Beyond the scope of the HPV triage strategy - proposals for consideration.
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ABSTRACT:
SUBMITTER: Bottcher B
PROVIDER: S-EPMC6916551 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Beyond the scope of the HPV triage strategy - proposals for consideration.
BJOG : an international journal of obstetrics and gynaecology 20191105 1
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Project description:ObjectiveWe attempted to evaluate the immediate high-grade squamous intraepithelial lesion-cervical intraepithelial neoplasia grade 2/3 or worse (HSIL-CIN2+/3+, hereafter referred to as CIN2+/3+) risk of specific human papillomavirus (HPV) genotype and form the precise risk-based triage strategy for atypical squamous cells of undetermined significance (ASC-US) women.MethodsThe clinical data of ASC-US women who underwent HPV genotyping testing and colposcopy were retrospectively reviewed. The distribution and CIN2+/3+ risks of specific HPV genotype were assessed by three approaches. The risk-based triage strategy was further established, and its efficacy in detecting CIN2+/3+ was estimated.ResultsTotally, 5553 ASC-US women including 3648 HPV-positive and 1905 HPV-negative were analysed. CIN2+/3+ were 662/319 cases, including 639/306 HPV-positive and 23/13 HPV-negative women. HPV16, HPV52, HPV58 and HPV18 were always among the top 5 ranking genotypes, no matter in HPV-positive women or in HPV-positive CIN2+/3+ cases. HPV16 and HPV33 carried the highest risk, while HPV73 and 26 carried the least risk for CIN2+/3+. Based on the immediate CIN2+/3+ risk of specific HPV genotype, 18 HPVs were divided into three risk-stratified groups. Only women infected with HPVs included in group A were necessary for immediate colposcopy. Compared with conventional strategy, this new risk-based strategy not only had higher specificity (CIN2+: p = .00; CIN3+: p = .01) and positive predictive value (CIN2+: p = .00; CIN3+: p = .03) for detecting CIN2+/3+, but also needed fewer colposcopies to identify each CIN2+/3+.ConclusionsA new triage strategy for ASC-US women was successfully constructed based on CIN2+/3+ risks of 14 high-risk and 4 intermediate-risk HPVs, which could significantly reduce unnecessary colposcopies.
| S-EPMC11749152 | biostudies-literature
Project description:Global health enables the harmonisation of international and domestic-health concerns-its outlook is much wider than a development or foreign-assistance perspective alone. Engaging globally in health requires the creation of relevant and effective partnerships to implement solutions for shared or common problems. To build on the UK's achievements and leadership in global health, the central government Department of Health is now leading the development of a UK Government-wide global strategy. This paper describes the rationale and process for developing the new UK Government-wide strategy for global health and highlights some of the issues that must be discussed.
| S-EPMC7159083 | biostudies-literature
Project description:Objective: According to the 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) recommendations, women with a positive high-risk human papillomavirus (HR-HPV) diagnosis and low-grade cervical intraepithelial lesion (LSIL) cytology result should be referred for further colposcopy examination. However, this strategy results in over-treatment in several cases. In this study, we assessed the performance of extended HR-HPV genotyping in women with a simultaneous positive HR-HPV and LSIL diagnosis with the aim of improving the current triage strategy. Methods: This study was an observational analysis of women from the Fujian Province Cervical Lesion Screening Cohorts (FCLSCs). Women who were HR-HPV-positive and had a cytological examination of LSIL, which were followed up with colposcopy and biopsy, from 2015 to 2018 were included. The study endpoint was defined as the detection of histological cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We combined HR-HPV genotypes according to the prevalence rate in histological CIN2+ and ranked them from high to low to establish HR-HPV genotyping models. Outcomes were assessed with respect to sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and colposcopy referral rate. Results: Overall, 56,788 women undergoing preliminary screening for HR-HPV genotyping were included in this study. Among them, 10,499 women positive for HR-HPV underwent a cytology examination, and 902 women with LSIL cytology diagnosed and subsequent biopsy results were included in the final evaluation. Among these patients, 25.1% (226/902) were found to have CIN2+ in histology. HPV-16, -58, -52, -18, -33, and -31 infections were the most common genotypes, and HPV-16, -18, -58, -33, and -31 (odds ratio [OR] = 5.41, 2.98, 1.38, 1.24, and 1.21, respectively) were associated with the potential for histological CIN2+, from the highest to lowest. In the detection of CIN2+ lesions in HR-HPV-positive LSIL women of different HR-HPV genotyping models, the extended HPV 16/18/31/33/52/58 genotyping model was found to have better efficacy with higher sensitivity (92.9%) and NPV (93.0%), but a significantly lower colposcopy referral rate (74.7%) than the ASCCP-recommended HR-HPV non-genotyping model. Conclusion: For HR-HPV-positive women with LSIL, the HPV 16/18/31/33/52/58 genotyping model can serve as an alternative approach to the ASCCP recommendations, potentially reducing the unnecessary colposcopy referral burden in China.
| S-EPMC8176432 | biostudies-literature
Project description:Sequencing-based spatial transcriptomics (sST) enables transcriptome-wide gene expression mapping but falls short of reaching the optical resolution (200-300 nm) of imaging-based methods. Here, we present Seq-Scope-X (Seq-Scope-eXpanded), which empowers submicrometer-resolution Seq-Scope with tissue expansion to surpass this limitation. By physically enlarging tissues, Seq-Scope-X minimizes transcript diffusion effects and increases spatial feature density by an additional order of magnitude. In liver tissue, this approach resolves nuclear and cytoplasmic compartments in nearly every single cell, uncovering widespread differences between nuclear and cytoplasmic transcriptome patterns. Independently confirmed by imaging-based methods, these results suggest that individual hepatocytes can dynamically switch their metabolic roles. Seq-Scope-X is also applicable to non-hepatic tissues such as brain and colon, and can be modified to perform spatial proteomic analysis, simultaneously profiling hundreds of barcode-tagged antibody stains at microscopic resolutions in mouse spleens and human tonsils. These findings establish Seq-Scope-X as a transformative tool for ultra-high-resolution whole-transcriptome and proteome profiling, offering unparalleled spatial precision and advancing our understanding of cellular architecture, function, and disease mechanisms.
| S-EPMC11838548 | biostudies-literature
Project description:BackgroundIn Norway, repeat cytology and HPV testing comprise delayed triage of women with minor cytological lesions. The objective of this study was to evaluate HPV DNA and HPV mRNA testing in triage of women with an ASC-US/LSIL diagnosis.Materials and methodsWe used repeat cytology, HPV DNA testing (Cobas 4800) and HPV mRNA testing (PreTect HPV-Proofer) to follow up 311 women aged 25-69 years with ASC-US/LSIL index cytology.ResultsOf 311 women scheduled for secondary screening, 30 women (9.6%) had ASC-H/HSIL cytology at triage and 281 women (90.4%) had ASC-US/LSIL or normal cytology. The HPV DNA test was positive in 92 (32.7%) of 281 instances, and 37 (13.2%) were mRNA positive. Of the 132 women with repeated ASC-US/LSIL, we received biopsies from 97.0% (65/67) of the DNA-positive and 92.9% (26/28) of the mRNA-positive cases. The positive predictive values for CIN2+ were 21.5% (14/65) for DNA positive and 34.6% (9/26) for mRNA positive (ns). The odds ratio for being referred to colposcopy in DNA-positive cases were 2.8 times (95% CI: 1.8-4.6) higher that of mRNA-positive cases. Compared to the mRNA test, the DNA test detected four more cases of CIN2 and one case of CIN3.ConclusionsThe higher positivity rate of the DNA test in triage leads to higher referral rate for colposcopy and biopsy, and subsequent additional follow-up of negative biopsies. By following mRNA-negative women who had ASC-US/LSIL at triage with cytology, the additional cases of CIN2+ gained in DNA screening can be discovered. Our study indicates that in triage of repeated ASC-US/LSIL, HPV mRNA testing is more specific and is more relevant in clinical use than an HPV DNA test.
| S-EPMC4236101 | biostudies-literature
Project description:ObjectiveWe investigated the relation between man papillomavirus (HPV) integration status and the immediate risk of cervical intraepithelial neoplasia (CIN), as well as the triage strategy based on HPV integration test.Methods4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective, population-based, clinical observational study to evaluate the triage performance of HPV integration. Cervical exfoliated cells were collected for HPV testing and cytologic test. If high-risk HPV was positive, HPV integration test was performed at baseline, 2-year and 5-year follow-up.ResultsAt baseline, HPV integration was positively correlated with the severity of cervical pathology, ranging from 5.0% (15/301) in normal diagnosis, 6.9% (4/58) in CIN1, 31.0% (9/29) in CIN2, 70% (14/20) in CIN3, and 100% (2/2) in cervical cancer (P < 0.001). Compared with cytology, HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+, higher specificity (92.8% [90.2%-95.4%] vs. 75.5% [71.2%-79.8%], P < 0.001) and higher positive predictive value (36.4% [22.1%-50.6%] vs. 15.2% [8.5%-21.8%], P < 0.001). HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy (10.7% [44/410] vs. 27.3% [112/410], P < 0.001). The HPV integration-negative group exhibited the lowest immediate risk for CIN3+ (1.6%) and accounted for the largest proportion of the total population (89.3%), when compared with the normal cytology group (risk, 1.7%; proportion, 72.7%).ConclusionAs a key molecular basis for the development of cervical cancer, HPV integration might be a promising triage strategy for HPV-positive patients.
| S-EPMC11674434 | biostudies-literature
Project description:We have developed a new dialkylbiaryl monophosphine ligand, GPhos, that supports a palladium catalyst capable of promoting carbon-nitrogen cross-coupling reactions between a variety of primary amines and aryl halides; in many cases, these reactions can be carried out at room temperature. The reaction development was guided by the idea that the productivity of catalysts employing BrettPhos-like ligands is limited by their lack of stability at room temperature. Specifically, it was hypothesized that primary amine and N-heteroaromatic substrates can displace the phosphine ligand, leading to the formation of catalytically dormant palladium complexes that reactivate only upon heating. This notion was supported by the synthesis and kinetic study of a putative off-cycle Pd complex. Consideration of this off-cycle species, together with the identification of substrate classes that are not effectively coupled at room temperature using previous catalysts, led to the design of a new dialkylbiaryl monophosphine ligand. An Ot-Bu substituent was added ortho to the dialkylphosphino group of the ligand framework to improve the stability of the most active catalyst conformer. To offset the increased size of this substituent, we also removed the para i-Pr group of the non-phosphorus-containing ring, which allowed the catalyst to accommodate binding of even very large α-tertiary primary amine nucleophiles. In comparison to previous catalysts, the GPhos-supported catalyst exhibits better reactivity both under ambient conditions and at elevated temperatures. Its use allows for the coupling of a range of amine nucleophiles, including (1) unhindered, (2) five-membered-ring N-heterocycle-containing, and (3) α-tertiary primary amines, each of which previously required a different catalyst to achieve optimal results.
| S-EPMC8057821 | biostudies-literature
Project description:ObjectiveTo explore the utility of extended Human Papillomavirus (HPV) genotyping to detect cervical intraepithelial neoplasia grade 2 or more (CIN2+) in a 'screen-and-treat' strategy for HPV-positive women in low-resource settings.DesignProspective study of diagnostic accuracy.SettingThe study took place in West Cameroon between September 2018 and March 2020.Participants2014 women were recruited. Asymptomatic, non-pregnant women aged 30-49 years without history of CIN treatment, anogenital cancer or hysterectomy were eligible.InterventionsParticipants performed self-sampling for HPV testing with GeneXpert followed by visual inspection with acetic acid and Lugol's iodine (VIA) triage before treatment if required.Main outcome measuresLiquid-based cytology, biopsies and endocervical brushing were performed in HPV-positive women as quality control. We assessed the detection rate of CIN2+ by HPV genotyping (two pools of genotypes obtained from the Xpert system, pool_1 (HPV 16, 18, 45) and pool_2 (HPV 16, 18, 45, 31, 33, 35, 52, 58)), VIA and cytology.Results382 (18.2%) women were HPV-positive among which 11.5% (n=44) were CIN2+. Of those 44 participants, 41 were triaged positive by extended genotyping, versus 35 by VIA and 33 by cytology. Overall, triage positivity was of 68.4% for extended genotyping, 59.3% for VIA and 14.8% for cytology, with false positive rates of 83.4%, 84.1% and 37.7%, respectively. Extended genotyping had a higher sensitivity for CIN2+ detection (93.2%, CI: 81.3 to 98.6) than VIA (79.5%, CI: 64.7 to 90.2, p=0.034) and cytology (75.0%, CI: 59.7 to 86.8, p=0.005). No significant difference was observed in the overtreatment rate in triaged women by extended genotyping or VIA (9.9%, CI: 8.6 to 11.3, and 8.8%, CI: 7.7 to 10.1), with a ratio of 6.0 and 6.3 women treated per CIN2+ diagnosed.ConclusionTriage of HPV-positive women with extended HPV genotyping improves CIN2+ detection compared with VIA with a minor loss of specificity and could be used to optimize the management of HPV-positive women.Trial registration numberNCT03757299.
| S-EPMC9791451 | biostudies-literature
Project description:ObjectiveTo assess triage compliance and the effect of the time from screening to triage on follow-up among HPV-positive women.MethodsWe recruited 1232 women in a screening campaign in Madagascar from February to October 2015. In the first period (February-May), HPV tests were performed remotely using the cobas test. In the second period (May-October), testing was performed on-site using the Xpert HPV assay. HPV-positive women were invited for triage with visual inspection with acetic acid (VIA) and Lugol's iodine (VILI). Systematic biopsy and endocervical brushing were performed on all HPV-positive women for quality control. Three groups were defined according to time from HPV testing to triage invitation for HPV-positive women-Group I: delayed (> 3 months), Group II: prompt (24-48 hours), and Group III: immediate (< 24 hours).ResultsA total 1232 self-sampled HPV tests were performed in the study period (496 in Group I, 512 in Group II, and 224 in Group III). Participants' mean age was 43.2 ± 9.3 years. Mean time from screening to VIA/VILI testing was 103.5 ± 43.6 days. Overall HPV prevalence was 28.0%. HPV prevalence was 27.2% in Group I (cobas test), 29.2% in Group 2 (Xpert test), and 26,7% in Group III (Xpert test). The VIA/VILI compliance rate was 77.8% for Group I, 82.7% for Group II, and 95.0% for Group III. Of women undergoing VIA/VILI, 56.3% in Group I and 43.5% in Groups II/III had positive results. Prevalence of cervical intraepithelial neoplasia grade 2 or worse among HPV-positive women was 9.8% for Group I and 6.8% for Groups II/III. Non-adherence was higher among rural women, uneducated women, and women in Group I.ConclusionHPV-positive women with immediate VIA/VILI triage invitation had the best triage compliance. A single-day test and triage strategy is preferred for low-resource settings.
| S-EPMC6692065 | biostudies-literature
Project description:ObjectiveReferring all women who tested positive for human papillomavirus (HPV) 16/18 to colposcopy may lead to potential over-referral issues. Triage tests based on cytology results face challenges in achieving accurate diagnoses. Our study aims to assess the clinical effectiveness of PAX1/JAM3 methylation (CISCER) test as a triage method for HPV 16/18-positive women.MethodsFrom November 2021 to December 2022, a total of 334 women who tested positive for HPV 16/18 and were referred to colposcopy at The Second Affiliated Hospital of Zhejiang University School of Medicine were studied. The clinical utility of the CISCER test, cytology, and the combination of CISCER with cytology as potential triage tests was compared.ResultsWe observed a significant increase in the methylation levels of PAX1 gene and JAM3 gene in women with cervical intraepithelial neoplasia (CIN) grade 2 or severe (CIN2+). The CISCER test demonstrated superior triage performance over cytology, even when used in combination with cytology, showing a high sensitivity of 89.0% (95% confidence interval [CI] 82.9-95.1%) and specificity of 95.3% (95% CI 92.6-98.0%). It achieved an area under the curve of 0.921 (95% CI 0.877-0.966) and an odds ratio of 164.02 (95% CI 68.64-391.95). The immediate CIN2+ risk based on positive CISCER results would be 89.0% (95% CI 80.8-94.1%), with an estimated average of 1.12 referrals needed to detect one CIN2+ case. Moreover, CISCER triaging successfully identified all cancer patients and did not miss any CIN3+ cases among women aged ≥ 30.ConclusionsThe PAX1/JAM3 methylation detection exhibited excellent accuracy in identifying cervical precancerous lesions in HPV 16/18-positive women and could be considered as a triage tool to reduce excessive referrals for colposcopy and overtreatment.
| S-EPMC11674251 | biostudies-literature