Accuracy of triage strategies for human papillomavirus DNA-positive women in low-resource settings: A cross-sectional study in China

CareHPV is a human papillomavirus (HPV) DNA test for low-resource settings (LRS). This study assesses optimum triage strategies for careHPV-positive women in LRS

Absolute Risk and Attributable Fraction of Type-Specific Human Papillomavirus in Cervical Cancer and Precancerous Lesions—A Population-Based Study of 6286 Women in Rural Areas of China

Background: To investigate the human papillomavirus (HPV) genotype distribution among the general population and assess the attribution of HPV genotypes targeted by vaccines to protect against cervical lesions theoretically. Methods: Cervical samples were collected from women aged 21 to 64 years old from Inner Mongolia and Shanxi Province in China who had not been vaccinated against HPV. HPV type-specific absolute risk (AR) to classified cervical lesions was calculated and then the attributable fraction (AF) was estimated, together with the combined contributions of the HPV types, targeted by four available HPV vaccines and five HPV vaccines in clinical trials in China to protect against cervical lesions. Results: A total of 6286 women with an average age of 44.1 years ± 8.41 (range: 21–64) participated in the study. The age distribution of 14 HR-HPV and HPV16/18 all showed a ‘U’ shape, which peaked in the ≤25 year-group and >55 year-group. The five most common genotypes were HPV16 (4.3%), HPV52 (4.1%), HPV58 (2.1%), HPV51 (2.1%), and HPV66 (1.7%). The prevalence of HPV types 6 and 11 infections was 1.1% and observed with n significant differences across age stratifications in China. AF to CIN2+ was predominated by HPV 16 with 56.2%, followed by HPV58 (12.0%), HPV52 (8.5%), HPV18 (4.3%), and HPV51 (2.9%). HPV52 and 58 in the prophylactic HPV vaccine would enhance the protection against CIN2+ by approximately 20%. Conclusions: Regarding multi-valent HPV vaccine development in China, the HPV types 16, 52, 58, and 18 should be given priority for their high prevalence at the population level, high AR, notable AF, and high relative risk to high-grade cervical lesions

Efficacy of the AS04-adjuvanted HPV-16/18 vaccine in young Chinese women with oncogenic HPV infection at baseline: post-hoc analysis of a randomized controlled trial

Human papillomavirus (HPV) vaccines are efficacious against HPV infections and associated lesions in women HPV-naïve at vaccination. However, vaccine efficacy (VE) against oncogenic, high-risk HPV (HR-HPV) types in women infected with any other HR-HPV type at first vaccination (baseline) remains unclear. This post-hoc analysis of a phase II/III study (NCT00779766) evaluated AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) VE against HR-HPV type infection in 871 Chinese women aged 18–25 years over a 72-month follow-up period. Study participants were DNA-negative at baseline to HR-HPV type(s) considered for VE and DNA-positive to any other HR-HPV type. Initial serostatus was not considered. Baseline DNA prevalence was 14.6% for any HR-HPV type and 10.6% excluding HPV-16/18. In the total vaccinated cohort for efficacy, VE against 6-month and 12-month HPV-16/18 persistent infections (PIs) in women DNA-negative to HPV-16/18 but DNA-positive to any other HR-HPV type at baseline was 100.0% (95% Confidence Interval [CI]: 79.8–100.0) and 100.0% (95%CI: 47.2–100.0), respectively. VE against HPV-16/18 incident infections in women DNA-positive to one vaccine type but DNA-negative to the other one at baseline was 66.8% (95%CI: −18.9–92.5). VE against HPV-31/33/45 incident infections, in women DNA-positive to HPV-16/18 and DNA-negative to the considered HPV type at baseline was 71.0% (95%CI: 27.3–89.8). No HPV-16/18 PIs were observed in vaccinated women with non-vaccine HPV A7/A9 species cervical infection at baseline. These findings indicated that women with existing HR-HPV infection at vaccination might still benefit from the AS04-HPV-16/18 vaccine. However, this potential benefit needs further demonstration in the future

Naturally acquired HPV antibodies against subsequent homotypic infection: A large-scale prospective cohort study

宫颈癌是全球15-44岁女性中第二常见的癌症，其主要病因是高危型HPV的感染，尤其是HPV 16型和18型的感染，在我国与约84%的宫颈癌有关。早期研究显示因自然免疫获得抗体的女性再次感染同型HPV的风险降低较为有限（约35%），但在这些研究中多依据IgG抗体而非中和抗体作为自然免疫指标进行保护效果分析。我校研究人员利用国产双价HPV疫苗III期临床试验中未接种HPV疫苗且HPV DNA为阴性的3600余名18-45岁健康女性队列，分别采用中和抗体和IgG抗体作为获得自然免疫的指标，分析其在之后5.5年的随访期间再次感染同型HPV的风险。该研究首次在大样本长期随访队列中以中和抗体作为免疫指标评价HPV自然免疫效果，获得了客观准确的HPV自然免疫数据，丰富了HPV自然史研究，为HPV疫苗接种策略的制订提供了重要依据。我校博士生姚星妹、中国医学科学院肿瘤医院陈汶教授和北京大学人民医院赵超教授为该论文共同第一作者。我校吴婷教授、张军教授、夏宁邵教授和中国医学科学院肿瘤医院乔友林教授、赵方辉教授为该论文的共同通讯作者。Background: Although recent studies have suggested that naturally acquired Human papillomavirus (HPV) antibodies are partly protective against subsequent homotypic infection, the extent of protection remains indecisive. Here, we evaluate the protective effect of neutralizing and IgG antibodies simultaneously. Methods: In a cohort of 3634 women aged 18-45 years from the control arm of a phase III trial of the HPV-16/18 bivalent vaccine, participants were tested for neutralizing antibodies by pseudovirion-based neutralization assay (PBNA) and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) at baseline. HPV-16/18 incident and persistent infections were identified using cervical specimens periodically collected during the 5.5 years of follow-up. The protective effects of HPV-16/18 neutralizing and IgG antibodies against homotypic infection were assessed using a Cox proportional hazard model. Findings: For the persistent infection (PI) endpoints of HPV-16/18 lasting for over 6/12 months, a prevalence of type-specific neutralizing antibodies was highly protective (6-month PI: hazard ratio (HR) = 0.16,95% confidence interval (CI): 0.04, 0.65; 12-month PI: HR = 0.23, 95% CI: 0.06, 0.94), whereas a prevalence of IgG antibodies was associated with minor and non-significant protection (6-month PI: HR = 0.66, 95% CI: 0.40, 1.09; 12-month PI: HR = 0.66, 95% CI: 0.36, 1.20). After increasing the cut-off value to the median IgG level, the risk of 6-month PI was significantly lower in seropositive vs seronegative women (HR = 0.38, 95% CI: 0.18, 0.83). Interpretation: Naturally acquired antibodies are associated with a substantially reduced risk of subsequent homotypic infection.We thank all the study participants and research staff of the HPV-003 Study Group for their contributions to the present study. In addition, we also thank Dr. Allan Hildesheim of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, National Institutes of Health for his helpful comments on this study.该研究获得国家自然科学基金、福建省卫生教育联合攻关计划项目、厦门市科技重大专项、中国医学科学院医学科学创新基金和厦门万泰沧海生物技术有限公司的支持。Funding: NSFC; The Fujian Province Health Education Joint Research Project; Xiamen Science and Technology Major Project; CIFMS; and Xiamen Innovax

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

ObjectivesAmong patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant.DesignSecondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).SettingOne hundred-fifty-three ICUs in 13 countries.PatientsAltogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).InterventionsNone.Measurements and main resultsTotal mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p p p p p p p p = 0.007).ConclusionsAmong STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation