county, Shanxi province were analyzed blindly by Hybrid Capture Assay (HC-II), which could detect 13 HPV types of high-risk. Unconditional logistics regression model was used to analyze the relation between HPV and cervical cancer/cervical intraepithelial neoplasia (CIN). Kappa coefficient was used to compare the agreement of the two tests. RESULTS: HPV DNA detection rate in the population was 20.8% while HPV infection rates increased with the seriousness of cervical lesions (chi 2 = 444.04, P = 0.000). Rates of the two groups (35-39 and 40-45) had no significant difference (20.9%: 20.6%, chi 2 = 0.03, P = 0.86). Unconditional logistic regression analysis showed, when comparing with the normal subjects, the risk odds ratio of HPV infection with cervical cancer/high grade CIN and low grade CIN were 254.2 and 26.4 respectively, with attributable risk proportions (ARP) 98.1% and 83.6% respectively. The sensitivity of self-collected vaginal swabs assayed for HPV DNA was lower than that of clinician-collected cervical samples assayed for HPV DNA (84%: 98%, chi 2 = 5.92, P = 0.015). No significant difference in specificity was seen between them (86%: 85%, chi 2 = 0.00, P = 0.997) and there was fair agreement between the two tests (kappa = 0.74). CONCLUSION: High-risk HPV infection in female genital tract was the major risk factor of cervical cancer and CIN in the areas. Prevention and control of cervical cancer should be focused on avoiding HPV infection, screening women for HPV infection and monitoring population infected by high-risk HPV. Self-collected vaginal swabs assayed for HPV DNA seemed a more practical method in primary screening for cervical cancer.

Adult↗
PubMed2002

[The evaluation how FIGO stage in cervical cancer depends on frequency of gynaecological control].

OBJECTIVES: The authors sought to evaluate how FIGO stage in cervical cancer depends on frequency of gynaecological control. MATERIAL AND METHODS: From March 2000 to January 2001, 74 patients with cervical cancer were treated in 2-nd Dept. of Obstetrics and Gynaecology Medical University of Gdańsk. The authors analysed frequency of gynaecological control, although patients age, number of delivery, socio-economic status, living place. RESULTS: The median interval, from last gynaecological examination to cervical cancer diagnosis was 8.6 year (1-26), number of delivery: 0-0.5%, 1-10%, 2-21%, 3-21%, 10-1%, 67% patients lived in town and 32.4% in villages. CONCLUSION: Women from Gdańsk area who developed cervical cancer were not gynaecological controlled from 1 to 26 year (median--8.6). Authors noticed that FIGO stage of ovarian cancer depends seriously on interval between last gynaecological control and cervical cancer diagnosis. The old, not working, and those who live in villages in Gdańsk area have an especially low level of health education.

Adult↗
PubMed2002

[Cytological history of 148 women presenting with invasive cervical cancer].

OBJECTIVES: The aim of this study was to analyse the cytological history of women presenting with invasive cervical cancer. MATERIAL AND METHODS: Retrospective study of 148 patients treated for invasive cervical cancer in three hospitals of the North Pas de Calais in France. RESULTS: The average age of patients was 49 (26-86). Squamous carcinomas represented 81% of cases (120/148), adenocarcinomas 17% (25/148) and adenosquamous carcinomas 2% (3/148). 36.5% of patients (54/148) had never had a Pap smear. 34.5% (51/148) had had an occasional Pap smear (the last one dated of more than three years). 8.1% (12/148) were lost for follow up after a positive Pap smear. 3.4% (5/148) were treated for cervical dysplasia less than three years before the diagnosis of the cervical cancer. 17.5% (26/148) had had a Pap smear reported as negative less than three years before the diagnosis of the cervical cancer. In this last group, squamous carcinomas represented 57.7% of cases (15/26), adenocarcinomas 38.5% (10/26) and adenosquamous carcinomas 3.8% (1/26). 18 Pap smears of 26 reported as negative less than three years before the diagnosis of the cancer were reviewed. These Pap smears came from 11 patients presenting with squamous carcinoma and seven other presenting with adenocarcinoma. After review, 15 Pap smears were reported as false negatives and two as true negatives. The review was not possible in one case. CONCLUSION: In this study, the failures of cervical cancer screening were essentially attributed to the lack or the insufficiency of screening and the existence of false negatives of the cytology.

Adenocarcinoma↗
PubMed2003

Cigarette smoking and cervical cancer: Part II: a geographic variability study.

Cigarette smoking is considered a causative factor in a variety of cancers. However, the role of smoking in cervical cancer is disputed, in part because women who smoke may have other risk factors for cervical cancer, particularly HPV infection. We reviewed cigarette smoking prevalence, cervical and lung cancer incidence, and gross domestic product (GDP) per capita in the US and 73 other countries. It appears that smoking may play a prominent role in cervical cancer in developing countries, but less of a role in other countries.

Female↗
PubMed2003

[Changes of mortality rate for cervical cancer during 1970's and 1990's periods in China].

OBJECTIVE: To describe the distribution changes of the mortality rate for cervical cancer in China between the 1970's and 1990's and provide the scientific evidence for the prevention and control strategies for cervical cancer campaign in China between next century. METHODS: Data from two National Surveys for the Causes of Death in 1970's and 1990's in China. The crude and adjusted mortality rates for the cervical cancer and the distributions based on age and area were calculated and described. The comparison of the differences of changes between two mortality rates periods and together with its trends were shown based on the age-standardized. RESULTS: During two decades, the mortality rate for cervical cancer was 10.7 per 100,000 in 1970's which declined to 3.89 per 100,000 in 1990's, and from the 3rd ranking among all female malignant tumors to the 6th in 1990's (decreased about 63.64%). But the declination was not evenly. There have still been some high-risk areas, most located in rural countries in the mid-west of China, with rates remain unchanged and even at the highest level in the world, such as Wudu in Gansu and Yangcheng in Shanxi. A big difference was showed between rural country and city, but in both of them, the mortality rates in 1990's were significantly much lower than in 1970's (P = 0.001) at each five-year age group. And in the city, there was a much sharper increased trend in young women in 1990's. CONCLUSIONS: The mortality rate for cervical cancer campaign in China has been substantially declined during past twenty years, but it's still a major health problem for women, especially in rural China. The focus of the prevention and control for the cervical cancer in the next century should put on rural areas, especially in mid-west of China and young women in the city.

Adult↗
PubMed2001

Age-incidence relationships and time trends in cervical cancer in Sweden.

Age-incidence relationships are informative of carcinogenic mechanisms. These have been previously assessed for cervical squamous cell carcinoma (SCC) but not for adenocarcinoma. The aim was to assess by means of age-, period- and cohort-specific analyses and Poisson regression modelling whether the two types of cervical cancer show an age-incidence maximum at a relatively young age, as shown in cross-sectional analyses. The Swedish Family-Cancer Database was used to analyse age-incidence relationships in cervical SCC and adenocarcinoma diagnosed in years 1958-1996, including a total of 15,118 and 1866 cases, respectively. Area of residence and socio-economic status were included in analyses because they were risk factors of cervical cancer. The analysis of cervical SCC confirmed an incidence maximum at ages 35-39 years. The data for adenocarcinoma also suggested a similar early age maximum but the curves differed extensively by birth cohort. The incidence of adenocarcinoma increased substantially at young age groups towards the end of follow-up. Endometrial adenocarcinoma and vaginal and vulvar SCC, which share some risk factors with cervical cancer, did not show an early age incidence maximum. The results also showed that there was a decrease in the incidence of cervical SCC around year 1960, almost 10 years before the organized population screening, probably due to introduced opportunistic pap testing. The benefits of the organized screening were observed as a further decline in the incidence rates. The unique age-incidence relationships in cervical cancer call for biological explanations.

Adenocarcinoma↗