124 research outputs found
Immunological responses in cervical neoplasia Immunological status of patients with cervical carcinoma and HPV-specific cytotoxic lymphocyte responses in women with cervical neoplasia
No full textSIGLEAvailable from British Library Document Supply Centre-DSC:DXN016734 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Quantitative measurement of Human Papillomavirus type 16 L1/L2 DNA methylation correlates with cervical disease grade
No full textBackgroundPersistent infection with Human Papillomavirus (HPV) type 16 causes the majority of cervical cancers. Genital HPV infection is very common, but neoplastic progression is uncommon. There is an urgent need to identify biomarkers associated with cervical neoplasia that can be used to triage women who test positive for HPV.ObjectivesTo assess the ability of quantitative measurement of HPV16 DNA methylation to separate samples of different cytology grades and cervical cancers, and determine which of the assessed regions of the HPV genome and individual CpGs are most informative.Study designDNA methylation was quantified by pyrosequencing of bisulphite converted DNA from liquid based cytology samples from 17 women with normal cytology and 20 women with severe dyskaryosis, and from fixed tissue from 24 women with cervical cancer. Methylation was assessed in the HPV Long Control Region (LCR), E2 and L1/L2 regions.ResultsIn cervical cancers, increased HPV DNA methylation was present in all regions. Increased methylation was also observed in severely dyskaryotic relative to normal samples, but only in the E2 and L1/L2 regions. The ability of methylation based classifiers to separate the three classes of material was assessed by ROC curve analyses. The best separation between normal and dyskaryotic samples was achieved by assessment of the L1/L2 CpGs at nucleotide positions 5600 and 5609 (AUC = 0.900, 95% CI: 0.793–1).ConclusionsThis study demonstrates the potential of quantification of HPV DNA methylation as a biomarker of cervical neoplasia. An algorithm considering methylation at specific L1/L2 CpGs appeared the most promising model
Human Papillomavirus DNA Methylation Predicts Response to Treatment Using Cidofovir and Imiquimod in Vulval Intraepithelial Neoplasia 3
No full textAbstractPurpose: Response rates to treatment of vulval intraepithelial neoplasia (VIN) with imiquimod and cidofovir are approximately 57% and 61%, respectively. Treatment is associated with significant side effects and, if ineffective, risk of malignant progression. Treatment response is not predicted by clinical factors. Identification of a biomarker that could predict response is an attractive prospect. This work investigated HPV DNA methylation as a potential predictive biomarker in this setting.Experimental Design: DNA from 167 cases of VIN 3 from the RT3 VIN clinical trial was assessed. HPV-positive cases were identified using Greiner PapilloCheck and HPV 16 type-specific PCR. HPV DNA methylation status was assessed in three viral regions: E2, L1/L2, and the promoter, using pyrosequencing.Results: Methylation of the HPV E2 region was associated with response to treatment. For cidofovir (n = 30), median E2 methylation was significantly higher in patients who responded (P ≤ 0.0001); E2 methylation &gt;4% predicted response with 88.2% sensitivity and 84.6% specificity. For imiquimod (n = 33), median E2 methylation was lower in patients who responded to treatment (P = 0.03; not significant after Bonferroni correction); E2 methylation &lt;4% predicted response with 70.6% sensitivity and 62.5% specificity.Conclusions: These data indicate that cidofovir and imiquimod may be effective in two biologically defined groups. HPV E2 DNA methylation demonstrated potential as a predictive biomarker for the treatment of VIN with cidofovir and may warrant investigation in a biomarker-guided clinical trial. Clin Cancer Res; 23(18); 5460–8. ©2017 AACR.</jats:p
Novel method for detection, typing, and quantification of human papillomaviruses in clinical samples
No full textWe report the development of a novel detection and typing methodology for human papillomaviruses (HPV) based on real-time PCR with the self-probing fluorescent primers known as Scorpions. This technique is quick, el simple, specific, sensitive, and capable of estimating viral load per cell. We report the results of over 100 typing reactions performed on cell lines, biopsies, and cervical cytobrush samples which, when compared to the current reference HPV detection and typing technique, present a kappa value of 0.89. We further report preliminary data suggesting a relationship between viral load per cell and grade of cervical disease
Evaluation of flexible senior registrar training in obstetrics and gynaecology
No full textOBJECTIVE: To evaluate part-time senior registrar training in obstetrics and gynaecology from the perspective of the trainees.
DESIGN: Postal questionnaire.
SUBJECTS: Past and present senior registrar trainees on the PM(79)3 scheme.
RESULTS: Thirty-two questionnaires were returned (86% response rate) from 20 current trainees (100% response) and 12 (71% response) past trainees. Family commitments were the main reason for training part-time. Of these, 84% were satisfied with their training and most (81%) thought the quality as good or better than full time training. Personalised timetables were seen to be of particular benefit. Negative attitudes towards part-time training and discrimination in favour of full time trainees were seen as some of the biggest difficulties associated with part-time training. Other problems included administrative delays in organising part-time posts, time restriction, and the length of training.
CONCLUSIONS: Part-time senior registrar training is effective in retaining trainees with domestic commitments within the speciality. It is regarded as being of high quality but with attendant problems, particularly those related to the negative attitudes of others. Recommendations for improvements have been made
The Prevention of Cervical Cancer in Africa
No full text In this article we aim to draw attention to the burden of cervical cancer in Africa for reproductive health and review strategies for prevention, including appropriate noncytology-based cervical screening and prophylactic human papillomavirus vaccination. We consider the heavy burden of disease attributable to human papillomavirus infection borne by developing countries, particularly in Africa. Following identification of the human papillomavirus as the infectious etiological agent and elucidation of the long natural history of cervical neoplasia, cervical cancer is now one of the most preventable of all cancers. Opportunities for primary prevention by prophylactic vaccination and secondary prevention by appropriate cervical screening are discussed, together with the importance of population coverage. Qualitative work on attitudes towards cervical cancer prevention, education needs, the creation of an environment for informed choice and uptake are essential aspects of effective prevention programs. Cervical cancer poses a huge health burden in Africa. It is a disease that is eminently preventable given political will, the availability of affordable vaccines, appropriate cervical screening and access to cheap, point-of-care human papillomavirus testing. There are a number of unanswered questions for the prevention of cervical cancer and a need for demonstration projects to address these and further develop prevention strategies. </jats:p
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