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Cervical Neoplasia (cervical + neoplasia)
Selected AbstractsMolecular variants of human papillomavirus type 16 and 18 and risk for cervical Neoplasia in PortugalJOURNAL OF MEDICAL VIROLOGY, Issue 12 2007Angela Pista Abstract Persistent high-risk human papillomavirus (HPV) infection is considered as the central cause of invasive cervical cancer. Specific HPV 16 and 18 sequence variations were associated with an increased risk for progression. The purpose of this study was to analyze intratypic variations of HPV 16 and 18 within the E6 gene, MY09/11 and LCR regions, and to evaluate the risk of these variants for cervical neoplasia among Portuguese women. Cervical samples from 187 HPV 16-positive and 41 HPV 18-positive women with normal epithelium, cervical intraepithelial neoplasia, or invasive cervical cancer were amplified by type-specific PCR, followed by sequence and phylogenetic analysis. Sixteen new HPV 16 and 18 patterns are described in this paper. European HPV 16 variants were the most frequent (74.3%), particularly Ep-T350 (44.4%), followed by African (16.1%), and Asian-American (9.6%). Non-European HPV 16 variants were more frequent in pre-invasive lesions than in normal tissue and low-grade lesions. However, when analyzed separately, only African variants were associated significantly with an increased risk for cervical cancer. For HPV 18, the AsAi variant showed a trend, which was not statistically significant to an enhanced oncogenicity. European variants seemed to be significantly associated with a lower risk for cervical cancer development. The distribution of HPV 16 and 18 variants was not related to age or race among women living in the same geographical region. Knowledge of variants will be important for risk determination as well as for designing primers or probes for HPV detection methods, and for appropriate cervical cancer prevention strategies. J. Med. Virol. 79:1889,1897, 2007. © Wiley-Liss, Inc. [source] Trials 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] Living with uncertainty: Equivocal Pap test results and the evolution of ASC terminologyDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2010Lydia Pleotis Howell M.D. Abstract Communication of equivocal findings and their significance has been a significant challenge related to Pap testing throughout its history. Terminology to report these findings has changed considerably to accommodate the changes in understanding of cervical neoplasia, and to accommodate new management strategies, tests, and technologies. This article reviews the evolution of terminology for equivocal Pap test findings from the original Papanicolaou classification to the current the Bethesda System 2001 atypical squamous cells terminology, the implication and use of these terms, and the changing landscape of cervical neoplasia screening, which prompted these terminology changes. Emerging issues related to improving risk stratification through the introduction of additional terms and the impact of human papillomavirus testing may alter terminology of equivocal findings in the future. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] HLA-B alleles, high-risk HPV infection and risk for cervical neoplasia in southern Chinese women,INTERNATIONAL JOURNAL OF CANCER, Issue 6 2006Paul K.S. Chan Abstract A population-based study was conducted on 256 southern Chinese with cervical intraepithelial neoplasia grade III (CIN III) or invasive cervical cancer (ICC) and on 258 controls to examine the associations between HLA-B alleles, infection with high-risk human papillomaviruses (HPVs) and the development of cervical neoplasia. HLA-B15 was found to be protective for CIN III/ICC overall (pcorrected = 0.003), and for HPV52-positive CIN III/ICC (pcorrected = 0.003). A marginal protective effect of B15 was observed for HPV16-positive CIN III/ICC, but no significant associations were revealed for HPV18- or HPV58-positive cases. None of the HLA-B alleles were found to confer an increased risk for cervical neoplasia. HLA-B15 is common among Asian for whom HPV52, a worldwide uncommon HPV type, also exists in a relatively high prevalence. It would also be worthwhile to assess the association between HLA-B15, HPV52 and cervical cancer in other Asian populations. © 2005 Wiley-Liss, Inc. [source] The role of diet and nutrition in cervical carcinogenesis: A review of recent evidenceINTERNATIONAL JOURNAL OF CANCER, Issue 4 2005Reina García-Closas Abstract Our objective was to provide an update on recent epidemiologic evidence about the role of diet and nutrition on the risk of human papillomavirus (HPV) persistence and cervical neoplasia, taking HPV into account. We conducted a systematic review and qualitative classification of all observational studies controlling for HPV infection published between March 1995 and November 2003 and of all randomized clinical trials published between January 1991 and November 2003. Scientific evidence was classified as convincing, probable, possible or insufficient, as used in a previous study on diet and cancer. Thirty-three studies were eligible for this review (10 clinical trials, 8 observational prospective studies and 15 case-control studies). The few studies on HPV persistence showed a possible protective effect of fruits, vegetables, vitamins C and E, beta- and alpha-carotene, lycopene, luterin/zeaxanthin and cryptoxanthin. Evidence for a protective effect of cervical neoplasia was probable for folate, retinol and vitamin E and possible for vegetables, vitamins C and B12, alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin and cryptoxanthin. Evidence for an increased risk of cervical neoplasia associated with high blood homocysteine was probable. Results did not differ between studies looking at preneoplastic and invasive lesions or between retrospective and prospective studies. The available evidence for an association between diet and nutritional status and cervical carcinogenesis taking HPV infection into account is not yet convincing. Large cohort studies are needed to adequately assess the role of foods and nutrients in cervical HPV carcinogenesis. © 2005 Wiley-Liss, Inc. [source] Human Papillomavirus (HPV) Infection in Southern Africa: Prevalence, Immunity, and Vaccine ProspectsIUBMB LIFE, Issue 4-5 2002Anna-Lise Williamson Abstract Human papillomavirus (HPV) associated cancers are more prevalent in developing countries compared to developed countries. The major cancer caused by HPV is cervical cancer. The humoral immune response to HPV can be a marker of past infection but may also reflect persistent infection and cervical disease. IgA antibodies to HPV in oral fluid were also found to be markers of cervical disease. Cell mediated immunity is important in clearing HPV infection and for regression of the associated lesions: this means that women infected with HIV have a high prevalence of co-infection with HPV. Good cervical screening programmes can control HPV associated cervical neoplasia. However, in countries such as South Africa, where these programmes are inadequate, there is a need for an HPV vaccine. The development of HPV vaccines is reviewed. There is a call for an inexpensive vaccine that will be accessible to the women that do not have access to adequate screening programmes and are therefore at the greatest risk of cervical cancer. [source] Prevalence and genotype distribution of cervical human papillomavirus infection in MacaoJOURNAL OF MEDICAL VIROLOGY, Issue 10 2010Yuk-Ching Yip Abstract Population-specific epidemiological data on human papillomavirus (HPV) infection are essential for formulating strategies to prevent cervical cancer. The age-specific prevalence of HPV infection was determined among 1,600 women enrolled for cervical screening in Macao. A U-shaped age-specific prevalence curve with a first peak (prevalence rate, 10%) at 20,25 years and a second peak (13%) at 51,55 years was observed. Co-infections with multiple types were detected in 32.5% of HPV-positive subjects and without significant variation among different age groups (P,=,0.318). The majority (84.6%) of the positive samples harbored high- or probable high-risk HPV types, and these types also exhibited a similar U-shaped age-specific prevalence curve. In contrast, low and unknown-risk HPV types remained at a low prevalence (1.5,2.5%) throughout the age groups between 20 and 50 years, and with a small peak (4.5%) at 51,55 years. HPV 52 was the most common type found in 26.8% of positive samples, followed by HPV 16 (15.5%), HPV 68 (11.4%), HPV 18 and HPV 58 (8.9% each), HPV 54 (8.1%), HPV 53 (7.3%), HPV 39 (6.5%), HPV 33 and HPV 66 (5.7% each). In conclusion, because of the early peak of infection, vaccination and educational campaigns in Macao should start early and target at teenagers. The presence of a second peak containing mainly high-risk HPV types in older women indicates the need to evaluate the cover of the cervical screening programme for older women. Further study to determine the contribution of HPV 52 in high-grade cervical neoplasia and invasive cancers in Macao is warranted. J. Med. Virol. 82:1724,1729, 2010. © 2010 Wiley-Liss, Inc. [source] Molecular variants of human papillomavirus type 16 and 18 and risk for cervical Neoplasia in PortugalJOURNAL OF MEDICAL VIROLOGY, Issue 12 2007Angela Pista Abstract Persistent high-risk human papillomavirus (HPV) infection is considered as the central cause of invasive cervical cancer. Specific HPV 16 and 18 sequence variations were associated with an increased risk for progression. The purpose of this study was to analyze intratypic variations of HPV 16 and 18 within the E6 gene, MY09/11 and LCR regions, and to evaluate the risk of these variants for cervical neoplasia among Portuguese women. Cervical samples from 187 HPV 16-positive and 41 HPV 18-positive women with normal epithelium, cervical intraepithelial neoplasia, or invasive cervical cancer were amplified by type-specific PCR, followed by sequence and phylogenetic analysis. Sixteen new HPV 16 and 18 patterns are described in this paper. European HPV 16 variants were the most frequent (74.3%), particularly Ep-T350 (44.4%), followed by African (16.1%), and Asian-American (9.6%). Non-European HPV 16 variants were more frequent in pre-invasive lesions than in normal tissue and low-grade lesions. However, when analyzed separately, only African variants were associated significantly with an increased risk for cervical cancer. For HPV 18, the AsAi variant showed a trend, which was not statistically significant to an enhanced oncogenicity. European variants seemed to be significantly associated with a lower risk for cervical cancer development. The distribution of HPV 16 and 18 variants was not related to age or race among women living in the same geographical region. Knowledge of variants will be important for risk determination as well as for designing primers or probes for HPV detection methods, and for appropriate cervical cancer prevention strategies. J. Med. Virol. 79:1889,1897, 2007. © Wiley-Liss, Inc. [source] Variation in human papillomavirus type-16 viral load within different histological grades of cervical neoplasiaJOURNAL OF MEDICAL VIROLOGY, Issue 9 2007A.N. Fiander Abstract The objective of this study was to investigate variation in human papillomavirus (HPV) type-16 load within histologically defined grades of cervical intraepithelial neoplasia. Two hundred and thirty-seven liquid based cytology samples were collected from women attending colposcopy clinics, DNA was extracted, and presence of virus determined by PCR-enzyme immunoassay. Quantitative real-time PCR was used to determine viral load for 70 HPV-16 positive single infections. Viral load was expressed as the ratio of copies of the viral L1 gene to copies of the human beta-globin gene. Measurements varied from 0.019 to 4,194 HPV genomes per cell. Our data demonstrate that in cervical neoplasia, HPV load tends to correlate with disease severity, but that the number of viral genomes/cell varies considerably within histological grades. This variation within disease grades currently limits the clinical utility of viral load measurement. [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] Expression of transketolase-like 1 (TKTL1) and p-Akt correlates with the progression of cervical neoplasiaJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2008Nico Kohrenhagen Abstract Aim:, It is supposed that increased glycolysis is crucial for the energy supply during tumor progression. Unfortunately, the relevance of glycolysis in cervical neoplasia is unknown, but what is certain is the fact that cervical cancer shows a high expression of glucose membrane transporters, which are necessary for glucose uptake as an energy source. Transketolase-like enzyme 1 (TKTL1) and the oncogene p-Akt have been described to play an important role in glycolysis during tumorigenesis. Thus, we were interested in their expression in cervical tissue. Methods:, We examined the expression of TKTL1 and p-Akt in 80 formalin-fixed, paraffin-embedded cervical specimens: 20 benign cervical tissues, 20 low-grade squamous intraepithelial lesions, 20 high-grade intraepithelial lesions, and 20 invasive squamous cell carcinomas (ISCC). Results:, Immunhistochemical analyses revealed that the intensity of the expression of TKTL1 and p-Akt increases significantly with an increase in the histopathological grade of cervical tissues. Conclusion:, The results suggest that both TKTL1 and p-Akt play an important role in the progression of cervical neoplasia, which may be due to their impact on glycolysis. [source] Human papillomavirus integration: detection by in situ hybridization and potential clinical applicationTHE JOURNAL OF PATHOLOGY, Issue 1 2004Mark F Evans Abstract Human papillomaviruses (HPVs) are accepted as a necessary cause of cervical neoplasia. However, the benefits of testing simply for high-risk HPV types are limited because of their high prevalence in intraepithelial lesions of all grades, the majority of which regress if left untreated. One factor considered to be of key importance for the progression of intraepithelial lesions to invasive disease is integration of HPV into the host cell genome. Although questions remain about the prevalence of integration amongst pre-invasive lesions, sensitive in situ hybridization techniques utilizing tyramide reagents may aid determination of the significance of HPV infection by enabling routine detection of both high-risk HPV and its physical status. This will provide important data relevant not only to our understanding of the biology of HPV-associated neoplasia, but also potentially to clinical testing for HPV. Copyright © 2003 John Wiley & Sons, Ltd. [source] HER2/neu (c-erbB-2) gene amplification and protein expression are rare in uterine cervical neoplasia: a tissue microarray study of 814 archival specimensAPMIS, Issue 10 2009IANA LESNIKOVA Published studies have reported widely variable incidence of HER2/neu (c-erbB-2) protein expression and HER2/neu (c-erbB-2) gene amplification in cervical carcinoma. We examined tissue microarrays (TMAs) constructed from 814 formaldehyde-fixed paraffin-embedded archival specimens of cervical intraepithelial neoplasia (CIN)1 (n = 262), CIN2 (n = 230), CIN3 (n = 186) and invasive carcinoma (n = 136), for HER2/neu protein expression by immunohistochemistry (IHC) and for HER2/neu gene amplification by chromogenic in situ hybridization (CISH). We found moderate or strong immunohistochemical positivity for HER2/neu in 64 of 814 specimens (7.9%). Using CISH, polysomy of the HER2/neu gene was detected in 87 cases (10.7%), low/borderline amplification in five cases (0.6%) and true amplification in four cases (0.5%). The correlation between IHC and CISH was statistically significant in CIN2, CIN3 and invasive cervical carcinoma specimens. When present, Her-2/neu positivity is more commonly seen in higher grades of cervical dysplasia and in carcinoma. However, this large TMA study shows that HER2/neu oncoprotein expression and HER2/neu gene amplification overall are uncommon events in cervical neoplasia. This provides compelling evidence that HER2/neu plays no major role in the development and progression of cervical neoplasia. [source] Autofluorescence spectroscopy for the diagnosis of cervical intraepithelial neoplasiaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2002Helmut Weingandt Objective To assess the feasibility of autofluorescence spectroscopy in the diagnosis of cervical intraepithelial neoplasia (CIN) using broadband light excitation. Design Feasibility study. Setting Colposcopy clinic of an university hospital. Population Sixty-eight patients at risk for CIN. Methods After excitation with a broadband light between 375 and 440 nm, spectral distribution of native tissue fluorescence (autofluorescence) was acquired from 685 cervical sites for the localisation and differentiation of CIN, and compared with colposcopically directed biopsy and human papillomavirus (HPV) DNA testing. Main outcome measure Detection of CIN. Results The evaluation of spectral measurements revealed significantly lower autofluorescence values for CIN 3 lesions compared with normal tissue (P < 0.001), and compared with CIN 1 or CIN 2 (P < 0.002). High grade CIN lesions (CIN 2/3) presented with a significant reduced autofluorescence compared with CIN 1 (P < 0.002). Patients with a positive HPV DNA testing showed a significantly lower autofluorescence than patients tested negative for HPV DNA (P < 0.05). Severe inflammation such as chronic cervicitis may lead to false positive results. Conclusions Autofluorescence spectroscopy represents an interesting approach for the detection of cervical neoplasia. Using an excitation wavelength band between 375 and 440 nm, significant differences between normal and precancerous lesions of the cervix can be seen. [source] Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasiaCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2007J. Visser Summary Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (Tregs) might be involved in the failure of the immune system to control the development of HPV-induced cancer. We investigated frequencies, phenotype and activity of Tregs in patients with cervical neoplasia. CIN and cervical cancer patients showed increased CD4+/CD25high T cell frequencies in peripheral blood and CD4+ T cell fraction. These CD4+/CD25high T cells represent Tregs as demonstrated by their low proliferation rate, low interferon (IFN)-,/interleukin (IL)-10 ratio, high expression of CD45RO, GITR, CTLA-4, forkhead box P3 (FoxP3) and low CD45RA expression. Moreover, in HPV16+ cervical cancer patients, in-vitro depletion of CD25+ T cells resulted in increased IFN-, T cell responses against HPV16 E6- and E7 peptides. Thus, increased frequencies of Tregs in cervical cancer patients may indeed suppress HPV-specific immunity. Longitudinal analysis of CD4+/CD25high T cell frequencies in patients showed a modest decline 1 year after curative surgery or chemoradiation. This study demonstrates increased frequencies and suppressive activity of Tregs in cervical cancer. These results imply that Tregs may suppress the immune control of cervical neoplasia and furthermore that suppression of immunity by Tregs will be another hurdle to overcome in therapeutic immunization strategies against cervical neoplasia. [source] | |||||||||||||||||||||||||