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Prediction of DNA methylation-based tumor types from histopathology in central nervous system tumors with deep learning
A deep learning model is used to classify central nervous system tumors based on their DNA methylation profile directly from histopathology, and showed high accuracy in a large set of external validation cohorts, potentially informing downstream treatment.
- Danh-Tai Hoang
- , Eldad D. Shulman
- & Kenneth Aldape
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Article |
Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial
In a prespecified interim analysis of the multicenter, randomized, phase 3 FLAMES trial, maintenance therapy with a PARP inhibitor in patients with ovarian cancer showed prolonged progression-free survival compared with placebo in all subgroups defined by BRCA or homologous recombination status.
- Xiaohua Wu
- , Jihong Liu
- & Linjuan Zeng
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Article
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Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial
Exploratory analyses of the DESTINY-Gastric01 trial show that baseline HER2-associated biomarkers in circulating tumor DNA or tissue samples were associated with therapeutic response in patients with HER2-positive tumors, and these analyses identify potential drivers of resistance.
- Kohei Shitara
- , Yung-Jue Bang
- & Kensei Yamaguchi
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News & Views |
Refining neoadjuvant immunotherapy for resectable lung cancer
In an era of expanding perioperative approaches for resectable non–small-cell lung cancer, new data demonstrate that dual neoadjuvant immunotherapy targeting PD-1 and LAG-3 is feasible; future analyses may enhance patient selection by identifying immune signatures predictive of response.
- Misty D. Shields
- & Christine M. Lovly
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Article
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Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer
In a prospective observational study, symptoms of anxiety and/or depression were associated with worse response to first-line treatment with immunotherapy in patients with advanced non-small-cell lung cancer.
- Yue Zeng
- , Chun-Hong Hu
- & Fang Wu
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Research Briefing |
Studying paired patient tissue and blood enables insights into immunotherapy toxicity
Using single-cell RNA and T cell receptor sequencing along with microscopy, we identified the cell types and genes associated with immune checkpoint inhibitor therapy-related colitis. Our study will help to identify targets for early diagnosis and lays the groundwork for the development of safer immunotherapy regimens.
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Article
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Pemigatinib in previously treated solid tumors with activating FGFR1–FGFR3 alterations: phase 2 FIGHT-207 basket trial
In a tumor-agnostic phase 2 basket trial, the oral FGFR1–FGFR3 inhibitor pemigatinib elicits responses in tumor types beyond cholangiocarcinoma and bladder cancer and in tumor types with rarer FGFR alterations, with insights provided into resistance mechanisms.
- Jordi Rodón
- , Silvia Damian
- & Lipika Goyal
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Research Highlight |
Sustainable, low-cost cancer diagnostics
Researchers have developed a low-resource, environmentally friendly cancer-diagnosis platform that detects metabolites in dried serum spots.
- Karen O’Leary
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Article
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Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development
Controlling for confounders calls into question the robustness of some associations of microbiota with colorectal cancer stages.
- Raúl Y. Tito
- , Sara Verbandt
- & Jeroen Raes
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Article
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Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses
In a phase 2 trial, nivolumab achieved a response rate of 58% in patients with mismatch-repair-deficient gynecological cancers, meeting the primary endpoint, and genomic and immunologic features correlated with response.
- Claire F. Friedman
- , Beryl L. Manning-Geist
- & Dmitriy Zamarin
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Article |
Risk-based lung cancer screening performance in a universal healthcare setting
Implementation of organized low-dose computed tomography screening in over 4,000 individuals with high risk for lung cancer as part of the Ontario Lung Cancer Screening Pilot reported high cancer detection rates, early detection of cancer and low serious harms.
- Martin C. Tammemägi
- , Gail E. Darling
- & Linda Rabeneck
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Article
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Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning
Developed on cytology images of hydrothorax and ascites from 57,220 cases at four hospitals, a deep-learning model shows high accuracy in tumor origin prediction and presents prognostic value when patient treatment is consistent with the cancer origin predicted by the model.
- Fei Tian
- , Dong Liu
- & Xiangchun Li
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News & Views |
Functional precision medicine for pediatric cancers
A small, prospective clinical study shows that ex vivo drug screening of pediatric cancer samples can identify effective therapeutic options. If validated, these findings could herald a new approach to precision medicine in this setting.
- M. Emmy M. Dolman
- & Paul G. Ekert
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Article
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Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers
In an observational study evaluating functional precision medicine in children and adolescents with relapsed or refractory solid and hematologic malignancies, it was feasible to provide personalized treatment recommendations to treating physicians on the basis of genomic profiling and ex vivo drug sensitivity testing within 4 weeks.
- Arlet M. Acanda De La Rocha
- , Noah E. Berlow
- & Diana J. Azzam
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Article
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Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial
Treatment of patients with advanced hepatocellular carcinoma with a personalized DNA vaccine in combination with anti-PD-1 therapy was safe and led to encouraging clinical efficacy, with immunological analyses confirming the induction of tumor antigen-specific T cell responses.
- Mark Yarchoan
- , Edward J. Gane
- & Niranjan Y. Sardesai
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Article |
A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results
In an interim analysis of a phase 1/2 trial, a heterologous prime boost vaccine comprised of a chimpanzee adenovirus and self-amplifying mRNA that encodes neoantigens derived from common oncogenic driver mutations in combination with immune checkpoint blockade was safe and elicited neoantigen-specific T cell responses in patients with advanced solid tumors.
- Amy R. Rappaport
- , Chrisann Kyi
- & Karin Jooss
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Article |
Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results
In an interim analysis of an ongoing phase 1 trial of CAR T cells targeting EGFR and IL13Ra2 in patients with multifocal, recurrent glioblastoma, intrathecal delivery is feasible and well tolerated, with some reductions seen in tumor size.
- Stephen J. Bagley
- , Meghan Logun
- & Donald M. O’Rourke
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Research Highlight |
MEGA CRISPR rejuvenates exhausted CAR T cells
MEGA is a new CRISPR-based RNA-editing platform with the ability to enhance the fitness of CAR T cells; it may also overcome certain limitations of conventional DNA-targeting CRISPR–Cas9 systems.
- Karen O’Leary
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Article |
Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors
An observational study reports the joint effects of polygenic risk scores and radiation treatment exposure with a subsequent increased risk of multiple solid cancers in two large cohorts of survivors of childhood cancer.
- Todd M. Gibson
- , Danielle M. Karyadi
- & Lindsay M. Morton
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Article
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Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial
In a large trial of patients with recurrent high-grade gliomas, IL-13Rα2-targeting CAR-T cells were feasible to manufacture and well tolerated when delivered via intratumoral and/or intraventricular routes.
- Christine E. Brown
- , Jonathan C. Hibbard
- & Behnam Badie
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Article |
Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial
In a randomized phase 2 trial comparing anti-PD-1 plus anti-VEGF plus an HDAC inhibitor versus anti-PD-1 plus an HDAC inhibitor in patients with MSS/pMMR colorectal cancer, the triplet combination led to significantly better 18-week progression-free survival.
- Feng Wang
- , Ying Jin
- & Rui-Hua Xu
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Article
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A gut microbial signature for combination immune checkpoint blockade across cancer types
Efforts to identify microbial signatures of response to immune checkpoint blockade suggest that strain-level associations may be cancer type agnostic but cancer therapy specific.
- Ashray Gunjur
- , Yan Shao
- & Trevor D. Lawley
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Research Highlight |
Improving the FITness of colorectal cancer screening
In a head-to-head study, a multitarget version of the widely used FIT (fecal immunochemical test) showed a higher cancer detection rate than the standard test.
- Karen O’Leary
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News & Views |
Immunotherapy at all stages of hepatocellular carcinoma
A flurry of emerging treatment options is transforming the therapeutic landscape of hepatocellular carcinoma; two new studies highlight the complexities and gaps in knowledge, but also hint at a greater understanding of how to apply immunotherapy in early and advanced disease.
- David J. Pinato
- , Claudia A. M. Fulgenzi
- & Antonio D’Alessio
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Research Briefing |
Longitudinal analysis shows how microbiome changes might influence responses to immune checkpoint blockade
Longitudinal analysis of stool samples reveals new insights into how the gut microbiome changes during immunotherapy. These findings could inform the application of microbiome-targeted interventions to maximize the outcomes of immune checkpoint blockade.
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Article
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Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial
In the phase 2 RENOBATE trial, the combination of regorafenib and nivolumab as first-line treatment for unresectable hepatocellular carcinoma exhibited a safe profile and met the primary endpoint with a 31% overall response rate.
- Hyung-Don Kim
- , Seyoung Jung
- & Changhoon Yoo
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Article
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Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma
Understanding the dynamics of the gut microbiota over the course of cancer treatment regimens and their associated adverse events can help identify microbial features that associate with response to immune checkpoint blockade.
- Johannes R. Björk
- , Laura A. Bolte
- & Rinse K. Weersma
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Article
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Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial
In the phase 2 HUDSON study, patients with advanced non-small-cell lung cancer received anti-PD-L1 combined with biomarker-guided therapy targeting ATR kinase, PARP, STAT3 or CD73, leading to encouraging clinical benefit in response to combination of the ATR kinase inhibitor ceralasertib with durvalumab.
- Benjamin Besse
- , Elvire Pons-Tostivint
- & John V. Heymach
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Article
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Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer
In an exploratory preplanned biomarker analysis of the phase 3 PARADIGM trial, a lack of resistance gene alterations in baseline circulating tumor DNA (negative hyperselection) was associated with prolonged overall survival after first-line panitumumab with chemotherapy in patients with RAS wild-type metastatic colorectal cancer.
- Kohei Shitara
- , Kei Muro
- & Takayuki Yoshino
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Article
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MYC targeting by OMO-103 in solid tumors: a phase 1 trial
In this first-in-human phase 1 dose-escalation trial of OMO-103, a MYC inhibitor, in patients with solid tumors, treatment was safe and showed preliminary clinical activity along with demonstrated target engagement and identification of potential pharmacodynamic markers.
- Elena Garralda
- , Marie-Eve Beaulieu
- & Emiliano Calvo
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Article |
First-line sugemalimab with chemotherapy for advanced esophageal squamous cell carcinoma: a randomized phase 3 study
In a prespecified interim analysis of the phase 3 trial GEMSTONE-304, anti-PD-L1 with chemotherapy versus chemotherapy alone led to significantly prolonged progression-free survival and overall survival of patients with unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.
- Jin Li
- , Zhendong Chen
- & Jason Yang
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Article |
Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma
Cohort-scale integration of clinical and proteomic data from tumor tissues in patients with pancreatic ductal adenocarcinoma led to the identification of a prognostic risk model for patient stratification as well as biomarkers of response to adjuvant chemotherapy, validated in independent external cohorts.
- Lingxi Jiang
- , Jiejie Qin
- & Baiyong Shen
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Research Highlight |
Personalized mRNA vaccine boosts melanoma immunotherapy
In patients with resected, high-risk melanoma, the addition of a personalized mRNA-based neoantigen therapy to adjuvant pembrolizumab was more effective than pembrolizumab alone.
- Karen O’Leary
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Correspondence |
A six-step quality-improvement model for cancer diagnosis and treatment in China
- Wenjing Yang
- & Jie He
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Brief Communication |
T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy
Profiling of a case of secondary T cell lymphoma following anti-CD19 CAR T cell therapy suggests that it was not caused by CAR insertional mutagenesis, with single-center analysis indicating that secondary T cell lymphoma risk after commercial CAR T cell treatment is low.
- Guido Ghilardi
- , Joseph A. Fraietta
- & Marco Ruella
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Article
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Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial
In the final report of a phase 1/2 trial evaluating allogeneic CD19-specific CAR-NK cells armored with IL-15 in patients with CD19+ hematologic malignancies, the therapy was shown to be safe and efficacious with distinct cord blood features associated with response.
- David Marin
- , Ye Li
- & Katayoun Rezvani
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Article
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Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma
Analysis of the pivotal phase 3 ZUMA-7 trial identifies tumor gene expression signatures that are uniquely predictive of anti-CD19 CAR T cell response and event-free survival in second-line treatment for patients with relapsed or refractory large B cell lymphoma.
- Frederick L. Locke
- , Simone Filosto
- & Jérôme Galon
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News & Views |
The grand challenge of moving cancer whole-genome sequencing into the clinic
The largest whole-genome sequencing study thus far has revealed myriad actionable alterations and potential biomarkers for 33 cancer types, but various logistical, technical and economic challenges must be overcome before this technique can become standard of care.
- Dilara Akhoundova
- & Mark A. Rubin
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Analysis
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Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme
The first report from the Cancer Programme of the 100,000 Genomes Project presents whole-genome sequencing profiles of 13,880 solid tumors spanning 33 cancer types, combined with real-world clinical data, providing insights for precision oncology.
- Alona Sosinsky
- , John Ambrose
- & Nirupa Murugaesu
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Comment |
Unanswered questions following reports of secondary malignancies after CAR-T cell therapy
Reports of T cell malignancies after CAR-T cell therapy should be investigated, but existing data from follow-up studies suggest a low risk compared with other cancer treatments.
- Bruce L. Levine
- , Marcelo C. Pasquini
- & Miguel-Angel Perales
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Article
| Open Access
Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial
In a phase 1 trial, a lymph node-targeting mutant KRAS peptide vaccine combined with CpG adjuvant is safe, reduces expression of tumor biomarkers and elicits mutant KRAS-specific T cells in patients with pancreatic cancer and colorectal cancer.
- Shubham Pant
- , Zev A. Wainberg
- & Eileen M. O’Reilly
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Article
| Open Access
Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial
A neoadjuvant treatment regimen of anti-PD-L1 monotherapy followed by anti-PD-L1 plus chemotherapy was well tolerated and led to a major pathologic response rate of 70% in patients with resectable gastric or gastroesophageal junction adenocarcinoma.
- Yara L. Verschoor
- , Joris van de Haar
- & Myriam Chalabi
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Article |
Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial
In this prespecified analysis of the ongoing TORCHLIGHT phase 3 trial, first-line treatment with toripalimab and nab-paclitaxel in patients with advanced triple-negative breast cancer led to significantly longer progression-free survival in the PD-L1-positive population compared to nab-paclitaxel alone.
- Zefei Jiang
- , Quchang Ouyang
- & Patricia Keegan
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Article
| Open Access
Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial
Exploratory ctDNA analyses from the phase 3 INTRIGUE trial indicate that ripretinib may provide benefits in patients with advanced gastrointestinal stromal tumors with KIT exon 11 + 17/18 mutations
- Michael C. Heinrich
- , Robin L. Jones
- & Sebastian Bauer
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Article |
Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial
A substudy of the CodeBreaK 101 trial, this phase 1b trial testing the KRAS-G12C inhibitor sotorasib with an anti-EGFR antibody shows an acceptable safety profile of this combination and encouraging preliminary clinical efficacy in patients with chemotherapy-refractory colorectal cancer.
- Yasutoshi Kuboki
- , Marwan Fakih
- & David S. Hong
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Article
| Open Access
Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial
Treatment of patients with relapsed or refractory multiple myeloma with a combination of the BCMA-targeting antibody–drug conjugate belatamab mafodotin with dexamethasone and pomlidomide is safe and shows promising preliminary clinical efficacy.
- Suzanne Trudel
- , Arleigh McCurdy
- & Donna Reece
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Article |
Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial
In the phase 2 trial NEOSUMMIT-01, perioperative treatment of patients with locally advanced gastric or gastro-esophageal junction adenocarcinoma with anti-PD-1 and SOX/XELOX versus SOX/XELOX alone improved pathological complete response or near-complete response rate.
- Shu-Qiang Yuan
- , Run-Cong Nie
- & Feng Wang
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News & Views |
Implementing plans for global elimination of cervical cancer
Evidence supports the use of primary HPV testing to accelerate the global elimination of cervical cancer, but such recommendations must be viewed in the context of the fragile healthcare systems and complex implementation challenges in low-income and lower-middle income countries.
- Diama Bhadra Vale
- & Julio Cesar Teixeira
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Article
| Open Access
Benefits and harms of cervical screening, triage and treatment strategies in women living with HIV
A model evaluating cervical screening, triage and treatment strategies to prevent cervical cancer in women living with HIV in Tanzania provides evidence to support the World Health Organization’s recommendation of primary HPV testing starting at age 25 years with 3–5-year regular screening intervals.
- Michaela T. Hall
- , Kate T. Simms
- & Karen Canfell
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