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Baba SK, Alblooshi SSE, Yaqoob R, Behl S, Al Saleem M, Rakha EA, Malik F, Singh M, Macha MA, Akhtar MK, Houry WA, Bhat AA, Al Menhali A, Zheng ZM, Mirza S. Human papilloma virus (HPV) mediated cancers: an insightful update. J Transl Med 2025; 23:483. [PMID: 40301924 PMCID: PMC12039116 DOI: 10.1186/s12967-025-06470-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 04/07/2025] [Indexed: 05/01/2025] Open
Abstract
Human papillomavirus (HPV), a DNA virus, is a well-documented causative agent of several cancers, including cervical, vulvar, vaginal, penile, anal, and head & neck cancers. Major factors contributing to HPV-related cancers include persistent infection and the oncogenic potential of particular HPV genotypes. High-risk HPV strains, particularly HPV-16 and HPV-18, are responsible for over 70% of cervical cancer cases worldwide, as well as a significant proportion of other genital and head and neck cancers. At the molecular level, the oncogenic activity of these viruses is driven by the overexpression of E6 and E7 oncoproteins. These oncoproteins dysregulate the cell cycle, inhibit apoptosis, and promote the accumulation of DNA damage, ultimately transforming normal cells into cancerous ones. This review aims to provide a comprehensive overview of the recent advances in HPV-related cancer biology and epidemiology. The review highlights the molecular pathways of HPV-driven carcinogenesis, focusing on the role of viral oncoproteins in altering host cell targets and disrupting cellular signalling pathways. The review explores the therapeutic potential of these viral proteins, and discusses current diagnostic and treatment strategies for HPV-associated cancers. Furthermore, the review highlights the critical role of HPV in the development of various malignancies, emphasizing the persistent challenges in combating these cancers despite advancements in vaccination and therapeutic strategies. We also emphasize recent breakthroughs in utilizing biomarkers to monitor cancer therapy responses, such as mRNAs, miRNAs, lncRNAs, proteins, and genetic markers. We hope this review will serve as a valuable resource for researchers working on HPV, providing insights that can guide future investigations into this complex virus, which continues to be a major contributor to global morbidity and mortality.
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Affiliation(s)
- Sadaf Khursheed Baba
- Department of Chemistry, College of Science (COS), United Arab Emirates University (UAEU), P.O. Box 15551, Al Ain, United Arab Emirates
| | | | - Reem Yaqoob
- Department of Chemistry, College of Science (COS), United Arab Emirates University (UAEU), P.O. Box 15551, Al Ain, United Arab Emirates
| | - Shalini Behl
- Omics Centre of Excellence, M42 Health, Abu Dhabi, United Arab Emirates
| | - Mansour Al Saleem
- Department of Applied Medical Sciences, Applied College, Qassim University, Qassim, Saudi Arabia
| | - Emad A Rakha
- Histopathology Department, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Pathology, Hamad Medical Corporation, Doha, Qatar
| | - Fayaz Malik
- Division of Cancer Pharmacology, CSIR-Indian Institute of Integrative Medicine, Srinagar, Jammu and Kashmir, 190005, India
| | - Mayank Singh
- Department of Medical Oncology (Lab), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India
| | - Muzafar A Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Kashmir, 192122, India
| | - Mohammed Kalim Akhtar
- Department of Chemistry, College of Science (COS), United Arab Emirates University (UAEU), P.O. Box 15551, Al Ain, United Arab Emirates
| | - Walid A Houry
- Department of Biochemistry, University of Toronto, Toronto, ON, M5G 1M1, Canada
- Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6, Canada
| | - Ajaz A Bhat
- Metabolic and Mendelian Disorders Clinical Research Program, Precision OMICs Research & Translational Science, Sidra Medicine, Doha, Qatar
| | - Asma Al Menhali
- Department of Biology, College of Science (COS), United Arab Emirates University (UAEU), Al Ain, United Arab Emirates
| | - Zhi-Ming Zheng
- Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA
| | - Sameer Mirza
- Department of Chemistry, College of Science (COS), United Arab Emirates University (UAEU), P.O. Box 15551, Al Ain, United Arab Emirates.
- Zayed Bin Sultan Centre for Health Sciences, United Arab Emirates University (UAEU), Al Ain, United Arab Emirates.
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Zhang Y, Qiu K, Ren J, Zhao Y, Cheng P. Roles of human papillomavirus in cancers: oncogenic mechanisms and clinical use. Signal Transduct Target Ther 2025; 10:44. [PMID: 39856040 PMCID: PMC11760352 DOI: 10.1038/s41392-024-02083-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 10/19/2024] [Accepted: 11/24/2024] [Indexed: 01/27/2025] Open
Abstract
Human papillomaviruses, particularly high-risk human papillomaviruses, have been universally considered to be associated with the oncogenesis and progression of various cancers. The genome of human papillomaviruses is circular, double-stranded DNA that encodes early and late proteins. Each of the proteins is of crucial significance in infecting the epithelium of host cells persistently and supporting viral genome integrating into host cells. Notably, E6 and E7 proteins, classified as oncoproteins, trigger the incidence of cancers by fostering cell proliferation, hindering apoptosis, evading immune surveillance, promoting cell invasion, and disrupting the balance of cellular metabolism. Therefore, targeting human papillomaviruses and decoding molecular mechanisms by which human papillomaviruses drive carcinogenesis are of great necessity to better treat human papillomaviruses-related cancers. Human papillomaviruses have been applied clinically to different facets of human papillomavirus-related cancers, including prevention, screening, diagnosis, treatment, and prognosis. Several types of prophylactic vaccines have been publicly utilized worldwide and have greatly decreased the occurrence of human papillomavirus-related cancers, which have benefited numerous people. Although various therapeutic vaccines have been developed and tested clinically, none of them have been officially approved to date. Enhancing the efficacy of vaccines and searching for innovative technologies targeting human papillomaviruses remain critical challenges that warrant continuous research and attention in the future.
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Affiliation(s)
- Yu Zhang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Ke Qiu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Jianjun Ren
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
| | - Yu Zhao
- Department of Otolaryngology-Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
| | - Ping Cheng
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
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Agelaki S, Boukovinas I, Athanasiadis I, Trimis G, Dimitriadis I, Poughias L, Morais E, Sabale U, Bencina G, Athanasopoulos C. A systematic literature review of the human papillomavirus prevalence in locally and regionally advanced and recurrent/metastatic head and neck cancers through the last decade: The "ALARM" study. Cancer Med 2024; 13:e6916. [PMID: 38247106 PMCID: PMC10905345 DOI: 10.1002/cam4.6916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 11/29/2023] [Accepted: 12/30/2023] [Indexed: 01/23/2024] Open
Abstract
AIMS The aim of this systematic literature review was to provide updated information on human papillomavirus (HPV) prevalence in locally and regionally advanced (LA) and recurrent/metastatic (RM) head and neck cancer (HNC) worldwide. METHODS Electronic searches were conducted on clinicaltrials.gov, MEDLINE/PubMed, Embase, and ASCO/ESMO journals of congresses for interventional studies (IS; Phase I-III trials) as well as MEDLINE and Embase for non-interventional studies (NIS) of LA/RM HNC published between January 01, 2010 and December 31, 2020. Criteria for study selection included: availability of HPV prevalence data for LA/RM HNC patients, patient enrollment from January 01, 2010 onward, and oropharyngeal cancer (OPC) included among HNC types. HPV prevalence per study was calculated as proportion of HPV+ over total number of enrolled patients. For overall HPV prevalence across studies, mean of reported HPV prevalence rates across studies and pooled estimate (sum of all HPV+ patients over sum of all patients enrolled) were assessed. RESULTS Eighty-one studies (62 IS; 19 NIS) were included, representing 9607 LA/RM HNC cases, with an overall mean (pooled) HPV prevalence of 32.6% (25.1%). HPV prevalence was 44.7% (44.0%) in LA and 24.3% (18.6%) in RM. Among 2714 LA/RM OPC patients from 52 studies with available data, mean (pooled) value was 55.8% (50.7%). The majority of data were derived from Northern America and Europe, with overall HPV prevalence of 46.0% (42.1%) and 24.7% (25.3%) across studies conducted exclusively in these geographic regions, respectively (Northern Europe: 31.9% [63.1%]). A "p16-based" assay was the most frequently reported HPV detection methodology (58.0%). CONCLUSION Over the last decade, at least one quarter of LA/RM HNC and half of OPC cases studied in IS and NIS were HPV+. This alarming burden is consistent with a potential implication of HPV in the pathogenesis of at least a subgroup of HNC, underscoring the relevance of HPV testing and prophylaxis to HNC prevention and management.
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Affiliation(s)
- Sofia Agelaki
- Laboratory of Translational Oncology, School of MedicineUniversity of CreteHerakleionGreece
- Department of Medical OncologyUniversity General Hospital of HerakleionHerakleionGreece
| | | | | | | | | | | | - Edith Morais
- MSD, Center for Observational and Real‐World Evidence (CORE)LyonFrance
| | - Ugne Sabale
- MSD, Center for Observational and Real‐World Evidence (CORE)StockholmSweden
| | - Goran Bencina
- MSD, Center for Observational and Real‐World Evidence (CORE)MadridSpain
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Human Papillomavirus: Oral Lesions and Vaccination. Cancers (Basel) 2023; 15:2711. [PMCID: PMC10216653 DOI: 10.3390/cancers15102711] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 05/09/2023] [Indexed: 06/12/2023] Open
Abstract
Human papillomavirus (HPV) is associated with benign and malignant lesions in various locations, such as the skin and oral and genital mucosa [...]
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Smit MJ, Sander AF, Ariaans MBPA, Fougeroux C, Heinzel C, Fendel R, Esen M, Kremsner PG, Ter Heine R, Wertheim HF, Idorn M, Paludan SR, Underwood AP, Binderup A, Ramirez S, Bukh J, Soegaard M, Erdogan SM, Gustavsson T, Clemmensen S, Theander TG, Salanti A, Hamborg M, de Jongh WA, McCall MBB, Nielsen MA, Mordmüller BG. First-in-human use of a modular capsid virus-like vaccine platform: an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2. THE LANCET. MICROBE 2023; 4:e140-e148. [PMID: 36681093 PMCID: PMC9848408 DOI: 10.1016/s2666-5247(22)00337-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUND Capsid virus-like particles (cVLP) have proven safe and immunogenic and can be a versatile platform to counter pandemics. We aimed to clinically test a modular cVLP COVID-19 vaccine in individuals who were naive to SARS-CoV-2. METHODS In this phase 1, single-centre, dose-escalation, adjuvant-selection, open-label clinical trial, we recruited participants at the Radboud University Medical Center in Nijmegen, Netherlands, and sequentially assigned them to seven groups. Eligible participants were healthy, aged 18-55 years, and tested negative for SARS-CoV-2 and anti-SARS-CoV-2 antibodies. Participants were vaccinated intramuscularly on days 0 and 28 with 6 μg, 12 μg, 25 μg, 50 μg, or 70 μg of the cVLP-based COVID-19 vaccine (ABNCoV2). A subgroup received MF59-adjuvanted ABNCoV2. Follow-up was for 24 weeks after second vaccination. The primary objectives were to assess the safety and tolerability of ABNCoV2 and to identify a dose that optimises the tolerability-immunogenicity ratio 14 days after the first vaccination. The primary safety endpoint was the number of related grade 3 adverse events and serious adverse events in the intention-to-treat population. The primary immunogenicity endpoint was the concentration of ABNCoV2-specific antibodies. The trial is registered with ClinicalTrials.gov, NCT04839146. FINDINGS 45 participants (six to nine per group) were enrolled between March 15 and July 15, 2021. Participants had a total of 249 at least possibly related solicited adverse events (185 grade 1, 63 grade 2, and one grade 3) within a week after vaccination. Two serious adverse events occurred; one was classified as a possible adverse reaction. Antibody titres were dose-dependent with levels plateauing at a vaccination dose of 25-70 μg ABNCoV2. After second vaccination, live virus neutralisation activity against major SARS-CoV-2 variants was high but was lower with an omicron (BA.1) variant. Vaccine-specific IFNγ+ CD4+ T cells were induced. INTERPRETATION Immunisation with ABNCoV2 was well tolerated, safe, and resulted in a functional immune response. The data support the need for additional clinical development of ABNCoV2 as a second-generation SARS-CoV-2 vaccine. The modular cVLP platform will accelerate vaccine development, beyond SARS-CoV-2. FUNDING EU, Carlsberg Foundation, and the Novo Nordisk Foundation.
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Affiliation(s)
- Merel J Smit
- Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Adam F Sander
- AdaptVac Aps, Copenhagen, Denmark; Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Maud B P A Ariaans
- Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | | | - Constanze Heinzel
- Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Rolf Fendel
- Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Tübingen, Germany
| | - Meral Esen
- Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Tübingen, Germany
| | - Peter G Kremsner
- Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Tübingen, Germany
| | - Rob Ter Heine
- Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Heiman F Wertheim
- Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Manja Idorn
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | | | - Alexander P Underwood
- Copenhagen Hepatitis C Program, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Alekxander Binderup
- Copenhagen Hepatitis C Program, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Santseharay Ramirez
- Copenhagen Hepatitis C Program, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens Bukh
- Copenhagen Hepatitis C Program, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Max Soegaard
- ExpreS2ion Biotechnologies Aps, Hørsholm, Denmark
| | - Sayit M Erdogan
- Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Tobias Gustavsson
- Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Thor G Theander
- Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ali Salanti
- Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Matthew B B McCall
- Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands; Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
| | - Morten A Nielsen
- Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
| | - Benjamin G Mordmüller
- Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
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Han X, Alu A, Liu H, Shi Y, Wei X, Cai L, Wei Y. Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy. Bioact Mater 2022; 17:29-48. [PMID: 35386442 PMCID: PMC8958282 DOI: 10.1016/j.bioactmat.2022.01.011] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 01/04/2022] [Accepted: 01/06/2022] [Indexed: 12/13/2022] Open
Abstract
Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications, as demonstrated in preclinical and clinical studies. However, the broad applications of biotherapy have been limited by critical challenges, including the lack of safe and efficient delivery systems and serious side effects. Due to the unique potentials of biomaterials, such as good biocompatibility and bioactive properties, biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy. The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions, enabling a sustained and localized release of drugs at the target sites. Furthermore, the biomaterials can provide a niche with specific extracellular conditions for the proliferation, differentiation, attachment, and migration of stem cells, leading to tissue regeneration. In this review, the state-of-the-art studies on the applications of biomaterials in biotherapy, including drug delivery, vaccine development, gene therapy, and stem cell therapy, have been summarized. The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.
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Affiliation(s)
- Xuejiao Han
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Aqu Alu
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Hongmei Liu
- Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Yi Shi
- Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Xiawei Wei
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Lulu Cai
- Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Yuquan Wei
- Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
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Sinha P, Seshadri JG, Chidambaram P. Effect of Health Education on Awareness of HPV Vaccination and its Acceptance Among Postpartum Women. INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2022. [DOI: 10.1007/s40944-022-00633-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Kwak HW, Shin W, Baik K, Kim M, Park Y, Hong SH, Park HJ, Park HJ, Bang YJ, Kim JY, Lee YS, Kim IB, Kim HL, Kim H, Nam JH. Single-stranded RNA adjuvant enhances the efficacy of 10-valent human papilloma virus-like particle vaccine. Microbiol Immunol 2022; 66:529-537. [PMID: 35979884 DOI: 10.1111/1348-0421.13024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 08/03/2022] [Accepted: 08/11/2022] [Indexed: 11/28/2022]
Abstract
Following the development of various types of vaccines, the use of adjuvants to boost vaccine efficacy has become a focus of research. Aluminum hydroxide (alum), the most commonly used adjuvant, induces a certain immune response and ensures safety in human trials. However, alum mainly induces only a Th2 response; its Th1 response is weak. Thus, we previously developed a single-stranded ribose nucleic acid (ssRNA) adjuvant that induces a Th1 response through toll-like receptors. Here, we explored whether 10-valent human papilloma virus (HPV)-like particle (VLP) vaccine formulated with ssRNA adjuvant and alum helped enhance immune response and maintained memory response. The mice were immunized intramuscularly twice at 2-week intervals and were inoculated 4 days after the second boost (after about 1 year). Antibody response and T cell activation were measured by Elispot, ELISA using harvested serum and splenocytes. 10-valent HPV VLP vaccine formulated with ssRNA adjuvant and alum increased antigen-specific immune response than alum used alone. It increased each type-specific IgG1/IgG2c titers, and antigen-specific IFN-γ cells. Furthermore, the ssRNA adjuvant with alum induced memory response. In memory response, each type-specific IgG1/IgG2c, IFN-γ, and IL-6 cytokines, and neutralizing antibodies were increased by the ssRNA adjuvant with alum. Overall, the ssRNA adjuvant with alum induced memory responses and balanced Th1/Th2 responses. The ssRNA adjuvant and alum may help to enhanced prophylactic vaccine efficacy. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Hye Won Kwak
- Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.,Department of R&D, SMLbiopharm, Bucheon, 14662, Republic of Korea
| | - Wooseok Shin
- Department of R&D, SK bioscience, Pangyoro, 332, Bundang-gu, Republic of Korea
| | - Kyunghwa Baik
- Department of R&D, SK bioscience, Pangyoro, 332, Bundang-gu, Republic of Korea
| | - Minsun Kim
- Department of R&D, SK bioscience, Pangyoro, 332, Bundang-gu, Republic of Korea
| | - YongWook Park
- Department of R&D, SK bioscience, Pangyoro, 332, Bundang-gu, Republic of Korea
| | - So-Hee Hong
- Department of Microbiology, College of Medicine, Ewha Womans University, Seoul, 07804, Republic of Korea
| | - Hyo-Jung Park
- Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea
| | - Hyeong-Jun Park
- Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.,Department of R&D, SMLbiopharm, Bucheon, 14662, Republic of Korea
| | - Yoo-Jin Bang
- Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.,Department of R&D, SMLbiopharm, Bucheon, 14662, Republic of Korea
| | - Jae-Yong Kim
- Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.,Department of R&D, SMLbiopharm, Bucheon, 14662, Republic of Korea
| | - Yu-Sun Lee
- Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea
| | - In-Beom Kim
- Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea
| | - Hong-Lim Kim
- Integrative Research Support Center, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea
| | - Hun Kim
- Department of R&D, SK bioscience, Pangyoro, 332, Bundang-gu, Republic of Korea
| | - Jae-Hwan Nam
- Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea.,Department of R&D, SMLbiopharm, Bucheon, 14662, Republic of Korea
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9
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Johansen S, Laegreid IJ, Ernstsen SL, Azrakhsh NA, Kittang AO, Lindås R, Gjertsen BT, Vetti N, Mørtberg TV, Sørvoll IH, Holme PA, Ahlen MT, Reikvam H. Thrombosis and thrombocytopenia after HPV vaccination. J Thromb Haemost 2022; 20:700-704. [PMID: 34817130 PMCID: PMC9906134 DOI: 10.1111/jth.15604] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/11/2021] [Accepted: 11/18/2021] [Indexed: 01/11/2023]
Abstract
BACKGROUND Vaccine-induced immune thrombotic thrombocytopenia (VITT) has so far only been reported after adenovirus vector severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. OBJECTIVE We report findings in a 25-year-old woman who presented with thrombocytopenia, venous thrombosis, elevated D-dimer levels, and high levels of platelet-activating antibodies to platelet factor 4-polyanion complexes 10 days after Gardasil 9 vaccination for human papillomavirus (HPV). The patient exhibited clinical and laboratory features in line with the recently defined VITT syndrome, described after adenoviral vector vaccination to prevent coronavirus disease 2019. CONCLUSION We report a case of VITT following HPV vaccination. This should raise awareness of the possibility of VITT also occurring after other vaccines, not exclusively adenoviral vector-based SARS-CoV-2 vaccines.
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Affiliation(s)
- Silje Johansen
- Section of Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Ingvild Jenssen Laegreid
- The Norwegian National Unit for Platelet Immunology, Division of Diagnostics, University Hospital of North Norway, Tromsø, Norway
| | - Siw Leiknes Ernstsen
- The Norwegian National Unit for Platelet Immunology, Division of Diagnostics, University Hospital of North Norway, Tromsø, Norway
| | - Nessar Ahmad Azrakhsh
- Section of Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Astrid Olsnes Kittang
- Section of Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Roald Lindås
- Section of Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Bjørn Tore Gjertsen
- Section of Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Nils Vetti
- Department of Radiology, Haukeland University Hospital, Bergen, Norway
- Department of Medical Science, University of Bergen, Bergen, Norway
| | - Trude Victoria Mørtberg
- The Norwegian National Unit for Platelet Immunology, Division of Diagnostics, University Hospital of North Norway, Tromsø, Norway
- Institute of Medical Biology, University of Tromsø - The Arctic University of Norway, Tromsø, Norway
| | - Ingvild Hausberg Sørvoll
- The Norwegian National Unit for Platelet Immunology, Division of Diagnostics, University Hospital of North Norway, Tromsø, Norway
| | - Pål André Holme
- Department of Hematology, Oslo University Hospital, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway
| | - Maria Therese Ahlen
- The Norwegian National Unit for Platelet Immunology, Division of Diagnostics, University Hospital of North Norway, Tromsø, Norway
| | - Håkon Reikvam
- Section of Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
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10
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Kurosawa M, Sekine M, Yamaguchi M, Kudo R, Hanley SJB, Hara M, Adachi S, Ueda Y, Miyagi E, Ikeda S, Yagi A, Enomoto T. Long-Term Effects of Human Papillomavirus Vaccination in Clinical Trials and Real-World Data: A Systematic Review. Vaccines (Basel) 2022; 10:vaccines10020256. [PMID: 35214713 PMCID: PMC8877934 DOI: 10.3390/vaccines10020256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/03/2022] [Accepted: 02/04/2022] [Indexed: 12/04/2022] Open
Abstract
The preventive effect of HPV vaccines against anogenital and oropharyngeal cancers has been proven in both clinical trials and real-world data. We reviewed the published evidence about the long-term efficacy and effectiveness of the HPV vaccine in available papers of clinical trials and real-world data. As far as we searched, the longest period of preventive effect for the bivalent, 4-valent, and 9-valent vaccine were 11 years in the Costa Rica trial, 14 years in the FUTURE II, and 8 years in the LTFU extension study of V503-002 and the Scandinavian study, respectively. The sustained clinical effect during the observation period was longest for the 4-valent vaccine. In real-world data, the longest observation period of the vaccine effectiveness was 12 years in an Australian study for the 4-valent vaccine. On the other hand, the longest period of long-term persistence of HPV vaccine-induced seropositivity was 14 years in FUTURE II for the 4-valent vaccine. For the bivalent vaccine, additional long-term follow-up studies may not have been planned due to the launch of the 4-valent and 9-valent vaccines. In some studies of the 9-valent vaccine, the results have not yet been published because of the short observation period. The additional results are expected in the future. In a national immunization program, most girls and boys are inoculated with HPV vaccine by the time puberty begins; thus, it is important to monitor the vaccine effect at least until the sexually active period in their 20s and 30s.
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Affiliation(s)
- Megumi Kurosawa
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
| | - Masayuki Sekine
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
- Correspondence:
| | - Manako Yamaguchi
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
| | - Risa Kudo
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
| | - Sharon J. B. Hanley
- Center for Environmental and Health Sciences, Hokkaido University, Sapporo 060-8638, Japan;
| | - Megumi Hara
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan;
| | - Sosuke Adachi
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
| | - Yutaka Ueda
- Departments of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; (Y.U.); (A.Y.)
| | - Etsuko Miyagi
- Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan;
| | - Sayaka Ikeda
- Division of Surveillance and Policy Evaluation, Institute for Cancer Control, National Cancer Center, Tokyo 104-0045, Japan;
| | - Asami Yagi
- Departments of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; (Y.U.); (A.Y.)
| | - Takayuki Enomoto
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8520, Japan; (M.K.); (M.Y.); (R.K.); (S.A.); (T.E.)
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11
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Kurosawa M, Sekine M, Yamaguchi M, Kudo R, Hanley SJB, Hara M, Adachi S, Ueda Y, Miyagi E, Ikeda S, Yagi A, Enomoto T. Long-term effectiveness of HPV vaccination against HPV infection in young Japanese women: real-world data. Cancer Sci 2022; 113:1435-1440. [PMID: 35100477 PMCID: PMC8990292 DOI: 10.1111/cas.15282] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 01/04/2022] [Accepted: 01/18/2022] [Indexed: 11/28/2022] Open
Abstract
In Japan, public funding for HPV vaccination began in 2010 for girls aged 13–16 years (birth cohort years 1994–1997) and women born in 1994 who turned 25 in 2019. We aimed to verify the long‐term effectiveness of the bivalent HPV vaccine in women aged 25 years. Subjects were women aged 25–26 years who underwent cervical cancer screening and HPV testing in Niigata from 2019 to 2020 (birth cohort years 1993–1994). Information on vaccination status and sexual behavior was obtained from a questionnaire and municipal records. We compared the HPV infection rates of the vaccinated and unvaccinated groups. Of the 429 registrants, 150 (35.0%) and 279 (65.0%) were vaccinated and unvaccinated, respectively. The average period from HPV vaccination to HPV testing was 102.7 months (8.6 years), with a median of 103 months (range 92–109 months). The HPV high‐risk infection rate was 21.3% (32/150) in the vaccinated group and 23.7% (66/279) in the unvaccinated group (P = 0.63). The HPV16/18 infection rate was 0% (0/150) in the vaccinated group and 5.4% (15/279) in the unvaccinated group, showing a significant difference (P = 0.0018), and the vaccine effectiveness was 100%. The cross‐protective type HPV31/45/52 infection rate in the vaccinated group was significantly lower than that in the unvaccinated group (3.3% vs. 10.0%, P = 0.013). There was no significant difference in the mean age at sexual debut and the number of previous sexual partners between the two groups. We have demonstrated the long‐term 9‐year effectiveness of the bivalent vaccine against HPV infection for the first time in Japan.
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Affiliation(s)
- Megumi Kurosawa
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Masayuki Sekine
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Manako Yamaguchi
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Risa Kudo
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Sharon J B Hanley
- Hokkaido University Center for Environmental and Health Sciences, Sapporo, Japan
| | - Megumi Hara
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Sosuke Adachi
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Yutaka Ueda
- Departments of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Etsuko Miyagi
- Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, Yokohama, Japan
| | - Sayaka Ikeda
- Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan
| | - Asami Yagi
- Departments of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Takayuki Enomoto
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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12
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Two-Component Nanoparticle Vaccine Displaying Glycosylated Spike S1 Domain Induces Neutralizing Antibody Response against SARS-CoV-2 Variants. mBio 2021; 12:e0181321. [PMID: 34634927 PMCID: PMC8510518 DOI: 10.1128/mbio.01813-21] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Vaccines pave the way out of the SARS-CoV-2 pandemic. Besides mRNA and adenoviral vector vaccines, effective protein-based vaccines are needed for immunization against current and emerging variants. We have developed a virus-like particle (VLP)-based vaccine using the baculovirus-insect cell expression system, a robust production platform known for its scalability, low cost, and safety. Baculoviruses were constructed encoding SARS-CoV-2 spike proteins: full-length S, stabilized secreted S, or the S1 domain. Since subunit S only partially protected mice from SARS-CoV-2 challenge, we produced S1 for conjugation to bacteriophage AP205 VLP nanoparticles using tag/catcher technology. The S1 yield in an insect-cell bioreactor was ∼11 mg/liter, and authentic protein folding, efficient glycosylation, partial trimerization, and ACE2 receptor binding was confirmed. Prime-boost immunization of mice with 0.5 μg S1-VLPs showed potent neutralizing antibody responses against Wuhan and UK/B.1.1.7 SARS-CoV-2 variants. This two-component nanoparticle vaccine can now be further developed to help alleviate the burden of COVID-19.
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13
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Gnade CM, Hill EK, Botkin HE, Hefel AR, Hansen HE, Sheets KA, Mott SL, Hardy-Fairbanks AJ, Stockdale CK. Is the age of cervical cancer diagnosis changing over time? J Gynecol Obstet Hum Reprod 2021; 50:102040. [DOI: 10.1016/j.jogoh.2020.102040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 12/06/2020] [Accepted: 12/08/2020] [Indexed: 12/28/2022]
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De Vincenzo R, Caporale N, Bertoldo V, Ricci C, Evangelista MT, Bizzarri N, Pedone Anchora L, Scambia G, Capelli G. HPV and Cytology Testing in Women Undergoing 9-Valent HPV Opportunistic Vaccination: A Single-Cohort Follow Up Study. Vaccines (Basel) 2021; 9:643. [PMID: 34204645 PMCID: PMC8231148 DOI: 10.3390/vaccines9060643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/08/2021] [Accepted: 06/08/2021] [Indexed: 11/16/2022] Open
Abstract
Background: This study evaluates the possible effect of 9-valent (9vHPV) vaccination on the results of HPV and cytological tests in a cohort of adult women. Methods: This study is a retrospective, single-cohort, monocentric study. Sexually active women aged 14-70 years, who underwent 9vHPV vaccination, were enrolled. Dose administration dates, side effects and data on Pap smears and HPV tests performed before and after the first vaccine dose were collected. Subjects were considered "unexposed" to the vaccine for all time intervals before the first dose administration, and "exposed" to the first, second and third vaccine doses in all time intervals following each specific dose. Results: A total of 512 women underwent the first 9vHPV dose administration and were enrolled in the study. Median age at vaccination was 30.5 (14-70). Log-rank tests and Cox regression analyses showed a highly statistically significant (p < 0.0001) difference in the time to negativization after the exposure to the third vaccine dose in the 207 women starting with a Pap+ smear (HR (95% C.I.), 2.66 (1.83-3.86)) and in the 198 women starting with an HPV HR+ test (HR (95% C.I.), 7.80 (4.83-12.60)). Conclusions: 9vHPV vaccination may play a role in shortening the clearance time of HPV HR+ or Pap positivity in sexually active adult women.
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Affiliation(s)
- Rosa De Vincenzo
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (N.C.); (V.B.); (C.R.); (M.T.E.); (N.B.); (L.P.A.); (G.S.)
- Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
| | - Nicola Caporale
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (N.C.); (V.B.); (C.R.); (M.T.E.); (N.B.); (L.P.A.); (G.S.)
- Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
| | - Valentina Bertoldo
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (N.C.); (V.B.); (C.R.); (M.T.E.); (N.B.); (L.P.A.); (G.S.)
| | - Caterina Ricci
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (N.C.); (V.B.); (C.R.); (M.T.E.); (N.B.); (L.P.A.); (G.S.)
| | - Maria Teresa Evangelista
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (N.C.); (V.B.); (C.R.); (M.T.E.); (N.B.); (L.P.A.); (G.S.)
| | - Nicolò Bizzarri
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (N.C.); (V.B.); (C.R.); (M.T.E.); (N.B.); (L.P.A.); (G.S.)
| | - Luigi Pedone Anchora
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (N.C.); (V.B.); (C.R.); (M.T.E.); (N.B.); (L.P.A.); (G.S.)
| | - Giovanni Scambia
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Roma, Italy; (N.C.); (V.B.); (C.R.); (M.T.E.); (N.B.); (L.P.A.); (G.S.)
- Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
| | - Giovanni Capelli
- Dipartimento di Scienze Umane, Sociali e della Salute, Università di Cassino e del Lazio Meridionale, 03043 Cassino, Italy
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15
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Salwa M, Al-Munim TA. HPV Vaccination in Bangladesh: Ethical Views. RECENT RESULTS IN CANCER RESEARCH. FORTSCHRITTE DER KREBSFORSCHUNG. PROGRES DANS LES RECHERCHES SUR LE CANCER 2021; 218:31-37. [PMID: 34019160 DOI: 10.1007/978-3-030-63749-1_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Human papillomavirus (HPV) vaccination of young adolescent girls as a part of primary prevention of cervical cancer is now a routine practice in many countries. Bangladesh, a lower-middle income country, observed a successful HPV vaccination demonstration program recently. As much as the benefits of the vaccination programs are well-recorded, the ethics of administration of it is not focused highly; rather the focus tends to be on the most efficient method to get it done. In countries like Bangladesh, vaccination-related ethical issues are often overlooked. Thus, addition of HPV vaccination to the existing immunization programs calls for logical discussion and consideration to preserve the highest ethical standard in administering this vaccine to a sensitive age group of adolescence. This chapter summarizes some ethical concerns related to the HPV vaccination implementation in Bangladesh.
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Affiliation(s)
- Marium Salwa
- Bangabandhu Sheikh Mujib Medical University, Shahbag,, Dhaka-1000,, Bangladesh.
| | - Tarek Abdullah Al-Munim
- Independent Consultant, House #238, Road #5, Mohammadi Housing Society, Mohammadpur,, Dhaka-1207,, Bangladesh
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16
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Fredsgaard L, Goksøyr L, Thrane S, Aves KL, Theander TG, Sander AF. Head-to-Head Comparison of Modular Vaccines Developed Using Different Capsid Virus-Like Particle Backbones and Antigen Conjugation Systems. Vaccines (Basel) 2021; 9:vaccines9060539. [PMID: 34063871 PMCID: PMC8224050 DOI: 10.3390/vaccines9060539] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/12/2021] [Accepted: 05/17/2021] [Indexed: 01/19/2023] Open
Abstract
Capsid virus-like particles (cVLPs) are used as molecular scaffolds to increase the immunogenicity of displayed antigens. Modular platforms have been developed whereby antigens are attached to the surface of pre-assembled cVLPs. However, it remains unknown to what extent the employed cVLP backbone and conjugation system may influence the immune response elicited against the displayed antigen. Here, we performed a head-to-head comparison of antigen-specific IgG responses elicited by modular cVLP-vaccines differing by their employed cVLP backbone or conjugation system, respectively. Covalent antigen conjugation (i.e., employing the SpyTag/SpyCatcher system) resulted in significantly higher antigen-specific IgG titers compared to when using affinity-based conjugation (i.e., using biotin/streptavidin). The cVLP backbone also influenced the antigen-specific IgG response. Specifically, vaccines based on the bacteriophage AP205 cVLP elicited significantly higher antigen-specific IgG compared to corresponding vaccines using the human papillomavirus major capsid protein (HPV L1) cVLP. In addition, the AP205 cVLP platform mediated induction of antigen-specific IgG with a different subclass profile (i.e., higher IgG2a and IgG2b) compared to HPV L1 cVLP. These results demonstrate that the cVLP backbone and conjugation system can individually affect the IgG response elicited against a displayed antigen. These data will aid the understanding and process of tailoring modular cVLP vaccines to achieve improved immune responses.
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Affiliation(s)
- Laurits Fredsgaard
- Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.F.); (L.G.); (K.-L.A.); (T.G.T.)
| | - Louise Goksøyr
- Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.F.); (L.G.); (K.-L.A.); (T.G.T.)
- AdaptVac Aps, 2970 Hørsholm, Denmark;
| | | | - Kara-Lee Aves
- Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.F.); (L.G.); (K.-L.A.); (T.G.T.)
| | - Thor G. Theander
- Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.F.); (L.G.); (K.-L.A.); (T.G.T.)
| | - Adam F. Sander
- Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; (L.F.); (L.G.); (K.-L.A.); (T.G.T.)
- AdaptVac Aps, 2970 Hørsholm, Denmark;
- Correspondence:
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17
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Wan Z, Zheng R, Moharil P, Liu Y, Chen J, Sun R, Song X, Ao Q. Polymeric Micelles in Cancer Immunotherapy. Molecules 2021; 26:1220. [PMID: 33668746 PMCID: PMC7956602 DOI: 10.3390/molecules26051220] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/19/2021] [Accepted: 02/22/2021] [Indexed: 02/07/2023] Open
Abstract
Cancer immunotherapies have generated some miracles in the clinic by orchestrating our immune system to combat cancer cells. However, the safety and efficacy concerns of the systemic delivery of these immunostimulatory agents has limited their application. Nanomedicine-based delivery strategies (e.g., liposomes, polymeric nanoparticles, silico, etc.) play an essential role in improving cancer immunotherapies, either by enhancing the anti-tumor immune response, or reducing their systemic adverse effects. The versatility of working with biocompatible polymers helps these polymeric nanoparticles stand out as a key carrier to improve bioavailability and achieve specific delivery at the site of action. This review provides a summary of the latest advancements in the use of polymeric micelles for cancer immunotherapy, including their application in delivering immunological checkpoint inhibitors, immunostimulatory molecules, engineered T cells, and cancer vaccines.
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Affiliation(s)
- Zhuoya Wan
- Institute of Regulatory Science for Medical Device, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; (Z.W.); (J.C.); (X.S.)
| | - Ruohui Zheng
- Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA;
| | - Pearl Moharil
- Department of Cell Biology, Harvard Medical School, Harvard University, Boston, MA 02115, USA;
| | - Yuzhe Liu
- Department of Materials Engineering, Purdue University, West Lafayette, IN 47906, USA;
| | - Jing Chen
- Institute of Regulatory Science for Medical Device, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; (Z.W.); (J.C.); (X.S.)
- Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA;
| | - Runzi Sun
- Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA;
| | - Xu Song
- Institute of Regulatory Science for Medical Device, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; (Z.W.); (J.C.); (X.S.)
| | - Qiang Ao
- Institute of Regulatory Science for Medical Device, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; (Z.W.); (J.C.); (X.S.)
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18
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Fougeroux C, Goksøyr L, Idorn M, Soroka V, Myeni SK, Dagil R, Janitzek CM, Søgaard M, Aves KL, Horsted EW, Erdoğan SM, Gustavsson T, Dorosz J, Clemmensen S, Fredsgaard L, Thrane S, Vidal-Calvo EE, Khalifé P, Hulen TM, Choudhary S, Theisen M, Singh SK, Garcia-Senosiain A, Van Oosten L, Pijlman G, Hierzberger B, Domeyer T, Nalewajek BW, Strøbæk A, Skrzypczak M, Andersson LF, Buus S, Buus AS, Christensen JP, Dalebout TJ, Iversen K, Harritshøj LH, Mordmüller B, Ullum H, Reinert LS, de Jongh WA, Kikkert M, Paludan SR, Theander TG, Nielsen MA, Salanti A, Sander AF. Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity. Nat Commun 2021; 12:324. [PMID: 33436573 PMCID: PMC7804149 DOI: 10.1038/s41467-020-20251-8] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 11/23/2020] [Indexed: 01/29/2023] Open
Abstract
The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.
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Affiliation(s)
| | - Louise Goksøyr
- AdaptVac Aps, 2970, Hørsholm, Denmark
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
| | - Manja Idorn
- Department of Biomedicine, Aarhus University, 8000, Aarhus, Denmark
| | | | - Sebenzile K Myeni
- Department of Medical Microbiology, Leiden University Medical Center, ZA, Leiden, 2333, Netherlands
| | - Robert Dagil
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
- VAR2pharmaceuticals, 2200, Copenhagen, Denmark
| | - Christoph M Janitzek
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
| | - Max Søgaard
- ExpreS2ion Biotechnologies Aps, 2970, Hørsholm, Denmark
| | - Kara-Lee Aves
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
| | - Emma W Horsted
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
| | - Sayit Mahmut Erdoğan
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
- Turkish Ministry of Agriculture and Forestry, 06800, Ankara, Turkey
| | - Tobias Gustavsson
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
- VAR2pharmaceuticals, 2200, Copenhagen, Denmark
| | - Jerzy Dorosz
- ExpreS2ion Biotechnologies Aps, 2970, Hørsholm, Denmark
| | | | - Laurits Fredsgaard
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
| | | | | | - Paul Khalifé
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
| | - Thomas M Hulen
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
| | - Swati Choudhary
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
- VAR2pharmaceuticals, 2200, Copenhagen, Denmark
| | - Michael Theisen
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
- Department for Congenital Disorders, Statens Serum Institute, 2300, Copenhagen, Denmark
| | - Susheel K Singh
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
- Department for Congenital Disorders, Statens Serum Institute, 2300, Copenhagen, Denmark
| | - Asier Garcia-Senosiain
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
- Department for Congenital Disorders, Statens Serum Institute, 2300, Copenhagen, Denmark
| | - Linda Van Oosten
- Department of Plant Sciences, Laboratory of Virology, 6700AA, Wageningen, Netherlands
| | - Gorben Pijlman
- Department of Plant Sciences, Laboratory of Virology, 6700AA, Wageningen, Netherlands
| | | | - Tanja Domeyer
- ExpreS2ion Biotechnologies Aps, 2970, Hørsholm, Denmark
| | | | | | | | | | - Søren Buus
- Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Danmark
| | - Anette Stryhn Buus
- Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Danmark
| | - Jan Pravsgaard Christensen
- Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Danmark
| | - Tim J Dalebout
- Department of Medical Microbiology, Leiden University Medical Center, ZA, Leiden, 2333, Netherlands
| | - Kasper Iversen
- Department of Cardiology, Herlev Hospital, 2730, Herlev, Denmark
| | - Lene H Harritshøj
- Department of Clinical Immunology, Copenhagen University Hospital, 2100, Copenhagen, Denmark
| | - Benjamin Mordmüller
- Universitätsklinikum Tübingen, Institut für Tropenmedizin, 72074, Tübingen, Germany
- Centre de Recherches Médicales de Lambaréné, BP 242, Lambaréné, Gabon
| | - Henrik Ullum
- Department of Cardiology, Herlev Hospital, 2730, Herlev, Denmark
| | - Line S Reinert
- Department of Biomedicine, Aarhus University, 8000, Aarhus, Denmark
| | - Willem Adriaan de Jongh
- AdaptVac Aps, 2970, Hørsholm, Denmark
- ExpreS2ion Biotechnologies Aps, 2970, Hørsholm, Denmark
| | - Marjolein Kikkert
- Department of Medical Microbiology, Leiden University Medical Center, ZA, Leiden, 2333, Netherlands
| | - Søren R Paludan
- Department of Biomedicine, Aarhus University, 8000, Aarhus, Denmark
| | - Thor G Theander
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
| | - Morten A Nielsen
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark.
| | - Ali Salanti
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark
- VAR2pharmaceuticals, 2200, Copenhagen, Denmark
| | - Adam F Sander
- AdaptVac Aps, 2970, Hørsholm, Denmark.
- Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark.
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Patel IS, Dongara AR, Mungala BM, Chapla A, Phatak AG, Nimbalkar SM. Knowledge and attitude about cervical cancer and human papillomavirus vaccine among medical and paramedical students of a university. J Family Med Prim Care 2021; 10:462-467. [PMID: 34017771 PMCID: PMC8132775 DOI: 10.4103/jfmpc.jfmpc_625_20] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 06/10/2020] [Accepted: 10/24/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Every year, globally 570,000 women are diagnosed with cervical cancer, out of which around 311,000 die. India contributes to about 132,000 new cases and 74,000 deaths yearly. One of the major risk factors for cervical cancer is infection with some types of human papillomavirus (HPV). This is both preventable (by vaccination) and detectable early (routine screening programs). OBJECTIVE The objective of this study is to assess the knowledge and attitude in medical and paramedical students about cervical cancer and HPV vaccination. MATERIAL AND METHODS A cross-sectional survey was conducted, using predesigned and validated questionnaire. It was segregated into three parts: Q1-demographic details, Q2a-questions assessing knowledge, Q2b-questions assessing attitude. Our target population was female students (18-25 years) studying in medical, nursing, and physiotherapy colleges. Descriptive statistics of data was analyzed using SPSS 16.0. RESULTS We had 73% response rate. Most participants belonged to upper middle and upper socioeconomic class, were pursuing MBBS, resided in villages, had educated parents, and had good health-care-seeking behavior. School education, television, and printed advertisements appeared to be underutilized. Around 50% of the participant had received chickenpox and typhoid vaccine, but only 8% had received HPV vaccine. The mean knowledge score was 5.19 ± 2.24, with 0.00 minimum and 11.0 maximum, out of a maximum possible score of 17. Only, place of residence appeared to effect the knowledge score. CONCLUSION The study shows the dismal knowledge levels about HPV amongst students. Participants were interested in seeking knowledge; consider HPV vaccination provided they were provided with sufficient knowledge.
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Affiliation(s)
- Ishani S. Patel
- Department of Pediatrics, Pramukhswami Medical College, Karamsad, Gujarat, India
| | | | - Bhavdeep M. Mungala
- Department of Pediatrics, Pramukhswami Medical College, Karamsad, Gujarat, India
| | - Apurva Chapla
- Department of Pediatrics, Pramukhswami Medical College, Karamsad, Gujarat, India
| | - Ajay G. Phatak
- Central Research Services, Charutar Arogya Mandal, Karamsad, Gujarat, India
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20
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Segal JP, Askari A, Clark SK, Hart AL, Faiz OD. The Incidence and Prevalence of Human Papilloma Virus-associated Cancers in IBD. Inflamm Bowel Dis 2021; 27:34-39. [PMID: 32080713 DOI: 10.1093/ibd/izaa035] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Indexed: 12/20/2022]
Abstract
AIM The human papilloma virus has been associated with anal, cervical, vaginal, and penile cancers. The primary aim of this population-based study is to determine whether HPV-associated cancers are more commonplace in patients with inflammatory bowel disease (IBD). METHOD The Hospital Episode Statistics (HES) database from 1997 to 2012, linked with officer for age standardized rates (ASR), were calculated using population data, and Cox regression analysis was used to determine whether IBD patients have poorer survival compared with non-IBD patients. RESULTS A total of 61,648 patients were included in this study; of these, 837 patients had a preexisting diagnosis of IBD (1.4%). Inflammatory bowel disease patients had a significantly higher ASR of anal cancers than the non-IBD population: 5.5 per 100,000 in the IBD group compared with 1.8 in the non-IBD group. The IBD group was also diagnosed with anal cancers at a younger age (60 years compared with 66 years in the non-IBD group, P < 0.001). The survival of IBD patients with anal cancer was also poorer than the non-IBD group (hazard ratio, 1.32; 95% confidence interval, 1.15-1.52; P < 0.001). On average, survival was significantly shorter in the IBD group with anal cancer (46 months) compared with the non-IBD group (61 months, P < 0.001). Age standardized rates for cervical cancer was significantly higher in the IBD group (5.2 of 100,000) compared with the non-IBD group (4.6 of 100,000 P = 0.042). CONCLUSION Patients with IBD have a higher rate of anal cancer compared with the general population. Survival is also worse for anal cancers in the IBD group.
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Affiliation(s)
- Jonathan P Segal
- Inflammatory Bowel Disease Department, St. Mark's Hospital, Harrow, United Kingdom.,Department of Surgery and Cancer, Imperial College, London, United Kingdom
| | - Alan Askari
- Department of Surgery, Luton and Dunstable University Hospital, Luton, United Kingdom
| | - Susan K Clark
- Inflammatory Bowel Disease Department, St. Mark's Hospital, Harrow, United Kingdom.,Department of Surgery and Cancer, Imperial College, London, United Kingdom
| | - Ailsa L Hart
- Inflammatory Bowel Disease Department, St. Mark's Hospital, Harrow, United Kingdom.,Department of Surgery and Cancer, Imperial College, London, United Kingdom
| | - Omar D Faiz
- Inflammatory Bowel Disease Department, St. Mark's Hospital, Harrow, United Kingdom.,Department of Surgery and Cancer, Imperial College, London, United Kingdom
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21
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Sasso E, D'Alise AM, Zambrano N, Scarselli E, Folgori A, Nicosia A. New viral vectors for infectious diseases and cancer. Semin Immunol 2020; 50:101430. [PMID: 33262065 DOI: 10.1016/j.smim.2020.101430] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Revised: 10/23/2020] [Accepted: 11/16/2020] [Indexed: 12/12/2022]
Abstract
Since the discovery in 1796 by Edward Jenner of vaccinia virus as a way to prevent and finally eradicate smallpox, the concept of using a virus to fight another virus has evolved into the current approaches of viral vectored genetic vaccines. In recent years, key improvements to the vaccinia virus leading to a safer version (Modified Vaccinia Ankara, MVA) and the discovery that some viruses can be used as carriers of heterologous genes encoding for pathological antigens of other infectious agents (the concept of 'viral vectors') has spurred a new wave of clinical research potentially providing for a solution for the long sought after vaccines against major diseases such as HIV, TB, RSV and Malaria, or emerging infectious diseases including those caused by filoviruses and coronaviruses. The unique ability of some of these viral vectors to stimulate the cellular arm of the immune response and, most importantly, T lymphocytes with cell killing activity, has also reawakened the interest toward developing therapeutic vaccines against chronic infectious diseases and cancer. To this end, existing vectors such as those based on Adenoviruses have been improved in immunogenicity and efficacy. Along the same line, new vectors that exploit viruses such as Vesicular Stomatitis Virus (VSV), Measles Virus (MV), Lymphocytic choriomeningitis virus (LCMV), cytomegalovirus (CMV), and Herpes Simplex Virus (HSV), have emerged. Furthermore, technological progress toward modifying their genome to render some of these vectors incompetent for replication has increased confidence toward their use in infant and elderly populations. Lastly, their production process being the same for every product has made viral vectored vaccines the technology of choice for rapid development of vaccines against emerging diseases and for 'personalised' cancer vaccines where there is an absolute need to reduce time to the patient from months to weeks or days. Here we review the recent developments in viral vector technologies, focusing on novel vectors based on primate derived Adenoviruses and Poxviruses, Rhabdoviruses, Paramixoviruses, Arenaviruses and Herpesviruses. We describe the rationale for, immunologic mechanisms involved in, and design of viral vectored gene vaccines under development and discuss the potential utility of these novel genetic vaccine approaches in eliciting protection against infectious diseases and cancer.
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Affiliation(s)
- Emanuele Sasso
- Nouscom srl, Via di Castel Romano 100, 00128 Rome, Italy; Ceinge-Biotecnologie Avanzate S.C. A.R.L., via Gaetano Salvatore 486, 80145 Naples, Italy.
| | | | - Nicola Zambrano
- Ceinge-Biotecnologie Avanzate S.C. A.R.L., via Gaetano Salvatore 486, 80145 Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University Federico II, Via Pansini 5, 80131 Naples, Italy.
| | | | | | - Alfredo Nicosia
- Ceinge-Biotecnologie Avanzate S.C. A.R.L., via Gaetano Salvatore 486, 80145 Naples, Italy; Department of Molecular Medicine and Medical Biotechnology, University Federico II, Via Pansini 5, 80131 Naples, Italy.
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22
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Liu A. HPV: Injecting Truth into the Vaccine and Making Effective Recommendations. Pediatr Ann 2020; 49:e244-e247. [PMID: 32520363 DOI: 10.3928/19382359-20200508-01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Human papillomavirus (HPV) immunization rates are significantly below the Healthy People 2020 target of 80% and lag behind other adolescent vaccines that are given at the same time. There is no top reason for parents' lack of HPV initiation, and many concerns could be addressed by talking to a health care provider. This article aims to equip clinicians with information regarding the impa-cts of HPV, address vaccine concerns, and guide clinicians with best practices regarding effective vaccine recommendations.[Pediatr Ann. 2020;49(6):e244-e247.].
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23
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Aves KL, Goksøyr L, Sander AF. Advantages and Prospects of Tag/Catcher Mediated Antigen Display on Capsid-Like Particle-Based Vaccines. Viruses 2020; 12:v12020185. [PMID: 32041299 PMCID: PMC7077247 DOI: 10.3390/v12020185] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 02/03/2020] [Accepted: 02/04/2020] [Indexed: 12/15/2022] Open
Abstract
Capsid-like particles (CLPs) are multimeric, repetitive assemblies of recombinant viral capsid proteins, which are highly immunogenic due to their structural similarity to wild-type viruses. CLPs can be used as molecular scaffolds to enable the presentation of soluble vaccine antigens in a similar structural format, which can significantly increase the immunogenicity of the antigen. CLP-based antigen display can be obtained by various genetic and modular conjugation methods. However, these vary in their versatility as well as efficiency in achieving an immunogenic antigen display. Here, we make a comparative review of the major CLP-based antigen display technologies. The Tag/Catcher-AP205 platform is highlighted as a particularly versatile and efficient technology that offers new qualitative and practical advantages in designing modular CLP vaccines. Finally, we discuss how split-protein Tag/Catcher conjugation systems can help to further propagate and enhance modular CLP vaccine designs.
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Affiliation(s)
- Kara-Lee Aves
- Faculty of Health Science, Institute for Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark; (K.-L.A.); (L.G.)
| | - Louise Goksøyr
- Faculty of Health Science, Institute for Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark; (K.-L.A.); (L.G.)
- AdaptVac Aps, Agern Alle 1, 2970 Hørsholm, Denmark
| | - Adam F. Sander
- Faculty of Health Science, Institute for Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark; (K.-L.A.); (L.G.)
- AdaptVac Aps, Agern Alle 1, 2970 Hørsholm, Denmark
- Correspondence:
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24
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Z G, D Z, X Y, W Q, F X, B L, Z H, S Y. Human papillomavirus infection rates before and after the introduction of prophylactic vaccines in Kunming, Yunnan, China. Indian J Med Microbiol 2020; 38:66-71. [PMID: 32719211 DOI: 10.4103/ijmm.ijmm_19_427] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Purpose The purpose of this study was to determine the prevalence of human papillomavirus (HPV) in the population in Kunming, Yunnan, China, before and after the introduction of HPV preventive vaccines. Materials and Methods In total, 28,959 patients were enrolled in this study between 1 January 2016 and 31 August 2019. HPVs were genotyped using a flow-through hybridisation technique, and differences in HPV infection rates before and after the introduction of an HPV vaccine were determined. Results The prevalence of HPV before and after the introduction of HPV vaccines was 17.74% and 17.11%, respectively. This difference was not statistically significant (χ2 = 1.920, P > 0.05). The HPV infection rates showed a bimodal U-shaped curve for all age groups. The most common genotypes of HPV detected were HPV52, HPV16, HPV58 and HPV39. Conclusion Although the overall HPV infection rate in Kunming did not change significantly after the introduction of HPV vaccines, differences in HPV infection rates and multi-typic HPV infection rates were evident in certain age groups.
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Affiliation(s)
- Guiqian Z
- Department of Clinical Laboratory, The First People's Hospital of Yunnan Province; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Ziqin D
- Department of Clinical Laboratory, The First People's Hospital of Yunnan Province; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Ya X
- Department of Clinical Laboratory, The First People's Hospital of Yunnan Province; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Qiong W
- Shizong County People's Hospital, Qujing City, Yunnan Province, China
| | - Xin F
- Department of Clinical Laboratory, The First People's Hospital of Yunnan Province; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Limei B
- Department of Clinical Laboratory, The First People's Hospital of Yunnan Province; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Hongyan Z
- Department of Clinical Laboratory, The First People's Hospital of Yunnan Province; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Yi S
- Department of Clinical Laboratory, The First People's Hospital of Yunnan Province; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
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Yusupov A, Popovsky D, Mahmood L, Kim AS, Akman AE, Yuan H. The nonavalent vaccine: a review of high-risk HPVs and a plea to the CDC. AMERICAN JOURNAL OF STEM CELLS 2019; 8:52-64. [PMID: 31976155 PMCID: PMC6971474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 11/25/2019] [Indexed: 06/10/2023]
Abstract
Two of the leading strategies to prevent cervical cancer are prophylactic human papillomavirus (HPV) vaccination and routine Papanicolaou (Pap) testing. However, regardless of being vaccinated with first-generation (bivalent and quadrivalent) HPV vaccines at the recommended dosing schedule, many women are still found to have low- and high-grade cervical intraepithelial lesions. Studies have shown that this is largely due to: (1) first-generation vaccines only protecting against 70% of high-risk HPV types that cause cervical cancer (HPVs 16/18) and (2) vaccinated women being more prone to infection with non-protected high-risk HPV types than unvaccinated women. Fortunately, the FDA recently approved a nonavalent vaccine that protects against 5 additional high-risk HPV types that cause 20% of cervical cancers (HPVs 31/33/45/52/58), which is the only HPV vaccine currently available in the United States. Although the Advisory Committee on Immunization Practices (ACIP) recommends the nonavalent vaccine in men and women up to the age of 45 years, it does not recommend the nonavalent vaccine in those previously vaccinated with 3 doses of bivalent or quadrivalent vaccine, deeming them "adequately vaccinated". As this population is most at risk, this review serves to provide background and argue for a change in their recommendation.
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Affiliation(s)
- Ariel Yusupov
- Georgetown University School of MedicineWashington, DC, USA
| | | | - Lyaba Mahmood
- Georgetown University School of MedicineWashington, DC, USA
| | - Andrew S Kim
- Georgetown University School of MedicineWashington, DC, USA
| | - Alex E Akman
- Georgetown University School of MedicineWashington, DC, USA
| | - Hang Yuan
- Department of Pathology, Georgetown University Medical CenterWashington, DC, USA
- Center for Cell Reprogramming, Georgetown University Medical CenterWashington, DC, USA
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Qi R, Miao Q, Zhu J, Tang J, Tang A, Wang X, Dong D, Guo H, Liu G. Construction and immunogenicity of novel bivalent virus-like particles bearing VP60 genes of classic RHDV(GI.1) and RHDV2(GI.2). Vet Microbiol 2019; 240:108529. [PMID: 31902498 DOI: 10.1016/j.vetmic.2019.108529] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 11/23/2019] [Accepted: 11/26/2019] [Indexed: 02/07/2023]
Abstract
Rabbit hemorrhagic disease (RHD) is an acute, inflammatory, septic, and devastating infectious disease caused by Rabbit hemorrhagic disease virus (RHDV), which poses a serious threat to the rabbit industry. RHDV2 (GI.2/RHDVb), a recently reported new variant could cause RHD in wild populations, but also RHDV-vaccinated rabbits. For now, both RHDV and RHDV2 are the main causes of RHD. To develop a new subunit vaccine that could protect rabbits against both classic RHDV and RHDV2 infections, we constructed a recombinant baculovirus (Bac-classic RHDV VP60-RHDV2 VP60) containing the VP60 genes of classic RHDV and RHDV2. Both VP60 genes were well expressed simultaneously in Spodoptera frugiperda cells (Sf9) after infection with the recombinant baculovirus. Transmission electron microscopy showed that the recombinant VP60 self-assembled into virus-like particles (VLPs). The antigenicity and immunogenicity of the bivalent VLPs vaccine were examined with animal experiments. Our results demonstrated that both the humoral and cellular immune responses were efficiently induced in rabbits by a subunit vaccine based on the recombinant baculovirus. In addition, all rabbits immunized with the bivalent VLPs vaccine survived after challenged with classic RHDV, and showed no clinical signs of RHD, whereas all the rabbits in the negative control group died from classic RHDV infection and showed typical clinical signs of RHD. In summary, our results indicated that the recombinant baculovirus carrying two VP60 genes is a candidate construct from which to develop a bivalent VLPs vaccine against both classic RHDV and RHDV2 infections.
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Affiliation(s)
- Ruibin Qi
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China
| | - Qiuhong Miao
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China; Laboratory of Virology, Wageningen University & Research, Wageningen, 6708 PB, the Netherlands
| | - Jie Zhu
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China
| | - Jingyu Tang
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China
| | - Aoxing Tang
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China
| | - Xiaoxue Wang
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China
| | - Dandan Dong
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China
| | - Hongyuan Guo
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China
| | - Guangqing Liu
- Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China.
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27
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Origoni M, Cristoforoni P, Mariani L, Costa S, Preti M, Sandri MT, Preti EP, Ghelardi A, Perino A. [HPV vaccination: not only female adolescents and not only prophylactic. Review and position paper of the Italian HPV Study Group (IHSG)]. ACTA ACUST UNITED AC 2019; 71:442-459. [PMID: 31741364 DOI: 10.23736/s0026-4784.19.04443-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
HPV vaccination has been introduced in clinical practice in recent years and represents the most effective strategy of primary prevention of cervical carcinoma and of female genital preneoplastic conditions. One of the major issues of the subject is represented by vaccination coverage of the target population. Since its introduction, HPV vaccine efficacy has been progressively demonstrated also towards extragenital HPV-correlated conditions and in males too. Moreover, even subjects of older age groups or subjects who already had HPV infections have been demonstrated to received benefits from vaccination, due to improvements of their immunological response. Recently, vaccine efficacy has also been investigated in terms of adjuvant administration after treatments of preneoplastic or benign conditions of the female lower genital tract caused by HPVs; preliminary results indicate an interesting and promising field of application. On this basis, in this article an analysis of the state of the art has been performed, with specific regard to the Italian scenario and with the focus of future perspectives of implementation of the HPV vaccination policy. From the available evidences, the Italian HPV Study Group recommends the extension of systematic HPV vaccination to males too, to adult subjects and also after conservative treatment of genital HPV correlated conditions.
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Affiliation(s)
- Massimo Origoni
- Dipartimento di Ginecologia e Ostetricia, Università Vita Salute San Raffaele, Milano, Italia -
| | | | | | | | - Mario Preti
- Dipartimento di Ginecologia e Ostetricia, Università di Torino, Torino, Italia
| | | | | | | | - Antonio Perino
- Dipartimento di Ginecologia e Ostetricia, Università di Palermo, Palermo, Italia
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Zhuang J, Holay M, Park JH, Fang RH, Zhang J, Zhang L. Nanoparticle Delivery of Immunostimulatory Agents for Cancer Immunotherapy. Theranostics 2019; 9:7826-7848. [PMID: 31695803 PMCID: PMC6831474 DOI: 10.7150/thno.37216] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 06/26/2019] [Indexed: 02/07/2023] Open
Abstract
Immunostimulatory agents, including adjuvants, cytokines, and monoclonal antibodies, hold great potential for the treatment of cancer. However, their direct administration often results in suboptimal pharmacokinetics, vulnerability to biodegradation, and compromised targeting. More recently, encapsulation into biocompatible nanoparticulate carriers has become an emerging strategy for improving the delivery of these immunotherapeutic agents. Such approaches can address many of the challenges facing current treatment modalities by endowing additional protection and significantly elevating the bioavailability of the encapsulated payloads. To further improve the delivery efficiency and subsequent immune responses associated with current nanoscale approaches, biomimetic modifications and materials have been employed to create delivery platforms with enhanced functionalities. By leveraging nature-inspired design principles, these biomimetic nanodelivery vehicles have the potential to alter the current clinical landscape of cancer immunotherapy.
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Affiliation(s)
- Jia Zhuang
- Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
| | - Maya Holay
- Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
| | - Joon Ho Park
- Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
| | - Ronnie H. Fang
- Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
| | - Jie Zhang
- Cello Therapeutics, Inc., San Diego, CA 92121, USA
| | - Liangfang Zhang
- Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
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Facilitators and barriers of human papillomavirus vaccine uptake in young females 18-26 years old in Singapore: A qualitative study. Vaccine 2019; 37:6030-6038. [PMID: 31473002 DOI: 10.1016/j.vaccine.2019.08.053] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 08/19/2019] [Accepted: 08/21/2019] [Indexed: 01/01/2023]
Abstract
BACKGROUND Around 70% of cervical cancers are caused by Types 16 and 18 of human papillomavirus (HPV). Vaccines against HPV have been shown to be safe and effective in preventing HPV and cervical cancer. OBJECTIVE To explore the facilitators and barriers of HPV vaccination in young females aged 18-26 years in Singapore, and to describe their recommended strategies to improve the uptake of HPV vaccination. DESIGN Qualitative, descriptive design guided by the socio-ecological model. PARTICIPANTS Young women studying in National University of Singapore (NUS), aged 18-26 (N = 40). Purposive sampling was used to recruit participants from various socio-economic levels and faculties, both vaccinated against HPV and unvaccinated. METHODS In-depth interviews (IDIs) and focus group discussions (FGDs) were conducted with the participants. IDIs and FGDs were transcribed and coded using NVIVO software. Thematic data analysis was performed using an inductive approach. RESULTS Barriers to HPV vaccination included lack of awareness, lack of perceived risk for cervical cancer, cost, lack of parental support, inconvenience of getting the vaccination, stigma associated with connection with sexual activity, and concern regarding safety. Facilitators include parental encouragement, protection of one's health, lack of logistical barriers, and perceived safety and efficacy of the vaccine. Participants recommended increasing awareness of HPV vaccination and cervical cancer, reducing cost of vaccination and making the vaccine compulsory to increase vaccine uptake. CONCLUSION Barriers and facilitators exist at different levels to influence vaccine uptake. Public education on cervical cancer and the vaccine should be stepped up to increase public awareness. A school-based national vaccination programme was proposed by the target group to increase the rate of uptake of HPV vaccination in Singapore.
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Wiyeh AB, Cooper S, Jaca A, Mavundza E, Ndwandwe D, Wiysonge CS. Social media and HPV vaccination: Unsolicited public comments on a Facebook post by the Western Cape Department of Health provide insights into determinants of vaccine hesitancy in South Africa. Vaccine 2019; 37:6317-6323. [PMID: 31521412 DOI: 10.1016/j.vaccine.2019.09.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 08/20/2019] [Accepted: 09/07/2019] [Indexed: 01/09/2023]
Abstract
On the 4 February 2019, the Western Cape Department of Health's Facebook page announced the implementation of a school-based vaccination campaign aimed to administer the first doses of human papillomavirus (HPV) vaccine in public schools to Grade 4 girls who are nine years old. This announcement was met with a flurry of social media responses posted on the campaign's Facebook page. This study identifies determinants of vaccine hesitancy amongst responses provided by social media users to this post. On 8 March 2019, we conducted a qualitative study including all 157 comments to the Facebook post. The post had 659 'emotion' reactions: 574 "likes", 62 "loves", 21 "angry faces", 2 "laughs", 2 "wows" and 1 "sad face". An overwhelming majority (636/659 i.e. 97%) of reactions were favourable to the HPV vaccination campaign. Out of the 157 comments, we judged 52 (33%) of them to be 'hesitant', suggesting that people with negative reactions though few in number, were more likely to be vocal deniers. Concern around the safety of HPV vaccines including effects on reproductive health was the most common theme identified. Other emerging themes included: risk of cervical cancer perceived as being low, issues around consent, concerns that girls are being used for research, questionable vaccine effectiveness, use of the school-based strategy for the campaign, risk-benefits calculations of HPV vaccination and constraints such as stock-outs. Knowing someone who had been affected or being at risk of cervical cancer, having knowledge about the causes of cervical cancer, confidence in the effectiveness and safety of the vaccine, knowing the vaccine was being used in high income settings, and having strong recommendations from the World Health Organisation and key actors seemed to increase the willingness to accept the vaccine. The magnitude and causes of HPV vaccine hesitancy need to be investigated to ensure the success of this programme.
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Affiliation(s)
- Alison B Wiyeh
- Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.
| | - Sara Cooper
- Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.
| | - Anelisa Jaca
- Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.
| | - Edison Mavundza
- Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.
| | - Duduzile Ndwandwe
- Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.
| | - Charles S Wiysonge
- Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa; Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa; Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
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31
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MacIntyre CR, Shaw PJ, Mackie FE, Boros C, Marshall H, Seale H, Kennedy SE, Moa A, Chughtai AA, Trent M, O'Loughlin EV, Stormon M. Long term follow up of persistence of immunity following quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children. Vaccine 2019; 37:5630-5636. [DOI: 10.1016/j.vaccine.2019.07.072] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 07/17/2019] [Accepted: 07/22/2019] [Indexed: 01/16/2023]
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Scavone C, Di Mauro C, Brusco S, Bertini M, di Mauro G, Rafaniello C, Sportiello L, Rossi F, Capuano A. Surveillance of adverse events following immunization related to human papillomavirus vaccines: 12 years of vaccinovigilance in Southern Italy. Expert Opin Drug Saf 2019; 18:427-433. [DOI: 10.1080/14740338.2019.1598969] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Cristina Scavone
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Cristina Di Mauro
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Simona Brusco
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Michele Bertini
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Gabriella di Mauro
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Concetta Rafaniello
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Liberata Sportiello
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Francesco Rossi
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Annalisa Capuano
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli”, Naples, Italy
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Effect of Multiple Vaccinations with Tumor Cell-Based Vaccine with Codon-Modified GM-CSF on Tumor Growth in a Mouse Model. Cancers (Basel) 2019; 11:cancers11030368. [PMID: 30875953 PMCID: PMC6468346 DOI: 10.3390/cancers11030368] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 03/07/2019] [Accepted: 03/11/2019] [Indexed: 12/11/2022] Open
Abstract
Ectopic expression of codon-modified granulocyte-macrophage colony-stimulating factor (cGM-CSF) in TC-1 cells (TC-1/cGM-CSF), a model cell line for human papillomavirus (HPV)-infected cervical cancer cells, increased the expression level of GM-CSF and improved the efficacy of tumor cell-based vaccines in a cervical cancer mouse model. The number of vaccine doses required to induce a long-term immune response in a cervical cancer mouse model is poorly understood. Here, we investigated one, three, and five doses of the irradiated TC-1/cGM-CSF vaccine to determine which dose was effective in inducing a greater immune response and the suppression of tumors. Our findings showed that three doses of irradiated TC-1/cGM-CSF vaccine elicited slower tumor growth rates and enhanced survival rates compared with one dose or five doses of irradiated TC-1/cGM-CSF vaccine. Consistently, mice vaccinated with three doses of irradiated TC-1/cGM-CSF vaccine exhibited stronger interferon gamma (IFN-γ) production in HPV E7-specific CD8⁺ T cells and CD4⁺ T cells. A higher percentage of natural killer cells and interferon-producing killer dendritic cells (IKDCs) appeared in the splenocytes of the mice vaccinated with three doses of irradiated TC-1/cGM-CSF vaccine compared with those of the mice vaccinated with one dose or five doses of irradiated TC-1/cGM-CSF vaccine. Our findings demonstrate that single or multiple vaccinations, such as five doses, with irradiated TC-1/cGM-CSF vaccine suppressed the immune response, whereas three doses of irradiated TC-1/cGM-CSF vaccine elicited a greater immune response and subsequent tumor suppression.
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Corkum MT, Shaddick H, Jewlal E, Patil N, Leung E, Sugimoto A, McGee J, Prefontaine M, D'Souza D. When Pap Testing Fails to Prevent Cervix Cancer: A Qualitative Study of the Experience of Screened Women Under 50 with Advanced Cervix Cancer in Canada. Cureus 2019; 11:e3950. [PMID: 30937248 PMCID: PMC6433450 DOI: 10.7759/cureus.3950] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 01/23/2019] [Indexed: 11/05/2022] Open
Abstract
INTRODUCTION While Papanicolaou (Pap) smears have resulted in a significant decline in cervical cancer incidence and mortality, our clinical experience indicates some women still present with locally advanced cervical cancer (LACC) despite having received Pap smear screening. Recent guidelines have decreased the recommended frequency of Pap smears to every three years. Our study sought to investigate the experiences of young women compliant with cervical screening who presented with LACC. METHODS Women under 50 with LACC, FIGO (International Federation of Gynecology and Obstetrics) stage IB1 to IVA who underwent a Pap smear within two years of diagnosis and received curative intent chemoradiotherapy between September 2010 and December 2012 were included. Participants were treated at a tertiary academic cancer centre and invited for a semi-structured, in-person interview, which was analysed qualitatively using thematic analysis. RESULTS Thirteen out of 38 women had Pap screening two or less years before diagnosis. Ten consented to participate in an interview. Several key themes emerged: I) Belief that LACC does not occur in those who undergo screening; II) Lack of understanding about LACC symptoms/diagnosis of cervix cancer; III) Reluctance from health care providers to perform a detailed pelvic examination in the presence of symptoms; IV) Negative emotions including anger, shame, regret, mistrust; V) Changes in quality of life from treatment; VI) Advice for other women. CONCLUSIONS One-third of women presenting with LACC had appropriate Pap screening prior to diagnosis. Patients believe delays in their diagnosis resulted in detrimental quality of life. There is a need to educate physicians and the public about the symptoms of cervix cancer and to consider this diagnosis even when Pap screening has occurred.
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Affiliation(s)
- Mark T Corkum
- Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, CAN
| | - Heather Shaddick
- Medical Physics, London Regional Cancer Program, University of Western Ontario, London, CAN
| | - Elizabeth Jewlal
- Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, CAN
| | | | - Eric Leung
- Radiation Oncology, Toronto Sunnybrook Hospital, University of Toronto, Toronto, CAN
| | - Akira Sugimoto
- Oncology, London Regional Cancer Program, University of Western Ontario, London, CAN
| | - Jacob McGee
- Oncology, London Regional Cancer Program, University of Western Ontario, London, CAN
| | - Michel Prefontaine
- Neurology, London Regional Cancer Program, University of Western Ontario, London, CAN
| | - David D'Souza
- Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, CAN
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Anderson J, Toh ZQ, Reitsma A, Do LAH, Nathanielsz J, Licciardi PV. Effect of peripheral blood mononuclear cell cryopreservation on innate and adaptive immune responses. J Immunol Methods 2018; 465:61-66. [PMID: 30447244 DOI: 10.1016/j.jim.2018.11.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Revised: 11/02/2018] [Accepted: 11/13/2018] [Indexed: 10/27/2022]
Abstract
Cryopreservation of blood-derived immune cells is commonly used in clinical trials to examine immunological responses. However, studies elucidating the effects of cryopreservation on peripheral blood mononuclear cell (PBMC) responses have shown inconsistent results making it difficult to draw meaningful conclusions. Therefore we sought to address this issue by comparing key innate and adaptive immune parameters between freshly-isolated and cryopreserved PBMCs from healthy adults. We examined the effect of cryopreservation on the expression of key markers on innate and adaptive immune cell populations (i.e. CD4+ and CD8+ [T cells], CD14+ [monocytes], CD19+ [B cells], CD56+ [NK cells] or CD19 + CD27+ [memory B cells]), on cytokine secretion (TNF-α, INF-γ, IL-1β, IL-10, IL-6, MCP-1 and RANTES) in cultured PBMC supernatants following stimulation with a range of Toll-like receptor (TLR) agonists, as well as on antigen-specific memory B cell enumeration by ELISpot. We found that cryopreservation had no effect on the expression of immune markers on innate and adaptive immune cells as well on the number of antigen-specific memory B cells. However, the response to TLR ligands such as FLA-ST, CpG and LPS was variable with increased cytokine production by cryopreserved PBMCs observed compared to freshly-isolated PBMCs. Our results suggest that the effect of cryopreservation on the biological response of immune cell populations needs to be carefully considered, particularly in the context of clinical studies that rely on these immune outcomes.
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Affiliation(s)
- Jeremy Anderson
- Pneumococcal Research, Murdoch Children's Research Institute, Melbourne, Melbourne, VIC 3052, Australia
| | - Zheng Quan Toh
- Pneumococcal Research, Murdoch Children's Research Institute, Melbourne, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Australia
| | - Andrea Reitsma
- Pneumococcal Research, Murdoch Children's Research Institute, Melbourne, Melbourne, VIC 3052, Australia
| | - Lien Anh Ha Do
- Pneumococcal Research, Murdoch Children's Research Institute, Melbourne, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Australia
| | - Jordan Nathanielsz
- Pneumococcal Research, Murdoch Children's Research Institute, Melbourne, Melbourne, VIC 3052, Australia
| | - Paul V Licciardi
- Pneumococcal Research, Murdoch Children's Research Institute, Melbourne, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Australia.
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36
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Dadar M, Chakraborty S, Dhama K, Prasad M, Khandia R, Hassan S, Munjal A, Tiwari R, Karthik K, Kumar D, Iqbal HMN, Chaicumpa W. Advances in Designing and Developing Vaccines, Drugs and Therapeutic Approaches to Counter Human Papilloma Virus. Front Immunol 2018; 9:2478. [PMID: 30483247 PMCID: PMC6240620 DOI: 10.3389/fimmu.2018.02478] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 10/08/2018] [Indexed: 02/05/2023] Open
Abstract
Human papillomavirus (HPV) is a viral infection with skin-to-skin based transmission mode. HPV annually caused over 500,000 cancer cases including cervical, anogenital and oropharyngeal cancer among others. HPV vaccination has become a public-health concern, worldwide, to prevent the cases of HPV infections including precancerous lesions, cervical cancers, and genital warts especially in adolescent female and male population by launching national programs with international alliances. Currently, available prophylactic and therapeutic vaccines are expensive to be used in developing countries for vaccination programs. The recent progress in immunotherapy, biotechnology, recombinant DNA technology and molecular biology along with alternative and complementary medicinal systems have paved novel ways and valuable opportunities to design and develop effective prophylactic and therapeutic vaccines, drugs and treatment approach to counter HPV effectively. Exploration and more researches on such advances could result in the gradual reduction in the incidences of HPV cases across the world. The present review presents a current global scenario and futuristic prospects of the advanced prophylactic and therapeutic approaches against HPV along with recent patents coverage of the progress and advances in drugs, vaccines and therapeutic regimens to effectively combat HPV infections and its cancerous conditions.
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Affiliation(s)
- Maryam Dadar
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran
| | - Sandip Chakraborty
- Department of Veterinary Microbiology, College of Veterinary Sciences and Animal Husbandry, West Tripura, India
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Minakshi Prasad
- Department of Animal Biotechnology, LLR University of Veterinary and Animal Sciences, Hisar, India
| | - Rekha Khandia
- Department of Genetics, Barkatullah University, Bhopal, India
| | - Sameer Hassan
- Department of Biomedical Informatics, National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chennai, India
| | - Ashok Munjal
- Department of Genetics, Barkatullah University, Bhopal, India
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, U P Pt. Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwavidyalay Evum Go-Anusandhan Sansthan, Mathura, India
| | - Kumaragurubaran Karthik
- Central University Laboratory, Tamil Nadu Veterinary and Animal Sciences University, Chennai, India
| | - Deepak Kumar
- Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Hafiz M. N. Iqbal
- Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey, Mexico
| | - Wanpen Chaicumpa
- Department of Parasitology, Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Faculty of Medicine SIriraj Hospital, Mahidol University, Bangkok, Thailand
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Attipoe-Dorcoo S, Singh V, Moodley J. A content analysis of online news media reporting on the human papillomavirus vaccination programme in South Africa. SOUTHERN AFRICAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 2018. [DOI: 10.1080/20742835.2018.1509928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
Affiliation(s)
- Sharon Attipoe-Dorcoo
- Health Science Center, School of Public Health, University of Texas, Houston, Texas, USA
- Cancer Research Initiative, University of Cape Town, Cape Town, South Africa
| | - Vedantha Singh
- Cancer Research Initiative, University of Cape Town, Cape Town, South Africa
| | - Jennifer Moodley
- Cancer Research Initiative, University of Cape Town, Cape Town, South Africa
- Women’s Health Research Unit, School of Public Health and Family Medicine, Cape Town, South Africa
- SAMRC Gynecological Cancer Research Centre, University of Cape Town, Cape Town, South Africa
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Skufca J, Ollgren J, Artama M, Ruokokoski E, Nohynek H, Palmu AA. The association of adverse events with bivalent human papilloma virus vaccination: A nationwide register-based cohort study in Finland. Vaccine 2018; 36:5926-5933. [PMID: 30115524 DOI: 10.1016/j.vaccine.2018.06.074] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 06/18/2018] [Accepted: 06/29/2018] [Indexed: 11/27/2022]
Abstract
BACKGROUND A bivalent HPV vaccine (Cervarix®; HPV2, GlaxoSmithKline) was introduced into the Finnish national vaccination programme (NVP) in November 2013 for girls aged 11-13 years with a catch-up for 14-15 year-olds. We evaluated the association between HPV2 and selected autoimmune diseases and clinical syndromes by conducting a nation-wide retrospective register-based cohort study. METHODS First life-time occurrences of the relevant ICD-10 codes in girls aged 11-15 years between Nov-2013 and Dec-2016 were obtained from the national hospital discharge register. Population denominators were obtained from the Population Information System and vaccination records from the National Vaccination Register. Registers were linked using unique personal identity codes. Association between HPV2 and 38 selected outcomes were studied using Cox regression, with age as the main time-scale and the first vaccination dose as the time-dependent exposure. The hazard ratios (HR) with 95%CI were assessed according to the time since exposure (entire follow-up, 0-180/181-365/>365 days). RESULTS Of 240 605 girls eligible for HPV2 vaccination, 134 615 (56%) were vaccinated. After adjustment for geographical area (6 hospital districts), country of origin (Finnish-born/not) and number of hospital contacts from 9 through 10 years of age, HRs ranged from 0.34 (95%CI 0.11-1.05) to 8.37 (95%CI 0.85-82.54) and HPV2 vaccination was not statistically significantly associated with a higher risk of any outcome during the entire follow-up. CONCLUSIONS This study found no significantly increased risk for the selected outcomes after the HPV vaccination in girls 11-15 years of age. These results provide valid evidence to counterbalance public scepticism, fears of adverse events and possible opposition to HPV vaccination and consequently can contribute to increase HPV vaccination coverage in Finland as well as elsewhere.
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Affiliation(s)
- Jozica Skufca
- Department of Health Security, Infectious Diseases Control and Vaccinations Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
| | - Jukka Ollgren
- Department of Health Security, Infectious Diseases Control and Vaccinations Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
| | - Miia Artama
- Department of Public Health Solutions, Public Health Evaluation and Projection Unit, National Institute for Health and Welfare (THL), Tampere, Finland.
| | - Esa Ruokokoski
- Department of Health Security, Infectious Diseases Control and Vaccinations Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
| | - Hanna Nohynek
- Department of Health Security, Infectious Diseases Control and Vaccinations Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
| | - Arto A Palmu
- Department of Public Health Solutions, Public Health Evaluation and Projection Unit, National Institute for Health and Welfare (THL), Tampere, Finland
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Bhurani V, Mohankrishnan A, Morrot A, Dalai SK. Developing effective vaccines: Cues from natural infection. Int Rev Immunol 2018; 37:249-265. [PMID: 29927676 DOI: 10.1080/08830185.2018.1471479] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The ultimate goal of any vaccine is to generate a heterogeneous and stable pool of memory lymphocytes. Vaccine are designed with the hope to generate antigen specific long-lived T cell responses, as it may be the case in natural infection; however, inducing such response by sub-unit vaccine has been a challenge. Although significant progress has been made, there is lot of scope for designing novel vaccine strategies by taking cues from the natural infection. This review focuses upon the roadblocks and the possible ways to overcome them leading to developing effective vaccines. Here we propose that mimicking the natural course of infection as well as the inclusion of non-target antigens in vaccine formulations might generate heterogeneous pool of memory T cells to ensure long-lived protection.
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Affiliation(s)
- Vishakha Bhurani
- a Institute of Science , Nirma University , Ahmedabad , Gujarat , India
| | | | - Alexandre Morrot
- b Faculdade de Medicina , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil.,c Instituto Oswaldo Cruz , Fiocruz , Rio de Janeiro , Brazil
| | - Sarat Kumar Dalai
- a Institute of Science , Nirma University , Ahmedabad , Gujarat , India
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Mouchet J, Salvo F, Raschi E, Poluzzi E, Antonazzo IC, De Ponti F, Bégaud B. Human papillomavirus vaccine and demyelinating diseases-A systematic review and meta-analysis. Pharmacol Res 2018; 132:108-118. [PMID: 29665426 DOI: 10.1016/j.phrs.2018.04.007] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 04/06/2018] [Accepted: 04/06/2018] [Indexed: 11/30/2022]
Abstract
Approved in 2006, human papillomavirus (HPV) vaccines were initially targeted for girls aged 9-14 years. Although the safety of these vaccines has been monitored through post-licensure surveillance programmes, cases of neurological events have been reported worldwide. The present study aimed to assess the risk of developing demyelination after HPV immunization by meta-analysing risk estimates from pharmacoepidemiologic studies. A systematic review was conducted in Medline, Embase, ISI Web of Science and the Cochrane Library from inception to 10 May 2017, without language restriction. Only observational studies including a control group were retained. Study selection was performed by two independent reviewers with disagreements solved through discussion. This meta-analysis was performed using a generic inverse variance random-effect model. Outcomes of interest included a broad category of central demyelination, multiple sclerosis (MS), optic neuritis (ON), and Guillain-Barré syndrome (GBS), each being considered independently. Heterogeneity was investigated; sensitivity and subgroup analyses were performed when necessary. In parallel, post-licensure safety studies were considered for a qualitative review. This study followed the PRISMA statement and the MOOSE reporting guideline. Of the 2,863 references identified, 11 articles were selected for meta-analysis. No significant association emerged between HPV vaccination and central demyelination, the pooled odds ratio being 0.96 [95% CI 0.77-1.20], with a moderate but non-significant heterogeneity (I2 = 29%). Similar results were found for MS and ON. Sensitivity analyses did not alter our conclusions. Findings from qualitative review of 14 safety studies concluded in an absence of a relevant signal. Owing to limited data on GBS, no meta-analysis was performed for this outcome. This study strongly supports the absence of association between HPV vaccines and central demyelination.
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Affiliation(s)
- Julie Mouchet
- University Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, UMR 1219, F-33000 Bordeaux, France.
| | - Francesco Salvo
- University Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, UMR 1219, F-33000 Bordeaux, France
| | - Emanuel Raschi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Elisabetta Poluzzi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Fabrizio De Ponti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Bernard Bégaud
- University Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, UMR 1219, F-33000 Bordeaux, France
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Leng T, Keeling MJ. Concurrency of partnerships, consistency with data, and control of sexually transmitted infections. Epidemics 2018; 25:35-46. [PMID: 29798812 DOI: 10.1016/j.epidem.2018.05.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 04/18/2018] [Accepted: 05/13/2018] [Indexed: 11/28/2022] Open
Abstract
Sexually transmitted infections (STIs) are a globally increasing public health problem. Mathematical models, carefully matched to available epidemiological and behavioural data, have an important role to play in predicting the action of control measures. Here, we explore the effect of concurrent sexual partnerships on the control of a generic STI with susceptible-infected-susceptible dynamics. Concurrency refers to being in more than one sexual partnership at the same time, and is difficult to measure accurately. We assess the impact of concurrency through the development of three nested pair-formation models: one where infection can only be transmitted via stable sexual partnerships, one where infection can also be transmitted via casual partnerships between single individuals, and one where those individuals in stable partnerships can also acquire infection from casual partnerships. For each model, we include the action of vaccination before sexual debut to inform about the ability to control. As expected, for a fixed transmission rate, concurrency increases both the endemic prevalence of infection and critical level of vaccination required to eliminate the disease significantly. However, when the transmission rate is scaled to maintain a fixed endemic prevalence across models, concurrency has a far smaller impact upon the critical level of vaccination required. Further, when we also constrain the models to have a fixed number of new partnerships over time (both long-term and casual), then increasing concurrency can slightly decrease the critical level of vaccination. These results highlight that accurate measures and models of concurrency may not always be needed for reliable forecasts when models are closely matched to prevalence data. We find that, while increases in concurrency within a population are likely to generate public-health problems, the inclusion of concurrency may be unnecessary when constructing models to determine the efficacy of the control of STIs by vaccination.
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Affiliation(s)
- Trystan Leng
- EPSRC & MRC Centre for Doctoral Training in Mathematics for Real-World Systems, University of Warwick, United Kingdom.
| | - Matt J Keeling
- Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research, Mathematics Institute and School of Life Sciences, University of Warwick, United Kingdom
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Arbyn M, Xu L, Simoens C, Martin‐Hirsch PPL. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev 2018; 5:CD009069. [PMID: 29740819 PMCID: PMC6494566 DOI: 10.1002/14651858.cd009069.pub3] [Citation(s) in RCA: 210] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. OBJECTIVES To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. SEARCH METHODS We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events. SELECTION CRITERIA Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine). DATA COLLECTION AND ANALYSIS We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets. MAIN RESULTS We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation.Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes.Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions.Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established.Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively). AUTHORS' CONCLUSIONS There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status.We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.
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Affiliation(s)
- Marc Arbyn
- SciensanoUnit of Cancer Epidemiology, Belgian Cancer CentreJuliette Wytsmanstreet 14BrusselsBelgiumB‐1050
| | - Lan Xu
- SciensanoUnit of Cancer Epidemiology, Belgian Cancer CentreJuliette Wytsmanstreet 14BrusselsBelgiumB‐1050
| | - Cindy Simoens
- University of AntwerpLaboratory of Cell Biology and HistologyGroenenborgerlaan 171AntwerpBelgiumB‐2020
| | - Pierre PL Martin‐Hirsch
- Royal Preston Hospital, Lancashire Teaching Hospital NHS TrustGynaecological Oncology UnitSharoe Green LaneFullwoodPrestonLancashireUKPR2 9HT
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Abstract
The major impediment to increased human papillomavirus (HPV) vaccination coverage in young males and females is lack of health care provider recommendation. Despite its efficacy in preventing cervical cancer, HPV vaccination in females (49.5%) and males (37.5%) ages 13 through 17 falls well below the Centers for Disease Control and Prevention's (CDC) Healthy People 2020 target of 80% coverage. Parents' willingness to vaccinate their child has been shown to be much higher when physicians share personal vaccination decisions for their own children as well as what other parents have done at that particular clinic. Furthermore, the vaccine must be presented presumptively as a "bundle" along with the rest of the standard adolescent vaccine panel. Multiple exemplars presented including in several European countries, low-income countries and Rwanda, demonstrate that school-based health care systems dramatically increase vaccination coverage. Finally, acceptability for vaccination of males must improve by increasing provider recommendation and by presenting the HPV vaccine as a penile, anal and oropharyngeal cancer prevention therapy in males and not merely a vaccine to prevent cervical cancers in females. Paediatricians, obstetrician/gynaecologists and primary care physicians should consider these data as a call-to-action. Key messages • Despite recent efforts in the US, only 49.5% of females and only 37.5% of males ages 13 through 17 have received all recommended HPV vaccine doses. These numbers fall well below the 80% target set forth by the Healthy People 2020 initiative. • According to the CDC, if health care providers increase HPV vaccination rates in eligible recipients to 80%, it is estimated that an additional 53,000 cases of cervical cancer could be prevented during the lifetime of those younger than 12 years. Furthermore, for every year that the vaccination rate does not increase, an additional 4400 women will develop cervical cancer. • First and foremost, healthcare providers (HCPs) must make a strong recommendation to vaccinate patients and these recommendations must become routine, including for males. • It is clear that HPV vaccination rates improve significantly when vaccine administration occurs at designated, well-organized sites such as school-based vaccination programmes. Furthermore, HPV vaccination should be a high school requirement and offered in the standard adolescent vaccine panel as a bundle with Tdap and MenACWY vaccines in order to promote maximum adherence. • Finally, research on immunogenicity and antibody titre longevity needs to be done in newborns. The HPV vaccine may be recommended in the newborn panel of vaccines to avoid any issues of sexualization and misplaced fears of sexual disinhibition, akin to the success of the Hepatitis B vaccine in the 1980s. • The HPV vaccine is a vaccine against cancer and should be aggressively marketed as such. As healthcare providers, we need to make every effort to overcome barriers, real or perceived, to protecting our population from potential morbidity and mortality associated with this virus.
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Affiliation(s)
- Aria C Attia
- a Department of Medicine , Drexel University College of Medicine , Philadelphia , PA , USA
| | - Judith Wolf
- a Department of Medicine , Drexel University College of Medicine , Philadelphia , PA , USA
| | - Ana E Núñez
- a Department of Medicine , Drexel University College of Medicine , Philadelphia , PA , USA
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Van Kriekinge G, Sohn WY, Aljunid SM, Soon R, Yong CM, Chen J, Lee IH. Comparative Cost-Effectiveness Analysis of Two Different Two-Dose Human Papillomavirus Vaccines in Malaysia. Asian Pac J Cancer Prev 2018; 19:933-940. [PMID: 29693347 PMCID: PMC6031794 DOI: 10.22034/apjcp.2018.19.4.933] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Purpose: To comparatively evaluate the results of a 2-dose human papillomavirus (HPV) vaccination programme with the AS04-adjuvanted HPV16/18 vaccine (AS04-HPV-16/18v) or HPV-6/11/16/18 vaccine (4vHPVv), in addition to cervical cancer (CC) screening, in Malaysia. Methods: A lifetime Markov model replicating the natural history of HPV in 13-year-old girls was adapted to Malaysia to assess the impact of vaccination on pre-cancerous lesions, genital warts and CC cases, CC deaths, quality-adjusted life years (QALYs), and costs from the perspective of the Malaysian Ministry of Health. Vaccine effectiveness was based on efficacy and HPV type distribution. Both vaccines were assumed to have equal efficacy against vaccine-type HPV but differed for protection against non-vaccine types. Vaccine price parity was used and health and cost outcomes were discounted at 3%/annum. Sensitivity analyses tested the robustness of the results. Results: The model predicted that AS04-HPV-16/18v would result in 361 fewer CC cases and 115 fewer CC deaths than 4vHPVv, whereas 4vHPVv averted 4,241 cases of genital warts over the cohort’s lifetime. Discounted total costs showed savings of 18.50 million Malaysian Ringgits and 246 QALYs in favour of AS04-HPV-16/18v. In one-way sensitivity analyses, the discount rate was the most influential variable for costs and QALYs, but AS04-HPV-16/18v remained dominant throughout. A two-way sensitivity analysis to assess the longevity of cross-protection for both vaccines confirmed the base-case. Conclusions: In Malaysia, the use of AS04-HPV-16/18v, in addition to screening, was modelled to be dominant over 4vHPVv, with greater estimated CC benefits and lower costs.
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45
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Tejada RA, Vargas KG, Benites-Zapata V, Mezones-Holguín E, Bolaños-Díaz R, Hernandez AV. Human papillomavirus vaccine efficacy in the prevention of anogenital warts: systematic review and meta-analysis. SALUD PUBLICA DE MEXICO 2018; 59:84-94. [PMID: 28423114 DOI: 10.21149/7824] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Accepted: 06/10/2016] [Indexed: 11/06/2022] Open
Abstract
Objective: To review evidence on the efficacy of HPV vaccines in the prevention of non-cancer lesions (anogenital warts [AGW], recurrent laryngeal papillomatosis and oral papillomatosis). Materials and methods: We conducted a systematic review of randomized trials. We performed random effect models and effects were reported as relative risks (RR) and their confidence intervals (95%CI) following both intention to treat (ITT) and per protocol (PP) analyses. Results: We included six studies (n=27 078). One study was rated as high risk of bias. One study could not be included in the meta-analysis because it provided combined results. We found that quadrivalent vaccine reduced the risk of AGW by 62% (RR: 0.38, 95%CI:0.32-0.45, I2:0%) in the ITT analysis and by 95% (RR: 0.05, 95%CI:0.01-0.25, I2:66%) in the PP analysis. Subgroup analyses of studies in women or with low-risk of bias provided similar results. Conclusion: HPV quadrivalent vaccine is efficacious in preventing AGW in men and women.
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Affiliation(s)
- Romina A Tejada
- Unidad de Análisis y Generación de Evidencias en Salud Pública, Centro Nacional de Salud Pública, Instituto Nacional de Salud. Lima, Perú
| | - Kris G Vargas
- Department of Epidemiology, Erasmus MC. Rotterdam. Netherlands
| | - Vicente Benites-Zapata
- Centro de Investigación de Salud Pública, Instituto de Investigación, Facultad de Medicina Humana, Universidad de San Martín de Porres. Lima, Perú
| | - Edward Mezones-Holguín
- Intendencia de Investigación y Desarrollo, Superintendencia Nacional de Salud. Lima, Perú.,School of Medicine, Universidad Peruana de Ciencias Aplicadas. Lima, Perú
| | - Rafael Bolaños-Díaz
- Unidad de Análisis y Generación de Evidencias en Salud Pública, Centro Nacional de Salud Pública, Instituto Nacional de Salud. Lima, Perú.,Organización médica para el desarrollo de la salud. Lima, Perú
| | - Adrián V Hernandez
- School of Medicine, Universidad Peruana de Ciencias Aplicadas. Lima, Perú.,Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic. Ohio, USA
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Abstract
Compared with biologics, vaccine potency assays represent a special challenge due to their unique compositions, multivalency, long life cycles and global distribution. Historically, vaccines were released using in vivo potency assays requiring immunization of dozens of animals. Modern vaccines use a variety of newer analytical tools including biochemical, cell-based and immunochemical methods to measure potency. The choice of analytics largely depends on the mechanism of action and ability to ensure lot-to-lot consistency. Live vaccines often require cell-based assays to ensure infectivity, whereas recombinant vaccine potency can be reliably monitored with immunoassays. Several case studies are presented to demonstrate the relationship between mechanism of action and potency assay. A high-level decision tree is presented to assist with assay selection.
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Pennisi M, Russo G, Ravalli S, Pappalardo F. Combining agent based-models and virtual screening techniques to predict the best citrus-derived vaccine adjuvants against human papilloma virus. BMC Bioinformatics 2017; 18:544. [PMID: 29297294 PMCID: PMC5751416 DOI: 10.1186/s12859-017-1961-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Background Human papillomavirus infection is a global social burden that, every year, leads to thousands new diagnosis of cancer. The introduction of a protocol of immunization, with Gardasil and Cervarix vaccines, has radically changed the way this infection easily spreads among people. Even though vaccination is only preventive and not therapeutic, it is a strong tool capable to avoid the consequences that this pathogen could cause. Gardasil vaccine is not free from side effects and the duration of immunity is not always well determined. This work aim to enhance the effects of the vaccination by using a new class of adjuvants and a different administration protocol. Due to their minimum side effects, their easy extraction, their low production costs and their proven immune stimulating activity, citrus-derived molecules are valid candidates to be administered as adjuvants in a vaccine formulation against Hpv. Results With the aim to get a stronger immune response against Hpv infection we built an in silico model that delivers a way to predict the best adjuvants and the optimal means of administration to obtain such a goal. Simulations envisaged that the use of Neohesperidin elicited a strong immune response that was then validated in vivo. Conclusions We built up a computational infrastructure made by a virtual screening approach able to preselect promising citrus derived compounds, and by an agent based model that reproduces HPV dynamics subject to vaccine stimulation. This integrated methodology was able to predict the best protocol that confers a very good immune response against HPV infection. We finally tested the in silico results through in vivo experiments on mice, finding good agreement.
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Affiliation(s)
- Marzio Pennisi
- Department of Mathematics and Computer Science, University of Catania, 95125, Catania, Italy
| | - Giulia Russo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy
| | - Silvia Ravalli
- Department of Drug Sciences, University of Catania, 95125, Catania, Italy
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Kim K, LeClaire AR. A systematic review of factors influencing human papillomavirus vaccination among immigrant parents in the United States. Health Care Women Int 2017; 40:696-718. [PMID: 29161198 DOI: 10.1080/07399332.2017.1404064] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
To critically appraise factors influencing human papillomavirus (HPV) vaccination among immigrant parents in the United States, a comprehensive search of electronic databases and reference lists was conducted. The findings from 22 articles were ordered based on a socioecological model. About 30% of children initiated and 14% completed a three-dose series. Correlates of HPV vaccine initiation rates included lack of information, concerns about vaccine safety and promiscuity, providers' recommendations, school mandates, financial issues, immigration laws, and living in disadvantaged neighborhoods. Upstream initiatives embracing cultural descriptors could facilitate HPV vaccination, reducing HPV-related disparities in cancer among immigrants in the US.
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Affiliation(s)
- Kyounghae Kim
- a School of Nursing, University of Connecticut , Storrs , CT , USA
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49
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Kim M, Lee H, Kiang P, Kim D. Human Papillomavirus: A Qualitative Study of Korean American Female College Students' Attitudes Toward Vaccination
. Clin J Oncol Nurs 2017; 21:E239-E247. [PMID: 28945722 DOI: 10.1188/17.cjon.e239-e247] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Human papillomavirus (HPV) vaccines have the potential to reduce Korean American women's high burden of cervical cancer, but information is limited about their awareness of HPV and its vaccine.
. OBJECTIVES This study aimed to explore Korean American female college students' awareness of and attitudes toward HPV vaccination.
. METHODS A qualitative descriptive study was used. Five focus group interviews were conducted with 20 Korean American female college students aged 18-26 years from Massachusetts. Data were analyzed using inductive content analysis.
. FINDINGS Major themes were awareness, misunderstandings, attitudes, social influences, and cultural influence. A critical need exists to develop and implement culturally and linguistically appropriate HPV prevention education programs to promote HPV vaccination in this population.
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Affiliation(s)
- Minjin Kim
- University of Massachusetts Medical School
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Mohsen MO, Zha L, Cabral-Miranda G, Bachmann MF. Major findings and recent advances in virus-like particle (VLP)-based vaccines. Semin Immunol 2017; 34:123-132. [PMID: 28887001 DOI: 10.1016/j.smim.2017.08.014] [Citation(s) in RCA: 354] [Impact Index Per Article: 44.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 08/18/2017] [Accepted: 08/23/2017] [Indexed: 01/03/2023]
Abstract
Virus-like particles (VLPs) have made giant strides in the field of vaccinology over the last three decades. VLPs constitute versatile tools in vaccine development due to their favourable immunological characteristics such as their size, repetitive surface geometry, ability to induce both innate and adaptive immune responses as well as being safe templates with favourable economics. Several VLP-based vaccines are commercially available including vaccines against Human Papilloma Virus (HPV) such as Cervarix®, Gardasil® & Gardasil9® and Hepatitis B Virus (HBV) including the 3rd generation Sci-B-Vac™. In addition, the first licensed malaria-VLP-based vaccine Mosquirix™ has been recently approved by the European regulators. Several other VLP-based vaccines are currently undergoing preclinical and clinical development. This review summarizes some of the major findings and recent advances in VLP-based vaccine development and technologies and outlines general principles that may be harnessed for induction of targeted immune responses.
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Affiliation(s)
- Mona O Mohsen
- Jenner Institute, University of Oxford, Roosevelt Dr, Oxford OX3 7BN, UK; Qatar Foundation, Doha, State of Qatar
| | - Lisha Zha
- Inselspital, Universitatsklinik RIA, Immunologie, Sahlihaus 1, 3010 Bern, Switzerland
| | | | - Martin F Bachmann
- Jenner Institute, University of Oxford, Roosevelt Dr, Oxford OX3 7BN, UK; Inselspital, Universitatsklinik RIA, Immunologie, Sahlihaus 1, 3010 Bern, Switzerland.
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