Summary Investments in cancer control—prevention, detection, diagnosis, surgery, other treatment, and palliative care—are increasingly needed in low-income and particularly in middle-income ...countries, where most of the world's cancer deaths occur without treatment or palliation. To help countries expand locally appropriate services, Cancer (the third volume of nine in Disease Control Priorities , 3rd edition) developed an essential package of potentially cost-effective measures for countries to consider and adapt. Interventions included in the package are: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioids. These interventions would cost an additional US$20 billion per year worldwide, constituting 3% of total public spending on health in low-income and middle-income countries. With implementation of an appropriately tailored package, most countries could substantially reduce suffering and premature death from cancer before 2030, with even greater improvements in later decades.
Summary Background Despite preventive vaccines for oncogenic human papillomaviruses (HPVs), cervical intraepithelial neoplasia (CIN) is common, and current treatments are ablative and can lead to ...long-term reproductive morbidity. We assessed whether VGX-3100, synthetic plasmids targeting HPV-16 and HPV-18 E6 and E7 proteins, delivered by electroporation, would cause histopathological regression in women with CIN2/3. Methods Efficacy, safety, and immunogenicity of VGX-3100 were assessed in CIN2/3 associated with HPV-16 and HPV-18, in a randomised, double-blind, placebo-controlled phase 2b study. Patients from 36 academic and private gynaecology practices in seven countries were randomised (3:1) to receive 6 mg VGX-3100 or placebo (1 mL), given intramuscularly at 0, 4, and 12 weeks. Randomisation was stratified by age (<25 vs ≥25 years) and CIN2 versus CIN3 by computer-generated allocation sequence (block size 4). Funder and site personnel, participants, and pathologists were masked to treatment. The primary efficacy endpoint was regression to CIN1 or normal pathology 36 weeks after the first dose. Per-protocol and modified intention-to-treat analyses were based on patients receiving three doses without protocol violations, and on patients receiving at least one dose, respectively. The safety population included all patients who received at least one dose. The trial is registered at ClinicalTrials.gov (number NCT01304524 ) and EudraCT (number 2012-001334-33). Findings Between Oct 19, 2011, and July 30, 2013, 167 patients received either VGX-3100 (n=125) or placebo (n=42). In the per-protocol analysis 53 (49·5%) of 107 VGX-3100 recipients and 11 (30·6%) of 36 placebo recipients had histopathological regression (percentage point difference 19·0 95% CI 1·4–36·6; p=0·034). In the modified intention-to-treat analysis 55 (48·2%) of 114 VGX-3100 recipients and 12 (30·0%) of 40 placebo recipients had histopathological regression (percentage point difference 18·2 95% CI 1·3–34·4; p=0·034). Injection-site reactions occurred in most patients, but only erythema was significantly more common in the VGX-3100 group (98/125, 78·4%) than in the placebo group (24/42, 57·1%; percentage point difference 21·3 95% CI 5·3–37·8; p=0·007). Interpretation VGX-3100 is the first therapeutic vaccine to show efficacy against CIN2/3 associated with HPV-16 and HPV-18. VGX-3100 could present a non-surgical therapeutic option for CIN2/3, changing the treatment outlook for this common disease. Funding Inovio Pharmaceuticals.
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.
Treatment of cancer in sub-Saharan Africa Kingham, T Peter, Dr; Alatise, Olusegun I, MD; Vanderpuye, Verna, MD ...
The lancet oncology,
04/2013, Letnik:
14, Številka:
4
Journal Article
Recenzirano
Summary Cancer is rapidly becoming a public health crisis in low-income and middle-income countries. In sub-Saharan Africa, patients often present with advanced disease. Little health-care ...infrastructure exists, and few personnel are available for the care of patients. Surgeons are often central to cancer care in the region, since they can be the only physician a patient sees for diagnosis, treatment (including chemotherapy), and palliative care. Poor access to surgical care is a major impediment to cancer care in sub-Saharan Africa. Additional obstacles include the cost of oncological care, poor infrastructure, and the scarcity of medical oncologists, pathologists, radiation oncologists, and other health-care workers who are needed for cancer care. We describe treatment options for patients with cancer in sub-Saharan Africa, with a focus on the role of surgery in relation to medical and radiation oncology, and argue that surgery must be included in public health efforts to improve cancer care in the region.
HPV-based screen and treat is the recommended approach for cervical cancer screening in low-resource settings, but quite low specificity of human papillomavirus (HPV) testing, particularly in women ...living with HIV, leads to overtreatment. We evaluated whether HPV type restriction and more stringent cutoffs on Xpert HPV optimise performance characteristics of this assay for screen and treat.
We recruited HIV-negative and HIV-positive women aged 30–65 years from a primary care facility and a referral colposcopy clinic in Cape Town, South Africa. Women included had no history of any anogenital cancer or treatment for cervical dysplasia, had no hysterectomy, and were not pregnancy at the time of recruitment. All women had cervical samples collected for Xpert HPV (an assay that detects high-risk HPV types in five channels: HPV type 16; HPV types 18 or 45, or both; HPV types 31, 33, 35, 52, or 58, or more than one of these types; HPV types 51 or 59, or both; and HPV types 39, 56, 66, or 68, or more than one of these types) and underwent colposcopy and histological sampling with consensus pathology review. Logistic regression and receiver operating characteristic curves were used to evaluate improvements in specificity attained by modifying cycle threshold cutoffs to define screen-positive results.
We recruited 1121 women aged 30–65 years, 586 of whom were HIV-negative and 535 HIV-positive. Sensitivity of detecting cervical intraepithelial neoplasia grade 2 or greater in HIV-negative women using manufacturer-defined cycle threshold cutoffs for all channels was 88·7% (95% CI 83·1–94·3), and specificity was 86·9% (83·4–90·4). Sensitivity was 93·6% (90·0–97·3) and specificity 59·9% (54·1–65·7) in HIV-positive women. Cycle threshold values from channels detecting HPV type 16, HPV types 18 or 45 (or both), and HPV types 31, 33, 35, 52, or 58 (or more than one of these types) were informative to predict cervical intraepithelial neoplasia grade 2 or greater. Shifting cycle threshold cutoffs on these three channels allowing sensitivity to decline to 75–85%, led to specificities of 91·3–95·3% in HIV-negative women and 77·0–85·8% in HIV-positive women.
More stringent cycle threshold cutoffs on selected channels in Xpert HPV improve specificity with only modest losses in sensitivity, making this assay an optimal choice for HPV-based screen and treat in settings with a high prevalence of HIV. These modifications can be made from standard output with no need for new engineering. Decision making about performance characteristics of HPV testing can be shifted to programme implementers and cutoffs selected according to resource availability and community preferences.
Supported by the National Cancer Institute UH2/3 CA189908.
This Atlas offers concrete diagnostic guidance for anatomic pathologists who are required to correctly identify cervical disease in cytology. It not only illustrates the cytomorphology of cervical ...specimens, but specifically presents and contrasts common problem areas that can lead to erroneous interpretation. Clearly and concisely written by leaders in the field, this volume in the series is a practical desk reference for all facets of the diagnostically challenging area of cervical cytopathology.
The Atlas contains over 500 carefully selected high-resolution color images detailing important aspects of gynecologic tract disease. Additionally, the book's images of the histopathology and characteristics of lesions provide morphologic correlations that will be of interest to cytopathologists and surgical pathologists alike. To provide a broader perspective, the Atlas features a special chapter on the colposcopic characteristics of surgical lesions to provide a differential diagnosis through the eyes of an experienced gynecologist. It also reviews the updated management guidelines of the American Society for Colposcopy and Cervical Pathology, providing a multidisciplinary approach to enhance the reader's understanding of how cytopathology, histopathology, and colposcopy together create a powerful tool for the prevention of cervical cancer.
Key Features of An Atlas of Gynecologic Cytopathology with Histopathologic Correlations:
Provides practical, expert diagnostic guidance for the full range of gynecologic cytopathology
Illuminates common diagnostic pitfalls
Presents over 500 high-resolution color images
Includes colposcopic-pathologic correlations from an expert gynecologist
Reviews updated ASCCP guidelines emphasizing a multidisciplinary management approach
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