Although urine‐based human papillomavirus (HPV) detection is promising in cervical cancer screening, it has not yet been well‐developed. Women aged 30–65 were invited to participate in the current ...study to provide one urine and two paired vaginal samples. Urine was detected by polymerase chain reaction (PCR)‐based HPV test (urine‐based HPV test). Two vaginal samples were tested by careHPV and GenPlex® HPV genotyping assay, respectively. Women with vaginal HPV positive were called back for colposcopy and biopsied if clinically indicated. The consistency was 79.0% (κ = 0.563) and 80.5% (κ = 0.605) between the urine‐based HPV test, careHPV test, and GenPlex® HPV genotyping assay. Against CIN2 detection, the careHPV test showed 77.4% sensitivity, and 71.0% specificity, while the GenPlex® HPV genotyping assay had a sensitivity of 100% and a specificity of 58.7%. For urine‐based HPV test, the corresponding rates were 96.8% and 58.7%. Moreover, no significant differences were observed between the urine‐based HPV test and careHPV test (p = 0.3395) and GenPlex® HPV genotyping assay (p = 0.338). The newly developed urine‐based HPV test demonstrated acceptable consistency and comparable clinical performance with referenced HPV tests for vaginal samples. Therefore, urine‐based HPV detection could be a useful alternative for women with difficulties to access cervical cancer screening.
Abstract
Background
The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to ...evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine.
Methods
A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission.
Results
In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months.
Conclusions
The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.
Summary Background Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done ...on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known. We assessed whether HPV testing on self-collected samples is equivalent to HPV testing on samples collected by clinicians. Methods We identified relevant studies through a search of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: a cervical cell sample was self-collected by a woman followed by a sample taken by a clinician; a high-risk HPV test was done on the self-sample (index test) and HPV-testing or cytological interpretation was done on the specimen collected by the clinician (comparator tests); and the presence or absence of cervical intraepithelial neoplasia grade 2 (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in women with one or more positive tests. The absolute accuracy for finding CIN2 or worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well as the relative accuracy of the index versus the comparator tests were pooled using bivariate normal models and random effect models. Findings We included data from 36 studies, which altogether enrolled 154 556 women. The absolute accuracy varied by clinical setting. In the context of screening, HPV testing on self-samples detected, on average, 76% (95% CI 69–82) of CIN2 or worse and 84% (72–92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or worse was 86% (83–89) and 87% (84–90) to exclude CIN3 or worse. The variation of the relative accuracy of HPV testing on self-samples compared with tests on clinician-taken samples was low across settings, enabling pooling of the relative accuracy over all studies. The pooled sensitivity of HPV testing on self-samples was lower than HPV testing on a clinician-taken sample (ratio 0·88 95% CI 0·85–0·91 for CIN2 or worse and 0·89 0·83–0·96 for CIN3 or worse). Also specificity was lower in self-samples versus clinician-taken samples (ratio 0·96 0·95–0·97 for CIN2 or worse and 0·96 0·93–0·99 for CIN3 or worse). HPV testing with signal-based assays on self-samples was less sensitive and specific than testing on clinician-based samples. By contrast, some PCR-based HPV tests generally showed similar sensitivity on both self-samples and clinician-based samples. Interpretation In screening programmes using signal-based assays, sampling by a clinician should be recommended. However, HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme. Some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs. Funding The 7th Framework Programme of the European Commission, the Belgian Foundation against Cancer, the International Agency for Research on Cancer, and the German Guideline Program in Oncology.
This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis ...of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up.
This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18–45 years, with intact cervix and 1–4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18–26 and 27–45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006.
Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2–100·0) against high-grade genital lesions (0 0% of 3310 participants in the vaccine group and 13 0·4% of 3302 participants in the control group) and 97·3% (89·9–99·7) against persistent infection (2 0·1% of 3262 participants in the vaccine group and 73 2·2% of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 7·2% of 3691 participants) and control groups (290 7·9% of 3681); none were considered related to vaccination.
The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention.
National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.
High‐risk (HR) human papillomavirus (HPV) prevalence has been shown to correlate well with cervical cancer incidence rates. Our study aimed to estimate the prevalence of HR‐HPV and cervical ...intraepithelial neoplasia (CIN) in China and indirectly informs on the cervical cancer burden in the country. A total of 30,207 women from 17 population‐based studies throughout China were included. All women received HPV DNA testing (HC2, Qiagen, Gaithersburg, MD), visual inspection with acetic acid and liquid‐based cytology. Women positive for any test received colposcopy‐directed or four‐quadrant biopsies. A total of 29,579 women had HR‐HPV testing results, of whom 28,761 had biopsy confirmed (9,019, 31.4%) or assumed (19,742, 68.6%) final diagnosis. Overall crude HR‐HPV prevalence was 17.7%. HR‐HPV prevalence was similar in rural and urban areas but showed dips in different age groups: at age 25–29 (11.3%) in rural and at age 35–39 (11.3%) in urban women. In rural and urban women, age‐standardized CIN2 prevalence was 1.5% 95% confidence interval (CI): 1.4–1.6% and 0.7% (95% CI: 0.7–0.8%) and CIN3+ prevalence was 1.2% (95% CI: 1.2–1.3%) and 0.6% (95% CI: 0.5–0.7%), respectively. Prevalence of CIN3+ as a percentage of either all women or HR‐HPV‐positive women steadily increased with age, peaking in 45‐ to 49‐year‐old women. High prevalence of HR‐HPV and CIN3+ was detected in both rural and urban China. The steady rise of CIN3+ up to the age group of 45–49 is attributable to lack of lesion removal through screening. Our findings document the inadequacy of current screening in China while indirectly raising the possibility that the cervical cancer burden in China is underreported.
Background/Aims: The development of atherosclerosis is accompanied by escalating inflammation and lipid accumulation within blood vessel walls. ABCA1 plays a crucial role in mediating cholesterol ...efflux from macrophages, which protects against atherogenesis. This research was designed to explore the effects and underlying mechanisms of apigenin (4’, 5, 7-trihydroxyflavone) on ABCA1-mediated cellular cholesterol efflux and LPS-stimulated inflammation in RAW264.7 macrophages and apoE-/- mice. Methods: Expression of genes or proteins was examined by RT-PCR or western blot analysis. Liquid scintillation counting was used to detect percent cholesterol efflux. Cellular cholesterol content was measured using HPLC assay. The secretion levels of pro-inflammatory cytokines were quantified by ELISA assay. Atherosclerotic lesion sizes were determined with Oil Red O staining. The contents of macrophages and smooth muscle cells in atherosclerotic lesion were evaluated using immunohistochemistry. Plasma TC, TG, HDL-C and LDL-C levels in apoE-/- mice were evaluated using commercial test kits. Results: Apigenin potently increased ABCA1 expression through miR-33 repression in a dose- and time-dependent manner. Treatment with apigenin significantly increased ABCA1-mediated cholesterol efflux, and reduced TC, FC and CE levels in macrophage-derived foam cells. In LPS-treated macrophages, the expression levels of TLR-4, MyD88 and p-IκB-α as well as nuclear NF-κB p65 were decreased by the addition of apigenin. Moreover, apigenin markedly decreased secretion levels of several pro-inflammatory cytokines. Lastly, in LPS-challenged apoE-/- mice, apigenin administration augmented ABCA1 expression, decreased the contents of macrophages and smooth muscle cells in atherosclerotic lesion, reduced miR-33, TLR-4, and NF-κB p65 levels, improved plasma lipid profile and relieved inflammation, which results in less atherosclerotic lesion size. Conclusions: Taken together, these results suggest that apigenin may attenuate atherogenesis through up-regulating ABCA1-mediated cholesterol efflux and inhibiting inflammation.
Improvement in managing HPV‐positive women is urgently needed. Based on a population‐based study which included 2112 women aged 49 to 69 from Shanxi, China, we aimed to evaluate the clinical ...performance of multiple triage strategies based on liquid‐based cytology (LBC), p16INK4a, viral load and partial genotyping, as a single or combined strategy for detecting cervical intraepithelial neoplasia grade 2/3 or higher (CIN2+/CIN3+) in women who tested positive by Hybrid Capture 2 (HC2). Among 452 HC2‐positive women, the test positivity of LBC (ASC‐US+), p16INK4a, HPV16/18 and HPV16/18/31/33/45 were 39.6%, 38.5%, 18.0% and 40.0%, respectively. Compared to LBC (ASC‐US+) triage, a single triage strategies using p16INK4a or extended genotyping (SureX HPV16/18/31/33/45) achieved comparable sensitivity (relative sensitivity: 1.08, 95% confidence interval CI: 0.93‐1.26 and 0.96, 95% CI: 0.76‐1.22) and specificity (relative specificity: 1.05, 95% CI: 0.96‐1.14 and 1.02, 95% CI: 0.92‐1.14) for CIN3+. Viral load triage using a ≥50 RLU/CO cut‐point also yielded similar results with LBC (ASC‐US+). Among combined triage strategies, HPV16/18 genotyping with reflex p16INK4a showed higher sensitivity and slightly lower specificity than LBC (ASC‐US+) for CIN3+ detection, however, the differences were not statistically significant. Of note, after a negative result by p16INK4a or LBC among HPV16/18 negative women, the posttest probability of CIN3+ was lower than 1%. Our study suggested that p16INK4a, extended genotyping and increased viral load cut‐point could be promising alternatives to cytology triage. Combined triage algorithms of HPV16/18 with reflex p16INK4a or cytology, if negative, are associated with the substantial low posttest risk sufficient to release women to next screening round.
What's new?
Cytology triage is widely used to manage the care of women with positive human papillomavirus (HPV) results following HPV‐based screening. Challenges with cytology in low‐resource settings, however, has fueled the development of other triage strategies. Whether these strategies are superior to cytology remains unclear. In this population‐based evaluation, promising alternatives to cytology triage were identified, including p16INK4a biomarker testing, extended genotyping, and viral load with increased cut‐point. These methods were especially suitable for settings that lack trained cytologists. Combined HPV16/18 with reflex p16INK4a or cytology provided optimal risk stratification, enabling double‐negative cases to be released to routine screening.
Recently, 2D organic–inorganic hybrid lead halide perovskites have attracted intensive attention in solid‐state luminescence fields such as single‐component white‐light emitters, and rational ...optimization of the photoluminescence (PL) performance through accurate structural‐design strategies is still significant. Herein, by carefully choosing homologous aliphatic amines as templates, isotypical perovskites DMEDAPbCl4 (1, DMEDA=N,N‐dimethylethylenediamine) and DMPDAPbCl4 (2, DMPDA=N,N‐dimethyl‐1,3‐diaminopropane) having tunable and stable broadband bluish white emission properties were rationally designed. The subtle regulation of organic cations leads to a higher degree of distortion of the 2D PbCl42− layers and enhanced photoluminescence quantum efficiencies (<1 % for 1 and 4.9 % for 2). The broadband light emissions could be ascribed to self‐trapped excitons on the basis of structural characterization, time‐resolved PL, temperature‐dependent PL emission, and theoretical calculations. This work gives a new guidance to rationally optimize the PL properties of low‐dimensional halide perovskites and affords a platform to probe the structure–property relationship.
Shining white: With the aim of optimizing the broadband white‐light emission performance of low‐dimensional perovskites, isomorphic 2D perovskites DMEDAPbCl4 and DMPDAPbCl4 were structurally designed on the basis of homologous amine templates. The subtle regulation of organic cations leads to increased distortion of the 2D PbCl42− layers and enhancement of the photoluminescence quantum efficiency from <1 to 4.9 %. DMEDA: dimethylethylenediamine, DMPDA: N,N‐dimethyl‐1,3‐diaminopropane.
Human papillomavirus (HPV) test, self‐sampling and thermal ablation for cervical intraepithelial neoplasia (CIN) have been developed separately to increase screening coverage and treatment compliance ...of cervical cancer screening programmes. A large‐scale study in rural China screened 9,526 women with their combinations to explore the optimal cervical cancer‐screening cascade in the real‐world. Participants received careHPV and polymerase chain reaction (PCR) HPV tests on self‐collected samples. Women positive on either HPV test underwent colposcopy, biopsy and thermal ablation in a single visit. Samples positive on either HPV test were retested for genotyping. Absolute and relative performance of HPV tests, triage strategies, ‘colposcopy and thermal ablation’ approach were statistically evaluated. PCR HPV test detected 33.3% more CIN grade two or worse (CIN2+) at a cost of 28.1% more colposcopies compared to careHPV. Sensitivities of PCR HPV and careHPV tests to detect CIN2+ were 96.7 and 72.5%. Specificities for the same disease outcome were 82.1 and 86.0%. Triaging HPV‐positive women with HPV16/18 genotyping considerably improved the positive predictive value for CIN2+ (4.8–5.0 to 18.2–19.2%). Ninety‐six women positive on HPV and having abnormal colposcopy were eligible for thermal ablation and all accepted same‐day treatment, contributing to 64.6% being treated appropriately (CIN1+ on histopathology), which reached up to 84.8% among women positive on HPV 16/18 triage. No serious side‐effects/complications were reported. The combination of PCR HPV test followed by HPV 16/18 triaging on self‐collected samples and colposcopy of triage positive women followed by immediate thermal ablation might be the appropriate screening cascade for rural China.
What's new?
To be effective, cervical cancer screening programs must be tailored to the needs of the target population. In rural China, screening coverage is low, and women may not return for separate diagnosis and treatment visits. Here, the authors evaluated various screening protocols under real world conditions. They found that self‐sampling, PCR HPV test and triage based on HPV16/18 genotyping, followed by colposcopy and immediate thermal ablation in a single visit, could be the most efficient screening cascade for this rural population. This plan reduced costs while increasing compliance for follow up care.
Agriculture production is crucial in mitigating climate change while securing food productivity. However, the impact of the practices such as organic waste (crop residue and animal manure) recycling ...or integrating crop-livestock system on productivity and carbon sequestration was unclear.
This study presents a potential crop-livestock model to enhance carbon sequestration from a whole system perspective. This study aimed to (i) examine the effect of different organic waste recycling on contents of SOC, MBC, and EOC at a depth of 0–60 cm of soil; (ii) analyze the sequestration potential of SOC for different organic wastes recycling models using the substance flow balance method; and (iii) propose suitable organic wastes recycling models for crop and livestock production system in China from the whole-system perspective.
This study conducted a comparative assessment of carbon sequestration of diverse organic wastes in China using a four-year field experiment and substance flow balance method. The field experiment involved three types of organic waste (raw maize straw (MS), biogas slurry (BS), dairy manure (DM)) and two fertilizer application treatments (unfertilized control (CK), and only chemical fertilizer (CF)). Based on the field results, the carbon flow for different organic waste recycle models was compared using the substance flow approach.
The content and sequestration of SOC and its fractions increased with the application of organic wastes. The effect of organic wastes on SOC sequestration followed the order DM > MS > BS. Additionally, organic waste, especially DM, significantly increased the sequestration of MBC and EOC by 198% and 359%, respectively, compared to CF. The SOC, MBC, and EOC sequestration rates for DM treatment were 2.9–3.2, 0.3–0.6, and 2.7–3.0 Mg ha−1 yr−1, respectively. On a per-crop yield basis, the “crop straw-livestock-manure-field” model contributed about six times more for SOC sequestration than CF. Future estimation showed that the DM model could reduce chemical fertilizer use by 36% compared to CF, resulting in lower costs. Therefore, the “crop straw-livestock-manure-field” system benefits carbon sequestration and emphasizes the importance of expanding the organic waste management chain.
The findings have significant implications for the agricultural system, highlighting the importance of integrating the “crop straw-livestock-manure-field” model for carbon sequestration and sustained productivity. The results demonstrate that this model has successfully increased carbon sequestration in the agricultural system. These findings provide an essential option for achieving carbon neutrality in China and promoting sustainable development in agricultural system in other regions.
Display omitted
•The field experiment and a whole-system approach were combined to analyze carbon sequestration.•Crop-livestock recoupling via maize straw significantly increased carbon and its fractions sequestration.•Maize straw based crop-livestock system increased crop yield and sustainable index.•Implementing the “crop straw-livestock-manure-field” model in the future agricultural system offers several benefits.
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