Performance characteristics of Pap test, VIA, VILI, HR-HPV testing, cervicography, and colposcopy in diagnosis of significant cervical pathology

We sought to evaluate the performance of diagnostic tools to establish an affordable setting for early detection of cervical cancer in developing countries. We compared the performance of different screening tests and their feasibility in a cohort of over 12,000 women: conventional Pap smear, liquid-based cytology, visual inspection with acetic acid (VIA), visual inspection with Iodine solution (VILI), cervicography, screening colposcopy, and high-risk human papillomavirus (HPV) testing (HR-HPV) collected by physician and by self-sampling. HR-HPV assay collected by the physician has the highest sensitivity (80 %), but high unnecessary referrals to colposcopy (15.1 %). HR-HPV test in self-sampling had a markedly lower (57.1 %) sensitivity. VIA, VILI, and cervicography had a poor sensitivity (47.4, 55, and 28.6 %, respectively). Colposcopy presented with sensitivity of 100 % in detecting CIN2+, but the lowest specificity (66.9 %). Co-testing with VIA and VILI Pap test increased the sensitivity of stand-alone Pap test from 71.6 to 87.1 % and 71.6 to 95 %, respectively, but with high number of unnecessary colposcopies. Co-testing with HR-HPV importantly increased the sensitivity of Pap test (to 86 %), but with high number of unnecessary colposcopies (17.5 %). Molecular tests adjunct to Pap test seems a realistic option to improve the detection of high-grade lesions in population-based screening programs.

Home-based urinary HPV DNA testing in women who do not attend cervical cancer screening clinics

International audience

Dust sampling and laboratory testing procedures after underground coal mine explosions /

"June 1996."

Good agreements between self and clinician-collected specimens for the detection of human papillomavirus in Brazilian patients

Women infected with human papillomavirus (HPV) are at a higher risk of developing cervical lesions. In the current study, self and clinician-collected vaginal and cervical samples from women were processed to detect HPV DNA using polymerase chain reaction (PCR) with PGMY09/11 primers. HPV genotypes were determined using type-specific PCR. HPV DNA detection showed good concordance between self and clinician-collected samples (84.6%; kappa = 0.72). HPV infection was found in 30% women and genotyping was more concordant among high-risk HPV (HR-HPV) than low-risk HPV (HR-HPV). HPV16 was the most frequently detected among the HR-HPV types. LR-HPV was detected at a higher frequency in self-collected; however, HR-HPV types were more frequently identified in clinician-collected samples than in self-collected samples. HPV infections of multiple types were detected in 20.5% of clinician-collected samples and 15.5% of self-collected samples. In this study, we demonstrated that the HPV DNA detection rate in self-collected samples has good agreement with that of clinician-collected samples. Self-collected sampling, as a primary prevention strategy in countries with few resources, could be effective for identifying cases of HR-HPV, being more acceptable. The use of this method would enhance the coverage of screening programs for cervical cancer.

TESTING THE JOINT ROLES OF CAREER DECISION SELF-EFFICACY AND PERSONALITY TRAITS IN THE PREDICTION OF CAREER INDECISION

Career decision-making self-efficacy and the Big Five traits of neuroticism, extraversion, and conscientiousness were examined as predictors of career indecision in a sample of 181 undergraduates. Participants completed an online survey. I predicted that the Big Five traits and career decision-making self-efficacy would (a) interrelate moderately and (b) each relate significantly and moderately to career indecision. In addition, I predicted that career decision-making self-efficacy would partially mediate the relationships between the Big Five traits and career indecision, while the Big Five traits were predicted to moderate the relationship between career decision-making self-efficacy and career indecision. Finally, I predicted that career decision-making self-efficacy would account for a greater amount of unique variance in career indecision than the Big Five traits. All predicted correlations were significant. Career decision-making self-efficacy fully mediated the relationship of Extraversion to career indecision and partially mediated the relationships of Neuroticism and Conscientiousness to career indecision. Conscientiousness was found to moderate the relationship of career decision-making self-efficacy to career indecision such that the negative relation between self-efficacy and career indecision was stronger in the presence of high conscientiousness. This study builds upon existing research on the prediction of career indecision by examining potential mediating and moderating relationships.

Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.

Cervical screening programme: HPV triage and test of cure protocol

Testing for high-risk human papillomavirus (HR-HPV) as triage and test of cure was introduced into the Northern Ireland Cervical Screening Programme on Monday 28 January 2013. This policy change will significantly alter the screening pathway for women with a mild dyskaryosis or borderline smear result. The link between HR-HPV infection and the development of cervical cancer has now been clearly established, with almost 100% of cervical cancers containing HPV DNA. Women with no evidence of HR-HPV infection are extremely unlikely to develop cervical cancer in the short to medium term. HPV triage is the process whereby HR-HPV testing is used to manage women with low grade cervical abnormalities. Only 15-20% of women with a borderline or mild smear result have a significant abnormality that needs treatment. HR-HPV testing is effective in identifying which women may need treatment and allows colposcopy resources to be allocated more effectively.The test of cure process is being introduced because it is now known that women with a normal or low grade smear test, and who are HR-HPV negative at six months after treatment, are at very low risk of residual disease. These women do not need to be recalled for another screening appointment for three years.The test of cure process means all post-treatment smears (at six months) that are reported as normal, borderline or mild dyskaryosis will be tested for HR-HPV. Those women who are HR-HPV positive will remain at colposcopy. HR-HPV negative women can be safely returned to recall in three years. It is estimated that the HR-HPV test of cure will allow approximately 80% of women who have been through treatment to avoid undergoing annual smear tests. This flowchart poster outlines the new triage and test of cure process. It was distributed to all GPs in Northern Ireland and is available to download as a PDF from this website.�

Cigarette smoking and high-risk HPV DNA as predisposing factors for high-grade cervical intraepithelial neoplasia (CIN) in young Brazilian women

Background. This cross-sectional study was designed to evaluate the role of cigarette smoking and high-risk HPV types as risk factors of CIN 2 and 3 in young, sexually active Brazilian women. Materials and method. A series of 100 consecutive women with abnormal Pap smears were recruited, subjected to colposcopy, punch biopsy, and questionnaire for their social, sexual and reproductive factors. Of these, 77 women between 20 and 35 years of age (median 26.5 years) with biopsy-confirmed CIN 1 or CIN 2 and 3, were enrolled in this study. Representative samples from the exocervix and endocervix were obtained for HPV testing with the Hybrid Capture HPV-DNA assay, including the probes for the oncogenic HPV types (16, 18, 31, 33, 35, 45, 51, 52 and 56). Results. The overall rate of CIN 2 and 3 was 23/77 (29.8%). The women with CIN 1, 2 and 3 did not differ from each other with regard to their age, race, schooling, marital status, life-time number of sexual partners, age at first intercourse, use of oral contraceptives, or parity. However, current cigarette smoking was strongly associated with CIN 2 and 3 (p < 0,001), and among smokers, the risk of high-grade CIN increased in parallel with the time of exposure (years of smoking) p = 0.07), HPV-DNA of the oncogenic types was detected in 43 (56%) women, the risk of being HPV DNA-positive was significantly higher in CIN 2 and 3 as compared with CIN 1 (p = 0.037). Importantly, the prevalence of high-risk HPV types was significantly higher in cigarette smokers than in non-smokers (p = 0.046). Conclusions. The results indicate that the severity of CIN lesions was clearly related to two fundamental risk factors: 1) high-risk HPV types, and 2) current cigarette smoking. These two risk factors were closely interrelated in that the high-risk HPV types were significantly more frequent in current smokers than in non-smokers, suggesting the possibility of a synergistic action between these two risk factors in cervical carcinogenesis.

Implementing Human Papillomavirus Testing in a Public Health Hospital: Challenges and Opportunities

Objectives: Robust evidence now supports human papillomavirus (HPV) testing as a more effective option to screening and as more sensitive than cytology in detecting high-grade cervical intraepithelial neoplasia. Our goal was to analyze the performance of the Hybrid Capture II (HC2) assay for high-risk HPV (hrHPV) in women undergoing gynecological examination at a public health hospital as part of the evaluation of HPV screening as an alternative or complement to cytology. Study Design: This analysis is a subset of a cross-sectional study carried out at a large public hospital serving a predominantly low-resource population. A total of 705 women were enrolled; the sensitivity and specificity of each test were estimated and compared. Results: The analysis identified 272 hrHPV-positive women (mean age 36.3 years) and 433 hrHPV-negative women (mean age 41.2 years). HPV testing showed a significantly increased sensitivity of the HC2 assay versus cytology (84.5 vs. 69.7%; p < 0.0001) but a lower specificity (49.90 vs. 88.78%; p < 0.0001). Conclusion: The combination of both methods seems to be useful in improving detection of cervical lesions. Copyright (C) 2012 S. Karger AG, Basel

Brain sources of EEG gamma frequency during volitionally meditation-induced, altered states of consciousness, and experience of the self.

Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG 'gamma' (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal populations were active. The brain areas predominantly involved during the self-induced meditation states aiming at visualization (right posterior) and verbalization (left central) agreed with known brain functional neuroanatomy. The brain areas involved in the self-induced, meditational dissolution and reconstitution of the experience of the self (right fronto-temporal) are discussed in the context of neural substrates implicated in normal self-representation and reality testing, as well as in depersonalization disorders and detachment from self after brain lesions.

Predictors of participation in genetic testing for hereditary breast and ovarian cancer

Up to 10% of all breast and ovarian cancers are attributable to mutations in cancer susceptibility genes. Clinical genetic testing for deleterious gene mutations that predispose to hereditary breast and ovarian cancer (HBOC) syndrome is available. Mutation carriers may benefit from following high-risk guidelines for cancer prevention and early detection; however, few studies have reported the uptake of clinical genetic testing for HBOC. This study identified predictors of HBOC genetic testing uptake among a case series of 268 women who underwent genetic counseling at The University of Texas M. D. Anderson Cancer Center from October, 1996, through July, 2000. Women completed a baseline questionnaire that measured psychosocial and demographic variables. Additional medical characteristics were obtained from the medical charts. Logistic regression modeling identified predictors of participation in HBOC genetic testing. Psychological variables were hypothesized to be the strongest predictors of testing uptake—in particular, one's readiness (intention) to have testing. Testing uptake among all women in this study was 37% (n = 99). Contrary to the hypotheses, one's actual risk of carrying a BRCA1 or BRCA2 gene mutation was the strongest predictor of testing participation (OR = 15.37, CI = 5.15, 45.86). Other predictors included religious background, greater readiness to have testing, knowledge about HBOC and genetic testing, not having female children, and adherence to breast self-exam. Among the subgroup of women who were at ≥10% risk of carrying a mutation, 51% (n = 90) had genetic testing. Consistent with the hypotheses, predictors of testing participation in the high-risk subgroup included greater readiness to have testing, knowledge, and greater self-efficacy regarding one's ability to cope with test results. Women with CES-D scores ≥16, indicating the presence of depressive symptoms, were less likely to have genetic testing. Results indicate that among women with a wide range of risk for HBOC, actual risk of carrying an HBOC-predisposing mutation may be the strongest predictor of their decision to have genetic testing. Psychological variables (e.g., distress and self-efficacy) may influence testing participation only among women at highest risk of carrying a mutation, for whom genetic testing is most likely to be informative. ^

Testing of Interposer-Based 2.5D Integrated Circuits

The unprecedented and relentless growth in the electronics industry is feeding the demand for integrated circuits (ICs) with increasing functionality and performance at minimum cost and power consumption. As predicted by Moore's law, ICs are being aggressively scaled to meet this demand. While the continuous scaling of process technology is reducing gate delays, the performance of ICs is being increasingly dominated by interconnect delays. In an effort to improve submicrometer interconnect performance, to increase packing density, and to reduce chip area and power consumption, the semiconductor industry is focusing on three-dimensional (3D) integration. However, volume production and commercial exploitation of 3D integration are not feasible yet due to significant technical hurdles.

At the present time, interposer-based 2.5D integration is emerging as a precursor to stacked 3D integration. All the dies and the interposer in a 2.5D IC must be adequately tested for product qualification. However, since the structure of 2.5D ICs is different from the traditional 2D ICs, new challenges have emerged: (1) pre-bond interposer testing, (2) lack of test access, (3) limited ability for at-speed testing, (4) high density I/O ports and interconnects, (5) reduced number of test pins, and (6) high power consumption. This research targets the above challenges and effective solutions have been developed to test both dies and the interposer.

The dissertation first introduces the basic concepts of 3D ICs and 2.5D ICs. Prior work on testing of 2.5D ICs is studied. An efficient method is presented to locate defects in a passive interposer before stacking. The proposed test architecture uses e-fuses that can be programmed to connect or disconnect functional paths inside the interposer. The concept of a die footprint is utilized for interconnect testing, and the overall assembly and test flow is described. Moreover, the concept of weighted critical area is defined and utilized to reduce test time. In order to fully determine the location of each e-fuse and the order of functional interconnects in a test path, we also present a test-path design algorithm. The proposed algorithm can generate all test paths for interconnect testing.

In order to test for opens, shorts, and interconnect delay defects in the interposer, a test architecture is proposed that is fully compatible with the IEEE 1149.1 standard and relies on an enhancement of the standard test access port (TAP) controller. To reduce test cost, a test-path design and scheduling technique is also presented that minimizes a composite cost function based on test time and the design-for-test (DfT) overhead in terms of additional through silicon vias (TSVs) and micro-bumps needed for test access. The locations of the dies on the interposer are taken into consideration in order to determine the order of dies in a test path.

To address the scenario of high density of I/O ports and interconnects, an efficient built-in self-test (BIST) technique is presented that targets the dies and the interposer interconnects. The proposed BIST architecture can be enabled by the standard TAP controller in the IEEE 1149.1 standard. The area overhead introduced by this BIST architecture is negligible; it includes two simple BIST controllers, a linear-feedback-shift-register (LFSR), a multiple-input-signature-register (MISR), and some extensions to the boundary-scan cells in the dies on the interposer. With these extensions, all boundary-scan cells can be used for self-configuration and self-diagnosis during interconnect testing. To reduce the overall test cost, a test scheduling and optimization technique under power constraints is described.

In order to accomplish testing with a small number test pins, the dissertation presents two efficient ExTest scheduling strategies that implements interconnect testing between tiles inside an system on chip (SoC) die on the interposer while satisfying the practical constraint that the number of required test pins cannot exceed the number of available pins at the chip level. The tiles in the SoC are divided into groups based on the manner in which they are interconnected. In order to minimize the test time, two optimization solutions are introduced. The first solution minimizes the number of input test pins, and the second solution minimizes the number output test pins. In addition, two subgroup configuration methods are further proposed to generate subgroups inside each test group.

Finally, the dissertation presents a programmable method for shift-clock stagger assignment to reduce power supply noise during SoC die testing in 2.5D ICs. An SoC die in the 2.5D IC is typically composed of several blocks and two neighboring blocks that share the same power rails should not be toggled at the same time during shift. Therefore, the proposed programmable method does not assign the same stagger value to neighboring blocks. The positions of all blocks are first analyzed and the shared boundary length between blocks is then calculated. Based on the position relationships between the blocks, a mathematical model is presented to derive optimal result for small-to-medium sized problems. For larger designs, a heuristic algorithm is proposed and evaluated.

In summary, the dissertation targets important design and optimization problems related to testing of interposer-based 2.5D ICs. The proposed research has led to theoretical insights, experiment results, and a set of test and design-for-test methods to make testing effective and feasible from a cost perspective.

Cervical screening: Frequently asked questions (FAQs)

Testing for high-risk human papillomavirus (HR-HPV) as triage and test of cure was introduced into the Northern Ireland Cervical Screening Programme on Monday 28 January 2013. This policy change will significantly alter the screening pathway for women with a mild dyskaryosis or borderline smear result. The link between HR-HPV infection and the development of cervical cancer has now been clearly established, with almost 100% of cervical cancers containing HPV DNA. Women with no evidence of HR-HPV infection are extremely unlikely to develop cervical cancer in the short to medium term. HPV triage is the process whereby HR-HPV testing is used to manage women with low grade cervical abnormalities. Only 15-20% of women with a borderline or mild smear result have a significant abnormality that needs treatment. HR-HPV testing is effective in identifying which women may need treatment and allows colposcopy resources to be allocated more effectively. The test of cure process is being introduced because it is now known that women with a normal or low grade smear test, and who are HR-HPV negative at six months after treatment, are at very low risk of residual disease. These women do not need to be recalled for another screening appointment for three years. The test of cure process means all post-treatment smears (at six months) that are reported as normal, borderline or mild dyskaryosis will be tested for HR-HPV. Those women who are HR-HPV positive will remain at colposcopy. HR-HPV negative women can be safely returned to recall in three years. It is estimated that the HR-HPV test of cure will allow approximately 80% of women who have been through treatment to avoid undergoing annual smear tests. These FAQs answer the most common and important queries in relation to HPV and the new screening process, and were distributed to all GPs in Northern Ireland. They can be downloaded as a PDF from this website.