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Find video protocols related to scientific articles indexed in Pubmed.
PKN1 modulates TGF? and EGF signaling in HEC-1-A endometrial cancer cell line.
Onco Targets Ther
PUBLISHED: 08-04-2014
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The response of cells to TGF? and EGF is mediated by a network of various intracellular regulators. The signaling crosstalk between different regulators is of key importance for tumorigenesis. The crosstalk may explain the modulation of cellular responses to the same regulator by another signaling molecule. As PKN1 - a serine/threonine kinase implicated in tumorigenesis - was identified as potential crosstalk node for TGF? and EGF signaling, the cellular functions that may be affected by PKN1 in a crosstalk of TGF? and EGF were explored.
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Expression pattern of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes in normal and cancer cervical tissues.
Int. J. Oncol.
PUBLISHED: 07-11-2014
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Cervical cancer is the second most prevalent malignancy among women worldwide, and additional objective diagnostic markers for this disease are needed. Given the link between cancer development and alternative splicing, we aimed to analyze the splicing patterns of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes, which are associated with different cancers, in normal cervical tissue, preinvasive cervical lesions and invasive cervical tumors, to identify new objective diagnostic markers. Biopsies of normal cervical tissue, preinvasive cervical lesions and invasive cervical tumors, were subjected to rapid amplification of cDNA 3' ends (3' RACE) RT?PCR. Resulting PCR products were analyzed on agarose gels, gel?purified and sequenced. Normal cervical tissue, preinvasive cervical lesions and invasive cervical tumors contained one PCR product corresponding to full?length PRDX2, RAB5A and RAB25 transcripts. All tissues contained two RAB1A?specific PCR products corresponding to the full?length transcript and one new alternatively spliced RAB1A transcript. Invasive cervical tumors contained one PCR product corresponding to the full?length RAB1B transcript, while all normal cervical tissue and preinvasive cervical lesions contained both the full?length RAB1B transcript and three new alternatively spliced RAB1B transcripts. Alternative splicing of the RAB1A transcript occurs in all cervical tissues, while alternative splicing of the RAB1B transcript occurs in normal cervical tissue and in preinvasive cervical lesions; not in invasive cervical tumors.
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Uneven distribution of human papillomavirus 16 in cervical carcinoma in situ and squamous cell carcinoma in older females: A retrospective database study.
Oncol Lett
PUBLISHED: 05-07-2014
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Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18/45 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.
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Mammalian sterile-like 1 kinase inhibits TGF? and EGF?dependent regulation of invasiveness, migration and proliferation of HEC-1-A endometrial cancer cells.
Int. J. Oncol.
PUBLISHED: 03-20-2014
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Transforming growth factor-? (TGF?) and epidermal growth factor (EGF) are two potent regulators of tumorigenesis. Signaling cross-talk of TGF? and EGF employs a number of regulators which define the impact on cell physiology. MST1 has recently been reported as a regulator of tumorigenesis and differentiation. To investigate the role of mammalian sterile-like 1 (MST1) in TGF? and EGF signaling, we established transiently MST1?transfected HEC-1-A endometrial cancer cells, and subjected the cells to treatment with TGF?1, EGF and their combination. We report MST1 as a negative regulator of combined TGF? and EGF signaling. We observed that enhanced expression of MST1 inhibited the combined action of TGF?1 and EGF on cell invasiveness, migration and proliferation. Monitoring of the intracellular regulatory proteins showed that MST1 contribution to the TGF?-EGF cross-talk may involve focal adhesion kinase and E-cadherin, but not activation of Smad2. Our data unveiled the role of MST1 as a negative feedback for TGF?1? and EGF?regulated cell invasiveness, migration and proliferation.
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Expression profiles of antimicrobial peptides in the genital tract of women using progesterone intrauterine devices versus combined oral contraceptives.
Am. J. Reprod. Immunol.
PUBLISHED: 01-31-2014
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Sex hormones can influence the immune defenses of the female genital tract (FGT) and its susceptibility to infections. Here we investigated the effect of different hormonal contraceptives on the production of antimicrobial peptides (AMPs) in different compartments of the female genital mucosa (FGM), secretions and tissue.
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Expression of the p53 Target Wig-1 Is Associated with HPV Status and Patient Survival in Cervical Carcinoma.
PLoS ONE
PUBLISHED: 01-01-2014
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The p53 target gene WIG-1 (ZMAT3) is located in chromosomal region 3q26, that is frequently amplified in human tumors, including cervical cancer. We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3) by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3) than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p?=?0.002) and in adenocarcinomas as compared to squamous cell lesions (p<0.0001). Cases with moderate nuclear Wig-1 staining and positive cytoplasmic Wig-1 staining showed longer survival than patients with strong nuclear and negative cytoplasmic staining (p?=?0.042). Nuclear Wig-1 expression levels were positively associated with age at diagnosis (p?=?0.023) and histologic grade (p?=?0.034). These results are consistent with a growth-promoting and/or anti-cell death function of nuclear Wig-1 and suggest that Wig-1 expression can serve as a prognostic marker in cervical carcinoma.
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Triage of HR-HPV positive women with minor cytological abnormalities: a comparison of mRNA testing, HPV DNA testing, and repeat cytology using a 4-year follow-up of a population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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Expression of the viral E6/E7 oncogenes of high-risk human papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more effectively predicts precancerous lesions and invasive cervical cancer than HR-HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat cytology.
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Human papillomavirus DNA and E6/E7 mRNA testing as triage in liquid-based cytology samples from primary screening.
Curr. Pharm. Des.
PUBLISHED: 08-30-2013
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We estimated the frequency of detection of different human papillomavirus (HPV) types in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology in a population-based primary screening programme. 247 liquid-based cytology (LBC) samples with ASCUS/LSIL results were tested using the LINEAR ARRAY HPV Genotyping Test (LA; Roche Diagnostics), which detects 37 HPV types. 79.4% of samples were positive by LA, and 60.7% were positive for high-risk HPV types (ASCUS: 41.2%; LSIL: 71.0%). 34 of the 37 HPV types included in LA were detected in our samples. HPV16 was detected in 18.6% of samples, and 66.8% of samples contained more than one HPV type, with a maximum of nine types observed in one LSIL sample. A random subset of 47 samples from the 247 samples tested by LA, was also analysed using the AMPLICOR HPV Test (Amplicor, Roche Diagnostics). A separate set of 42 samples, which were positive by LA for the five high-risk HPV types included in the PreTect HPV-Proofer (Proofer, NorChip AS), was also analysed for E6/E7 mRNA expression using Proofer. Concordance between LA and Amplicor was 91.5% (kappa=0.83). One false-negative and three false-positives were recorded for Amplicor, using LA as the "gold standard". Concordance between LA and Proofer was 88.0%; 100% of Proofer samples that were HPV18- positive by LA, and 75.0% of HPV16-positive samples, expressed E6/E7 mRNA. In the present study using LBC samples in a triage situation, where negative predictive value is paramount, LA gave the most reliable results.
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Liquid-based cytology with HPV triage of low-grade cytological abnormalities versus conventional cytology in cervical cancer screening.
Curr. Pharm. Des.
PUBLISHED: 08-30-2013
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Liquid-based cytology with supplementary human papillomavirus triage (LBC+HPV triage) of low-grade cytological abnormalities may improve the detection of cervical intraepithelial neoplasia (CIN) compared with conventional cytology. To investigate this subject, LBC+HPV triage and conventional cytology were alternated in a population-based screening setting. Cases with abnormal cytology were referred for colposcopy.
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Prognostic significance of cell cycle- and invasion-related molecular markers and genomic instability in primary carcinoma of the vagina.
Int. J. Gynecol. Cancer
PUBLISHED: 06-06-2013
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This study aimed to analyze the prognostic value of DNA content and biological markers for cell cycle regulation and invasion in primary carcinoma of the vagina (PCV).
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Acceptance of human papillomavirus (HPV) vaccination among young women in a country with a high prevalence of HPV infection.
Int. J. Oncol.
PUBLISHED: 04-16-2013
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Cervical cancer is the second most common cancer among women in Argentina and the mortality has remained unchanged for the last 30 years. The 2011 national implementation of human papillomavirus (HPV) vaccination will be a key component of future cervical cancer prevention. Vaccination of young adult women is not included in the program, although these women could also benefit from the vaccine, especially in underserved areas with a high prevalence of HPV. However, research on acceptance of HPV vaccination within this group is scarce. The aim of this study was to investigate acceptance of HPV vaccination, the correlation between acceptance and cost, as well as other factors and perceptions of HPV vaccination among young adult women in Argentina. In total, 174 young women aged 18-30 years were included in this quantitative cross-sectional hospital-based study in a low resource area of the Mendoza Province, conducted through structured questionnaire-based interviews. Multinomial logistic regression models were used to investigate correlates of acceptance. Acceptance of HPV vaccination was high if it was free (95%) and even if it was not (75%). A significant positive association was found between acceptance and belief in vaccine safety (p=0.01) and between acceptance and not being a welfare recipient (p=0.00). Nearly half the participants incorrectly believed that they would be fully protected against cervical cancer after vaccination. Our findings suggest that acceptance of HPV vaccination is high among young women in a high-risk, relatively underserved area, even if vaccination is not free. Extensive misconceptions about the vaccine, however, highlight the need for further education about HPV vaccination.
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Projected cost-effectiveness of repeat high-risk human papillomavirus testing using self-collected vaginal samples in the Swedish cervical cancer screening program.
Acta Obstet Gynecol Scand
PUBLISHED: 03-19-2013
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Human papillomavirus (HPV) testing is not currently used in primary cervical cancer screening in Sweden, and corresponding cost-effectiveness is unclear.
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Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma in situ.
Oncol Lett
PUBLISHED: 03-07-2013
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The incidence rates of cervical adenocarcinoma have been increasing over the last two decades, contrary to those of squamous cell carcinoma. This trend is particularly evident among females aged <40 years and has occurred despite extensive cytology-based screening programs. The aim of the present retrospective database study was to investigate adenocarcinoma in situ (AIS) with respect to previous cytological results, high-risk (HR) human papillomavirus (HPV) infections and histological results from AIS-adjacent squamous mucosa. Databases were used to identify 32 female patients with AIS treated for various conditions between 2009 and 2012 at the Department of Gynecology, Uppsala University Hospital (Uppsala, Sweden) and previous cytological, HPV and histological results. Of the individuals in the study, 64.3% had a previously recorded cytological result showing squamous cell abnormalities; five had glandular cell abnormalities (18%) and two had AIS (7.1%). Among the patients with available HPV results, 95% were HR-HPV-positive; HPV18/45 predominated (77%), followed by HPV16 (27%). The patients with multiple HPV infections were aged ?32 years, while patients aged ?38 years were only infected with HPV18/45. All but three patients had cervical intraepithelial neoplasia (CIN) in the AIS-adjacent squamous mucosa, 79% of which was CIN2 or worse. The present retrospective database study suggests that AIS is detected at screening mainly due to simultaneous squamous precursor lesions and that HPV18/45 infection is an increasing cofactor for AIS in older patients. HPV analyses of glandular precursor lesions aid in the identification of female individuals at risk of progression to invasive disease, and thus have a favorable effect on adenocarcinoma prevention, together with vaccination.
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High-risk HPV L1 capsid protein as a marker of cervical intraepithelial neoplasia in high-risk HPV-positive women with minor cytological abnormalities.
Oncol. Rep.
PUBLISHED: 02-14-2013
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Human papillomavirus (HPV) L1 capsid protein is only produced during a productive HPV infection at the end of the natural viral life cycle and is a major target of the immune response in women with HPV-related squamous intraepithelial lesions. We evaluated the usefulness of L1 detection by immunocytochemistry in high-risk (HR) HPV-positive women with minor cytological abnormalities detected at organised population-based cervical cancer screening in Sweden, and assessed the relationship with histological diagnoses. Cytological slides were immunocytochemically stained using an HPV L1-specific monoclonal antibody for all known HPV types. HPV DNA analysis was performed using Linear Array test. Out of thirteen L1-positive women infected with HPV16, only two (15.0%) progressed to cervical intraepithelial neoplasia grade 2 or worse (CIN2+); compared to four L1-positive women infected with other HR-HPV types. Among L1-positive women with CIN2+, 35.7% harboured both HR and low-risk HPV types, 25.0% harboured HR-HPV types only and 13.3% were infected with HPV16. Loss of L1 expression could be a prognostic marker for the development of preinvasive cervical lesions. We show that different HPV types may initiate a parallel oncogenic process, but only loss of L1 expression predicts the development of CIN2+, suggesting that HPV typing in combination with L1 detection could be used for more focused investigations of women with minor cytological abnormalities.
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Cervical cancer in the screening era: who fell victim in spite of successful screening programs?
J Gynecol Oncol
PUBLISHED: 02-11-2011
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To compare profiles of a prescreening and screening cohort of women with cervical cancer regarding histopathology and clinical variables in order to identify those remaining at risk despite successful screening programs. By analyzing these profiles we hope to improve future screening methods.
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Carcinoma of the cervical stump: fifty years of experience.
Oncol. Rep.
PUBLISHED: 01-13-2011
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A series of patients with carcinoma of the cervical stump in relation to age, clinical stage, histopathology, changes in relative incidence, treatment outcome and long-term survival, were studied and the findings were compared with matched controls that have an intact uterus and cancer of the cervix. Of 8,028 women treated for invasive cervical carcinoma between 1959-2004, 161 were diagnosed with stump cancer, accounting for 2.0% of all cervical cancers. The mean time interval between subtotal hysterectomy and stump cancer diagnosis was 17.6 years, with a range of 1-46 years. In 80% of cases, symptoms drove the patient to seek medical attention and postcoital, intermenstrual or postmenopausal bleeding was the main reason. Among 161 stump cancer cases 89% were squamous cell carcinoma (SCC) and the remaining 17 cases were adenocarcinomas (AC). Cumulative cause-specific survival rate was significantly worse for adenocarcinoma than for squamous cell carcinoma (SCC) of the cervical stump (Log-rank p = 0.027, Cox-Mantel p = 0.015, Cox F-test p = 0.01). The stump cancer cases show a worse stage profile compared with the cancer cases in intact uterus. We conclude that the total effect of stump cancers following subtotal hysterectomies is not to be neglected.
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Slumbering mucosal immune response in the cervix of human papillomavirus DNA-positive and -negative women.
Int. J. Oncol.
PUBLISHED: 11-03-2010
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Persistent human papillomavirus (HPV) infection is a prerequisite for cervical cancer and results from bypassing the local immune response. Twenty-four volunteers underwent an ectocervical biopsy, Pap smear, tests for sexually transmitted infections including HIV and HPV genotyping. All answered a questionnaire regarding medical history. Repeat Pap smear and HPV genotyping was performed 9-26 months later. Quantitative reverse transcriptase (qRT-)PCR was used to assess expression of CD3, CD4, CD8, CD19, CD27, IL-2, IL-12, IL-4, IL-10, IL-17, HLA-DR?, TGF?, IFN?, PD-1, PD-L1, CTLA-4, LAG3, IgA, IgG, CCR5, CCL5/RANTES and the IL-7 receptor in the biopsies. Eleven of 24 volunteers were HPV DNA-positive at baseline. Four of 10 were infected with a persistent HPV genotype at follow-up. All target molecules were successfully amplified and quantified except for IL-4. We found no difference in mRNA expression of these molecules when comparing HPV DNA-positive and -negative women, neither when comparing persistently infected individuals or those who cleared the infection. However, mRNA expression of the B cell phenotypic marker CD19 was higher in women using hormonal contraception than those not (p<0.05). HPV infection does not evoke a local inflammatory immune response in the ectocervix measurable with qRT-PCR. Hormonal contraception may influence B cell activity in the cervix.
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Economic analysis of human papillomavirus triage, repeat cytology, and immediate colposcopy in management of women with minor cytological abnormalities in Sweden.
Acta Obstet Gynecol Scand
PUBLISHED: 09-18-2010
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To assess the cost-effectiveness of using human papillomavirus testing (HPV triage) in the management of women with minor cytological abnormalities in Sweden.
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Randomized healthservices study of human papillomavirus-based management of low-grade cytological abnormalities.
Int. J. Cancer
PUBLISHED: 07-27-2010
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Human papillomavirus (HPV)-based management of women with borderline atypical squamous cells of undetermined significance (ASCUS) or mildly abnormal cervical intraepithelial neoplasia (CINI) cervical cytology has been extensively studied in the research setting. We wished to assess safety and health care resource use of a real-life health care policy using HPV triaging. All 15 outpatient clinics involved in the organized population-based screening program in Stockholm, Sweden screening program were randomized to either continue with prior policy (colposcopy of all women with ASCUS/CINI) or to implement a policy with HPV triaging and colposcopy only of HPV-positive women. The trial enrolled the 3,319 women who were diagnosed with ASCUS (n = 1,335) or CINI (n = 1,984) in Stockholm during 17th March 2003 to 16th January 2006. Detection of high-grade cervical lesions (CINII+) and health care cost consumption was studied by registry linkages. The proportion of histopathology-verified CINII+ was similar for the two policies (395 of 1,752 women (22.5%; 95% Confidence interval [CI]: 20.6-24.6%) had CINII+ diagnosed with HPV triaging policy, 318 of 1,567 women (20.3%; 95%CI: 18.3-22.4%) had CINII+ with colposcopy policy). Sixty-four percent of women with ASCUS and 77% of women with CINI were HPV positive. HPV-positivity was age-dependent, with 81% of women below 35 years of age and 44% of women above 45 years of age testing HPV-positive. HPV triaging was cost-effective only above 35 years of age. In conclusion, a real-life randomized healthservices study of HPV triaging of women with ASCUS/CINI demonstrated similar detection of CINII+ as colposcopy of all women.
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Prospective study of human papillomavirus and risk of cervical adenocarcinoma.
Int. J. Cancer
PUBLISHED: 05-18-2010
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Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population-based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow-up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6-46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8-66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5-192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8-206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal.
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E6/E7 mRNA expression analysis: a test for the objective assessment of cervical adenocarcinoma in clinical prognostic procedure.
Int. J. Oncol.
PUBLISHED: 04-30-2010
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Detection of E6/E7 mRNA expression using the real-time nucleic acid sequence-based amplification assay (NASBA) PreTect HPV-Proofer was compared with results of human papillomavirus (HPV) DNA detection in 98 paraffin-embedded samples from patients with cervical adenocarcinoma. HR-HPV DNA was detected in 61 (62%), while HR-HPV E6/E7 mRNA was detected in 63 (64%) of the samples. Correlation between results from DNA analyses and the E6/E7 mRNA assay showed consistent results in 87% of samples (47 of 54). The results from these two methods in detecting presence of HPV infection of any type agreed in 77%. Overall agreement between the methods was seen in 82 of the 98 cases (84%). When evaluating change in sensitivity for detection of HPV positives by adding more HPV types to the HPV DNA assay, maximum sensitivity was reached by targeting four HPV types. The coverage of HPV DNA presence was 76.9%, while the E6/E7 mRNA assay achieved a maximum coverage of 80.8% using only three HPV types. Thus, E6/E7 oncogene expression analysis may provide a more objective test for assessment of neoplastic glandular cells. Further studies may reveal whether the clinical performance of the E6/E7 mRNA assay will be of prognostic value in management of cervical adenocarcinoma.
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Invasive carcinoma of the uterine cervix associated with pregnancy: 90 years of experience.
Cancer
PUBLISHED: 03-09-2010
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This study is a representation of 90 years of experience with carcinoma of the uterine cervix in pregnancy. The objective was to retrospectively study changes in the distribution of cervical carcinoma (CC) by age, disease stage, histopathology, survival, and the development of second primary cancers.
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Detection of genomic amplification of the human telomerase gene TERC, a potential marker for triage of women with HPV-positive, abnormal Pap smears.
Am. J. Pathol.
PUBLISHED: 11-03-2009
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The vast majority of invasive cervical carcinomas harbor additional copies of the chromosome arm 3q, resulting in genomic amplification of the human telomerase gene TERC. Here, we evaluated TERC amplification in routinely collected liquid based cytology (LBC) samples with histologically confirmed diagnoses. A set of 78 LBC samples from a Swedish patient cohort were analyzed with a four-color fluorescence in situ hybridization probe panel that included TERC. Clinical follow-up included additional histological evaluation and Pap smears. Human papillomavirus status was available for all cases. The correlation of cytology, TERC amplification, human papillomavirus typing, and histological diagnosis showed that infection with high-risk human papillomavirus was detected in 64% of the LBC samples with normal histopathology, in 65% of the cervical intraepithelial neoplasia (CIN)1, 95% of the CIN2, 96% of the CIN3 lesions, and all carcinomas. Seven percent of the lesions with normal histopathology were positive for TERC amplification, 24% of the CIN1, 64% of the CIN2, 91% of the CIN3 lesions, and 100% of invasive carcinomas. This demonstrates that detection of genomic amplification of TERC in LBC samples can identify patients with histopathologically confirmed CIN3 or cancer. Indeed, the proportion of TERC-positive cases increases with the severity of dysplasia. Among the markers tested, detection of TERC amplification in cytological samples has the highest combined sensitivity and specificity for discernment of low-grade from high-grade dysplasia and cancer.
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Diagnostic protein marker patterns in squamous cervical cancer.
Proteomics Clin Appl
PUBLISHED: 05-07-2009
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Cervical cancer is the second most prevalent malignancy of women. Our aim was to identify additional marker protein patterns for objective diagnosis of squamous cervical cancer (SCC).
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Hysteroscopic female sterilization with Essure in an outpatient setting.
Acta Obstet Gynecol Scand
PUBLISHED: 05-05-2009
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The aim of this study is to evaluate the short and long-term results of hysteroscopic sterilization in an outpatient setting. Sixty-one women underwent hysteroscopic sterilization. At follow-up, all of the women were asked to complete a questionnaire concerning possible pregnancy, bleeding patterns, side-effects, or need for further therapy after sterilization. Technical feasibility, complications, patient satisfaction, and tubal occlusion based on X-ray or ultrasound were measured. Fifty-eight (95%) women were sterilized according to this method. Successful bilateral device placement was achieved in 52 women (85%) during the first attempt and in six (9.8%) during the second. A total of 50 (81.9%) women submitted completed outcome questionnaires. The mean follow-up period was 23 (range 7-67) months. No pregnancies were reported. All questionnaire respondents expressed overall satisfaction with the procedure. To conclude, Essure sterilization is a safe effective method for female sterilization that is feasible in the outpatient setting.
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Abundant and superficial expression of C-type lectin receptors in ectocervix of women at risk of HIV infection.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 04-14-2009
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Dendritic cells (DCs) are among the first cells to encounter HIV after mucosal exposure and can bind virus via C-type lectin receptors (CLRs). Here, we characterized the distribution of various DC subtypes and the density of the CLRs, DC-SIGN, langerin, and mannose receptor in the ectocervix of HIV-seronegative women with low- and high-risk behavior for acquiring HIV.
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Laser capture microdissection of cervical human papillomavirus infections: copy number of the virus in cancerous and normal tissue and heterogeneous DNA methylation.
Virology
PUBLISHED: 03-09-2009
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Research on the pathogenicity of human papillomaviruses (HPVs) during cervical carcinogenesis often relies on the study of homogenized tissue or cultured cells. This approach does not detect molecular heterogeneities within the infected tissue. It is desirable to understand molecular properties in specific histological contexts. We asked whether laser capture microdissection (LCM) of archival cervical tumors in combination with real-time polymerase chain reaction and bisulfite sequencing permits (i) sensitive DNA diagnosis of small clusters of formalin-fixed cells, (ii) quantification of HPV DNA in neoplastic and normal cells, and (iii) analysis of HPV DNA methylation, a marker of tumor progression. We analyzed 26 tumors containing HPV-16 or 18. We prepared DNA from LCM dissected thin sections of 100 to 2000 cells, and analyzed aliquots corresponding to between nine and 70 cells. We detected nine to 630 HPV-16 genome copies and one to 111 HPV-18 genome copies per tumor cell, respectively. In 17 of the 26 samples, HPV DNA existed in histologically normal cells distant from the margins of the tumors, but at much lower concentrations than in the tumor, suggesting that HPVs can infect at low levels without pathogenic changes. Methylation of HPV DNA, a biomarker of integration of the virus into cellular DNA, could be measured only in few samples due to limited sensitivity, and indicated heterogeneous methylation patterns in small clusters of cancerous and normal cells. LCM is powerful to study molecular parameters of cervical HPV infections like copy number, latency and epigenetics.
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Mutation of PIK3CA: possible risk factor for cervical carcinogenesis in older women.
Int. J. Oncol.
PUBLISHED: 01-17-2009
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PIK3CA encodes the p110alpha catalytic subunit of PI 3-kinase, which regulates signaling pathways important for neoplasia, cell proliferation and apoptosis. Somatic mutations in this gene have been detected in several solid human tumors. We investigated these mutations in cervical carcinoma and its precursors, and their association with HPV infection and patient clinical data. The mutations were analyzed using post-PCR direct genomic DNA sequencing. Samples included 9 cervical cancer cell lines, 184 invasive cervical carcinomas, and 30 cervical neoplasias. Missense mutations of PIK3CA were identified in 15/184 (8.15%) invasive cervical carcinomas. One novel mutation G1638C (Q546H) was found. Three mutations were identified in the cervical cancer lines. No mutations were found in the precursors. The difference in mutation frequency between invasive and pre-invasive lesions was not significant (p=0.1372). In relation to age and HPV, the mutation rate was significantly higher in patients>or=60 years (p=0.001), while the rate of HPV infection was higher in patients
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Follow-up after treatment of cervical intraepithelial neoplasia by human papillomavirus genotyping.
Am. J. Obstet. Gynecol.
PUBLISHED: 01-12-2009
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To assess the use of human papillomavirus genotyping in cervical intraepithelial neoplasia posttreatment follow-up.
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Expression of LRIG1 and LRIG3 correlates with human papillomavirus status and patient survival in cervical adenocarcinoma.
Int. J. Oncol.
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The incidence of cervical adenocarcinoma, which accounts for 10-20% of all cervical cancers, has increased continuously in developed countries during the last two decades, unlike squamous cell cervical carcinoma. This increasing trend, noted particularly among women under the age of 40 years, has occurred despite extensive cytological Pap smear screening. A deeper understanding of the etiology of cervical adenocarcinoma, better preventive measures and reliable prognostic markers are urgently needed. The human leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family includes: LRIG1, LRIG2 and LRIG3. LRIG expression has proven to be of prognostic value in different types of human cancers, including breast cancer, early stage invasive squamous cervical cancer, cutaneous squamous cell carcinoma, oligodendroglioma and astrocytoma. LRIG1 functions as a tumor suppressor, while less is known about the functions of LRIG2 and LRIG3. This study evaluated the expression of the three LRIG proteins in tumor specimens from 86 women with pure cervical adenocarcinoma by immunohistochemistry. Possible correlations between LRIG expression and known prognostic factors, including human papillomavirus (HPV) status, FIGO stage and histology were investigated. Patient survival data were collected retrospectively and the possible prognostic value of LRIG protein expression was investigated. High staining intensity of LRIG1 and high fraction of LRIG3-positive cells were significantly associated with patient survival, and positive correlations were found between LRIG1 and LRIG3 staining intensity and HPV status. Thus, the LRIG proteins may be important determinants of cervical adenocarcinoma progression and their diagnostic and prognostic potential should be studied further.
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High-risk human papillomavirus E6/E7 mRNA and L1 DNA as markers of residual/recurrent cervical intraepithelial neoplasia.
Oncol. Rep.
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The aim of this study was to assess the use of human papillomavirus (HPV) E6/E7 mRNA testing in the follow-up of women treated for cervical intraepithelial neoplasia (CIN) by conization and to compare the prognostic value of HPV E6/E7 mRNA to HPV L1 DNA and cytology. One hundred and forty-three women underwent cytological/histological testing, HPV DNA genotyping by Linear Array, and HPV E6/E7 mRNA testing by APTIMA HPV assay during follow-up after surgical treatment for histologically verified CIN. High-grade residual/recurrent disease (CIN2+/HSIL+) was identified in 7 (4.9%) women, and low-grade disease (CIN1/LSIL) in 25 (17.5%). At the inclusion visit 33 (23%) women were HPV DNA-positive; 13 (9.0%) were HPV E6/E7 mRNA-positive. HPV E6/E7 mRNA did not identify three women with high-grade disease. Presence of high-risk HPV DNA at the inclusion visit predicted 100% (95% CI 64.6-100) of high-grade residual/recurrent disease, with a specificity of 80.9% (95% CI 73.5-86.6); cytology had a sensitivity of 85.7%, and a specificity of 87.5%. HPV E6/E7 mRNA testing was a poor predictor of treatment failure, with a sensitivity of 57.1% (95% CI 25.0-84.2), but high specificity (93.4%; 95% CI 87.9-96.5). Detection of high-risk HPV DNA after treatment by conization identified 100% of women with residual/recurrent high-grade disease, whereas HPV E6/E7 mRNA testing was a poor predictor of treatment failure. This study suggests that a negative HPV mRNA result cannot exclude the risk of malignant progression, and that HPV E6/E7 mRNA testing by APTIMA HPV assay is not useful in the follow-up of women treated for CIN.
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