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Find video protocols related to scientific articles indexed in Pubmed.
Altered phenotype and function of NK cells infiltrating human papillomavirus (HPV)-associated genital warts during HIV infection.
Clin. Immunol.
PUBLISHED: 01-21-2014
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HIV-infected individuals experience more persistent HPV infections and are less likely to resolve genital warts. This study compared phenotype and functions of NK and T cells from genital warts and blood from 67 women. We compared in vitro functional responses of NK and T cells by multiparametric flow cytometry. HIV+ women had significantly lower frequencies of CD4 T cells in warts (p = 0.001) and blood (p = 0.001). While the distribution of NK cell subsets was similar, HIV+ women tended to have lower frequencies of CD56(Dim) NK cells in both blood (p = 0.0001) and warts (p = 0.006) than HIV- women. Wart NK cells from HIV+ women expressed significantly lower CD107a and produced IFN-?. HAART status was not associated with differences in NK cell functionality. We conclude that wart NK cells from HIV+ women have defects in their ability to degranulate and/or secrete IFN-?, which may provide insights into why HIV+ women fail to spontaneously resolve genital warts.
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Distribution of Human Papillomavirus Genotypes among HIV-Positive and HIV-Negative Women in Cape Town, South Africa.
Front Oncol
PUBLISHED: 01-01-2014
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HIV-positive women are known to be at high-risk of human papillomavirus (HPV) infection and its associated cervical pathology. Here, we describe the prevalence and distribution of HPV genotypes among HIV-positive and -negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN).
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Comprehensive control of human papillomavirus infections and related diseases.
Vaccine
PUBLISHED: 12-17-2013
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Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph Comprehensive Control of HPV Infections and Related Diseases Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters.
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Trials and projects on cervical cancer and human papillomavirus prevention in sub-saharan Africa.
Vaccine
PUBLISHED: 12-17-2013
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Cervical cancer is the leading cause of cancer morbidity and mortality in women in sub-Saharan Africa (SSA), accounting for about 50,000 deaths annually. Until recently, cytology was the gold standard for screening and prevention of cervical cancer. This method of screening has not been successful in SSA due to a lack of human, financial and material resources and poor health care infrastructure. It is estimated that less than 5% of at risk women have ever being screened. In the past two decades alternative approaches to cytology for cervical cancer screening have been evaluated in low- and medium-income countries. Visual inspection with acetic acid (VIA) and/or Lugols iodine (VILI) have been shown to have adequate sensitivity, although low specificity, in a number of cross-sectional research and demonstration projects. Visual inspection methods require minimal resources, are technologically accessible, and are feasible for screening for precancerous lesions. Linking screening with VIA/VILI to treatment with cryotherapy may enable screening and treatment to take place in one visit, but this is likely to result in large numbers of women being subjected to unnecessary treatment. A number of studies have shown that cryotherapy is not associated with significant side effects or complications and is well tolerated. Creating the infrastructure for screening of older women is considered desirable, despite the limitations of visual inspection methods as screening tests. Understanding the role of human papillomavirus (HPV) infection in the etiology of cervical cancer and the discovery of HPV rapid test kits, as well as the development of vaccines against the HPV oncogenic types, have created new opportunities for prevention of cervical cancer. Trials and projects have established (and are still ongoing) the feasibility of using these molecular tests for screening. The ultimate in prevention method is primary prevention, offered by the advent of prophylactic vaccines against the most important oncogenic types, namely HPV16 and 18. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Sub-Saharan Africa Region" Vaccine Volume 31, Supplement 5, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
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Infrastructure requirements for human papillomavirus vaccination and cervical cancer screening in sub-saharan Africa.
Vaccine
PUBLISHED: 12-17-2013
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The availability of both human papillomavirus (HPV) vaccination and alternative screening tests has greatly improved the prospects of cervical cancer prevention in sub-Saharan African (SSA) countries. The inclusion of HPV vaccine in the portfolio of new vaccines offered by the Gobal Alliance for Vaccines and Immunization (GAVI) to GAVI-eligible countries has vastly improved the chances of introducing HPV vaccination. Further investments to improve vaccine storage, distribution and delivery infrastructure and human resources of the Extended Programme of Immunization will substantially contribute to the faster introduction of HPV vaccination in SSA countries through both school- and campaign-based approaches. Alternative methods to cytology for the prevention of cervical cancer through the early detection and treatment of cervical cancer precursors have been extensively evaluated in the past 15 years, in Africa as well as in other low-resource settings. Visual inspection with 3-5% dilute acetic acid (VIA) and HPV testing are the two alternative screening methods that have been most studied, in both cross-sectional and randomised clinical trials. VIA is particularly suitable to low-resource settings; however, its efficacy in reducing cervical cancer is likely to be significantly lower than HPV testing. The introduction of VIA screening programmes will help develop the infrastructure that will, in turn, facilitate the introduction of affordable HPV testing in future. Links with the existing HIV/AIDS control programmes is another strategy to improve the infrastructure and screening services in SSA. Infrastructural requirements for an integrated approach aiming to vaccinate single-year cohorts of girls in the 9-13 years age-range and to screen women over 30 years of age using VIA or affordable rapid HPV tests are outlined in this manuscript. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Sub-Saharan Africa Region" Vaccine Volume 31, Supplement 5, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
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The burden of human papillomavirus infections and related diseases in sub-saharan Africa.
Vaccine
PUBLISHED: 12-17-2013
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Despite the scarcity of high quality cancer registries and lack of reliable mortality data, it is clear that human papillomavirus (HPV)-associated diseases, particularly cervical cancer, are major causes of morbidity and mortality in sub-Saharan Africa (SSA). Cervical cancer incidence rates in SSA are the highest in the world and the disease is the most common cause of cancer death among women in the region. The high incidence of cervical cancer is a consequence of the inability of most countries to either initiate or sustain cervical cancer prevention services. In addition, it appears that the prevalence of HPV in women with normal cytology is higher than in more developed areas of the world, at an average of 24%. There is, however, significant regional variation in SSA, with the highest incidence of HPV infection and cervical cancer found in Eastern and Western Africa. It is expected that, due to aging and growth of the population, but also to lack of access to appropriate prevention services and the concomitant human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic, cervical cancer incidence and mortality rates in SSA will rise over the next 20 years. HPV16 and 18 are the most common genotypes in cervical cancer in SSA, although other carcinogenic HPV types, such as HPV45 and 35, are also relatively more frequent compared with other world regions. Data on other HPV-related anogenital cancers including those of the vulva, vagina, anus, and penis, are limited. Genital warts are common and associated with HPV types 6 and 11. HIV infection increases incidence and prevalence of all HPV-associated diseases. Sociocultural determinants of HPV-related disease, as well as the impact of forces that result in social destabilization, demand further study. Strategies to reduce the excessive burden of HPV-related diseases in SSA include age-appropriate prophylactic HPV vaccination, cervical cancer prevention services for women of the reproductive ages, and control of HIV/AIDS. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in the Sub-Saharan Africa Region" Vaccine Volume 31, Supplement 5, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
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Comprehensive control of human papillomavirus infections and related diseases.
Vaccine
PUBLISHED: 12-17-2013
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Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph Comprehensive Control of HPV Infections and Related Diseases Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters.
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Comprehensive control of human papillomavirus infections and related diseases.
Vaccine
PUBLISHED: 11-16-2013
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Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph Comprehensive Control of HPV Infections and Related Diseases Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters.
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Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study.
Vaccine
PUBLISHED: 05-30-2013
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In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18-25 years (N=120) were stratified by CD4? T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline Vaccines) or placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4? T-cell responses, CD4? T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4? T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4? T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4? T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection. Study ID: 107863/NCT00586339.
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Treatment of cancer in sub-Saharan Africa.
Lancet Oncol.
PUBLISHED: 04-09-2013
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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.
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Challenges and opportunities in cancer control in Africa: a perspective from the African Organisation for Research and Training in Cancer.
Lancet Oncol.
PUBLISHED: 04-09-2013
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Sub-Saharan Africa has a disproportionate burden of disease and faces a major public-health challenge from non-communicable diseases. Although infectious diseases continue to afflict Africa, the proportion of the overall disease burden in sub-Saharan Africa attributable to cancer is rising. The region is predicted to have a greater than 85% increase in cancer burden by 2030. Approaches to minimise the burden of cancer in sub-Saharan Africa in the past few years have had little success because of low awareness of the cancer burden and a poor understanding of the potential for cancer prevention. Success will not be easy, and will need partnerships and bridges to be built across countries, economies, and professions. A strategic approach to cancer control in sub-Saharan Africa is needed to build on what works there and what is unique to the region. It should ideally be situated within strong, robust, and sustainable health-care systems that offer quality health care to all people, irrespective of their social or economic standing. However, to achieve this will need new leadership, critical thinking, investment, and understanding. We discuss the present situation in sub-Saharan Africa and propose ideas to advance cancer control in the region, including the areas of cancer awareness, advocacy, research, workforce, care, training, and funding.
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Sexual and reproductive health and HIV services: integrating HIV/AIDS and cervical cancer prevention and control.
Int J Gynaecol Obstet
PUBLISHED: 03-08-2013
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People living with HIV are at an increased risk of acquiring HPV and of developing evolutive cervical cancers (women) and penile and anal cancers (men). Low-cost screening-visual inspection with acetic acid, HPV DNA diagnostics and primary care level treatment, cryotherapy for cervical intraepithelial neoplasia (CIN 2), and primary prevention through HPV vaccination of girls aged 9-13 years-makes the goal of eliminating cervical cancer possible in the long term. Integration of cervical cancer screening and treatment into a sexual and reproductive health service package raises programmatic questions and calls for a continuum of care. The latter is only possible when adequate cytopathology skills and treatment for advanced cancer conditions are available. The present paper highlights the role of member societies of the International Federation of Gynecology and Obstetrics (FIGO) in developing the base for an integrated package that responds to womens sexual and reproductive health needs.
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Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa.
Int. J. Cancer
PUBLISHED: 02-04-2013
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In sub-Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross-sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtained from women aged ?21 years with lesions clinically suggestive of ICC. Histopathological diagnosis of ICC was determined by light microscopy examination of hematoxylin and eosin stained sections of paraffin-embedded cervical specimens; samples with a confirmed histopathological diagnosis underwent HPV DNA testing by polymerase chain reaction. HPV-positive specimens were typed by reverse hybridization line probe assay. Between October 2007 and March 2010, cervical specimens from 659 women were collected (167 in Ghana, 192 in Nigeria and 300 in South Africa); 570 cases were histologically confirmed as ICC. The tumor type was identified in 551/570 women with ICC; squamous cell carcinoma was observed in 476/570 (83.5%) cases. The HPV-positivity rate in ICC cases was 90.4% (515/570). In ICC cases with single HPV infection (447/515 [86.8%]), the most commonly detected HPV types were HPV16 (51.2%), HPV18 (17.2%), HPV35 (8.7%), HPV45 (7.4%), HPV33 (4.0%) and HPV52 (2.2%). The prevalence of single and multiple HPV infections seemed higher among HIV-positive women and HPV type distribution appeared to differ according to tumor type and HIV status. In conclusion, HPV16, 18, 45 and 35 were the most common HPV types in sub-Saharan African women with ICC and HPV infections were more common in HIV-positive women.
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HIV-specific T-cell responses detected in the genital tract of chronically HIV-infected women are largely monofunctional.
Immunology
PUBLISHED: 01-16-2013
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HIV-specific T cells that produce interferon-? (IFN-?) are present in the genital tract of HIV-infected women although these do not provide protection against genital HIV shedding. Because polyfunctional HIV-specific T cells have been implicated in better HIV control than those with a single function, this study aimed to investigate whether polyfunctional T cells were present at the female genital mucosa. Cervical cytobrush-derived T cells were obtained from chronically HIV-infected women and compared with blood. CD3(+) T cells from both compartments were expanded with Dynal anti-CD3/CD28 expander beads for 14 days and flow cytometry was used to evaluate four T-cell functions (CD107a, IFN-?, tumour necrosis factor-? and macrophage inflammatory protein-1?) from 16 women. The majority of Gag-specific T-cell responses in the female genital tract were monofunctional, although low frequencies of HIV Gag-specific polyfunctional CD8(+) T cells were detected at the cervix in 81·3% (13/16) of women. The ability of CD8(+) T cells at both the cervix and in blood to express CD107a and to exhibit polyfunctional responses (two or more functions) following Gag stimulation was inversely associated with plasma viral load and positively associated with blood CD4 counts, suggesting that clinical status impacted on the functionality of HIV-specific T cells at the mucosa, in a similar way to blood. HIV Gag-specific cervical T cells were largely monofunctional. Polyfunctional T cells were detected at the cervix in women with high blood CD4 count and low plasma viral load but these did not protect from HIV genital shedding.
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Gestational trophoblastic neoplasia and human immunodeficiency virus infection: a 10-year review.
Int. J. Gynecol. Cancer
PUBLISHED: 10-15-2011
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The objective of the study was to describe the management of gestational trophoblastic neoplasia (GTN), with particular reference to concurrent human immunodeficiency virus (HIV) infection.
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Cervical cancer treatment in Africa.
Curr Opin Oncol
PUBLISHED: 07-08-2011
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This review is to inform the reader about the current situation with regard to treatment of cervical cancer in Africa and the barriers and complexities faced in most African countries. It also reviews the natural history of cervical cancer, the new 2009 International Federation of Gynecology and Obstetrics staging, and current treatment guidelines for cervical cancer.
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Cytological screening for cervical cancer prevention.
Best Pract Res Clin Obstet Gynaecol
PUBLISHED: 07-07-2011
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Historically, the incidence and mortality of cervical cancer has declined in countries that have instituted and sustained mass-organised cytology-based screening programmes. These programmes, however, required frequent repeats of the screening tests. They also require a functioning healthcare infrastructure, with laboratories for smear processing and interpretation, mechanisms for quality control, referral for colposcopy, treatment of precursors, and follow-up to detect failures of treatment. Although this approach has been successful in preventing cervical cancer where implemented correctly, it has proved inordinately complex and expensive for developing countries. Consequently, no successful screening programmes have been established in poor countries, and cervical cancer remains the most common cancer among women in developing countries, despite the existence of cytology and the knowledge of cervical cancer prevention. New technologies, specifically the development of liquid-based cytology, have improved the performance of cytology as a screening test, but do not obviate the infrastructural challenges posed to health systems by cytology-based screening programmes. In this chapter, the history of cytological screening and the challenges posed by secondary prevention strategies are reviewed.
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A comparison of human papillomavirus testing of clinician-collected and self-collected samples during follow-up after screen-and-treat.
Int. J. Cancer
PUBLISHED: 04-01-2011
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Screen-and-treat cervical cancer prevention programs based on high-risk human papillomavirus (HPV) testing and cryotherapy have been shown to be effective in resource-limited settings. However, because cryotherapy is not 100% effective, follow-up is needed after treatment to detect post-treatment failures. We compared the test performances of high-risk HPV testing (Hybrid Capture 2) using self-collected and clinician-collected samples as well as cervical cytology for identifying cervical intraepithelial neoplasia grades 2 or 3 or invasive cervical cancer (CIN2+) among women who did (n=812) and did not (n=1858) undergo cryotherapy in a South African screen-and-treat trial. At 6 months after enrolment (and after cryotherapy, if performed), women were tested using all three screening methods and then underwent colposcopy/biopsy. A predefined subset of women (n=1,455) had extended follow-up with colposcopy/biopsy at 12 months. A total of 33 and 91 cases of CIN2+ were detected among treated and untreated women, respectively. The sensitivity of HPV testing using clinician-collected samples and cervical cytology did not differ by treatment status. HPV testing of clinician-collected samples detected the most cases of CIN2+ among both treated (85%) and untreated (91%) women (p=0.31). Cytology (at a cutoff of atypical squamous cells of undetermined significance or greater) detected 76% of cases among both treated and untreated women. However, the sensitivity of HPV testing using self-collected samples was significantly lower among treated versus untreated women (55% vs. 78%, p=0.01). HPV testing using self-collected vaginal specimens may be useful in primary screening but performs poorly for detecting post-treatment failures.
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Eurogin 2010 roadmap on cervical cancer prevention.
Int. J. Cancer
PUBLISHED: 03-25-2011
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The EUROGIN 2010 roadmap represents a continuing effort to provide and interpret updated information on cervical cancer screening and vaccination against the cause of the disease, high-risk human papillomavirus (HPV). Contrary to the two previous reports in 2008 and 2009, the present roadmap gives equal room to HPV-based screening and HPV vaccination, as a result of the recent strengthening of the evidence on the efficacy and feasibility of both approaches. The superiority of HPV testing in primary screening compared to cytology (in more developed countries) and to cytology or visual inspection methods (in less developed countries) has been demonstrated in several randomised trials. High vaccine efficacy has been confirmed up to 7 years after vaccination; school-based programmes in some countries have been able to reach over 70% coverage among adolescent girls. Demonstration projects have indicated that the delivery of HPV vaccines in less developed countries is feasible and favourably received by populations where cervical cancer is very common. HPV-based screening can diminish cervical cancer incidence more quickly than HPV vaccination, but vaccination can eventually facilitate screening efforts, especially if new vaccines against a greater number of HPV types are introduced. The availability of two highly complementary prevention tools such as HPV testing and HPV vaccination makes it possible to conceive integrated strategies for the elimination of cervical cancer that have no precedent in the cancer field. HPV tests and HPV vaccines remain, however, too expensive, and large-scale financing of screening and vaccination in less developed countries is sorely lacking.
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Stability and transport of cervical cytobrushes for isolation of mononuclear cells from the female genital tract.
J. Immunol. Methods
PUBLISHED: 01-21-2011
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Cervical cytobrushing, biopsy, or lavages have previously been used to collect mononuclear cells from the female genital tract. Compared with blood, obtaining cells from the female genital tract is more invasive and generally yields few cells for subsequent immune studies. Because of the value of including mucosal sampling in HIV vaccine trials, standardisation of methods for collection, processing, and analysis of immunity from cells derived from the female genital tract is important. The aim of this study was to assess the effect of transport conditions on the viability, recovery and antigenic responsiveness of cervical T cells. This was investigated in cervical cytobrush specimens collected from 215 chronically HIV-infected women. Cytobrushes were either processed immediately, after cryopreservation, or after 24h at 37°C, 4°C or room temperature. CD3(+) T cell numbers were quantified using Guava automated cell counting. Viability was assessed using Trypan and Annexin/PI staining. Intracellular cytokine staining was used to evaluate IFN-? responses to PMA, PHA and CEF peptides in cytobrush-derived T cells ex vivo and after delayed processing. In vitro polyclonal expansion of thawed cervical lymphocytes was conducted for 14days in the presence of anti-CD3 and IL-2. We found that CD3(+) T cell recovery and viability was similar in cytobrushes processed immediately or after 24h irrespective of the conditions at which they were maintained. Fifty percent of the CD3(+) T cells could be recovered after cryopreservation of cytobrushes and these could be polyclonally expanded in half of the cryopreserved samples. IFN-? production following mitogenic stimulation was similar in ex vivo and delayed processing cytobrushes. Maintaining cytobrushes at 37°C prior to processing significantly improved the detection of CEF-specific T cell responses compared to ex vivo. We conclude that cervical cytobrush-derived T cells are robust and can preserve their viability, phenotype and function over 24h of mock transport.
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Rapid rise in detection of human papillomavirus (HPV) infection soon after incident HIV infection among South African women.
J. Infect. Dis.
PUBLISHED: 01-07-2011
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It is well established that the prevalence of human papillomavirus (HPV) infection is increased among human immunodeficiency virus (HIV)-positive individuals, but the temporal relationships between these infections are unclear.
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Human papillomavirus-based cervical cancer prevention: long-term results of a randomized screening trial.
J. Natl. Cancer Inst.
PUBLISHED: 09-30-2010
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Screen-and-treat approaches to cervical cancer prevention are an attractive option for low-resource settings, but data on their long-term efficacy are lacking. We evaluated the efficacy of two screen-and-treat approaches through 36 months of follow-up in a randomized trial.
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Efficacy of human papillomavirus-based screen-and-treat for cervical cancer prevention among HIV-infected women.
AIDS
PUBLISHED: 08-14-2010
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Cervical cancer prevention should be provided as part of primary healthcare services for HIV-infected women but conventional screening programs are difficult to implement in low-resource settings. Here, we evaluate the efficacy among HIV-infected women of a simpler, screen-and-treat strategy in which all women with a positive screening test are treated with cryotherapy.
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Persistence of genital tract T cell responses in HIV-infected women on highly active antiretroviral therapy.
J. Virol.
PUBLISHED: 08-04-2010
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Initiation of highly active antiretroviral therapy (HAART) for HIV-infected individuals is associated with control of viremia, improved CD4 counts, and declining systemic HIV-specific immune responses. While HAART effectively reduces plasma viremia, it remains unclear how effectively antiretroviral drugs reach mucosal surfaces, such as those of the genital tract. The aim of this study was to determine the effect of HAART on genital tract CD4 T cell reconstitution, HIV shedding, and HIV-specific T cell responses. Cervical cytobrush and blood specimens were obtained from 35 HIV-infected, HAART-naïve women and 27 women on HAART in order to investigate HIV Gag-specific T cell responses by intracellular gamma interferon (IFN-?) staining. Interleukin 1? (IL-1?), IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assays (ELISA). We show that for HIV-infected women, HAART is associated with significantly improved CD4 T cell counts both in blood and at the cervix. While HAART effectively suppressed both blood and cervical viremia, HIV-specific CD8 T cell responses in blood were lost, while those at the cervix were preserved.
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Reduced acquisition and reactivation of human papillomavirus infections among older women treated with cryotherapy: results from a randomized trial in South Africa.
BMC Med
PUBLISHED: 05-12-2010
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Treatment of women for high-grade cervical cancer precursors frequently results in clearance of the associated high-risk human papillomavirus (hrHPV) infection but the role of treatment among women without hrHPV is unknown. We investigated whether cervical cryotherapy reduces newly detected hrHPV infections among HIV-positive and HIV-negative women who were hrHPV negative when treated.
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Utilisation and outcomes of cervical cancer prevention services among HIV-infected women in Cape Town.
S. Afr. Med. J.
PUBLISHED: 05-01-2010
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An audit of outcomes of cervical cancer screening and prevention services for HIV-positive women in Cape Town, South Africa.
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Comparison of polyclonal expansion methods to improve the recovery of cervical cytobrush-derived T cells from the female genital tract of HIV-infected women.
J. Immunol. Methods
PUBLISHED: 02-02-2010
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Cervical cytobrushing is a useful and non-invasive method for obtaining mucosal mononuclear cells from the female genital tract, but yields few cells. The aim of this study was to compare in vitro expansion protocols (anti-CD3, anti-CD3/CD28 or Dynal anti-CD3/CD28 beads) and cytokine combinations (IL-2, IL-7 and IL-15) to improve cervical T cell yields and viability. Eighteen HIV-infected women were included in this study to compare methods for polyclonal expansion of T cells from the female genital tract and blood. Comparison of T cell yields, viability and maturational status (by differential staining with CD45RO, CCR7 and CD27) was determined following 7 days of in vitro expansion. Anti-CD3 and IL-2 resulted in a 4.5-fold (range 3.7-5.3) expansion of cervical CD3+ T cells in 7 days compared to day 0. Inclusion of anti-CD28 or addition of IL-7 and IL-15 to this combination did not improve expansion. Culturing cells with Dynal beads (1:1) and IL-2, IL-7 and IL-15 gave rise to the highest yields after 7 days in both blood (7.1-fold) and cervix (5.6-fold). While expansion with anti-CD3 led to the accumulation of effector memory T cells (CD45RO+CCR7-CD27-), expansion with Dynabeads selected for accumulation of central memory T cells (CD45RO+CCR7+CD27+). We conclude that in vitro expansion with Dynabeads (1:1) in the presence of IL-2, IL-7 and IL-15 resulted in the greatest increase in viable T cells from both blood and cytobrush. Irrespective of the expansion method used, the T cell memory profile was altered following expansion.
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CD57 expression by T cells in the female genital tract of HIV-zx1 infected women.
Clin. Immunol.
PUBLISHED: 01-25-2010
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Despite an influx of T cells to the cervix during HIV infection, genital T cells are not associated with control of HIV shedding. CD57 expression by T cells has been associated with enhanced migratory potential and CD57+ T cells have been shown to accumulate in tissues during the late stages of HIV disease. We investigated the impact of HIV-infection and clinical status on the expression of CD57 by T cells from the female genital tract in 13 HIV-infected and 5 uninfected women. We found that cervical and blood-derived T cells expressed similar frequencies of CD57. The frequency of CD57 expression by cervical or blood T cells was not associated with clinical status (CD4 counts). No impairment in IFN-gamma production by CD57+ T cells from the genital tract was observed. We conclude that increased T cell senescence does not appear to be a hallmark of genital mucosal HIV-1 infection.
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Polyclonal expansion of cervical cytobrush-derived T cells to investigate HIV-specific responses in the female genital tract.
Immunology
PUBLISHED: 08-17-2009
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Human immunodeficiency virus (HIV) -specific T-cell responses are detectable in the female genital tract of HIV-infected women but little is known about their frequency or the factors that influence their detection. We investigated the feasibility of polyclonal in vitro expansion of cervical cytobrush-derived T cells to investigate HIV-specific responses in the female genital tract in HIV-infected women. Cytobrush-derived cervical cells were isolated from 22 HIV-infected women and expanded with anti-CD3 and recombinant interleukin-2. Cervical T-cell lines were investigated for Gag-specific responses by interferon-gamma ELISPOT and compared with those detected in matched blood samples. Cervical T-cell lines were established from 16/22 (72.7%) participants. Although the absolute number of CD3(+/-) cells recovered after expansion was positively associated with the number of cells isolated ex vivo (P = 0.01; R = 0.62), we observed a significant negative correlation between fold expansion and ex vivo cell number (P = 0.004; R = -0.68). We show that both the magnitude (P = 0.002; R = 0.7) and specific Gag regions targeted by cervical T-cell lines (P < 0.0001; R = 0.5) correlated significantly with those detected in blood. With one exception, cervical interferon-gamma T-cell responses to Gag were detected only in HIV-infected women with blood Gag-specific response > 1000 spot-forming units/10(6) cells. We conclude that cervical Gag-specific T-cell responses in expanded lines are most easily detectable in women who have corresponding high-magnitude Gag-specific T-cell responses in blood.
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Chemoradiation in advanced vulval carcinoma.
Int. J. Gynecol. Cancer
PUBLISHED: 06-11-2009
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Vulval carcinoma is uncommon, affecting approximately 2 per 100,000 women annually. The treatment of choice is radical vulvectomy and inguinal lymph node dissection. Advanced vulval carcinomas involve midline structures (such as clitoris, urethra, or anus) and/or adjacent pelvic organs or bone, and adequate excision may require urinary diversion, colostomy, or pelvic exenteration. Less morbid and less mutilating therapeutic alternatives have been investigated, particularly chemoradiation, which has shown success in the management of anal carcinomas. Chemoradiation has been used, instead of primary radical surgery, to treat advanced vulval carcinomas at Groote Schuur Hospital (GSH) since 1982. This is a retrospective study of the GSHs experience of the use of chemoradiation as primary therapy for women with advanced vulval carcinoma.
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Impact of human immunodeficiency virus 1 infection and inflammation on the composition and yield of cervical mononuclear cells in the female genital tract.
Immunology
PUBLISHED: 03-26-2009
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Cervical cytobrush sampling is a relatively non-invasive method for obtaining mucosal cells from the female genital tract. To define mucosal immune cells sampled by cervical cytobrushing and to validate this approach for local immunity studies, we investigated the impact of human immunodeficiency virus (HIV) status and inflammation on the yield and composition of cervical cytobrush specimens. Cervical cytobrush samples were obtained from 89 chronically HIV-infected and 46 HIV-negative women. The HIV-infected women had significantly higher yields of CD3(+), CD45(+), CD19(+), CD14(+), Langerin(+) and CD24(+) cells than the uninfected women. While cytobrush-derived T cells from uninfected women were predominantly CD4(+) (4.2 CD4 : 1 CD8), CD8(+) T cells were predominant in HIV-infected women (0.6 CD4 : 1 CD8). The majority of CD4(+) and CD8(+) T cells from HIV-infected and uninfected women were of the effector memory (CD45RA(-) CCR7(-) CD27(-)) phenotype. HIV-infected women had significantly elevated levels of interleukin (IL)-1beta, IL-6 and IL-8 in cervical supernatants compared with uninfected women. We observed a significant positive correlation between T-cell counts and IL-1beta, tumour necrosis factor (TNF)-alpha and IL-12 concentrations. Neutrophil counts correlated significantly with cervical concentrations of IL-1beta, TNF-alpha, IL-8, IL-6 and IL-10. Antigen-presenting cell numbers correlated significantly with TNF-alpha and IL-12 concentrations. HIV-infected women on antiretroviral therapy had similar levels of cervical lymphocyte infiltration and inflammation to women naïve to therapy. In conclusion, we suggest that inflammation at the cervix and HIV infection are likely to be key determinants in the absolute number of mucosal immune cells recovered by cervical cytobrushing.
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Program spending to increase adherence: South African cervical cancer screening.
PLoS ONE
PUBLISHED: 03-05-2009
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Adherence is crucial for public health program effectiveness, though the benefits of increasing adherence must ultimately be weighed against the associated costs. We sought to determine the relationship between investment in community health worker (CHW) home visits and increased attendance at cervical cancer screening appointments in Cape Town, South Africa.
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The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.
Int. J. Cancer
PUBLISHED: 01-01-2009
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The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest they are important in nuclear envelope component assembly, mitosis and replication. Since these are all critical cellular functions, alterations in the expression of the Karyopherins may have an impact on the biology of cancer cells. In this study, we examined the expression of the Karyopherins, Crm1, Karyopherin beta1 (Kpnbeta1) and Karyopherin alpha2 (Kpnalpha2), in cervical tissue and cell lines. The functional significance of these proteins to cancer cells was investigated using individual siRNAs to inhibit their expression. Microarrays, quantitative RT-PCR and immunofluorescence revealed significantly higher expression of Crm1, Kpnbeta1 and Kpnalpha2 in cervical cancer compared to normal tissue. Expression levels were similarly elevated in cervical cancer cell lines compared to normal cells, and in transformed epithelial and fibroblast cells. Inhibition of Crm1 and Kpnbeta1 in cancer cells significantly reduced cell proliferation, while Kpnalpha2 inhibition had no effect. Noncancer cells were unaffected by the inhibition of Crm1 and Kpnbeta1. The reduction in proliferation of cancer cells was associated with an increase in a subG1 population by cell cycle analysis and Caspase-3/7 assays revealed increased apoptosis. Crm1 and Kpnbeta1 siRNA-induced apoptosis was accompanied by an increase in the levels of growth inhibitory proteins, p53, p27, p21 and p18. Our results demonstrate that Crm1, Kpnbeta1 and Kpnalpha2 are overexpressed in cervical cancer and that inhibiting the expression of Crm1 and Kpnbeta1, not Kpnalpha2, induces cancer cell death, making Crm1 and Kpnbeta1 promising candidates as both biomarkers and potential anticancer therapeutic targets.
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Human papillomavirus, human immunodeficiency virus and immunosuppression.
Vaccine
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The vast majority of women infected with human immunodeficiency virus (HIV) will be co-infected with human papillomavirus (HPV). The interaction between the two sexually transmitted infections appears to be related to the alteration in cell-mediated immunity in HIV infected persons, increased susceptibility, and possibly reactivation of latent HPV infection. Linkage studies of HIV/AIDs and Cancer registries have indicated a 2- to 22-fold increase in cervical cancer in HIV-positive women compared to HIV-negative women. Data on the prevalence of HPV types in invasive cervical carcinoma (ICC) suggest that the proportion of infection with types HPV16/18 (responsible for over 70% of all cervical cancers) is similar in HIV-negative and HIV-positive women. The biological interaction between HIV and HPV needs further elucidation, although there is some evidence that the presence of HPV infection may be associated with increased HIV transmission. Adolescents perinatally infected by HIV are known to have higher rates of HPV infection and also have been shown to seroconvert in response to HPV vaccination with the quadrivalent vaccine, albeit to lower titers than HIV-negative individuals. Anal cancer incidence is greatly increased in HIV-positive individuals, particularly in HIV-positive men who have sex with men. Screening for anal cancer precursors is feasible and effective; however, the impact on reduction of anal cancer remains to be demonstrated. There are ongoing studies on the safety, immunogenicity, and efficacy of current HPV vaccines in HIV-positive individuals and mature data are awaited. Male circumcision may be another approach to prevention of HPV transmission, which also requires further study. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.
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Distribution of high-risk human papillomavirus genotypes among HIV-negative women with and without cervical intraepithelial neoplasia in South Africa.
PLoS ONE
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Large studies describing the profile of high-risk Human papillomavirus (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN).
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Cervical cancer: prevention and treatment.
Discov Med
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Cervical cancer is the commonest cancer cause of death among women in developing countries and efforts to prevent the disease using newer approaches and HPV vaccination need to be explored. Detection of cervical cancer at an early stage is associated with excellent survival but most women in developing countries present with advanced and often untreatable disease, with very poor survival. The ratio between incidence and mortality from cervical cancer remains very high, largely due to lack of access to appropriate anti-cancer therapies in developing countries. In developed countries with functional screening programs, cervical cancer has been rendered a relatively rare disease. Ongoing efforts to refine the characteristics of screening tests continue, as does implementation of current HPV vaccines for the primary prevention of cervical cancer.
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Cervical cancer prevention: new opportunities for primary and secondary prevention in the 21st century.
Int J Gynaecol Obstet
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Cervical cancer is a relatively rare disease in countries that have instituted and maintained national screening programs, with call and recall of women at various intervals and built-in quality control with appropriate monitoring and evaluation. Unfortunately, this process has failed in most areas of the world where over 80% of new cases of cervical cancer are diagnosed. Cervical cancer affects women in the prime of their lives and causes premature and needless suffering and death in a critically important segment of the worlds population-despite being the only cancer that can be prevented with simple testing. In the past 15 years, innovative approaches to both primary and secondary prevention of cervical cancer have been subjected to a number of large-scale scientifically valid and applicable studies that have opened the way for new approaches. This article reviews these new approaches.
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South african sexual assault survivors experiences of post-exposure prophylaxis and individualized nursing care: a qualitative study.
J Assoc Nurses AIDS Care
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South African sexual assault survivors face the risk of potential HIV exposure, but relatively little is known about their experiences of post-exposure prophylaxis (PEP) and post-sexual assault care. Researchers conducted 10 semistructured interviews with sexual assault survivors who had participated in an initial quantitative study of a post-sexual assault intervention that administered PEP and provided proactive individualized follow-up care. The qualitative study examined survivors experiences of PEP and their participation in the initial observational study itself. Participants demonstrated a range of emotional reactions to PEP, while almost all equated their study experiences to positive interactions with the study nurses who administered PEP and provided informal psychosocial support. The results highlight important opportunities for nurses to enhance the quality of post-sexual assault care in order to improve patients emotional and psychosocial outcomes and potentially increase the likelihood of survivor PEP adherence.
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Cervical cancer in Africa.
Cancer Epidemiol. Biomarkers Prev.
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Cervical cancer is a relatively rare disease in countries that have instituted and maintained national screening programs, with call and recall of women at various intervals and built-in quality control with appropriate monitoring and evaluation. Unfortunately, this process has failed in most areas of the world where more than 80% of new cases of cervical cancer are diagnosed. Cervical cancer affects women in the prime of their lives causing premature and needless suffering and death in a critically important segment of the worlds population, despite being one of the few cancers that can be prevented with simple testing. In the past 15 years innovative approaches to both primary and secondary prevention of cervical cancer have been subjected to a number of large scale, scientifically valid and applicable studies that have opened the way for new approaches. Treatment of cervical cancer in Africa is hampered by the lack of diagnostic and treatment facilities, lack of healthcare infrastructure and poor pathology services. Further, there is a significant brain drain of trained healthcare workers in Africa that exacerbates the problem. Cancer is becoming an increasingly important public health problem as more people live longer. It is time to develop programs for the prevention, early detection, treatment, and palliation of cancer sufferers in Africa.
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The gynaecological subspecialties: advances in womens health.
S. Afr. Med. J.
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Under Professor Dennis Daveys leadership, the Department of Obstetrics and Gynaecology recognised the need for subspecialist expertise and training. Thus, the gynaecological subspecialties were developed, the first of which was gynaecological oncology. We review the research, and subsequent clinical application, which has evolved from the subspecialist units.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.