Summary Breast and cervical cancers are the commonest cancers diagnosed in women living in low-income and middle-income countries (LMICs), where opportunities for prevention, early detection, or ...both, are few. Yet several cost-effective interventions could be used to reduce the burden of these two cancers in resource-limited environments. Population- wide vaccination against human papillomavirus (HPV) linked to cervical screening, at least once, for adult women has the potential to reduce the incidence of cervical cancer substantially. Strategies such as visual inspection with acetic acid and testing for oncogenic HPV types could make prevention of cervical cancer programmatically feasible. These two cancers need not be viewed as inevitably fatal, and can be cured, particularly if detected and treated at an early stage. Investing in the health of girls and women is an investment in the development of nations and their futures. Here we explore ways to lessen the divide between LMICs and high-income countries for breast and cervical cancers.
Human papillomavirus and cervical cancer Schiffman, Mark, Prof; Castle, Philip E, PhD; Jeronimo, Jose, MD ...
The Lancet (British edition),
09/2007, Letnik:
370, Številka:
9590
Journal Article
Recenzirano
Summary Cervical cancer is the second most common cancer in women worldwide, and knowledge regarding its cause and pathogenesis is expanding rapidly. Persistent infection with one of about 15 ...genotypes of carcinogenic human papillomavirus (HPV) causes almost all cases. There are four major steps in cervical cancer development: infection of metaplastic epithelium at the cervical transformation zone, viral persistence, progression of persistently infected epithelium to cervical precancer, and invasion through the basement membrane of the epithelium. Infection is extremely common in young women in their first decade of sexual activity. Persistent infections and precancer are established, typically within 5–10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35–55 years of age. Each genotype of HPV acts as an independent infection, with differing carcinogenic risks linked to evolutionary species. Our understanding has led to improved prevention and clinical management strategies, including improved screening tests and vaccines. The new HPV-oriented model of cervical carcinogenesis should gradually replace older morphological models based only on cytology and histology. If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings.
Background Differential diagnosis of solid pancreatic masses remains a challenge. EUS elastography, by analyzing tissue stiffness of the mass, may be of help in this setting. Objective To evaluate ...the different elastographic patterns of solid pancreatic masses and the diagnostic accuracy of EUS elastography for malignancy. Design Prospective, consecutive, descriptive study with a second blind evaluation of elastographic patterns for concordance analysis and use of a well-defined reference method for calculation of diagnostic accuracy. Patients This study involved 130 consecutive patients with solid pancreatic masses and 20 controls with normal pancreases. Intervention EUS elastography was performed by using a linear Pentax echoendoscope and Hitachi EUB-8500 US. Main Outcome Measurements Elastographic patterns of solid pancreatic masses and accuracy of the technique for malignancy. Results Mean (SD) size of the masses was 30.9 (12.5) mm. The final diagnosis was malignant tumor in 78 patients, inflammatory mass in 42 patients, and neuroendocrine tumor in 10 patients. Four elastographic patterns were described, with a high concordance among 2 blinded investigators. A green-predominant pattern, either homogeneous or heterogeneous, excluded malignancy with a high accuracy. On the contrary, a blue-predominant pattern, either homogeneous or heterogeneous, supported the diagnosis of malignant tumor. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of EUS elastography for diagnosis of malignancy were 100%, 85.5%, 90.7%, 100%, and 94.0%, respectively. Limitation Single-center study. Conclusion EUS elastography is a useful tool for differential diagnosis of solid pancreatic masses. It provides specific patterns supporting the benign or malignant nature of the disease.
Advances in screening and diagnosis make it increasingly possible to prevent cervical cancer. However, if misused or poorly understood, these new tools will only increase costs and potentially harm ...patients without benefit. As a framework for standardized care that maximizes patient safety and well-being, we propose that a risk model be adopted to guide clinical management now and in the future. The model would use thresholds of increasing risk for cervical precancer and treatable cancer to guide clinical decision making for screening intensity, diagnostic evaluation, or treatment. Experts would decide on these risk thresholds and stratum based on the patient risk to benefit, independent of current (eg, cytology, carcinogenic HPV testing, and colposcopy) and future methods of measuring risk. A risk management model for cervical cancer prevention, based on appropriate clinical actions that correspond to risk stratum, can result in better allocation of resources to and increased safety for women at the greatest risk and increased well-being for women at the lowest risk.
Objective We sought to determine demographic and behavioral factors associated with human papillomavirus (HPV) positivity in a community-based HPV self-collection cervical cancer screening pilot ...project. Study design HPV self-collected samples were obtained from 199 women aged 30-69 years in the impoverished urban Ugandan community of Kisenyi, during September through November 2011. Demographic and behavioral information was collected. Descriptive statistics and a logistic regression model were used to analyze factors associated with HPV positivity. Results There was overwhelming acceptance of HPV self-collection in this community. High-risk HPV prevalence was found to be 17.6%. Lower levels of formal education (adjusted odds ratio AOR, 0.40; 95% confidence interval CI, 0.08–2.03) were associated with higher prevalence of HPV as was use of oral contraception (AOR, 2.01; 95% CI, 0.83–4.90) and human immunodeficiency virus status (AOR, 0.43; 95% CI, 0.14–1.37). Conclusion Screening should be targeted and prioritized for women with lower levels of education, oral contraceptive use, and human immunodeficiency virus positivity as they have the highest HPV prevalence in this low-resource population.
Background Data on the clinical effectiveness of oseltamivir in patients with pandemic 2009 influenza A(H1N1) (AH1N1) virus infection are scarce. We aimed to determine the effect of timing of ...oseltamivir administration on outcomes in hospitalized adults with A(H1N1). Methods Observational analysis of a prospective cohort of adults hospitalized with laboratory-confirmed A(H1N1) was performed at 13 Spanish hospitals. Time from onset of symptoms to oseltamivir administration was the independent variable. Outcomes were duration of fever, hospital length of stay (LOS), need for mechanical ventilation, and mortality during hospitalization. Multivariate logistic regression was used to describe the association between the independent variable and the outcomes. Results Five hundred thirty-eight hospitalized patients with A(H1N1) were studied. The median time from onset of symptoms to oseltamivir administration was 3 days (interquartile range IQR, 2-5 days). With regard to outcomes, the median duration of fever was 2 days (IQR, 1-3 days), the median LOS was 5 days (IQR, 3-8 days), 49 patients (9.1%) underwent mechanical ventilation, and 11 patients (2%) died during hospitalization. In univariate analysis, prolonged duration of fever (above the median), prolonged LOS (above the median), need for mechanical ventilation, and mortality all increased with time to oseltamivir administration (χ2 test for trend P = .001, P ≤ .001, P = .008, and P = .001, respectively). After adjustment for confounding factors, time from onset of symptoms to oseltamivir administration (+ 1-day increase) was associated with a prolonged duration of fever (OR, 1.10; 95% CI, 1.02-1.19), prolonged LOS (OR, 1.07; 95% CI, 1.00-1.15), and higher mortality (OR, 1.20; 95% CI, 1.06-1.35). Conclusions Timely oseltamivir administration has a beneficial effect on outcomes in hospitalized adults with A(H1N1), even in those who are admitted beyond 48 h after onset of symptoms.
Objective Infection with carcinogenic human papillomaviruses (HPVs) is necessary for cervical precancer and cancer, but the effects of type-specific HPV infection on cervical appearance are poorly ...understood. Study Design Twenty expert colposcopists evaluated a total of 939 digitized cervigrams that were obtained during the ASCUS (atypical squamous cells of undetermined significance)-LSIL (low-grade squamous intraepithelial lesion) Triage study after the application of 5% acetic acid. Each reviewer rated the number and severity of lesions in 112 pictures that were matched on histologic diagnoses and HPV typing results so that ≥2 reviewers rated each image. We used standard tests of association and correlation to relate HPV type and visual appearance. Results Pairs of reviewers were significantly ( P < .05) more likely to agree that a definite lesion was present when HPV DNA was found, particularly HPV16, regardless of histologic diagnosis. However, the link between infection status and visual appearance was weak for each individual reviewer. Interestingly, many women with multiple HPV infections had no visible lesions and vice versa. Conclusion HPV16 causes more definite visual abnormalities than other HPV types, regardless of eventual histologic diagnosis. Otherwise, the associations between HPV infection and lesion recognition are weak.
Patients with coronary artery disease may develop not only ischemic events but also heart failure and death due to previous myocardial damage. The purpose of this study was to test the prognostic ...value of a panel of plasma biomarkers related to vascular (monocyte chemoattractant protein-1 MCP-1 and soluble tumor necrosis factor-like weak inducer of apoptosis) and myocardial damage (galectin-3, N-terminal fragment of brain natriuretic peptide NT-proBNP, and neutrophil gelatinase-associated lipocalin) in 706 patients with chronic coronary artery disease followed for 2.2 ± 0.99 years. Secondary outcomes were the incidence of acute ischemic events (ST elevation myocardial infarction, non-ST elevation acute coronary syndrome, stroke, or transient ischemic attack) and death or heart failure. The primary outcome was the combination of the secondary outcomes. Cox proportional hazards model was used for analysis. Fifty-three patients developed acute ischemic events. Increasing MCP-1 plasma levels (p = 0.002), age, and body mass index predicted this outcome independently. Thirty-three patients developed death and/or heart failure. Galectin-3 (p = 0.007), NT-proBNP plasma levels (p = 0.004), hypertension, glomerular filtration rate, and the use of nitrates and anticoagulants were associated with this outcome independently. The development of the primary outcome was predicted independently by MCP-1 (p <0.001), NT-proBNP (p = 0.005), and galectin-3 (p = 0.019); hypertension; atrial fibrillation; and treatment with nitrates. Every biomarker with a value above the median increased the risk of developing this outcome by 1.832 (95% confidence interval 1.356 to 2.474, p <0.001). High-sensitivity C-reactive protein and lipid levels were not associated with any outcome. In conclusion, increasing MCP-1, galectin-3, and NT-proBNP plasma levels are associated with a greater incidence of cardiovascular events.
To demonstrate the usefulness of biologic material obtained from distal embolic protection devices (DEPDs) used in carotid angioplasty for the study of atherosclerosis protein markers and to ...establish the effect of systemic inflammation on the protein expression of carotid atheromatous plaques.
Two-dimensional gel electrophoresis and mass spectrometry were used to study proteins obtained from debris captured in DEPDs from patients who underwent carotid angioplasty. In addition, protein expression obtained from angioplasty samples in patients with different types of systemic inflammation (measured by serum levels of high-sensitivity C-reactive protein CRP with a cutoff value of 3 mg/L) was compared. Finally, immunohistochemistry of atherosclerotic plaques obtained by endarterectomy was used to validate the results obtained using DEPDs.
Proteomic studies were successfully performed using debris from DEPDs. Protein expression differences were found in debris from patients with high systemic inflammation compared with debris from patients with low systemic inflammation. Annexin A5 (ANXA5), haptoglobin precursor, purine nucleoside phosphorylase, transgelin-2 (TAGLN2), and bisphosphoglycerate mutase were upregulated in debris from patients with high systemic inflammation, and proteasome subunit 8 beta type and glutathione-S-transferase kappa 1 (GSTK1) levels were higher in debris from patients with low levels of systemic inflammation.
Atherosclerotic plaque debris captured in DEPDs is a suitable and valid source of material for proteomic studies of atherosclerosis. Protein expression in DEPD debris is affected by systemic inflammation.
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