Progress in prophylactic human papillomavirus (HPV) vaccination in 2016: A literature review

Prophylactic human papillomavirus (HPV) vaccine represents a revolutionary step forward in preventing HPV-related cancers, especially cervical carcinoma. Alongside appropriate screening, it has the potential to dramatically reduce cervical cancer incidence and even eradicate it. Following extensive evaluations in clinical trials, the first decade of routine HPV vaccine use provides overwhelming evidence of the vaccines’ safety and their real-life effectiveness. In 2016, further clinical trials showed high vaccine efficacy in adult women, especially those that were HPV DNA-negative at baseline, and indicated possible protection from HPV-related diseases after treatment of precancerous cervical lesions. The recommendation for a two-dose schedule in individuals under 15 is further supported for all three licensed vaccines by immunogenicity studies that show non-inferior immune responses and similar clinical efficacy compared to the three-dose schedule. So far, natural competition between HPV types has not been confirmed and therefore vaccine-induced clinically significant type replacement is unlikely. The real-world effectiveness data showed cross-sectional reduction in the prevalence/incidence of vaccine-related HPV types, genital warts and precancerous cervical lesions in countries and regions with HPV vaccination coverage. These declines were evident not only in vaccinated females, but also in unvaccinated females and males, strongly suggesting herd protection. Despite an excellent safety profile consistently demonstrated in clinical trials and confirmed in real-life settings, recently invented controversial syndromes allegedly linked to HPV vaccines temporarily compromised some previously very successful vaccination programs and significantly contributed to the failure of HPV vaccine implementation in some countries with the highest prevalence of cervical cancer. However, several safety studies failed to confirm any association of these syndromes with HPV vaccination in various settings and geographic locations. The main challenges remain implementing HPV vaccination in national vaccination programs, especially in low-and middle-income countries with the highest burden of cervical cancer, and achieving and sustaining high vaccine coverage rates.     

A systematic review of the social and economic burden of influenza in low- and middle-income countries

ObjectivesThe economic burden of seasonal influenza outbreaks as well as influenza pandemics in lower- and middle-income countries (LMIC) has yet to be specifically systematically reviewed. The aim of this systematic review is to assess the evidence of influenza economic burden assessment methods in LMIC and to quantify the economic consequences of influenza disease in these countries, including broader opportunity costs in terms of impaired social progress and economic development.MethodsWe conducted an all language literature search across 5 key databases using an extensive list of key words for the time period 1950–2013. We included studies which explored direct costs (medical and non-medical), indirect costs (productivity losses), and broader economic impact in LMIC associated with different influenza outcomes such as confirmed seasonal influenza infection, influenza-like illnesses, and pandemic influenza.ResultsWe included 62 full-text studies in English, Spanish, Russian, Chinese languages, mostly from the countries of Latin American and the Caribbean and East Asia and Pacific with pertinent cost data found in 39 papers. Estimates for direct and indirect costs were the highest in Latin American and the Caribbean. Compared to high-income economies, direct costs in LMIC were lower and productivity losses higher. Evidence on broader impact of influenza included impact on the wider national economy, security dimension, medical insurance policy, legal frameworks, distributional impact, and investment flows.ConclusionThe economic burden of influenza in LMIC encompasses multiple dimensions such as direct costs to the health service and households, indirect costs due to productivity losses as well as broader detriments to the wider economy. Evidence from sub-Saharan Africa and in pregnant women remains very limited. Heterogeneity of methods used to estimate cost components makes data synthesis challenging. There is a strong need for standardizing research, data collection and evaluation methods for both direct and indirect cost components.     

Vaxvec: The first web-based recombinant vaccine vector database and its data analysis

A recombinant vector vaccine uses an attenuated virus, bacterium, or parasite as the carrier to express a heterologous antigen(s). Many recombinant vaccine vectors and related vaccines have been developed and extensively investigated. To compare and better understand recombinant vectors and vaccines, we have generated Vaxvec (http://www.violinet.org/vaxvec), the first web-based database that stores various recombinant vaccine vectors and those experimentally verified vaccines that use these vectors. Vaxvec has now included 59 vaccine vectors that have been used in 196 recombinant vector vaccines against 66 pathogens and cancers. These vectors are classified to 41 viral vectors, 15 bacterial vectors, 1 parasitic vector, and 1 fungal vector. The most commonly used viral vaccine vectors are double-stranded DNA viruses, including herpesviruses, adenoviruses, and poxviruses. For example, Vaxvec includes 63 poxvirus-based recombinant vaccines for over 20 pathogens and cancers. Vaxvec collects 30 recombinant vector influenza vaccines that use 17 recombinant vectors and were experimentally tested in 7 animal models. In addition, over 60 protective antigens used in recombinant vector vaccines are annotated and analyzed. User-friendly web-interfaces are available for querying various data in Vaxvec. To support data exchange, the information of vaccine vectors, vaccines, and related information is stored in the Vaccine Ontology (VO). Vaxvec is a timely and vital source of vaccine vector database and facilitates efficient vaccine vector research and development.     

Association of weight-adjusted-waist index with all-cause and cardiovascular mortality in China: A prospective cohort study

Background and aimsAs a new simple anthropometric index, the weight-adjusted-waist index (WWI) appears to be superior to body mass index (BMI) and waist circumference (WC) in assessing both muscle and fat mass. We aimed to explore the association of WWI with all-cause and cardiovascular mortality in southern China.Methods and resultsA total of 12,447 participants (mean age, 59.0 ± 13.3 years; 40.6% men) in Jiangxi Province from the China Hypertension Survey study were included. WWI was defined as WC divided by the square root of weight. The outcome was all-cause and cardiovascular mortality. During a median follow-up of 5.6 years, 838 all-cause deaths occurred, with 390 cardiovascular deaths. Overall, there was a nonlinear positive relationship of WWI with all-cause and cardiovascular mortality. Accordingly, compared with participants in quartiles 1–3 (<11.2 cm/√kg), a significant higher risk of all-cause mortality (HR: 1.36, 95% CI: 1.17, 1.58) and cardiovascular mortality (HR: 1.43, 95% CI: 1.15, 1.77) were found in quartile 4 (≥11.2 cm/√kg). Further adjustment for BMI and WC did not substantially alter the results. No significant interactions were found in any of the subgroups (sex, age, area, physical activity, current smoking, current alcohol drinking, hypertension, and stroke).ConclusionHigher WWI levels (≥11.2 cm/√kg) were associated with increased the risk of all-cause and cardiovascular mortality in southern China. These findings, if confirmed by further studies, suggested that WWI may serve as a simple and effective anthropometric index in clinical practice.     

High leptin status indicates an increased risk of mortality and heart failure in stable coronary artery disease

Background and aimsLeptin is an adipocyte-derived peptide involved in energy homeostasis and body weight regulation. The position of leptin in cardiovascular pathophysiology remains controversial. Some studies suggest a detrimental effect of hyperleptinemia on the cardiovascular (CV) system, while others assume the role of leptin as a neutral or even protective factor. We have explored whether high leptin affects the mortality and morbidity risk in patients with stable coronary heart disease.Methods and resultsWe followed 975 patients ≥6 months after myocardial infarction or coronary revascularization in a prospective study. All-cause or cardiovascular death, non-fatal cardiovascular events (recurrent myocardial infarction, stroke, or any revascularization), and hospitalizations for heart failure (HF) we used as outcomes.High serum leptin concentrations (≥18.9 ng/mL, i.e., 4th quartile) were associated with worse survival, as well as with a higher incidence of fatal vascular events or hospitalizations for HF. Even after full adjustment for potential covariates, high leptin remained to be associated with a significantly increased 5-years risk of all-cause death [Hazard risk ratio (HRR) 2.10 (95%CIs:1.29–3.42), p < 0.003], CV death [HRR 2.65 (95%CIs:1.48–4.74), p < 0.001], and HF hospitalization [HRR 1.95 (95% CIs:1.11–3.44), p < 0.020]. In contrast, the incidence risk of non-fatal CV events was only marginally and non-significantly influenced [HRR 1.27 (95%CIs:0.76–2.13), p = 0.359].ConclusionsHigh leptin concentration entails an increased risk of mortality, apparently driven by fatal CV events and future worsening of HF, on top of conventional CV risk factors and the baseline status of left ventricular function.     

Risk of vertebral fractures: evaluation on vertebral trabecular attenuation value and hydroxyapatite concentration in patients by chest spectral CT

Objectives:To analyze vertebral fractures risk in patients with chest scans by evaluating vertebral hydroxyapatite concentration measured on spectral CT compared to trabecular attenuation value measured on conventional CT.Methods:Our retrospective study reviewed CT of 216 patients. Analysis of vertebral (T11 – L1) hydroxyapatite concentration by spectral imaging and trabecular attenuation value by conventional CT imaging were performed in patients with chest CT examinations. Specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) were performed by using receiver operating characteristic (ROC) curves in patients with and without vertebral fractures.Results:In male patients, vertebral hydroxyapatite concentration had high area under the ROC curve (0.916), by using the optimal threshold of 72.27 mg/cm³, specificity, sensitivity, NPV, and PPV were 91.7, 80.2, 36.7, and 98.7%, respectively. In female patients, vertebral hydroxyapatite concentration also had high area under the ROC curve (0.870), by using the optimal threshold of 74.79 mg/cm³, specificity, sensitivity, NPV, and PPV were 100.0, 77.8, 47.4, and 100.0%, respectively. Area under the ROC curve was significantly different between spectral CT-measured bone hydroxyapatite concentration and conventional CT-measured attenuation value in distinguishing vertebral fractures (p = 0.007 for males; p = 0.005 for females).Conclusions:Quantitative assessment with spectral CT may appear as higher accuracy than that of conventional CT imaging to analyze risk of vertebral fractures. Hydroxyapatite concentration measured with chest spectral CT may be used to evaluate risk of bone fractures.Advances in knowledge:Hydroxyapatite concentration measured with chest spectral CT may be used to evaluate risk of bone fractures.     

Detection and genotyping of human papillomavirus by real-time PCR assay

BackgroundDiagnosis of human papillomavirus (HPV) disease remains a challenge due to several factors related to the cost, the workload of available commercial assays to detect and genotype HPV, and to the low prevalence of infected patients.ObjectiveOur study aimed to develop a real-time PCR, based on SPF10 primers, in order to combine HPV-DNA detection and genotype identification avoiding the negative samples.Study designValidation of SYBR-green based SPF10 real-time PCR on HPV-DNA plasmids followed by the investigation of the viral status in 92 samples from oropharyngeal (94%) cutaneous biopsies (3%) and anal smears (3%) which had previously been HPV-genotyped by LiPA hybridization. In-house HPV viral loads were performed to evaluate the SPF10 real-time PCR sensitivity.ResultsData showed that 100% of HPV plasmids, assessable by LiPA hybridization, were detected and genotyped appropriately after SPF10 real-time PCR assays. These results defined a range of melting temperature peaks for HPV positivity by real-time PCR. The efficient determination of the presence of HPV-DNA by SPF10 real-time PCR was validated for 98% of clinical samples compared to commercial method. Discordant results were due to a low HPV-DNA amount and to a supplementary HPV genotype identified. The SPF10 real-time PCR sensitivity was evaluated between 1 and 10 copies/10³ cells using in-house HPV (6, 11 and 16) viral load assays.ConclusionThe real-time PCR method was efficient in combining screening and genotyping of HPV-DNA. Cost and workload reduction by SPF10 real-time PCR approach may facilitate earlier diagnosis and clinical management of HPV infected patients.     

Postoperative stability of conventional bimaxillary surgery compared with maxillary impaction surgery with mandibular autorotation for patients with skeletal class II retrognathia

We aimed to compare the postoperative stability of conventional bimaxillary surgery (with bilateral sagittal split osteotomy) with that of maxillary impaction surgery (with mandibular autorotation without bilateral sagittal split osteotomy) in patients with skeletal class II retrognathia. Patients were assigned to have conventional bimaxillary surgery (conventional group, n = 6) or mandibular autorotation (experimental group, n = 7). Measurements were made using serial lateral cephalometric radiographs taken immediately preoperatively (T0), immediately postoperatively (T1), and one year later (T2) to assess the variation in operative change (T1-T0) and relapse (T2-T1). There was no significant difference in median (range) surgical change in the anterior movement at point B (conventional group, 4.5 (3.0–11.0) mm; experimental group 4.1 (2.1–6.4) mm). However, there was a significant difference in median (range) surgical posterior movement relapse at point B (conventional group −1.7 (−2.3 to −0.5) mm; experimental group −0.6 (−1.0 to 1.0) mm; p = 0.032). Mandibular advancement with mandibular autorotation is therefore a more stable procedure than mandibular advancement with bilateral sagittal split osteotomy in patients with skeletal class II retrognathia.     

Rare presentation of multi-organ abdominal echinococcosis: report of a case and review of literature

Hydatid disease, which is also known as cystic echinococcosis, is a zoonotic infection caused by the cestode tapeworm Echinococcus granulosus and rarely by Echinococcus multilocularis. In this report we describe an unusual case of a 19-year-old woman who was admitted to our hospital for abdominal pain, nausea, and vomiting. Computed tomography revealed multi-organ abdominal echinococcosis. The patient recovered after undergoing surgery to excise the cyst. The diagnosis, clinical features, treatment, and prevention in this case of multi-organ abdominal echinococcosis are discussed, in light of the relevant literature.