Cervical cancer is a major public health problem in developing countries. In Guyana, factors associated with increasing cervical cancer cases among Indigenous Amerindian women (IAW), Afro- women (AGW), and Indo-Guyanese women (IGW) have not been fully examined. In this comparative cross-sectional study, 5,800 cervical cancer cases were selected from Guyanese women age 13 and above for ethnicity (Indigenous Amerindian, Afro- and Indo Guyanese women), geographical region, marital status, and year and stage at diagnosis. Secondary data from Guyana Cancer Registry for the 2000-2012 study periods were analyzed using chi-square test, multinomial logistic regression, poisson regression, and relative risk. Geographical region was a strong predictor of cervical cancer cases for all three ethnic groups (p < 0.05). The relative risk for cervical cancer for IAW in Regions 2 (RR = 1.2) and 6 (RR = 1.07) was greater than for IAW in Region 4, the reference group for the study period. Comparatively, the relative risk for cervical cancer for AGW in Region 4 was greater than AGW in all other regions except Region 3 (RR = 1.05). Additionally, the relative risk for cervical cancer for IGW in Region 3 (RR = 1.03) was greater than that of IGW in all other regions. Single IAW (1.05) have a higher risk of getting cervical cancer than their married counterparts as compared to AGW (0.96) and IGW (1.00). Implications for social change include development of tailored programs which utilize a socio-ecological model to address cervical cancer issues at the individual, interpersonal, cultural, and community levels. Future research should focus on understanding the epidemiology of cervical cancer and the social factors among the ethnic groups of women.

Cervical cancer is the single most common cancer in India, affecting an estimated 134,420 women in 2008. With access to early detection and basic treatments, most cases of cervical cancer are preventable. Moreover, if treatment is administered during the earliest stages of cervical cancer, 5-year survival rates can be increased to higher than 90 percent. Unfortunately, despite the availability of methods for prevention, more than 95 percent of women in India have never been screened for cervical cancer. Consequently, women in India are most often diagnosed during later stages of cervical cancer, significantly reducing survival prognosis. The objective of this study was to explore the role of awareness and knowledge of cervical cancer as a barrier to screening participation among urban women in Tamil Nadu; and further to identify the potential impact of increased cervical cancer awareness and knowledge on screening attitude. Quantitative and qualitative methods were used to characterize existing levels of awareness and knowledge of cervical cancer and screening among 207 women from the metropolitan area of Chennai. The results suggest that the majority of women (69.6%) were not aware of cervical cancer and very few (16.4%) were aware of screening. Demographically, women with secondary levels of education or higher were significantly more likely to have heard of cervical cancer and screening. Of the women that were aware of cervical cancer screening, most reported receiving information through television (33%) or a healthcare provider (28.6%). To describe the potential benefit of providing women with basic information about the secondary prevention of cervical cancer, levels of knowledge, measured before and after an educational session, were compared. This study further explored changes in associations between awareness, knowledge, perceived susceptibility, and screening attitude. It was observed that an overwhelming majority of women were receptive to participating in free cervical cancer screening, independent of previous knowledge of cervical cancer. Results also suggest that although lack of awareness appears to be a major barrier to participation in cervical cancer screening, providing women with information about cervical cancer has the potential to change the attitude of a significant proportion (58.3%) of women who were previously unreceptive to screening. Further, perceived susceptibility to cervical cancer appeared to be strongly associated with a positive screening attitude before and after receiving information. Finally, we examined and compared the socio-demographic characteristics of three subgroups of women: those who were receptive to screening without information, those who were receptive to screening after receiving information, and those who were not receptive to screening at either point. We found that younger, more educated women were receptive to screening without information. In addition, previously unscreened women who were less educated and illiterate in Tamil were most likely to acquire a positive attitude toward screening after receiving information. It also appeared that women who were most likely to be unreceptive to cost-free cervical cancer screening were more likely to be older and previously screened. These findings from our exploratory research with insights from additional comments made by several participants who were unreceptive to cost-free screening suggest that perceptions of free versus private healthcare may have influenced responses in this study.

Human Papillomavirus (HPV) is one of the most common causes of sexually transmitted disease worldwide. Infections by high-risk HPVs, such as HPV-18, have been associated etiologically with cervical cancer. The successful development of HPV vaccines may be beneficial to the HPV-na??ve population, but women that have already been exposed to the virus are still at risk of developing HPV-associated malignancies. A need for a systemic cure for HPV-infection therefore still exists. Gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers; however, few studies have explored this possibility for cervical cancer. The aim of this project is to construct a gene expression vector that can specifically target HPV-infected cervical cancer cells, by making use of the activity and selectivity of the P105 promoter which is determined by transcription control elements within the HPV-18 long control region (LCR). The first part of this study involved the construction of LCR deletion plasmids, and examining the subsequent level of gene expression induced within different mammalian cell lines. The results suggest the LCR to be capable in achieving cervical cancer-specific gene expression. The 3′-end of the viral L1 gene upstream of the LCR appeared to have a repressive effect on the promoter and therefore should be excluded for maximum LCR promoter activity. The second part of the project involved site-directed mutagenesis studies performed on selected transcription factor binding sites with an attempt to further increase the level of LCR promoter activity and specificity towards HPV-infected cervical cancer cells. The results suggest that a GRE/YY1 mutation may significantly enhance promoter activity. In terms of promoter regulation, the E2BSs appeared to be responsible for promoter activation in the absence of viral E2 proteins. The findings of this study suggest a possible gene therapy approach towards the treatment of cervical cancer. By making use of the activity and specificity of the HPV-18 P105 promoter to induce cervical carcinoma-specific expression of appropriate therapeutic genes, suicidal phenotypes can be introduced selectively within HPV-positive cervical cancer cells while normal HPV-negative cells are unaffected.

Human papillomavirus (HPV) is a double-stranded DNA virus, typically infecting mucosal or cutaneous epithelial keratinocytes. Today, more than 118 different HPV types have been formally described. Sexual transmission of mucosal HPVs is very common and generally asymptomatic, but HPV infection can be associated with benign lesions such as condylomata acuminata or, in rare cases, with malignant lesions such as cervical cancer. Two prophylactic vaccines are currently available in Europe, protecting against HPV-16 and HPV-18 (Cervarix) or against HPV-6, HPV-11, HPV-16 and HPV-18 (Gardasil). In order to assess the impact of the vaccination program, it is mandatory to obtain geographically widespread date on the baseline HPV prevalence and type distribution in cervical samples from women, presenting or not, normal or abnormal cytologic or histologic results. We undertook an epidemiological study in the Capital Region of Brussels to determine the HPV prevalence and type-distribution in 1526 cervical samples of women presenting a cytology within normal limits (WINL), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intra-epithelial lesions (LSIL), high-grade squamous intra-epithelial lesions (HSIL) or invasive cervical cancer (ICC). The HPV prevalence was 10.8% (95%CI: 8.8-12.8) for NILM, 34.5% (95%CI: 28.3-40.8) for ASC-US, 54.0% (95%CI: 47.4-60.6) for LSIL and 100% for HSIL and ICC. With an HPV-16 and HPV-18 prevalence of 63.3% (95%CI: 44.1-67.7) and 73.5% (95%CI: 63.0-84.0) in mono-infected HSIL and ICC, respectively, HPV 16/18 L1 VLP vaccines would be expected to significantly reduce the management and treatment of women suffering from HSIL and ICC in the Capital Region of Brussels. We also detected HPV-30, HPV-53, HPV-66 and HPV-68 in mono-infected HSIL and ICC samples, possibly providing arguments for the reconsideration of the carcinogenicity of these types. Vertical transmission of HPV was also previously reported, but in most cases one could not exclude a placental contamination by HPV positive cells from an infected birth canal. In order to confirm that the placenta can be infected with HPV, we analysed residual cells from 35 transabdominally obtained placental samples from pregnant women undergoing chorionic villous sampling for screening of suspected foetal abnormalities and found that two samples were positive for HPV-16 and HPV-62, respectively. The clinical importance of these results remains to be elucidated, but the previously observed association between placental HPV infection and pregnancy loss might gain further in importance. HPV gene regulation in placental trophoblastic cells has not been studied so far. We studied the HPV-16 early gene expression regulation in transiently transfected monolayer cultured trophoblastic cells with an HPV-16 long control region (LCR) driven reporter plasmid. We observed important differences in constitutive HPV-16 LCR activities between trophoblastic cell lines and could identify progesterone as an important inducer of HPV-16 early gene expression. Steroid hormones are induced during pregnancy and could therefore lead to an enhanced expression of the E5, E6 and E7 proteins upon placental HPV infection. Since these proteins were previously shown to affect trophoblast adhesion, survival, migration and invasion, their enhanced expression might eventually contribute to pregnancy loss. We furthermore found that the transcription of episomally maintained HPV-16 is not regulated by E2 or E1, but by E5, E6 and/or E7.

Purpose: The objective of this study was to investigate both depression and psychological distress as determinants of breast and cervical cancer screening. Methods: Ontario female respondents to the Canadian Community Health Survey version 1.2 (2002) were assessed for both Major Depressive Disorder (World Mental Health-Composite International Diagnostic Interview for depression) and psychological distress (Kessler 6-item Distress Scale (K6)>/= 8). Respondents eligible for screening (N=4042 for cervical cancer; N=1403 for breast cancer) were linked to Ontario administrative health service data to prospectively ascertain screening outcomes. Results: Women with K6 >/= 8 had reduced breast cancer screening compliance in adjusted analyses (AOR 0.63, 95% CI 0.40-0.97). The association between K6 >/= 8 and cervical cancer screening approached significance in women over age 40 (AOR=0.65, 95%CI 0.41-1.04). Conclusion: Decreased likelihood of screening in women with clinically significant psychological distress suggests that attention to adequacy of preventive services is a potential target for intervention.

Purpose: The objective of this study was to investigate both depression and psychological distress as determinants of breast and cervical cancer screening. Methods: Ontario female respondents to the Canadian Community Health Survey version 1.2 (2002) were assessed for both Major Depressive Disorder (World Mental Health-Composite International Diagnostic Interview for depression) and psychological distress (Kessler 6-item Distress Scale (K6)>/= 8). Respondents eligible for screening (N=4042 for cervical cancer; N=1403 for breast cancer) were linked to Ontario administrative health service data to prospectively ascertain screening outcomes. Results: Women with K6 >/= 8 had reduced breast cancer screening compliance in adjusted analyses (AOR 0.63, 95% CI 0.40-0.97). The association between K6 >/= 8 and cervical cancer screening approached significance in women over age 40 (AOR=0.65, 95%CI 0.41-1.04). Conclusion: Decreased likelihood of screening in women with clinically significant psychological distress suggests that attention to adequacy of preventive services is a potential target for intervention.

The Wnt signaling pathway is highly conserved and participates in many important cellular functions including differentiation, embryonic development and tissue generations. £]-catenin, the central mediator of the Wnt signaling, interacts with the TCF/LEF family of transcription factors in the nucleus and initiates downstream gene transcription. In addition, £]-catenin is known as a proto-oncogene implicated in numerous cancers including colorectal, cervical, endometrial and skin cancer. Chibby (Cby) is evolutionarily conserved in many species and acts as a repressor of Wnt/£]-catenin signaling. In our previous study, we have established that Cby over-expression attenuated £]-catenin translocation to nucleus and its transcriptional activity. Thus, it was hypothesized that Cby may possess potential tumor suppressing capabilities. In the present study, we first explored endogenous Cby expression status in human cervical cancer cells: HeLa and SiHa cell lines. It was observed that Cby mRNA and protein levels were significantly down-regulated in both cancer lines compared with primary cervical cells. We then conducted functional assays of tumorigenicity on both cells using adenoviral-encoded Cby and its NLS (nuclear localization signaling) deleted variant (Cby∆NLS). It was found that gene delivery of Cby or Cby∆NLS inhibited the proliferation, invasiveness, and colony forming in HeLa and SiHa cells. Immunofluorescent analysis revealed that Cby or Cby∆NLS gene transfer reduced the expression of Ki-67, a cell proliferative marker. Furthermore, Cby or Cby∆NLS restoration induced apoptosis and perturbed cell cycle progression in both cervical cancer cells. Finally, Cby over-expression decreases the expression of £]-catenin/TCF4 regulated genes such as c-myc and PCNA, which might contributed to the anti-neoplastic mechanism for Cby in cervical cancer cell lines. Our results strongly suggest that Cby may serve as a tumor suppressor gene during cervical carcinogenesis, and may facilitate in creation of new therapeutic methods.

No description available.

Cancer is the leading cause of death for Hispanics, and cervical cancer incidence is higher (64%) for Hispanics than for non-Hispanic whites. In Texas Hispanic women 50 and older are the lowest screened and present with higher incidence of invasive cervical cancer as compared to non-Hispanic white women. They are diagnosed at a peak age of 65-74, which suggests that Hispanic women need to be screened past the recommended screening age. An estimated 90 million people in the U.S. lack basic literacy skills and low literacy may contribute to low screening. Few studies have addressed the relationship between low health literacy and cervical cancer screening among older women of Mexican-American ancestry. This study sought to uncover the cervical cancer screening beliefs, practices, health literacy, knowledge, and experiences of English and/or Spanish-speaking older women of Mexican-American ancestry. Thirty women participated in focus group or individual interviews in English and/or Spanish. Women 50 years of age or older living in the community were recruited from senior centers in South Texas from a purposeful convenience sample. Data collection was conducted through audio-taped semi-structured interviews following a moderator guide developed using Zarcadoolas, Pleasant, and Greer’s (2005) health literacy model. Data were transcribed, analyzed in original language, translated for meaning, aggregated for analysis using qualitative content analysis; matrices were developed and analyzed individually, and then data were aggregated. The Newest Vital Sign, a health literacy tool, was used to partially assess fundamental literacy. Major themes elucidated were (a) Reasons “I don’t go” [fundamental literacy], (b), Prevention of cancer and “everything else” [science literacy], (c) We are different,[cultural literacy], (d) There is always “consejos” (advice, messages) [civic literacy], and media literacy, (e) Telenovelas (soap-operas) teach a lot, and (f) Learning from Internet brochures. The study supports a multidimensional model of health literacy and focus group research, accounting for the group’s cultural norms, language, and educational preferences. It adds information for nurse clinicians about providing holistic care, for nurse educators regarding communication strategies for diverse older populations, and for researchers to continue developing strategies that improve health literacy and health outcomes for minority older women. / text

Η λεμφαγγειογένεση η σχετιζόμενη με όγκους πρόσφατα έχει θεωρηθεί σαν ένας νέος μηχανισμός εξάπλωσης του καρκίνου. Όμως υπάρχει μεγάλη ετερογένεια στα αποτελέσματα των μελετών που συσχετίζουν την έκφραση λεμφαγγειακών δεικτών στο ενδοθήλιο των λεμφαγγείων με κλινικοπαθολογοανατομικές παραμέτρους των όγκων και με την πρόγνωση των ασθενών. Επίσης ένα μεγάλο θέμα διαφωνίας είναι το ποια είναι η σημασία των περιογκικών σε σχέση με τα ενδοογκικά λεμφαγγεία για την μετάσταση των όγκων. Στην παρούσα μελέτη διερευνήσαμε την έκφραση και την πιθανή προγνωστική σημασία των δεικτών του λεμφαγγειακού ενδοθηλίου, VEGFR-3, Ρodoplanin και LYVE-1 σε διηθητικά καρκινώματα εκ πλακώδους επιθηλίου του τραχήλου της μήτρας . Υλικά και Μέθοδοι: Το υλικό της μελέτης αποτέλεσαν 51 παρασκευάσματα υστερεκτομών με διηθητικό καρκίνωμα εκ πλακώδους επιθηλίου τραχήλου. Με την μέδοδο της Ανοσοϊστοχημείας εξετάσθηκε η πρωτεϊνική έκφραση των δεικτών CD31, VEGFR-3, Ρodoplanin και LYVE-1.Ο έλεγχος της παρουσίας ανοσοθετικών αγγείων για όλα τα ανωτέρω μόρια έγινε σε όλη την έκταση της ιστολογικής τομής, μέσα στο παρέγχυμα και σε όλη την περιφέρεια του όγκου με μικρή μεγέθυνση φωτονικού μικροσκοπίου( x 4 ).Η αγγειακή πυκνότης εκτιμήθηκε στις περιοχές με την μεγαλύτερη αγγειοβρίθεια (hot spots) σε πέντε συνεχόμενα μεγάλα οπτικά πεδία (HPF=. x 400) και ορίσθηκε ως ο μέσος όρος του αριθμού των αγγείων στα πεδία αυτά. Χρησιμοποιήθηκε στατιστικό πρόγραμμα ανάλυσης SPSS for windows με σκοπό την εκτίμηση της πιθανής συσχέτισης μεταξύ του βαθμού της αγγειακής πυκνότητας και κλινικοπαθολογοανατομικών παραμέτρων όπως είναι ο βαθμός κακοηθείας ,το στάδιο του όγκου και η παρουσία λεμφαδενικών μεταστάσεων.. Αποτελέσματα: Η Ρodoplanin και LYVE-1 εκφράσθηκαν στο ενδοθήλιο των λεμφαγγείων ενώ έκφραση του VEGFR-3 παρατηρήθηκε στα λεμφαγγεία αλλά και στα αιμοφόρα αγγεία.. Η αγγειακή πυκνότης με βάση την έκφραση του VEGFR3 συσχετίσθηκε στατιστικά σημαντικά με την αγγειακή πυκνότητα με βάση την έκφραση του CD31 .Η αγγειακή πυκνότης όπως αναδείχθηκε με την έκφραση του VEGFR3 σχετίσθηκε σημαντικά με όγκους αυξημένου βαθμού κακοηθείας .Αυξημένη ενδοογκική λεμφαγγειακή πυκνότης όπως αναδείχθηκε με την έκφραση LYVE-1 σχετίσθηκε επίσης στατιστικά σημαντικά με όγκους προχωρημένου σταδίου. Όμως δεν παρατηρήθηκε συσχέτιση της έκφρασης των λεμφαγγειακών δεικτών με την παρουσία λεμφαδενικών μεταστάσεων. Συμπέρασμα: Τα αποτελέσματα αυτής της μελέτης δηλώνουν ότι ο VEGFR-3 δεν αποτελεί πιθανόν ένα ειδικό δείκτη λεμφαγγείων αλλά φαίνεται να εμπλέκεται και στην αγγειογένεση των όγκων .Ο VEGFR3 και LYVE-1 αλλά όχι η Ρodoplanin συσχετίσθηκαν με προγνωστικές παραμέτρους του καρκινώματος του τραχήλου όπως είναι ο βαθμός κακοηθείας και το στάδιο της νόσου. Αυτό το γεγονός υποδηλώνει ότι η χρήση πολλαπλών λεμφαγγειακών δεικτών είναι απαραίτητη για την εκτίμηση της προγνωστικής σημασίας της λεμφαγγειογένεσης που σχετίζεται με όγκους .Λόγω του ότι δεν βρέθηκε συσχέτιση μεταξύ της λεμφαγγειακής πυκνότητος και της μετάστασης σε λεμφαδένες , η σχετιζόμενη με όγκους λεμφαγγειογένεση πιθανόν να αποτελεί μία επιπλέον οδό καρκινικής διασποράς αλλά όχι απαραίτητη προϋπόθεση για την μετάσταση του καρκίνου του τραχήλου της μήτρας. / Tumor-associated lymphangiogenesis has now been firmly established as a novel mechanism of cancer progression. However, results regarding correlation of lymphatic markers expression to clinicopathological tumor parameters and prognosis of cancer patients are heterogenous. In the present study we assessed the expression and prognostic significance of the lymphatic endothelial markers VEGFR-3, podoplanin and LYVE-1 and the panendothelial marker CD31 in invasive squamous cell carcinoma (SCC) of the uterine cervix. Design. The study comprised of 51 hysterectomy specimens with invasive SCC of the uterine cervix. Protein expression of CD31, VEGFR-3, podoplanin and LYVE-1 was examined by means of immunohistochemistry.Vessel counting was performed in whole tumor histologic section as well as in inner tumor areas and invasive tumor fronts separately. Vessel density scores were evaluated in areas of higher vascularization (hot spots). Statistical analysis was performed using SPSS v.12 to evaluate potential correlation between vessel density scores and clinicopathological parameters such as tumor grade, presence of lymph node metastases and disease stage. Results. While podoplanin and LYVE-1 was mainly expressed in lymphatic endothelium VEGFR-3 expression was observed in both lymphatic and blood vessels. Intratumoral vessel density for all markers used was significantly higher in intratumoral compared with peritumoral areas. There was a significant correlation between vessel density scores as assessed by VEGFR3 and CD31 (p<0.001, r=0.5). Intratumoral and peritumoral VEGFR3 vessel density significantly correlated with advancing tumor grade (p=0.001 and p=0.035 respectively). Intratumoral LVD (lymph vessel density) as assessed by LYVE-1 immunostaining was also significantly higher in high stage tumors (p=0.008). However there was no correlation of lymphatic markers expression with nodal metastases. Conclusions. Our results suggest that VEGFR-3 does not probably represent a specific lymphatic marker but it is also implicated in tumor angiogenesis. VEGFR3 and LYVE-1 but not podoplanin correlated with prognostic parameters of cervical carcinomas such as grade and stage, suggesting that the use of multiple lymphatic markers is required for the evaluation of the prognostic significance of tumor associated lymphangiogenesis. While both intratumoral and peritumoral VEGFR3 correlated with grade only intratumoral LVD for LYVE-1 correlated with stage suggesting that the relative significance of intartumoral versus peritumoral lymphatics remains a matter of debate. Finally, since there was no correlation between LVD scores and nodal status, tumor associated lymphatics should be regarded as an additional pathway rather than a necessity for lymph node metastasis in cervical cancer.