Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate

Introduction Methods Results Discussion Conclusion Abstract Consistent evidence underlines the utility of human papillomavirus (HPV) DNA testing in the management of women with equivocal cervical cytological abnormalities, but not in case of low-grade lesions. We performed a meta-analysis including studies where the high-risk probe of the Hybrid Capture-II is used to triage these two cytological categories. The triage test-positivity rate reflects the colposcopy referral workload.Data were pooled on the HPV test positivity rate in women with atypical squamous cells of undetermined significance (ASCUS/ASC-US) or low-grade squamous intraepithelial lesions (LSIL), derived from different cytological classification systems. The meta-analysis was restricted to studies, published between 1991 and 2007. A random-effect model was applied for meta-analytical pooling and the influence of covariates on the HPV positivity rate was analyzed by meta-regression. The variation by age was assessed within individual studies since age strata were not defined uniformly. On an average, 43% (95% CI: 40-46%) of women with ASCUS/ASC-US were high-risk HPV positive (range 23-74%). In women with LSIL, the pooled positivity rate was 76% (95% CI: 71-81%; range 55-89%). In spite of considerable inter-study heterogeneity, the difference in HPV positivity between the two triage groups was large and highly significant: 32% (95% CI: 27-38%). HPV rates dropped tremendously as age and cutoffs of test positivity increased. Other factors (cytological classification system, country, continent, collection method and year of publication) had no statistically significant impact, except in LSIL triage where HPV positivity was significantly lower in European compared to American studies. Women with LSIL, especially younger women, have high HPV positivity rates suggesting limited utility of reflex HPV triaging these cases. Research is needed to identify more specific methods to triage women with low-grade squamous cervical lesions

Young children with fetal alcohol spetrum disorder - communication profiles

The aim of the article is to describe the communication profiles of five young children with fetal alcohol spectrum disorder (FASD) from 4 to 58months of age. A collective case-study design following a quantitative and descriptive approach was used to describe the communication profilesof the participants. The results are described according to the participants’ case histories and a four-level early communication assessment framework.The significant findings were that all participants were in foster care, and presented with incomplete case histories, general developmentaldelays and delays regarding all aspects of their communication abilities. An increase in the severity of the spectrum disorder across the participants’combined communication profiles was also identified. Participants presented with complex multiple neurodevelopmental needs thatshould be viewed within a developmental systems and ecological framework. The importance of early identification, diagnosis and assessmentof infants and young children prenatally exposed to alcohol, the identification of precursors to communication impairment at a very early age,and the need for individualised early communication intervention to improve developmental outcomes within a family-centred approach arediscussed. Suggestions for future research to accumulate knowledge about FASD in the field of early communication intervention are made

MASS HYSTERIA OF BTS ARMY FANDOM IN TWITTER

This study focuses on examining mass hysteria in ARMY fandom on Twitter. This study uses descriptive analytical method as the research design in analyzing the classified texts based on J.R. Martin and P.R.R. White’s affect classification in the study of Attitude, and Simon Wessely’s mass hysteria theory. The results of this study is to reveals that words, phrases, sentences, emoticons, photos, and videos that represent mass hysteria according to the main classification in affect and symptoms of mass hysteria. The main classification of affect that shows the most symptoms of mass hysteria are Insecurity: disquiet, Security: confidence, Satisfaction: pleasure, and Happiness: cheering. In determining the symptoms of mass hysteria on fans tweets not only based on the lexis and phrases they use, but also based on emoticons, photos, and videos to convey their feelings or reactions to BTS’s events on Twitter. Them this is seen in the way fans participate in the ARMY fandom which not only used the official hashtag from Bighit Entertainment but also produced their own hashtag for BTS and other fans, besides they also made other works such as fan-edit, fan-art, BTS Universe theory, and others. In conclusion, the mass hysteria phenomenon of BTS ARMY fandom is how the fandom tries to express their affection to BTS and to build BTS’ brand on social media. Keywords: mass hysteria, main classification of affect, hysteria in fandom, Twitter fando

Evaluation of adjunctive HPV testing by Hybrid Capture II(® )in women with minor cytological abnormalities for the diagnosis of CIN2/3 and cost comparison with colposcopy

BACKGROUND: As a proportion of high grade cervical intraepithelial neoplasia (CIN2/3) are associated with equivocal cervical smears, which show borderline or mild dyskaryosis, follow up with repeat smears, colposcopy and biopsy is required. Since infection with oncogenic Human Papilloma Virus (HR HPV) has been found to be associated with the development of cervical cancer, HRHPV testing appears to be an alternative. OBJECTIVE: The present study assesses if HRHPV testing can predict CIN2/3 in women referred for mild dyskaryosis and borderline cytological changes in an health authority with a referral policy to colposcopy after one single mild dyskaryotic Pap smear. STUDY DESIGN: The HPV DNA Hybrid Capture II (Digene/Abbott, Maidenhead) was evaluated on 110 consenting women with mild dyskaryosis and 23 women with persistent borderline changes, who were referred for colposcopy between May and November 2001. A cost comparison between two referral policies was performed. RESULTS: CIN2/3 was diagnosed histologically in 30 of 133 women (22%) with minor cytological abnormalities. As the Receiver Operator Characteristics plot suggested a cut-off of 3 pg/ml the HRHPV HCII was evaluated at 3 RLU (relative light units) and at the manufacturer's recommendation of 1 RLU. At both cut-offs sensitivity and negative predictive value were high at 97%. Specificity was low at 37% at a cut-off of 1 pg/ml and 46% at a cut-off of 3 RLU. To remain cost neutral in comparison to immediate colposcopy the costs for one HR HPV HC II must not exceed £34.37 per test at a cut off of 3 pg/ml. CONCLUSION: The negative likelihood ratio (NLR) was of good diagnostic value with 0.089 at 1 RLU and 0.072 at 3 RLU, which reduces the post-test probability for CIN2/3 to 2% in this population. Women with minor cytological disorders can be excluded from colposcopy on a negative HR HPV result. Specificity can be improved by restricting HR HPV testing to women with persistent borderline cytological changes or to women over 30 years

Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain

<p>Abstract</p> <p>Background</p> <p>A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US.</p> <p>Methods</p> <p>During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +.</p> <p>Results</p> <p>Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (<it>p </it>< 0.01).</p> <p>At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions -HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63.1-73.2). The odds ratio for CIN2+ was 45.3 (95% CI: 6.2-333.0), when among ASC-US hrHPV positive women were compared to ASC-US hrHPV negative women.</p> <p>Conclusions</p> <p>Triage of ASC-US with hrHPV testing showed a high sensitivity for the detection of CIN2+ and a high negative predictive value after 3 years of follow-up. The results of this study are in line with the current guidelines for triage of women with ASC-US in the target age range of 25-65. Non adherence to guidelines will lead to unnecessary medical interventions. Further investigation is needed to improve specificity of ASC-US triage.</p

Analysis of genetic copy number changes in cervical disease progression

<p>Abstract</p> <p>Background</p> <p>Cervical dysplasia and tumorigenesis have been linked with numerous chromosomal aberrations. The goal of this study was to evaluate 35 genomic regions associated with cervical disease and to select those which were found to have the highest frequency of aberration for use as probes in fluorescent in-situ hybridization.</p> <p>Methods</p> <p>The frequency of gains and losses using fluorescence in-situ hybridization were assessed in these 35 regions on 30 paraffin-embedded cervical biopsy specimens. Based on this assessment, 6 candidate fluorescently labeled probes (8q24, Xp22, 20q13, 3p14, 3q26, CEP15) were selected for additional testing on a set of 106 cervical biopsy specimens diagnosed as Normal, CIN1, CIN2, CIN3, and SCC. The data were analyzed on the basis of signal mean, % change of signal mean between histological categories, and % positivity.</p> <p>Results</p> <p>The study revealed that the chromosomal regions with the highest frequency of copy number gains and highest combined sensitivity and specificity in high-grade cervical disease were 8q24 and 3q26. The cytological application of these two probes was then evaluated on 118 ThinPrep™ samples diagnosed as Normal, ASCUS, LSIL, HSIL and Cancer to determine utility as a tool for less invasive screening. Using gains of either 8q24 or 3q26 as a positivity criterion yielded specificity (Normal +LSIL+ASCUS) of 81.0% and sensitivity (HSIL+Cancer) of 92.3% based on a threshold of 4 positive cells.</p> <p>Conclusions</p> <p>The application of a FISH assay comprised of chromosomal probes 8q24 and 3q26 to cervical cytology specimens confirms the positive correlation between increasing dysplasia and copy gains and shows promise as a marker in cervical disease progression.</p

Lifestyle and socio-demographic factors associated with high-risk HPV infection in UK women

The world age-standardised prevalence of high-risk HPV (hrHPV) infection among 5038 UK women aged 20–59 years, with a low-grade smear during 1999–2002, assessed for eligibility for TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) was 34.2%. High-risk HPV prevalence decreased with increasing age, from 61% at ages 20–24 years to 14–15% in those over 50 years. The age-standardised prevalence was 15.1, 30.7 and 52.7%, respectively, in women with a current normal, borderline nuclear abnormalities (BNA) and mild smear. In overall multivariate analyses, tertiary education, previous pregnancy and childbirth were associated with reduced hrHPV infection risk. Risk of infection was increased in non-white women, women not married/cohabiting, hormonal contraceptives users and current smokers. In stratified analyses, current smear status and age remained associated with hrHPV infection. Data of this type are relevant to the debate on human papillomavirus (HPV) testing in screening and development of HPV vaccination programmes