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Cervical Cancers (cervical + cancers)
Kinds of Cervical Cancers Selected AbstractsTrials update in walesCYTOPATHOLOGY, Issue 2007A. Fiander Three ongoing studies will be presented and discussed. Prevalence of Human Papillomavirus Infection in a South Wales Screening population Methods: A total of 10 000 consecutive, anonymous liquid based cytology screening samples were collected over a five month period in 2004. Age, cytology result and social deprivation score was provided for each specimen. The methodology was chosen to ensure inclusion of all women attending routine cervical screening, avoiding potential constraints associated with obtaining individual informed consent. The liquid based cytology samples were processed and reported by the receiving cytology laboratory and the residual specimens sent to the HPV Research Laboratory, Wales College of Medicine, where they were processed and stored at -80°C until analysis. High risk and low risk HPV Typing was undertaken using PCR , EIA (Jacobs et al 1997). Full high risk typing was performed on HPV positive specimens. Results: The study population had a mean age of 38 years with 92% negative, 5% borderline and 3% dyskaryotic cytology. The average social deprivation score was 17.4 (based upon the Welsh Index of multiple deprivation). The following results will be presented: HPV prevalence by age. HPV prevalence by cytology result. Type specific HPV prevalence in single and multiple infection. Conclusion: This study represents the largest type specific HPV Prevalence Study in the UK to date. As such it will form a useful base line against which to access performance of marketed HPV tests and evaluating the impact following implementation of HPV vaccination. [Funded by Welsh Office for Research and Development] CRISP , 1 Study (Cervical Randomized Intervention Study Protocol -1) Background: Indole-3-carbinol (I3C) and Diindolylmethane (DIM) are found in cruciferous vegetables and have been identified as compounds that could potentially prevent or halt carcinogenesis. I3C spontaneously forms DIM in vivo during acid digestion. I3C has been shown to prevent the development of cervical cancer in HPV 16 transgenic mice and both I3C and DIM have been shown to promote cell death in cervical cancer cell models. DIM is the major active bi-product of I3C and preliminary data indicate that DIM is active in cervical dysplasia and may be better tolerated than I3C. Aim: To investigate chemoprevention of high grade cervical neoplasia using Diindolylmethane (DIM) supplementation in women with low grade cytological abnormalities on cervical cytology. Objectives: To observe any reduction in the prevalence of histological proven high-grade cervical intraepithelial neoplasia (CIN) after 6 months of supplementation. ,,To observe any reduction in the prevalence of cytological abnormalities. ,,To observe any changes in the clinical appearance of the cervix. To assess acceptability and monitor any side effects of DIM supplementation. ,,To assess whether any benefit is seen in relation to Human Papillomavirus (HPV) status including HPV Type, Viral load and integration. Methods: This is a double blind randomized placebo-controlled trial involving 600,700 women with low grade cytological abnormalities on a cervical smear. Randomization is in the ratio of 2 : 1 in favour of active medication. Women with first mildly dyskaryotic smear or second borderline smear are eligible. They are asked to take two capsules daily for 6 months. At the end of 6 months they undergo repeat cervical cytology, HPV testing and colposcopy. Results: A progress report will be given for this ongoing study. [Funded: - Cancer Research UK] Type Specific HPV Infection in Welsh Cervical Cancers Background: Whilst there have been numerous studies of HPV infection associated with cervical cancer and on prevalence of Human Papillomavirus in diverse populations there have been no studies of these variables in the same population. Against a background of prophylactic HPV vaccination it is important to assess potential protection against cervical cancer within a given population. The most comprehensive analysis of HPV type specific cervical cancer is a meta-analysis published by the IARC in 2003. This however included only three UK based studies, totalling 118 cases, 75 of which were only investigated by HPV type PCR for four high risk types. None of this data was presented with associated population based prevalence data. Therefore, the research objectives for this study in combination with the first study above, are as follows: To determine the frequency of specific HPV types in cervical cancers in Wales. To compare the distribution of specific HPV types amongst cervical cancers with their prevalence in the general population. This will allow accurate delineation of the relationship between prevalence of specific HPV types in the general population and their association with clinically relevant disease. This information is a pre-requisite to assess the potential impact of prophylactic vaccination against HPV infection in Wales. Methods: Welsh Cervical Cancer specimens from 2000,2005 will be identified from pathology departments within Wales. The pathology of each tumour will be reviewed by a single Gynaecological Pathologist. The age of the patient and pathological features of the tumour will be noted. DNA will be extracted from the paraffin sections and HPV typed by PCR-EIA. Results: A progress report will be given for this ongoing study. [Funded by Welsh Office for Research and Development] [source] ThinPrep Pap test of endocervical adenocarcinoma with lymph node metastasis: Report of a case in a 17-year-old woman,DIAGNOSTIC CYTOPATHOLOGY, Issue 9 2010David G. Wagner M.D. Abstract Endocervical adenocarcinoma is an uncommon malignancy that is composed of multiple subtypes and accounts for ,15% of all cervical cancers. In this article, we describe the cytomorphology and differential diagnosis of an AJCC clinical stage IIIb, FIGO IB2 endocervical adenocarcinoma in a 17-year-old woman in a ThinPrep Pap test. The patient was a 17-year-old G0P0 white woman with no significant past medical history and no prior history of cervical dysplasia. She presented to her physician with a putrid vaginal discharge. A sample was sent to cytology that was interpreted as atypical endocervical cells, favor neoplasia. A subsequent cervical biopsy was diagnosed as endocervical adenocarcinoma with villoglandular features and ultimately, a hysterectomy with lymph node dissection was performed. The final diagnosis was endocervical adenocarcinoma with metastasis to three pelvic lymph nodes. The cytomorphology of endocervical adenocarcinoma on ThinPrep Pap test is similar to that described for conventionally-processed Pap smears. This difficult diagnosis should be considered on a ThinPrep Pap test, regardless of age when the characteristic cytomorphology is observed. On a cytology sample, it is advisable to state atypical endocervical cells, adenocarcinoma in situ, or endocervical adenocarcinoma without providing a specific subtype even if there is a predominance of features for a particular subtype. Diagn. Cytopathol. 2010;38:633,638. © 2009 Wiley-Liss, Inc. [source] DNA vaccine encoding endosome-targeted human papillomavirus type,16 E7,protein generates CD4+ T cell-dependent protectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007Jean-Marc Brulet Abstract Human papillomavirus type,16 is commonly implicated in cervical cancers. The viral genome encodes potential targets like the oncoprotein,E7, expressed in transformed cells but thought to represent a poorly immunogenic antigen. We describe in this work a DNA-based vaccination protocol aimed at inducing an efficient anti-E7 immune response in vivo. Plasmids allowing the expression of the E7,protein in distinct cellular compartments were generated and assayed in an in vivo model of tumor growth. Our data demonstrate that mice vaccinated with a plasmid encoding for an E7,protein fused to a domain of the MHC class,II-associated invariant chain (IiE7) were protected against tumor challenge. Mice immunized against an ubiquitinated form of E7 (Ub(Ala)E7) failed to control tumor growth. Protection induced by IiE7 was correlated with the development of CD8+ CTL and required the presence of CD4+ cells. In vitro studies confirmed that the IiE7 fusion protein was expressed at high levels in the endosomal compartment of transfected cells, while the natural and the ubiquitin-modified form of E7 were mainly nuclear. The present study suggests that an efficient anti-tumor response can be induced in vivo by DNA constructs encoding for E7,protein forms localizing at the endosomal compartment. See accompanying commentary: http://dx.doi.org/10.1002/eji.200636233 [source] Dehydroepiandrosterone inhibits the proliferation and induces the death of HPV-positive and HPV-negative cervical cancer cells through an androgen- and estrogen-receptor independent mechanismFEBS JOURNAL, Issue 19 2009Roma A. Girón Dehydroepiandrosterone (DHEA) has a protective role against epithelial-derived carcinomas; however, the mechanisms remain unknown. We determined the effect of DHEA on cell proliferation, the cell cycle and cell death in three cell lines derived from human uterine cervical cancers infected or not with human papilloma virus (HPV). We also determined whether DHEA effects are mediated by estrogen and androgen receptors. Proliferation of C33A (HPV-negative), CASKI (HPV16-positive) and HeLa (HPV18-positive) cells was evaluated by violet crystal staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction. Flow cytometry was used to evaluate the phases of the cell cycle, and cell death was detected using a commercially available carboxyfluorescein apoptosis detection kit that determines caspase activation. DNA fragmentation was determined using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Flutamide and ICI 182,780 were used to inhibit androgen and estrogen receptors, respectively, and letrozol was used to inhibit the conversion of DHEA to estradiol. Our results show that DHEA inhibited cell proliferation in a dose-dependent manner in the three cell lines; the DHEA IC50 doses were 50, 60 and 70 ,m for C33A, CASKI and HeLa cells, respectively. The antiproliferative effect was not abrogated by inhibitors of androgen and estrogen receptors or by an inhibitor of the conversion of testosterone to estradiol, and this effect was associated with an increase in necrotic cell death in HPV-negative cells and apoptosis in HPV-positive cells. These results suggest that DHEA strongly inhibits the proliferation of cervical cancer cells, but its effect is not mediated by androgen or estrogen receptor pathways. DHEA could therefore be used as an alternative in the treatment of cervical cancer. [source] The potential impact of human papillomavirus vaccination in contemporary cytologically screened populations may be underestimated: An observational retrospective analysis of invasive cervical cancersINTERNATIONAL JOURNAL OF CANCER, Issue 10 2009Ned Powell Abstract The aim of this study was to determine the proportion of invasive cervical cancers attributable to human papillomavirus (HPV) types 16 and 18 in a contemporary, cytologically well-screened UK population. This was achieved in a retrospective observational analysis by HPV typing 453 archival invasive cervical cancers diagnosed between January 1, 2000 and September 1, 2006. Pathological material was collected from 9 hospitals across Wales (UK), and HPV typing and pathology review was conducted at a central laboratory. Genotyping for high-risk HPV DNA was performed by PCR-enzyme immunoassay using the GP5+/6+ primer set. DNA was successfully extracted from 297 cases. Two hundred and eighty cases were included in the final analysis. The proportion of cases which had only HPV 16 and/or 18 was 219 of 280 (78.2%, 95% CI = 73.0,82.7); the proportion of cases which had HPV 16 or 18 and another HPV type was 230 of 280 (82.1%, 95% CI = 77.2,86.2). The proportion of cervical cancers associated with infection with HPV types 16 and 18 has previously been estimated at around 70%. The appropriate figure for a cytologically well-screened UK population appears to be approximately 80%. Hence, the potential impact of the current vaccination programme may be underestimated. © 2009 UICC [source] Identification of novel DNA methylation markers in cervical cancer,INTERNATIONAL JOURNAL OF CANCER, Issue 1 2008Hung-Cheng Lai Abstract Testing for DNA methylation has potential in cancer screening. Most previous studies of DNA methylation in cervical cancer used a candidate gene approach. The aim our study was to identify novel genes that are methylated in cervical cancers and to test their potential in clinical applications. We did a differential methylation hybridization using a CpG island (CGI) microarray containing 8640 CGI tags to uncover methylated genes in squamous cell carcinomas (SCC) of the uterine cervix. Pooled DNA from cancer tissues and normal cervical swabs were used for comparison. Methylation-specific polymerase chain reaction, bisulfite sequencing and reverse transcription polymerase chain reaction were used to confirm the methylation status in cell lines, normal cervices (n = 45), low-grade lesions (n = 45), high-grade lesions (HSIL; n = 58) and invasive squamous cell carcinomas (SCC; n = 22 from swabs and n = 109 from tissues). Human papillomavirus (HPV) was detected using reverse line blots. We reported 6 genes (SOX1, PAX1, LMX1A, NKX6-1, WT1 and ONECUT1) more frequently methylated in SCC tissues (81.5, 94.4, 89.9, 80.4, 77.8 and 20.4%, respectively) than in their normal controls (2.2, 0, 6.7, 11.9, 11.1 and 0%, respectively; p < 0.0001). Parallel testing of HPV and PAX1 methylation in cervical swabs confers an improved sensitivity than HPV testing alone (80% vs. 66%) without compromising specificity (63% vs. 64%) for HSIL/SCC. Testing PAX1 methylation marker alone, the specificity for HSIL/SCC is 99%. The analysis of these novel DNA methylations may be a promising approach for the screening of cervical cancers. © 2008 Wiley-Liss, Inc. [source] Human papillomavirus (HPV) genotype distribution in invasive cervical cancers in France: EDITH study ,INTERNATIONAL JOURNAL OF CANCER, Issue 2 2008Jean-Luc Prétet Abstract Invasive cervical cancer (ICC) remains a significant cause of morbidity and mortality in France. Since human papillomavirus (HPV) is the necessary cause of ICC, the aim of this study was to assess the type-specific prevalence of HPV in ICC in France in order to locally evaluate the potential benefit of an HPV 16/18 L1 virus-like particles (VLP) vaccination. A total of 516 histological specimens collected in 15 centers were analyzed. Among them, 86% had a diagnosis of squamous cell carcinoma (SCC) whereas 14% were adenocarcinomas (ADC). HPV genotyping was performed using the INNO-LiPA assay allowing the specific detection of 24 HPV genotypes both high risk (HR) and low risk (LR). The overall HPV prevalence in ICC was 97%. The most prevalent genotypes were HPV 16 (73%) and HPV 18 (19%) followed by HPV 31 (7%), 33, 68, 45, 52 and 58 (4.1,2.3%). HPV 16 and/or 18 were associated with 82% of ICC, 10% being HPV 16 and 18 coinfections. While HPV 16 was the most prevalent type in both SCC (74%) and ADC (64%), HPV 18 was by far more prevalent in ADC (37%) compared to SCC (16%; p < 0.001). Multiple infections with at least two different HR HPV genotypes were observed in 22% of ICC. Given the high HPV 16/18 prevalence and taking into account possible production of crossneutralizing antibodies against other HPV types, HPV 16/18 L1 VLP vaccination would be expected to significantly reduce the burden of ICC in France. © 2007 Wiley-Liss, Inc. [source] Cancer incidence patterns among Vietnamese in the United States and Ha Noi, Vietnam,INTERNATIONAL JOURNAL OF CANCER, Issue 4 2002Gem M. Le Abstract Nearly 600,000 persons have immigrated to the United States from Vietnam since the end of the Vietnam War. Despite the rapid growth of the U.S. Vietnamese population, little is known about cancer incidence in this migrant group. Using population-based data from the Surveillance, Epidemiology and End Results program, California Cancer Registry and International Agency for Research on Cancer, we compared cancer incidence rates for Vietnamese in the United States (1988,1992) to rates for residents of Ha Noi, Vietnam (1991,1993); non-Hispanic whites were included to serve as the U.S. reference rates. Lung and breast cancers were the most common among Vietnamese males and females, respectively, regardless of geographic region. Rates of cancers more common to U.S. whites, such as breast, prostate and colon cancers, were elevated for U.S. Vietnamese compared to residents in Ha Noi but still lower than rates for U.S. whites. Rates of cancers more common to Asian countries, such as stomach, liver, lung and cervical cancers, were likewise elevated for U.S. Vietnamese compared to residents of Ha Noi and exceeded corresponding rates for whites. Incidence patterns for stomach, liver, lung and cervical cancers may reflect increased risk of exposures in this migrant population and should be further explored to uncover the relative contributions of environmental and genetic factors to cancer etiology. © 2002 Wiley-Liss, Inc. [source] Diseases caused by human papillomaviruses (HPV)JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 5 2009Alessandra Handisurya Summary Human papillomaviruses (HPV) are non-enveloped tumor viruses with a double stranded DNA approximately 8 kilobases in length. The viral genome is enclosed by a spherical capsid with icosahedral symmetry and a diameter of about 55 nm. More than 100 HPV types have been identified. They infect the squamous epithelia of skin and mucosa and usually cause benign papillomas or warts. Persistent infection with high-risk oncogenic HPV causes all cervical cancers, most anal cancers, and a subset of vulvar, vaginal, penile and oropha-ryngeal cancers. In recent years cutaneous beta-HPV types have been associated with the pathogenesis of non-melanoma skin cancers. Two prophylactic HPV vaccines based on virus-like particles (VLP) are licensed. These are up to 100% effective in preventing HPV 16 and HPV 18 infections and associated genital lesions in women, who have not been previously infected with these types. One vaccine also prevents genital warts caused by HPV 6 and HPV 11. [source] Lipophilic but not hydrophilic statins selectively induce cell death in gynaecological cancers expressing high levels of HMGCoA reductaseJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5 2010S. Kato Abstract Recent reports have suggested that statins induce cell death in certain epithelial cancers and that patients taking statins to reduce cholesterol levels possess lower cancer incidence. However, little is known about the mechanisms of action of different statins or the effects of these statins in gynaecological malignancies. The apoptotic potential of two lipophilic statins (lovastatin and simvastatin) and one hydrophilic statin (pravastatin) was assessed in cancer cell lines (ovarian, endometrial and cervical) and primary cultured cancerous and normal tissues. Cell viability was studied by MTS assays and apoptosis was confirmed by Western blotting of PARP and flow cytometry. The expressions of key apoptotic cascade proteins were analysed. Our results demonstrate that both lovastatin and simvastatin, but not pravastatin, selectively induced cell death in dose- and time-dependent manner in ovarian, endometrial and cervical cancers. Little or no toxicity was observed with any statin on normal cells. Lipophilic statins induced activation of caspase-8 and -9; BID cleavage, cytochrome C release and PARP cleavage. Statin-sensitive cancers expressed high levels of HMG-CoA reductase compared with resistant cultures. The effect of lipophilic statins was dependent on inhibition of enzymatic activity of HMG-CoA reductase since mevalonate pre-incubation almost completely abrogated the apoptotic effect. Moreover, the apoptotic effect involved the inhibition of synthesis of geranylgeranyl pyrophosphate rather than farnesyl pyrophosphate. In conclusion, lipophilic but not hydrophilic statins induce cell death through activation of extrinsic and intrinsic apoptotic cascades in cancerous cells from the human female genital tract, which express high levels of HMG-CoA reductase. These results promote further investigation in the use of lipophilic statins as anticancer agents in gynaecological malignancies. [source] Human papillomavirus genotypes and their association with cervical neoplasia in a cohort of Western Australian womenJOURNAL OF MEDICAL VIROLOGY, Issue 1 2005Brian Brestovac Abstract Human papillomavirus (HPV) is known to be the cause of almost all cervical cancers. The genotypes have been classified into high and low risk types according to their oncogenic potential. However, data for many of the genotypes are limited and some (HPV-26, 53, and 66) have no agreed status. A study was undertaken to determine the HPV genotype distribution in women of Western Australia and the association with cervical neoplasia. Liquid based cervical samples from a cohort of 282 Western Australian women were tested for HPV DNA by PCR followed by DNA sequencing to determine HPV genotypes. HPV-53 and HPV-16 were the most common genotypes found in this population. In addition 86 archived liquid based cervical samples from women with cervical intraepithelial neoplasia grades 1,3 (CIN 1,3) were tested for HPV DNA. Also 32 archived paraffin biopsy samples from women with squamous cell carcinoma were also tested. HPV-16 was the most common genotype found in these samples. Of the cohort of Western Australian women tested, 27% were found to contain HPV and approximately half of these contained known high-risk HPV genotypes, but only 30% of these were types 16 or 18. The data from this study indicate that HPV-53 is not oncogenic based on an R value and odds ratio (OR) of zero. The data also suggest that HPV-73 may be oncogenic, while HPV-66 is unlikely to be. Two high-risk HPV genotypes that are associated with the Asian region (HPV-52 and HPV-58) were found in Western Australian women suggesting a possible epidemiological link between women in these countries. J. Med. Virol. 76:106,110, 2005. © 2005 Wiley-Liss, Inc. [source] Comparative study of four candidate strategies to detect cervical cancer in different health care settingsJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2007Meherbano M. Kamal Abstract Aim:, Considering the differing but potentially supplementary properties of visual inspection of the cervix with acetic acid (VIA) and the cytological examination (CYTO) of cervical smears for the screening of cervical cancers, we examined the performance of these two tests and their combinations for the screening of cervical cancer in different health care settings. Methods:, In this cross-sectional diagnostic test performance evaluation study of 4235 female subjects in the reproductive age group, we assessed the screening performance of four strategies: VIA alone, CYTO alone, VIA and CYTO combined in a parallel fashion, and VIA and CYTO combined in tandem. Subjects were recruited from three settings: Hospital, Urban Community and Rural Community. Colposcopy was used as the reference standard. Screening performance was assessed using sensitivity, specificity, post-test probabilities and likelihood ratios (LR), diagnostic odds, area under receiver operating characteristic curve and LR ,2. Results:, Both VIA and CYTO when used alone had a low sensitivity but high specificity, especially in the Rural Community setting. A combination of the results of VIA and CYTO improved the diagnostic accuracy but the strategy using a parallel combination of VIA and CYTO was the most accurate. In general, all screening strategies using VIA and CYTO showed a modest screening performance. Conclusions:, In the settings of varying levels of health care and low resources, caution is needed for a generalized use of VIA for cervical cancer screening. Further evaluation of the cost-effective ways of combining VIA and CYTO is needed in these circumstances. [source] Down-regulation of members of glycolipid-enriched membrane raft gene family, MAL and BENE, in cervical squamous cell cancersJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2004Mitsuko Hatta Abstract Persistent human papillomavirus infections cause infected epithelial cells to lose cellular polarity leading to cell transformation. Glycolipid-enriched membrane (GEM) rafts are implicated in polarized sorting of apical membrane proteins in epithelial cells and even in signal transduction. The MAL and BENE are essential component of the GEM raft's machinery for apical sorting of membrane proteins. In this study we demonstrated down-regulation of MAL and BENE mRNA in over two-thirds of primary cervical squamous cell cancers (14 and 15 of 20 cases, for MAL and BENE, respectively) when compared to corresponding non-cancerous uterine squamous cells. Allelic loss or hyper-methylation was not accompanied by MAL or BENE mRNA down-expression in human primary cervical cancers in microsatellite allelic analysis and HpaII-PCR-based methylation analysis of the MAL and BENE genomic region. In addition, we note down-regulation of these genes in established cervical cancer cell lines. These results suggest that down-regulation of MAL and BENE genes, which are essential components of the cellular polarized sorting system, play an important role in human cervical squamous cell cancer development. [source] Stabilization of human papillomavirus virus-like particles by non-ionic surfactantsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2005Li Shi Abstract Human papillomavirus (HPV) virus-like-particles (VLPs) produced by recombinant expression systems are promising vaccine candidates for prevention of cervical cancers as well as genital warts. At high protein concentrations, HPV VLPs, comprised of the viral capsid protein L1 and expressed and purified from yeast, are protected against detectable aggregation during preparation and storage by high concentrations of NaCl. At low protein concentrations, however, high salt concentration alone does not fully protect HPV VLPs from aggregation. Moreover, the analytical analysis of HPV VLPs proved to be a challenge due to surface adsorption of HPV VLPs to storage containers and cuvettes. The introduction of non-ionic surfactants into HPV VLP aqueous solutions provides significantly enhanced stabilization of HPV VLPs against aggregation upon exposure to low salt and protein concentration, as well as protection against surface adsorption and aggregation due to heat stress and physical agitation. The mechanism of non-ionic surfactant stabilization of HPV VLPs was extensively studied using polysorbate 80 (PS80) as a representative non-ionic surfactant. The results suggest that PS80 stabilizes HPV VLPs mainly by competing with the VLPs for various container surfaces and air/water interfaces. No appreciable binding of PS80 to intact HPV VLPs was observed although PS80 does bind to the denatured HPV L1 protein. Even in the presence of stabilizing level of PS80, however, an ionic strength dependence of HPV VLP stabilization against aggregation is observed indicating optimization of both salt and non-ionic surfactant levels is required for effective stabilization of HPV VLPs in solution. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1538,1551, 2005 [source] The HPV Vaccine: Framing the Arguments FOR and AGAINST Mandatory Vaccination of All Middle School GirlsJOURNAL OF SCHOOL HEALTH, Issue 6 2008Cheryl A. Vamos MPH ABSTRACT Background:, Human papillomavirus (HPV), the virus responsible for cervical cancer, is the most common viral sexually transmitted infection in the United States. A vaccine was approved in 2006 that is effective in preventing the types of HPV responsible for 70% of cervical cancers and 90% of genital warts. Proposals for routine and mandatory HPV vaccination of girls have become sources of controversy for parents of school-aged youth, legislators, members of the medical community, and the public at large. Methods:, The purpose of this article was to articulate the arguments used by advocates who either oppose or endorse routine, mandatory administration of the vaccine to school-aged girls, thereby assisting school health personnel in being effective participants in framing the relevant issues. Results:, Controversy is grounded in moral, religious, political, economic, and sociocultural arguments including whether concerns that the vaccine increases sexual risk taking, sends mixed messages about abstaining from sexual intercourse, usurps parental authority, and increases the potential for development of new health disparities are offset by the value of administering a cost-effective, age-appropriate public health measure targeting a life-threatening problem. Conclusions:, Careful consideration of the medical evidence and public health implications is critical but understanding the context of the debate is no less important to the task of responding to public concerns. School health personnel have a role in the discussion about HPV immunization. Being able to articulate the arguments presented herein can help authorities' responsiveness to parents and community groups as the dialogue about this particular health issue evolves further. [source] Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancersPATHOLOGY INTERNATIONAL, Issue 10 2004Takaaki Sano 14-3-3 sigma (,) has been a major G2/M checkpoint control gene and has demonstrated that its inactivation in various cancers occurs mostly by epigenetic hypermethylation, not by genetic change. In order to confirm 14-3-3, protein expression together with p16 and p53 in cervical cancers, immunohistochemistry was performed using various histological subtypes of cervical cancers and dysplasia. Strong and diffuse immunoreactivity for 14-3-3, was uniformly observed in all the cervical dysplasia (17/17) and squamous cell carcinomas (29/29) including human papillomavirus (HPV)-negative cases. Even in adenosquamous carcinomas and adenocarcinomas of the cervix, immunohistochemical expression of 14-3-3, was shown with relatively high frequency (13/15, 87% and 22/27, 81%). In the in situ hybridization study, mRNA of 14-3-3, was expressed in six of eight immunohistochemical-negative cases. Therefore, the undetectable expression of 14-3-3, protein in cervical cancers might, at least in part, be due to a proteolysis not epigenetic hypermethylation. It is of interest that cancers without 14-3-3, expression were predominantly those lacking HPV DNA, and that there were no cases with concomitant inactivation of 14-3-3, and p16 in the present study. These observations are consistent with the hypothesis that inactivation of either 14-3-3, or p16 has an effect equivalent to the expression of E6 and E7 oncoproteins of HPV. [source] Expression of CPEB, GAPDH and U6snRNA in cervical and ovarian tissue during cancer developmentAPMIS, Issue 1 2009CHRISTINA NEIGAARD HANSEN Persistent infection with high-risk human papillomavirus (HPV) and expression of the proteins E6 and E7 is a prerequisite for development of cervical cancer. The distal non-coding part of E6/E7 messengers from several HPV types is able to downregulate synthesis of a reporter gene through mechanisms with involvement of cytoplasmic polyadenylation elements (CPEs) in the messengers. We here show that the mRNA levels of one of the four known CPE-binding proteins (CPEBs), the CPEB3, were downregulated in HPV-positive cervical cancers, whereas in ovarian cancer the CPEB1 mRNA level was downregulated. In addition, we showed that the RNA levels of the widely used reference marker GAPDH were upregulated in both cancer forms, and the level of the reference marker U6snRNA was upregulated in cervical cancers. Moreover, a possible correlation between the degree of U6snRNA upregulation and cervical cancer propagation was shown. These changes observed in CPEB1 and CPEB3 might indicate regulatory functions of CPEBs in cancer development of HPV-positive and HPV-negative tumors, respectively, and the U6snRNA, GAPDH mRNA and CPEB1 mRNA levels may be useful as tumor markers for genital cancers although further investigations are needed. [source] Potential role of human papillomavirus in the development of subsequent primary in situ and invasive cancers among cervical cancer survivors,,CANCER, Issue S10 2008Appathurai Balamurugan MD Abstract BACKGROUND. The recent licensure of human papillomavirus (HPV) vaccines will likely decrease the development of primary in situ and invasive cervical cancers and possibly other HPV-associated cancers such as vaginal, vulvar, and anal cancers. Because the HPV vaccine has the ability to impact the development of >1 HPV-associated cancer in the same individual, the risk of developing subsequent primary cancers among cervical cancer survivors was examined. METHODS. Using the 1992 through 2004 data from the Surveillance, Epidemiology, and End Results (SEER) program, 23,509 cervical cancer survivors were followed (mean of 4.8 person-years) for the development of subsequent primary cancers. The observed number (O) of subsequent cancers of all sites were compared with those expected (E) based on age-/race-/year-/site-specific rates in the SEER population. Standardized incidence ratios (SIRs = O/E) were considered statistically significant if they differed from 1, with an , level of 0.05. RESULTS. Among cervical cancer index cases, there was a significant elevated risk for subsequent in situ cancers of the vagina and vulva (SIRs of 53.8 and 6.6, respectively); and invasive vaginal, vulvar, and rectal cancers (SIRs of 29.9, 5.7, and 2.2, respectively). Significantly elevated risks were observed across race and ethnic populations for subsequent vaginal in situ (SIR for whites of 49.4; blacks, 52.8; Asian/Pacific Islander [API], 91.4; and Hispanics, 55.7) and invasive cancers (SIR for whites of 25.7; blacks, 34.5; API, 48.5; and Hispanics, 25.2). CONCLUSIONS. The results of the current study demonstrate a substantially increased risk of the development of subsequent primary in situ and invasive cancers among cervical cancer survivors and have implications for the development of prevention and early detection strategies as the role of HPV infection becomes evident. Cancer 2008;113(10 suppl):2919,25. Published 2008 by the American Cancer Society. [source] DNA ploidy compared with human papilloma virus testing (Hybrid Capture II) and conventional cervical cytology as a primary screening test for cervical high-grade lesions and cancer in 1555 patients with biopsy confirmationCANCER, Issue 2 2006Martial Guillaud PhD Abstract BACKGROUND. Because 80% of cervical cancers arise in low-resource settings, many inexpensive strategies are being tested. In that spirit, the authors are testing large-scale genomic or DNA ploidy measurements as an inexpensive and semiautomated strategy. METHODS. Patients entered either a screening or diagnostic study of several optical technologies: quantitative cytology, quantitative histopathology, and fluorescence and reflectance spectroscopy using a point probe, a multispectral digital colposcope, or a combination of the two. We calculated sensitivities, specificities, positive and negative predictive values, and their confidence interval testing conventional cytology, Hybrid Capture (HC) II testing, and DNA ploidy measured on the Feulgen-stained quantitative Pap smear. RESULTS. The current investigation reports on 1555 patients for whom colposcopically directed biopsies were read 3 times by study pathologists. The final histopathologic diagnosis was high grade (cervical intraepithelial neoplasia [CIN] 2, CIN 3, carcinoma in situ [CIS], and cancer) in 16% of patients. Using high-grade squamous intraepithelial lesions (SILs) histopathology as the threshold and gold standard, the sensitivity and specificity, respectively, were: 0.47 and 0.96 for conventional cytology, 0.91 and 0.80 for HC II, and 0.59 and 0.93 for DNA ploidy. The positive and negative predictive values (PPV, NPV) for conventional cytology were 0.70 and 0.90, 0.46 and 0.98 for HC II, and 0.63 and 0.92 for DNA ploidy. CONCLUSIONS. DNA ploidy shows comparable sensitivity, specificity, PPV, and NPV values to conventional cytology and HC II. Unlike conventional cytology, DNA ploidy is semiautomated and can be performed in less than 8 hours. Cost effectiveness studies are under way, but in the authors' laboratory DNA ploidy is inexpensive. Cancer 2006. © 2006 American Cancer Society. [source] Personalized peptide vaccines: A new therapeutic modality for cancerCANCER SCIENCE, Issue 10 2006Kyogo Itoh Therapeutic cancer vaccines have enjoyed little success so far, although many clinical trials have been conducted. Therefore, the creation of new protocols capable of inducing an objective response is required. We examined two of these protocols in the present review. The first is a personalized protocol to take into account the immunological diversity of cytotoxic T lymphocyte responses among patients. The second is a combination therapy designed to adapt to the presence of major histocompatibility complex (MHC)-loss cancer cells. The objective response rates of our classical (non-personalized) peptide vaccines were 0%, whereas that of personalized vaccines was 11.1% in the total advanced cancers and ,20% in malignant glioma and cervical cancers, respectively. A ,50% decrease in serum prostate-specific antigen (PSA) was seen in 8.7% of advanced hormone refractory prostate cancer patients by personalized vaccination alone, whereas such a decrease was seen in 54% of patients when the personalized vaccination was combined with a low dose of estramustine. Based on these experiences, we propose a personalized peptide vaccine combined with chemotherapy as a new treatment modality for cancers. (Cancer Sci 2006; 97: 970,976) [source] Plausible linkage of hypoxia inducible factor-1, in uterine cervical cancerCANCER SCIENCE, Issue 9 2006Jiro Fujimoto Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with angiogenic transcription factor hypoxia inducible factors (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine cervical cancers. Although there was no significant difference in HIF-1, histoscores and mRNA levels according to histopathological type or lymph node metastasis, HIF-1, histoscores and mRNA levels increased significantly with advancing cancer stages. The prognosis of 30 patients with high HIF-1, in uterine cervical cancers was poor (73% survival), whereas the 24-month survival rate of the other 30 patients with low HIF-1, was 93%. HIF-1, histoscores and mRNA levels were correlated with the levels of the angiogenic factors thymidine phosphorylase and interleukin-8, and HIF-1, might be linked with these factors in cervical cancer tissue. HIF-1, is a candidate for prognostic indicator as an angiogenic mediator in uterine cervical cancer. (Cancer Sci 2006; 97: 861,867) [source] | ||||||||||||||||||||||||||||