Long-lasting insecticidal activity in plants driven by chlorogenic acid-loaded metal-organic frameworks.

Metal-organic frameworks (MOFs) possess a variety of interesting features related to their composition and structure that make them excellent candidates to be used in agriculture. However, few studies have reported their use as delivery agents of agrochemicals. In this work, the natural polyphenol chlorogenic acid (CGA) was entrapped via simple impregnation in the titanium aminoterephthalate MOF, MIL-125-NH2. A combination of experimental and computational techniques was used to understand and quantify the encapsulated CGA in MIL-125-NH2. Subsequently, CGA delivery studies were carried out in water at different pHs, showing a fast release of CGA during the first 2 h (17.3 ± 0.3% at pH = 6.5). In vivo studies were also performed against larvae of mealworm (Tenebrio molitor), evidencing the long-lasting insecticidal activity of CGA@MIL-125-NH2. This report demonstrates the potential of MOFs in the efficient release of agrochemicals, and paves the way to their study against in vivo models.

Cervical cancer screening coverage in the Americas region: a synthetic analysis.

Background: The Americas region has the lowest (North America) and the second highest (Latin America and Caribbean) cervical cancer (CC) mortality worldwide. The lack of reliable data on screening coverage in the region hinders proper monitoring of the World Health Organization (WHO) CC elimination initiative. Methods: For this synthetic analysis, we searched data on CC screening coverage from official sources and national health surveys, supplemented with a formal WHO country consultation. Context data were obtained from official sources (income, health expenditure, inequality-adjusted human development index -IHDI-, universal health coverage, CC incidence/mortality). Country age-specific coverages for 2019 by screening interval were computed. Missing data were imputed through a multi-step algorithm. Beta-regression and Poisson-regression models were used to analyse associations between context variables, screening coverage, and CC mortality. Findings: We included data from 37 countries in the Americas. Data on coverage of HPV testing was scarce, and for many countries only Pap-smear coverage data was available. Overall, 78%, 34%, 60%, and 67% of women aged 25-65 years have been screened ever in their lifetime, and in the previous year, 3 years, and 5 years, respectively. By sub-region, 3-year coverage ranges from 48% (South America) to 72% (North America). Twenty-four countries showed screening coverage below 70%. Income and health system type were associated with screening coverage, but coverage was not associated with CC mortality. Interpretation: In the Americas region 35.1% and 56.8% of countries report 3-year and 5-year coverage over 70%, respectively. Inequalities remain a major challenge for screening programs in the region. The elimination campaign should reinforce the transition to HPV testing and strengthen surveillance systems. Funding: Instituto de Salud Carlos III, European Regional Development Fund, Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, and Horizon 2020.

Everything causes cancer? Beliefs and attitudes towards cancer prevention among anti-vaxxers, flat earthers, and reptilian conspiracists: online cross sectional survey.

OBJECTIVE: To evaluate, using an online non-probability sample, the beliefs about and attitudes towards cancer prevention of people professing vaccination scepticism or conspiracy theories. DESIGN: Cross sectional survey. SETTING: Data collected mainly from ForoCoches (a well known Spanish forum) and other platforms, including Reddit (English), 4Chan (English), HispaChan (Spanish), and a Spanish language website for cancer prevention (mejorsincancer.org) from January to March 2022. PARTICIPANTS: Among 1494 responders, 209 were unvaccinated against covid-19, 112 preferred alternative rather than conventional medicine, and 62 reported flat earth or reptilian beliefs. MAIN OUTCOME MEASURES: Cancer beliefs assessed using the Cancer Awareness Measure (CAM) and Cancer Awareness Measure Mythical Causes Scale (CAM-MYCS) (both validated tools). RESULTS: Awareness of the actual causes of cancer was greater (median CAM score 63.6%) than that of mythical causes (41.7%). The most endorsed mythical causes of cancer were eating food containing additives or sweeteners, feeling stressed, and eating genetically modified food. Awareness of the actual and mythical causes of cancer among the unvaccinated, alternative medicine, and conspiracy groups was lower than among their counterparts. A median of 54.5% of the actual causes was accurately identified among each of the unvaccinated, alternative medicine, and conspiracy groups, and a median of 63.6% was identified in each of the three corresponding counterparts (P=0.13, 0.04, and 0.003, respectively). For mythical causes, medians of 25.0%, 16.7%, and 16.7% were accurately identified in the unvaccinated, alternative medicine, and conspiracy groups, respectively; a median of 41.7% was identified in each of the three corresponding counterparts (P<0.001 in adjusted models for all comparisons). In total, 673 (45.0%) participants agreed with the statement "It seems like everything causes cancer." No significant differences were observed among the unvaccinated (44.0%), conspiracist (41.9%), or alternative medicine groups (35.7%), compared with their counterparts (45.2%, 45.7%, and 45.8%, respectively). CONCLUSIONS: Almost half of the participants agreed that "It seems like everything causes cancer," which highlights the difficulty that society encounters in differentiating actual and mythical causes owing to mass information. People who believed in conspiracies, rejected the covid-19 vaccine, or preferred alternative medicine were more likely to endorse the mythical causes of cancer than their counterparts but were less likely to endorse the actual causes of cancer. These results suggest a direct connection between digital misinformation and consequent erroneous health decisions, which may represent a further preventable fraction of cancer.

Cervical cancer screening programs in Latin America: current recommendations for facing elimination challenges.

OBJECTIVE: To describe current cervical cancer screening program guidelines in Latin America. MATERIALS AND METHODS: We searched official recommendations for the general population and women living with HIV (WLHIV) by reviewing official sources from 19 countries; these data were supplemented with a consultation carried out by the WHO with the Ministries of Health. RESULTS: Screening policies vary significantly in regard to target populations, primary tests, and screening intervals. Sixteen countries have recently updated their recommendations; however, cytology remains the primary screening test for most countries. Eleven countries have introduced HPV tests, and eight countries have implemented screen-and-treat algorithms; only three countries have developed evidence-based guidelines. All countries but Costa Rica have specific recommendations for WLHIV. CONCLUSIONS: Although most countries have updated their screening policies, only a few are properly alig-ned with the WHO elimination strategy. Recommendations for WLHIV require better integration with cervical cancer screening programs.

Cervical cancer screening programmes and age-specific coverage estimates for 202 countries and territories worldwide: a review and synthetic analysis.

BACKGROUND: Cervical cancer screening coverage is a key monitoring indicator of the WHO cervical cancer elimination plan. We present global, regional, and national cervical screening coverage estimates against the backdrop of the 70% coverage target set by WHO. METHODS: In this review and synthetic analysis, we searched scientific literature, government websites, and official documentation to identify official national recommendations and coverage data for cervical cancer screening for the 194 WHO member states and eight associated countries and territories published from database inception until Oct 30, 2020, supplemented with a formal WHO country consultation from Nov 27, 2020, to Feb 12, 2021. We extracted data on the year of introduction of recommendations, the existence of individual invitation to participate, financing of screening tests, primary screening and triage tests used, recommended ages and screening intervals, use of self-sampling, and use of screen-and-treat approaches. We also collected coverage data, either administrative or survey-based, as disaggregated as possible by age and for any available screening interval. According to data completeness and representativeness, different statistical models were developed to produce national age-specific coverages by screening interval, which were transformed into single-age datapoints. Missing data were imputed. Estimates were applied to the 2019 population and aggregated by region and income level. FINDINGS: We identified recommendations for cervical screening in 139 (69%) of 202 countries and territories. Cytology was the primary screening test in 109 (78%) of 139 countries. 48 (35%) of 139 countries recommended primary HPV-based screening. Visual inspection with acetic acid was the most recommended test in resource-limited settings. Estimated worldwide coverage in women aged 30-49 years in 2019 was 15% in the previous year, 28% in the previous 3 years, and 32% in the previous 5 years, and 36% ever in lifetime. An estimated 1·6 billion (67%) of 2·3 billion women aged 20-70 years, including 662 million (64%) of 1·0 billion women aged 30-49 years, had never been screened for cervical cancer. 133 million (84%) of 158 million women aged 30-49 years living in high-income countries had been screened ever in lifetime, compared with 194 million (48%) of 404 million women in upper-middle-income countries, 34 million (9%) of 397 million women in lower-middle-income countries, and 8 million (11%) of 74 million in low-income countries. INTERPRETATION: Two in three women aged 30-49 years have never been screened for cervical cancer. Roll-out of screening is very low in low-income and middle-income countries, where the burden of disease is highest. The priority of the WHO elimination campaign should be to increase both screening coverage and treatment of detected lesions; however, expanding the efforts of surveillance systems in both coverage and quality control are major challenges to achieving the WHO elimination target. FUNDING: Instituto de Salud Carlos III, European Regional Development Fund, Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, and Horizon 2020. TRANSLATIONS: For the French, Spanish translations of the abstract see Supplementary Materials section.

New surgical realities: implementation of an enhanced recovery after surgery protocol for gynecological laparoscopy-a prospective study.

BACKGROUND: Multimodal rehabilitation allows optimization of functional recovery in surgery patients by reducing the postoperative stress and hospital stay duration, without increasing the morbidity and mortality. It is reportedly successful in other surgical disciplines, and guidelines for its application to gynecological surgery are available; however, most evidence for these guidelines is derived from observational and/or retrospective studies. Therefore, this study aimed to investigate the applicability of an enhanced recovery after surgery (ERAS) protocol in laparoscopic gynecological surgery and its influence on the postoperative stay, morbidity, mortality, and readmission, through a prospective approach. METHODS: This prospective cohort study was performed on 90 patients who underwent laparoscopic hysterectomy for benign causes from October 2017 to October 2019. Patients in whom the ERAS (ERAS group, n = 30) and traditional (control group, n = 60) protocols were implemented were compared. All patients were followed for 6 months. RESULTS: The groups were homogeneous and did not differ significantly with respect to the demographic characteristics (age, ASA score, body mass index), surgical indications, and surgery types. Adherence to the ERAS protocol was over 99%. The postoperative hospital-stay durations were 1.73 days (r = 1-3) and 2.97 days (r = 2-6) in the ERAS and control groups, respectively (p = 0.000). No significant intergroup differences were observed in the rates of complications and readmissions. CONCLUSIONS: The ERAS protocol is applicable in laparoscopic gynecological surgery and can be implemented with good adherence. This can allow optimization of patient recovery by reducing the hospital stay duration, without increasing the rates of morbidity, mortality, or readmission.

Burden of Human papillomavirus (HPV)-related disease and potential impact of HPV vaccines in the Republic of Korea.

BACKGROUND: We aimed to review the burden and the potential impact of human papillomavirus (HPV) vaccines on HPV-related diseases in the Republic of Korea and to discuss cervical cancer prevention practices in this country. METHODS: Cancer burden statistics were retrieved from GLOBOCAN-2018 and Statistics Korea. HPV disease burden was assessed via systematic review. Vaccine types relative contribution (RC) was estimated using data from an international project using formalin-fixed paraffin-embedded specimens. RESULTS: Despite a downtrend in cervical cancer in recent years, Korean rates remain high. In contrast, oropharyngeal cancer incidence has gradually increased and other anogenital cancers remain rare. In Korea, HPV prevalence in general population is around 20%. In cervical cancer, RC of HPVs 16/18 (74.0%) increased to 92.0% when including HPVs 31/33/45/52/58. Limited information was available for other HPV-related cancer sites. Regarding prevention, since the inclusion of the HPV vaccine into the National Immunization Program, almost half (49%) of the target cohort in 2016 had received the first dose of vaccine. Further, percentage of women screened with pap has increased from 41.1%-2009 to 53.0%-2016. CONCLUSIONS: HPV-related disease burden in Korea is significant. Results suggest that the combination of effective and high coverage HPV vaccination and screening programmes could substantially impact on HPV-related disease in Korea.

Modelos matemáticos de parámetros reológicos y su influencia en el sistema de bombeo de fluidos no newtonianos / Mathematical models of rheological parameters and their influence on the pumping system of non-Newtonian fluids / Modelos matemáticos de parâmetros reológicos e sua influência no sistema de bombeamento de fluidos não-newtonianos

Resumen En la presente investigación se realizó un estudio de la influencia de los parámetros reológicos de las hidromezclas lateríticas con los parámetros energéticos de los sistemas de bombeo que garantizan la productividad en la obtención de sulfuro de níquel. A partir de estudios experimentales como técnicas de difracción de rayos-X, fluorescencia de rayos-X y análisis de tamaño de partículas se modelaron los comportamientos de la viscosidad aparente, el esfuerzo cortante inicial, el índice de consistencia másica y el índice de flujo. Lo anterior, en función de los siguientes factores: temperatura, contenido de sólidos, composición química y granulométrica. Los resultados evidenciaron que las suspensiones lateríticas se comportan como fluidos no newtonianos con plasticidad, debido a su carácter de materiales polidispersos, con un predominio de granulometría fina (partículas menores de 0,045 mm). Esto explica sus comportamientos reológicos, ajustables al modelo de Bulkley-Herschel a valores de temperatura de 28 a 90 °C y concentración de sólidos de 37 a 48 % (p/p). Se concluye que el uso de un modelo matemático que relaciona los parámetros reológicos de la pulpa laterítica y los parámetros energéticos del sistema de bombeo contribuye con la eficiencia energética de la alimentación de la pulpa requerida en el proceso de lixiviación ácida.

Abstract The present paper presents a study of the rheological parameters influence of lateritic hydromixtures with the energetic parameters of the pumping systems, which guarantee productivity when obtaining nickel sulphide. Experimental studies such as X-ray diffraction techniques, X-ray fluorescence and particle size analysis were carried out to model apparent viscosity, initial shear stress, mass consistency index and flow index. The above, based on the following factors: temperature, solids content, chemical and granulometric composition. The results showed that the lateritic suspensions behaved as non-Newtonian fluids with plasticity, due to their character of polydispersed materials, with a predominance of fine granulometry (particles less than 0.045 mm), which explains their rheological behavior, adjustable to the Bulkley - Herschel model at temperature values of 28 to 90 °C and solids concentration of 37 to 48 % (w/w). it is concluded that the use of a mathematical model that relates the rheological parameters of the lateritic pulp and the energy parameters of the pumping system contributes to energy-efficiency of the pulp feeding in the acid leaching process.

Resumo Na presente investigação, apresenta-se a influência dos parâmetros reológicos das hidromisturas lateríticas com os parámetros energéticos dos sistemas de bombeamento que garantem a produtividade na obtenção de sulfato de níquel. A partir de estudos experimentais, tais como técnicas de difracção de raios X, fluorescência de raios X e analise do tamanho de partícula, o comportamento da viscosidade aparente, o esforço de cisalhamento inicial, o índice de consistência de massa e o índice de fluxo são modelados. Acima, com base nos fatores a seguir: temperatura, teor de sólidos, composição química e granulométrica. Os resultados mostraram que as suspensões lateríticas se comportam como fluxos não-newtonianos com plasticidade, devido ao seu caráter de materiais polidispersos, com predominância de granulometria fina (partículas menores do que 0,045 mm), o que explica seu comportamento reológico, ajustável ao modelo de Bulkley - Herschel a valores de temperatura de 28 a 90 °C e concentração de sólidos de 37 a 48 % (p/p). Conclui-se que o uso de um modelo matemático que relaciona os parâmetros reológicos da polpa laterítica e os parâmetros de energia do sistema de bombeamento contribui para a eficiência energética da polpa de alimentação no processo de lixiviação ácida.

Burden of Human Papillomavirus (HPV)-Related Cancers Attributable to HPVs 6/11/16/18/31/33/45/52 and 58.

BACKGROUND: Many countries, mainly high- and upper-middle income, have implemented human papillomavirus (HPV) vaccination programs, with 47 million women receiving the full course of vaccine (three doses) in 2014. To evaluate the potential impact of HPV vaccines in the reduction of HPV-related disease, we aimed to estimate the HPV type distribution and burden of anogenital and head and neck cancers attributable to HPV types (HPVs 16/18/31/33/45/52/58/6/11) included in currently licensed HPV vaccines. METHODS: In all, 18 247 formalin-fixed paraffin-embedded specimens were retrieved from 50 countries. HPV DNA detection and typing were performed with the SPF-10 PCR/DEIA/LiPA25 system. With the exception of cervical cancer, HPV DNA-positive samples were additionally subjected to HPV E6*I mRNA detection and/or p16INK4a immunohistochemistry. For cervical cancer, estimates were based on HPV DNA, whereas for other sites, estimates were based on HPV DNA, E6*I mRNA, and p16INK4a biomarkers. RESULTS: The addition of HPVs 31/33/45/52/58 to HPVs 16/18/6/11 in the nonavalent HPV vaccine could prevent almost 90% of cervical cancer cases worldwide. For other sites, the nonavalent HPV vaccine could prevent 22.8% of vulvar, 24.5% of penile, 60.7% of vaginal, 79.0% of anal cancers, 21.3% of oropharyngeal, 4.0% of oral cavity, and 2.7% of laryngeal cancer cases. CONCLUSIONS: Our estimations suggest a potential impact of the nonavalent HPV vaccine in reducing around 90% of cervical cancer cases and a global reduction of 50% of all the cases at HPV-related cancer sites.

Epidemiology and burden of HPV-related disease.

Human papillomavirus (HPV) infection is recognized as one of the major causes of infection-related cancer in both men and women. High-risk HPV types are not only responsible for virtually all cervical cancer cases but also for a fraction of cancers of the vulva, vagina, penis, anus, and head and neck cancers. Furthermore, HPV is also the cause of anogenital warts and recurrent respiratory papillomatosis. Despite the availability of multiple preventative strategies, HPV-related cancer remains a leading cause of morbi-mortality in many parts of the world, particularly in less developed countries. Thus, in this review, we summarize the latest estimates of the global burden of HPV-related diseases, trends, the attributable fraction by HPV types, and the potential preventative fraction.

Antiviral treatment and liver-related complications in hepatitis delta.

Hepatitis delta virus (HDV) is the most severe form of viral hepatitis. Pegylated interferon alfa (PEG-IFNα) is effective in only 25%-30% of patients and is associated with frequent side effects. The aim of this study was to analyze the clinical long-term outcome of hepatitis delta in relation to different antiviral treatment strategies. We studied 136 anti-HDV-positive patients who were followed for at least 6 months in a retrospective single-center cohort (mean time of follow-up, 5.2 years; range, 0.6-18.8). Liver cirrhosis was already present in 62 patients at first presentation. Twenty-nine percent of patients did not receive any antiviral treatment, 38% were treated with interferon alfa (IFNα)-based therapies, and 33% received nucleos(t)ide analogues (NAs) only. Clinical endpoints defined as hepatic decompensation (ascites, encephalopathy, and variceal bleeding), hepatocellular carcinoma, liver transplantation, and liver-related death developed in 55 patients (40%). Patients who received IFNα-based therapies developed clinical endpoints less frequently than those treated with NA (P = 0.02; HR, 4.0) or untreated patients (P = 0.05; HR, 2.2; 17%, 64%, and 44%), respectively, which was significant in both chi-square and Kaplan-Meier analysis. In addition, considering various clinical and virological parameters, IFNα therapy was independently associated with a more benign clinical long-term outcome in multivariate logistic regression analysis (P = 0.04; odds ratio, 0.25; 95% confidence interval, 0.07-0.9). Loss of HDV RNA during follow-up was more frequent in IFNα-treated patients and strongly linked with a lower likelihood to experience liver-related complications. CONCLUSION: IFNα-based antiviral therapy of hepatitis delta was independently associated with a lower likelihood for clinical disease progression. Durable undetectability of HDV RNA is a valid surrogate endpoint in the treatment of hepatitis delta. (Hepatology 2017;65:414-425).

Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan.

Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7-19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases.

Human papillomavirus genotype attribution for HPVs 6, 11, 16, 18, 31, 33, 45, 52 and 58 in female anogenital lesions.

OBJECTIVE: Human papillomavirus (HPV) vaccines can potentially control cervical cancer and help to reduce other HPV-related cancers. We aimed to estimate the relative contribution (RC) of the nine types (HPVs 16/18/31/33/45/52/58/6/11) included in the recently approved 9-valent HPV vaccine in female anogenital cancers and precancerous lesions (cervix, vulva, vagina and anus). METHODS: Estimations were based on an international study designed and coordinated at the Catalan Institute of Oncology (Barcelona-Spain), including information on 10,575 invasive cervical cancer (ICC), 1709 vulvar, 408 vaginal and 329 female anal cancer cases and 587 Vulvar Intraepitelial Neoplasia grade 2/3 (VIN2/3), 189 Vaginal Intraepitelial Neoplasia grade 2/3 (VaIN2/3) and 29 Anal Intraepitelial Neoplasia grade 2/3 (AIN2/3) lesions. Consecutive histologically confirmed paraffin-embedded cases were obtained from hospital pathology archives from 48 countries worldwide. HPV DNA-detection and typing was performed by SPF10-DEIA-LiPA25 system and RC was expressed as the proportion of type-specific cases among HPV positive samples. Multiple infections were added to single infections using a proportional weighting attribution. RESULTS: HPV DNA prevalence was 84.9%, 28.6%, 74.3% and 90.0% for ICC, vulvar, vaginal and anal cancers, respectively, and 86.7%, 95.8% and 100% for VIN2/3, VaIN2/3 and AIN2/3, respectively. RC of the combined nine HPV types was 89.5% (95% confidence interval (CI): 88.8-90.1)-ICC, 87.1% (83.8-89.9)-vulvar, 85.5% (81.0-89.2)-vaginal, 95.9% (93.0-97.9)-female anal cancer, 94.1% (91.7-96.0)-VIN2/3, 78.7% (71.7-84.2)-VaIN2/3 and 86.2% (68.3-96.1)-AIN2/3. HPV16 was the most frequent type in all lesions. Variations in the RC of HPVs 31/33/45/52/58 by cancer site were observed, ranging from 7.8% (5.0-11.4)-female anal cancer to 20.5% (16.1-25.4)-vaginal cancer. CONCLUSIONS: The addition of HPVs 31/33/45/52/58 to HPV types included in current vaccines (HPV16/18) could prevent almost 90% of HPV positive female anogenital lesions worldwide. Taking into account that most HPV-related cancers are ICC ones, the 9-valent HPV vaccine could potentially avoid almost 88% of all female anogenital cancers.

[Human papillomavirus vaccine. Efficacy and safety]. / Vacuna frente al virus del papiloma humano. Eficacia y seguridad.

Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases.

Potential impact of a 9-valent HPV vaccine in HPV-related cervical disease in 4 emerging countries (Brazil, Mexico, India and China).

BACKGROUND: We estimated the potential impact of an investigational 9-valent human papillomavirus (HPV) vaccine (HPVs 6/11/16/18/31/33/45/52/58) in HPV-related cervical disease in Brazil, Mexico, India and China, to help to formulate recommendations on cervical cancer prevention and control. METHODS: Estimations for invasive cervical cancer (ICC) were based on an international study including 1356 HPV-positive cases for the four countries altogether, and estimations for precancerous cervical lesions were extracted from a published meta-analysis including 6 025 HPV-positive women from the four mentioned countries. Globocan 2012 and 2012 World Population Prospects were used to estimate current and future projections of new ICC cases. RESULTS: Combined proportions of the 9 HPV types in ICC were 88.6% (95%CI: 85.2-91.3) in Brazil, 85.7% (82.3-88.8) in Mexico, 92.2% (87.9-95.3) in India and 97.3% (93.9-99.1) in China. The additional HPV 31/33/45/52/58 proportions were 18.8% (15.3-22.7) in Brazil, 17.6% (14.2-21.2) in Mexico, 11.3% (7.5-16.1) in India and 11.9% (7.5-17.2) in China. HPV6 and 11 single types were not identified in any of the samples. Proportion of the individual 7 high risk HPV types included in the vaccine varied by cytological and histological grades of HPV-positive precancerous cervical lesions. HPV 16 was the dominant type in all lesions, with contributions in low grade lesions ranging from 16.6%(14.3-19.2) in Mexico to 39.8% (30.0-50.2) in India, and contributions in high grade lesions ranging from 43.8% (36.3-51.4) in Mexico to 64.1% (60.6-67.5) in Brazil. After HPV 16, variations in other majors HPV types were observed by country, with an under representation of HPV 18 and 45 compared to ICC. CONCLUSION: The addition of HPVs 31/33/45/52/58 to HPV types included in current vaccines could increase the ICC preventable fraction in a range of 12 to 19% across the four countries, accounting the 9-types altogether 90% of ICC cases. Assuming the same degree of efficacy of current vaccines, the implementation of the 9-valent HPV vaccine in Brazil, Mexico, India and China would substantially impact on the reduction of the world cervical cancer burden.

Implementation of human papillomavirus immunization in the developing world.

Cervical cancer is the second leading cause of cancer death in women in less developed regions of the world and the leading cause of cancer deaths in GAVI-eligible countries, where 54% of worldwide cervical cancer deaths occur. If prevention is not implemented in these countries, population growth alone will lead to a 63% increase in deaths by 2025. Human papillomavirus (HPV) vaccines are routinely used in the National Immunization Programs in most industrial countries, and the decision by the GAVI Alliance to accept applications from eligible developing countries for HPV vaccine support is the single most important opportunity for children in these countries to be protected against HPV-related diseases. As it has done for other vaccines, such as Haemophilus influenzae type b, rotavirus and pneumococcal conjugate vaccines, GAVI should strongly consider developing and funding a group dedicated to working on all aspects of HPV vaccine introduction in the developing world. Immunization in middle-income developing countries not eligible for GAVI support will depend on "tiered" pricing policies or regional procurement schemes to make vaccine available at prices significantly lower than those in industrial countries. Immunization coverage of infants has reached high levels in many of the poorest developing countries where complementary strategies for HPV control, such as adult screening and treatment, are poorly developed. Immunizing young adolescents will require expansion of immunization infrastructure to reach cohorts that currently are largely unreached, but the success of school-based strategies in industrial countries and developing country demonstration projects provides hope that relatively high coverage may be achieved in many countries. Communication and advocacy strategies for HPV control need to carefully consider local cultural attitudes toward HPV-related issues. Current strategies supported by health economic analyses call for female only immunization, but concerns have been expressed as to whether this is the optimal strategy for the developing world. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

Hepatitis delta and HIV infection.

Hepatitis delta is the most severe of all chronic viral infections of the liver. Its agent, the hepatitis delta virus (HDV), is unique in many aspects. Because of similar transmission pathways, triple infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and HDV occurs frequently in intravenous drug users. The addition of HDV to an HIV/HBV coinfection is associated with a particularly aggressive course of liver disease, frequently leading to cirrhosis, decompensation, and death. Thus, screening for antibodies against HDV should be mandatory in all HBsAg-positive/HIV-positive patients. There is no specific treatment for HDV. The only therapeutic options currently available are long-duration interferon regimens, which are effective in <30% of the patients. Additionally, long-term treatment with HBV polymerase inhibitors as part of antiretroviral treatment may lower HBsAg- and HDV-ribonucleic acid levels in some patients. Early initiation of anti-HIV therapy seems to be reasonable in patients with hepatitis delta - even though controlled studies are not available.

HBeAg-positive hepatitis delta: virological patterns and clinical long-term outcome.

BACKGROUND AND AIMS: The presence of the hepatitis B virus (HBV)-eAg in patients with hepatitis B is associated with higher HBV replication and with an increased risk to develop liver-related clinical endpoints defined as liver related death, liver transplantation, development of hepatocellular carcinoma and hepatic decompensation. The aim of this study was to investigate the role of HBeAg in patients co-infected with the hepatitis D virus (HDV). METHODS: We studied virological markers of HBV and HDV infection and as well as biochemical and clinical features of liver disease in a cohort of 534 anti-HDV-positive patients. In addition, we compared the clinical long-term outcome of HBeAg-positive HDV-infected patients with HBeAg-negative control patients matched for age, gender and baseline-MELD score. RESULTS: HBeAg-positive hepatitis delta was detected in 71 of 534 patients (13.3%). HBeAg positivity was associated with a higher biochemical disease activity and higher HBsAg levels in HDV co-infected patients. Sixty one per cent of the HBeAg-positive HDV-infected patients presented with HBV DNA levels below 2000 IU/ml, at least once during follow-up. Both HBeAg-positive and -negative patients showed a similar severe clinical long-term course with about half of the patients developing a liver-related clinical complication after a median follow-up period of 51 months (range: 9-193 months). CONCLUSIONS: HBV DNA levels are low in both HBeAg-negative and HBeAg-positive patients suggesting suppressive effects of HDV on HBV irrespective of the phase of HBV infection. The clinical long-term outcome of HBeAg-positive patients is not different to HBeAg-negative patients infected with the HDV.

Phase III results of Boceprevir in treatment naïve patients with chronic hepatitis C genotype 1.

INTRODUCTION: Chronic hepatitis C virus infection affects approximately 2% of the world population and can result in cirrhosis and hepatocellular carcinoma. Until 2011, the standard of care (SOC) has been therapy with pegylated interferon alfa and ribavirin (PEG-IFN/RBV). Sustained virologic response rates (SVR) after SOC in patients infected with genotype 1 have been 40-50%. The development of new direct antiviral agents (DAA) is vital. The first drugs that specifically target the HCV protease have been approved in 2011. This review summarizes the results of SPRINT-2, a phase III double blind, placebo controlled study in which the efficacy and safety of Boceprevir, a new HCV protease inhibitor, was compared to SOC. DESIGN: A total of 1097 treatment-naïve, genotype 1, chronic hepatitis C patients were randomized into three different groups. All patients received a 4-week lead in phase with peginterferon alfa-2b and ribavirin. A total of 363 patients were randomized to the control group and received 44 additional weeks of PEG-IFN/RBV; of the 368 patients randomized to group 2, the response-guided treatment regimen (RGT), patients with undetectable HCV RNA through week 8 and 24 received 24 weeks of triple therapy (PEG-IFN/RBV/Boceprevir); patients whose HCV-RNA was detectable between weeks 8 and 24 but undetectable at week 24 received subsequently 20 weeks of (PEG-IFN/RBV); 366 patients in group 3 were treated with lead-in followed by triple therapy through week 48. RESULTS: Treatment with Boceprevir triple therapy increased SVR to 63-66% compared to 38% receiving PEG-IFN/RBV therapy. Non-Black patients achieved higher SVR rates compared to Black patients. Responsiveness to interferon in the lead-in phase was predictive for SVR. SVR rates did not differ between patients randomized to RGT with Boceprevir and those treated with a fixed duration. Anaemia was the most important adverse event leading to dose reduction of RBV in 13% of controls and 21% of Boceprevir recipients. CONCLUSION: Triple therapy of Boceprevir in combination with PEG-IFN 2b/RBV is more effective than SOC alone. RGT is possible without reducing the SVR rates. Management of anaemia has to be considered.

Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease.

BACKGROUND: Information on human papillomavirus (HPV) type distribution is necessary to evaluate the potential impact of current and future HPV vaccines. We estimated the relative contribution (RC) to invasive cervical cancer (ICC) and precancerous cervical lesions of the nine HPV types (HPV 6/11/16/18/31/33/45/52/58) included in an HPV vaccine currently under development. METHODS: Estimations on ICC were based on an international study of 8,977 HPV positive cases and estimations on precancerous cervical lesions were extracted from a published meta-analysis including 115,789 HPV positive women. Globocan 2008 and 2010 World Population Prospects were used to estimate current and future projections of new ICC cases. RESULTS: RC of the 9 HPV types in ICC was 89.4%, with 18.5% of cases positive for HPV 31/33/45/52/58. Regional variations were observed. RCs varied by histology, ranging between 89.1% in squamous cell carcinomas (SCC) and 95.5% in adenocarcinomas (ADC). HPV 16/18/45 were detected in 94.2% of ADC. RC of the 9 types altogether decreased with age (trend test p < 0.0001), driven by the decrease in older ages of HPV 16/18/45. In contrast, the RC of HPV 31/33/52/58 increased with age. Due to population growth alone, projected estimates of ICC cases attributable to the 9 types are expected to rise from 493,770 new cases in 2012 to 560,887 new cases in 2025.The RCs of individual high risk HPV types varied by cytological and histological grades of HPV-positive precancerous cervical lesions, and there was an under representation of HPV 18 and 45 compared to ICC. CONCLUSIONS: The addition of HPV 31/33/45/52/58 to HPV types included in current vaccines could prevent almost 90% of ICC cases worldwide. If the nine-valent vaccine achieves the same degree of efficacy than previous vaccines, world incidence rates could be substantially reduced.