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Lehtinen M, Gray P, Luostarinen T, Eriksson T, Apter D, Bly A, Harjula K, Heikkilä K, Hokkanen M, Kuortti M, Nieminen P, Nummela M, Paavonen J, Palmroth J, Petäjä T, Pimenoff VN, Pukkala E, Dillner J. Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ-population-based follow-up of two cluster-randomized trials. Front Cell Infect Microbiol 2024; 14:1437704. [PMID: 39315334 PMCID: PMC11417099 DOI: 10.3389/fcimb.2024.1437704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 07/29/2024] [Indexed: 09/25/2024] Open
Abstract
Introduction We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women. Methods These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy. Results Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Discussion Long-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer.
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Affiliation(s)
- Matti Lehtinen
- Department of CLINTEC, Karolinska Institute, Stockholm, Sweden
- Faculty of Medicine, Tampere University, Tampere, Finland
| | - Penelope Gray
- Department of CLINTEC, Karolinska Institute, Stockholm, Sweden
| | - Tapio Luostarinen
- Institute for Epidemiological Cancer Research, Finnish Cancer Registry, Helsinki, Finland
| | - Tiina Eriksson
- Faculty of Medicine, Tampere University, Tampere, Finland
| | - Dan Apter
- Youth Clinic, VL-Medi, Helsinki, Finland
| | - Anne Bly
- Faculty of Medicine, Tampere University, Tampere, Finland
| | - Katja Harjula
- Faculty of Medicine, Tampere University, Tampere, Finland
| | - Kaisa Heikkilä
- Faculty of Medicine, Tampere University, Tampere, Finland
| | - Mari Hokkanen
- Faculty of Medicine, Tampere University, Tampere, Finland
| | - Marjo Kuortti
- Faculty of Medicine, Tampere University, Tampere, Finland
| | - Pekka Nieminen
- Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland
| | - Mervi Nummela
- Faculty of Medicine, Tampere University, Tampere, Finland
| | - Jorma Paavonen
- Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland
| | - Johanna Palmroth
- Department of Obstetrics and Gynecology, University of East-Finland,
Kuopio, Finland
| | - Tiina Petäjä
- Faculty of Medicine, Tampere University, Tampere, Finland
| | | | - Eero Pukkala
- Institute for Epidemiological Cancer Research, Finnish Cancer Registry, Helsinki, Finland
| | - Joakim Dillner
- Department of CLINTEC, Karolinska Institute, Stockholm, Sweden
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Piyathilake CJ, Badiga S, Thao N, Jolly PE. Micronutrients and prevention of cervical pre-cancer in HPV vaccinated women: a cross-sectional study. KOREAN JOURNAL OF COMMUNITY NUTRITION 2023; 28:61-73. [PMID: 37674548 PMCID: PMC10481701 DOI: 10.5720/kjcn.2023.28.1.61] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 02/16/2023] [Accepted: 02/18/2023] [Indexed: 09/08/2023]
Abstract
Objectives Prophylactic vaccines against high-risk human papillomaviruses (HR-HPVs) hold promise to prevent the development of higher grade cervical intraepithelial neoplasia (CIN 2+) and cervical cancer (CC) that develop due to HR-HPV genotypes that are included, in HPV vaccines, but women will continue to develop CIN 2+ and CC due to HR-HPV genotypes that are not included in the quadrivalent HPV vaccine (qHPV) and 9-valent HPV vaccine (9VHPV). Thus, the current vaccines are likely to decrease but not entirely prevent the development of CIN 2+ or CC. The purpose of the study was to determine the prevalence and determinants of CIN 2+ that develop due to HR-HPVs not included in vaccines. Methods Study population consisted of 1476 women tested for 37 HPVs and known to be negative for qHPVs (6/11/16/18, group A, n = 811) or 9VHPVs (6/11/16/18/31/33/45/52/58, group B, n = 331), but positive for other HR-HPVs. Regression models were used to determine the association between plasma concentrations of micronutrients, socio-demographic, lifestyle factors and risk of CIN 2+ due to HR-HPVs that are not included in vaccines. Results The prevalence of infections with HPV 31, 33, 35 and 58 that contributed to CIN 2+ differed by race. In group A, African American (AA) women and current smokers were more likely to have CIN 2 (OR = 1.76, P = 0.032 and 1.79, P = 0.016, respectively) while in both groups of A and B, those with higher vitamin B12 were less likely to have similar lesions (OR = 0.62, P = 0.036 and 0.45, P = 0.035, respectively). Conclusions We identified vitamin B12 status and smoking as independent modifiable factors and ethnicity as a factor that needs attention to reduce the risk of developing CIN 2+ in the post vaccination era. Continuation of tailored screening programs combined with non-vaccine-based approaches are needed to manage the residual risk of developing HPV-related CIN 2+ and CC in vaccinated women.
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Affiliation(s)
- Chandrika J Piyathilake
- Department of Nutrition Sciences, The University of Alabama at Birmingham (UAB), Birmingham, AL, USA
| | - Suguna Badiga
- Department of Nutrition Sciences, UAB, Birmingham, AL, USA
| | - Nongnut Thao
- Awardee of the Minority Health Research Training grant, St. Olaf college, Birmingham, AL, USA
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Lehtinen M, Lagheden C, Luostarinen T, Eriksson T, Apter D, Bly A, Gray P, Harjula K, Heikkilä K, Hokkanen M, Karttunen H, Kuortti M, Nieminen P, Nummela M, Paavonen J, Palmroth J, Petäjä T, Pukkala E, Soderlund-Strand A, Veivo U, Dillner J. Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial. BMJ Open 2021; 11:e050669. [PMID: 35149535 PMCID: PMC8719207 DOI: 10.1136/bmjopen-2021-050669] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer. METHODS Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts. FINDINGS During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05). INTERPRETATION Vaccination is effective against invasive HPV-positive cancer. TRIAL REGISTRATION NUMBER NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results.
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Affiliation(s)
- Matti Lehtinen
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
- Tampere University Hospital, Tampere, Finland
| | - Camilla Lagheden
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | | | | | | | - Anne Bly
- Tampere University Hospital, Tampere, Finland
| | - Penelope Gray
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | | | | | | | | | - Marjo Kuortti
- Faculty of Social Sciences, Tampereen Yliopisto, Tampere, Finland
| | | | | | - J Paavonen
- Department of Gynecology and Obstetrics, University of Helsinki, Helsinki, Finland
| | - Johanna Palmroth
- University of Eastern Finland School of Medicine, Kuopio, Pohjois-Savo, Finland
| | - Tiina Petäjä
- Obstetrics & Gynecology, Tampereen Yliopisto, Seinäjoki, Finland
| | | | | | - Ulla Veivo
- Tampere University Hospital, Tampere, Finland
| | - Joakim Dillner
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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Artemchuk H, Eriksson T, Poljak M, Surcel HM, Dillner J, Lehtinen M, Faust H. Long-term Antibody Response to Human Papillomavirus Vaccines: Up to 12 Years of Follow-up in the Finnish Maternity Cohort. J Infect Dis 2019; 219:582-589. [PMID: 30239832 DOI: 10.1093/infdis/jiy545] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Accepted: 09/11/2018] [Indexed: 01/11/2023] Open
Abstract
Background Most cervical cancers are caused by vaccine-preventable infections with human papillomaviruses (HPV). The HPV prophylactic vaccines Gardasil and Cervarix have been widely used for >10 years and are reported to induce high antibody levels. A head-to-head comparison of the antibody responses induced by the 2 vaccines has been performed only up to 5 years. Methods Among 3300 Finnish females aged 16-17 years who got 1 of the 2 HPV vaccines in phase 3 licensure trials, virtually all consented to registry-based long-term follow-up. Linkage with the Finnish Maternity Cohort found that they donated >2500 serum samples up to 12 years later. Sera of 337 (38.6%) Gardasil and 730 (30.3%) Cervarix vaccine recipients were retrieved from the Finnish Maternity Cohort biobank and type-specific anti-HPV antibody levels were determined using in-house multiplexed heparin-HPV pseudovirion Luminex assay. Results Anti-HPV-16 and anti-HPV-18 antibody levels remained stable and above natural infection-related antibody levels for up to 12 years for most vaccine recipients. The median antibody levels were higher among Cervarix recipients 7-12 years post vaccination (P < .0001). Conclusions The stability of vaccine-induced antibody levels is in accordance with the high long-term protection reported previously. The differences in antibody levels induced by the 2 vaccines imply that continued follow-up to identify possible breakthrough cases and estimation of the minimal protective levels of serum antibodies is a research priority.
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Affiliation(s)
- Hanna Artemchuk
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | | | - Mario Poljak
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia
| | - Heljä-Marja Surcel
- Faculty of Medicine, University of Oulu, Oulu, Finland.,European Science Infrastructure Services, Oulu, Finland
| | - Joakim Dillner
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Clinical Pathology/Cytology, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden
| | - Matti Lehtinen
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,University of Tampere, Finland
| | - Helena Faust
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
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Nanomedicinal strategies as efficient therapeutic interventions for delivery of cancer vaccines. Semin Cancer Biol 2019; 69:43-51. [PMID: 31618687 DOI: 10.1016/j.semcancer.2019.10.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 10/06/2019] [Accepted: 10/08/2019] [Indexed: 12/13/2022]
Abstract
The applications of gene therapy-based treatment of cancers were started almost two decades back as a boon over the chemotherapeutic treatment strategies. Gene therapy helps in correcting the genetic sequences for treatment of cancers, thus also acts like a vaccine to induce the cellular and humoral immunity. However, the cancer vaccines typically suffer from a series of biopharmaceutical challenges due to poor solubility, low systemic availability and lack of targeting ability. Owing to these challenges, the physicians and pharmaceutical scientists have explored the applications of nanocarriers as quite promising systems for effective treatment against the tumors. A series of nanotherapeutic systems are available to date for diverse drug therapy applications. Systematic understanding on the preparation, evaluation and application of nanomedicines as a carrier system for delivering the cancer vaccines is highly important. The present review article provides an in-depth understanding on the challenges associated with cancer vaccine delivery and current opportunities with diverse nanomedicinal carriers being available for treatment of cancers.
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Sanchez-Sandoval AL, Gomora JC. Contribution of voltage-gated sodium channel β-subunits to cervical cancer cells metastatic behavior. Cancer Cell Int 2019; 19:35. [PMID: 30814913 PMCID: PMC6377746 DOI: 10.1186/s12935-019-0757-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 02/12/2019] [Indexed: 01/23/2023] Open
Abstract
Background Voltage-gated sodium (NaV) channels are heteromeric proteins consisting of a single pore forming α-subunit associated with one or two auxiliary β-subunits. These channels are classically known for being responsible of action potential generation and propagation in excitable cells; but lately they have been reported as widely expressed and regulated in several human cancer types. We have previously demonstrated the overexpression of NaV1.6 channel in cervical cancer (CeCa) biopsies and primary cultures, and its contribution to cell migration and invasiveness. Here, we investigated the expression of NaV channels β-subunits (NaVβs) in the CeCa cell lines HeLa, SiHa and CaSki, and determined their contribution to cell proliferation, migration and invasiveness. Methods We assessed the expression of NaVβs in CeCa cell lines by performing RT-PCR and western blotting experiments. We also evaluated CeCa cell lines proliferation, migration, and invasion by in vitro assays, both in basal conditions and after inducing changes in NaVβs levels by transfecting specific cDNAs or siRNAs. The potential role of NaVβs in modulating the expression of NaV α-subunits in the plasma membrane of CeCa cells was examined by the patch-clamp whole-cell technique. Furthermore, we investigated the role of NaVβ1 on cell cycle in SiHa cells by flow cytometry. Results We found that the four NaVβs are expressed in the three CeCa cell lines, even in the absence of functional NaV α-subunit expression in the plasma membrane. Functional in vitro assays showed differential roles for NaVβ1 and NaVβ4, the latter as a cell invasiveness repressor and the former as a migration abolisher in CeCa cells. In silico analysis of NaVβ4 expression in cervical tissues corroborated the downregulation of this protein expression in CeCa vs normal cervix, supporting the evidence of NaVβ4’s role as a cell invasiveness repressor. Conclusions Our results contribute to the recent conception about NaVβs as multifunctional proteins involved in cell processes like ion channel regulation, cell adhesion and motility, and even in metastatic cell behaviors. These non-canonical functions of NaVβs are independent of the presence of functional NaV α-subunits in the plasma membrane and might represent a new therapeutic target for the treatment of cervical cancer. Electronic supplementary material The online version of this article (10.1186/s12935-019-0757-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ana Laura Sanchez-Sandoval
- Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Mexico City, Mexico
| | - Juan Carlos Gomora
- Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Mexico City, Mexico
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Lehtinen M, Baussano I, Paavonen J, Vänskä S, Dillner J. Eradication of human papillomavirus and elimination of HPV-related diseases - scientific basis for global public health policies. Expert Rev Vaccines 2019; 18:153-160. [PMID: 30657348 DOI: 10.1080/14760584.2019.1568876] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 01/09/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Infections with oncogenic human papillomaviruses (HPV) globally cause about 9% of cancers in females and 1% of cancers in males. HPV disease burden can be effectively controlled by prophylactic HPV-vaccination provided it has high impact. AREAS COVERED A unique series of biobank-based and health registry-based studies that exploit randomized intervention cohorts has provided data on population-level safety of HPV vaccination, duration of vaccine-induced protection and impact of gender-neutral HPV vaccination, providing a scientific basis for policies to eradicate oncogenic HPV types and associated diseases worldwide. EXPERT COMMENTARY The ultimate goal of HPV vaccination is the eradication of high-risk (hr) HPVs. Seventy-five percent coverage gender-neutral vaccination of early adolescents will rapidly eradicate also HPV16 from the general population.
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Affiliation(s)
- Matti Lehtinen
- a Department of Laboratory Medicine , Karolinska Institute , Stockholm , Sweden
- b Faculty of Social Sciences , University of Tampere , Tampere , Finland
| | | | - Jorma Paavonen
- d Department of Obstetrics and Gynecology , University of Helsinki , Helsinki , Finland
| | - Simopekka Vänskä
- e Department of Vaccines , National Institute for Health and Welfare , Helsinki , Finland
| | - Joakim Dillner
- a Department of Laboratory Medicine , Karolinska Institute , Stockholm , Sweden
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Fitzpatrick T, Perrier L, Shakik S, Cairncross Z, Tricco AC, Lix L, Zwarenstein M, Rosella L, Henry D. Assessment of Long-term Follow-up of Randomized Trial Participants by Linkage to Routinely Collected Data: A Scoping Review and Analysis. JAMA Netw Open 2018; 1:e186019. [PMID: 30646311 PMCID: PMC6324362 DOI: 10.1001/jamanetworkopen.2018.6019] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 10/26/2018] [Indexed: 12/21/2022] Open
Abstract
Importance Follow-up of participants in randomized trials may be limited by logistic and financial factors. Some important randomized trials have been extended well beyond their original follow-up period by linkage of individual participant information to routinely collected data held in administrative records and registries. Objective To perform a scoping review of randomized clinical trials extended by record linkage to characterize this literature and explore any additional insights into treatment effectiveness provided by long-term follow-up using record linkage. Data Sources A literature search in Embase, CINAHL, MEDLINE, and the Cochrane Register of Controlled Trials was performed for the period January 1, 1945, through November 25, 2016. Study Selection Various combinations of search terms were used, as there is no accepted terminology. Determination of study eligibility and extraction of information about trial characteristics and outcomes, for both original and extended trial reports, were performed in duplicate. Data Extraction and Synthesis Assessment of study eligibility and data extraction were performed independently by 2 reviewers. All analyses were descriptive. Main Outcomes and Measures Outcomes in the pairs of original and extended trials were categorized according to whether any benefits or harms from interventions were sustained, were lost, or emerged during long-term follow-up. Results A total of 113 extended trials were included in the study. Linkage to administrative and registry data extended follow-up by between 1 and 55 years. The most common interventions were pharmaceuticals (47 [41.6%]), surgery (19 [16.8%]), and disease screening (19 [16.8%]). End points most frequently studied through record linkage included mortality (88 [77.9%]), cancer (41 [36.3%]), and cardiovascular events (37 [32.7%]). One hundred four trial extensions (92.0%) were analyzed according to the original trial randomization. The reports provided details of 155 analyses of study outcomes. Seventy-four analyses (47.7%) identified statistically significant benefits in the trial extension phase. In 21 of these (28.4%), benefits were significant only in this period. Null results in both the original and extended trials were seen in 34 of the analyses (21.9%). Loss of significant benefits of an intervention were seen in 12 analyses (7.7%). Statistically significant harms were seen in 16 trial extension analyses (10.3%), and in 14 of these (87.5%), the harms were significant only in the trial extension phase. Conclusions and Relevance Trial extension by linkage to routinely collected data is a versatile underused approach that may add critical insights beyond those of the original trial. Some beneficial and harmful outcomes of interventions are captured only in the extension phase of randomized trials.
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Affiliation(s)
- Tiffany Fitzpatrick
- Ontario Strategy for Patient-Oriented Research (SPOR) SUPPORT Unit, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Laure Perrier
- University of Toronto Libraries, Toronto, Ontario, Canada
| | - Sharara Shakik
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Zoe Cairncross
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Andrea C. Tricco
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Lisa Lix
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Manitoba Centre for Health Policy, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Merrick Zwarenstein
- Department of Family Medicine, University of Western Ontario, London, Ontario, Canada
- Institute for Clinical Evaluative Sciences, Ontario, Canada
| | - Laura Rosella
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Institute for Clinical Evaluative Sciences, Ontario, Canada
| | - David Henry
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Institute for Clinical Evaluative Sciences, Ontario, Canada
- Centre for Research in Evidence-Based Practice, Bond University, Gold Coast, Queensland, Australia
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Ferreira Costa AP, Gonçalves AK, Machado PRL, Souza LBFCD, Sarmento A, Cobucci RNO, Giraldo PC, Witkin SS. Immune Response to Human Papillomavirus One Year after Prophylactic Vaccination with AS04-Adjuvanted HPV-16/18 Vaccine: HPV-Specific IgG and IgA Antibodies in the Circulation and the Cervix. Asian Pac J Cancer Prev 2018; 19:2313-2317. [PMID: 30141308 PMCID: PMC6171383 DOI: 10.22034/apjcp.2018.19.8.2313] [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: 01/24/2023] Open
Abstract
Objective: This study was designed to describe the course of IgG/IgA responses in cervical secretions and in serum one year after the first dose of intramuscular administration of the HPV16/18 AS04-adjuvant vaccine. Methods: Blood and cervical mucus samples were collected for immunologic assays, 7 months after the first doses and 1 year following the last boost vaccination (month 7) by enzyme linked immunosorbent assay (ELISA). The detection of IgG and IgA anti-HPV/VLP was developed for this purpose. Result: A total of 100% of serum samples were IgG antibody positive at a titer of 1:100 at both time periods and decreased according to the serum dilution. For serum IgA antibody, 95% were positive one month after vaccination and 79% were positive 1 year later. Similar results were observed with the cervical samples positive for both IgG and IgA antibodies at one month and decreasing after 1 year to 33% and 29%. The median absorbance in serum and the cervix for IgG and IgA anti-HPV-VLP antibodies was significantly higher at one month after vaccination when compared to 1 year post-vaccination (P<0.0001). Conclusion: Immune responses were significant one year after immunization, however it decreased in cervical and serum samples when compared to levels observed one month after the last dose. This suggests that a vaccine booster may be necessary to increase antibody titers.
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Affiliation(s)
- Ana Paula Ferreira Costa
- Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil.
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Pukkala E, Engholm G, Højsgaard Schmidt LK, Storm H, Khan S, Lambe M, Pettersson D, Ólafsdóttir E, Tryggvadóttir L, Hakanen T, Malila N, Virtanen A, Johannesen TB, Larønningen S, Ursin G. Nordic Cancer Registries - an overview of their procedures and data comparability. Acta Oncol 2018; 57:440-455. [PMID: 29226751 DOI: 10.1080/0284186x.2017.1407039] [Citation(s) in RCA: 248] [Impact Index Per Article: 35.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND The Nordic Cancer Registries are among the oldest population-based registries in the world, with more than 60 years of complete coverage of what is now a combined population of 26 million. However, despite being the source of a substantial number of studies, there is no published paper comparing the different registries. Therefore, we did a systematic review to identify similarities and dissimilarities of the Nordic Cancer Registries, which could possibly explain some of the differences in cancer incidence rates across these countries. METHODS We describe and compare here the core characteristics of each of the Nordic Cancer Registries: (i) data sources; (ii) registered disease entities and deviations from IARC multiple cancer coding rules; (iii) variables and related coding systems. Major changes over time are described and discussed. RESULTS All Nordic Cancer Registries represent a high quality standard in terms of completeness and accuracy of the registered data. CONCLUSIONS Even though the information in the Nordic Cancer Registries in general can be considered more similar than any other collection of data from five different countries, there are numerous differences in registration routines, classification systems and inclusion of some tumors. These differences are important to be aware of when comparing time trends in the Nordic countries.
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Affiliation(s)
- Eero Pukkala
- Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
- Faculty of Social Sciences, University of Tampere, Tampere, Finland
| | | | | | - Hans Storm
- Danish Cancer Society, Copenhagen, Denmark
| | - Staffan Khan
- Swedish Cancer Registry, the Swedish National Board of Health and Welfare, Stockholm, Sweden
| | - Mats Lambe
- Regional Cancer Centre Uppsala-Örebro, Uppsala, Sweden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - David Pettersson
- Swedish Cancer Registry, the Swedish National Board of Health and Welfare, Stockholm, Sweden
| | | | - Laufey Tryggvadóttir
- Icelandic Cancer Registry, Icelandic Cancer Society, Reykjavik, Iceland
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Tiina Hakanen
- Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
| | - Nea Malila
- Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
- Faculty of Social Sciences, University of Tampere, Tampere, Finland
| | - Anni Virtanen
- Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
- Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland
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11
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Luostarinen T, Apter D, Dillner J, Eriksson T, Harjula K, Natunen K, Paavonen J, Pukkala E, Lehtinen M. Vaccination protects against invasive HPV-associated cancers. Int J Cancer 2018; 142:2186-2187. [PMID: 29280138 DOI: 10.1002/ijc.31231] [Citation(s) in RCA: 107] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 11/17/2017] [Accepted: 11/28/2017] [Indexed: 11/07/2022]
Affiliation(s)
- Tapio Luostarinen
- Finnish Cancer Registry, Helsinki, Finland.,Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | | | - Joakim Dillner
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - Tiina Eriksson
- School of Health Sciences, University of Tampere, Tampere, Finland
| | - Katja Harjula
- School of Health Sciences, University of Tampere, Tampere, Finland
| | - Kari Natunen
- School of Health Sciences, University of Tampere, Tampere, Finland
| | - Jorma Paavonen
- Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland
| | - Eero Pukkala
- Finnish Cancer Registry, Helsinki, Finland.,School of Health Sciences, University of Tampere, Tampere, Finland
| | - Matti Lehtinen
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.,School of Health Sciences, University of Tampere, Tampere, Finland
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12
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Lehtinen M, Eriksson T, Apter D, Hokkanen M, Natunen K, Paavonen J, Pukkala E, Angelo MG, Zima J, David MP, Datta S, Bi D, Struyf F, Dubin G. Safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in adolescents aged 12-15 years: Interim analysis of a large community-randomized controlled trial. Hum Vaccin Immunother 2017; 12:3177-3185. [PMID: 27841725 PMCID: PMC5215585 DOI: 10.1080/21645515.2016.1183847] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
This community-randomized controlled trial was initiated to assess the overall and herd effects of 2 different human papillomavirus (HPV) immunization strategies in over 80,000 girls and boys aged 12–15 y in 33 communities in Finland (ClinicalTrials.gov NCT00534638). Overall, 14,838 adolescents received HPV-16/18 vaccine (2,440 boys and 12,398 girls) and 17,338 received hepatitis-B virus (HBV) vaccine (9,221 boys and 8,117 girls). In an interim analysis, vaccine safety was assessed by active monitoring and surveillance via health registry linkage. Active monitoring showed that the HPV-16/18 vaccine has acceptable safety and reactogenicity in boys. In all study participants, the observed incidences (per 100,000 person-years) of serious adverse events (SAEs) possibly related to vaccination were 54.3 (95% Confidence Interval [CI]: 34.0–82.1) in the HPV-16/18 group and 64.0 (95% CI: 43.2–91.3) in the HBV group. During the follow-up period for this interim analysis, the most common new-onset autoimmune diseases (NOADs; with incidence rate ≥15 per 100,000) in any group based on hospital discharge registry (HILMO) download were ulcerative colitis, juvenile arthritis, celiac disease, insulin-dependent diabetes mellitus (IDDM) and Crohn's disease. No increased NOAD incidences were observed in HPV-16/18 vaccine recipients compared to HBV vaccine recipients. In both the SAE possibly related- and HILMO-analyses, a lower incidence of IDDM was observed in HPV-16/18 vaccinees compared to HBV vaccinees (relative risks, 0.26 [95% CI: 0.03–1.24] and 0.16 [95% CI: 0.03–0.55], respectively).
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Affiliation(s)
| | | | - Dan Apter
- b Family Federation of Finland , Helsinki , Finland
| | | | | | | | | | | | | | | | | | - Dan Bi
- d GSK Vaccines , Wavre , Belgium
| | | | - Gary Dubin
- e GSK Vaccines , King of Prussia , PA , USA
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13
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Lehtinen M, Lagheden C, Luostarinen T, Eriksson T, Apter D, Harjula K, Kuortti M, Natunen K, Palmroth J, Petäjä T, Pukkala E, Siitari-Mattila M, Struyf F, Nieminen P, Paavonen J, Dubin G, Dillner J. Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point-registry-based follow-up of three cohorts from randomized trials. BMJ Open 2017; 7:e015867. [PMID: 28821519 PMCID: PMC5629648 DOI: 10.1136/bmjopen-2017-015867] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE Due to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+). METHODS We report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials' end. RESULTS During the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88). CONCLUSIONS Ten years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects. TRIAL REGISTRATION NUMBER NCT01393470.
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Affiliation(s)
- Matti Lehtinen
- University of Tampere, Tampere, Finland
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - Camilla Lagheden
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - Tapio Luostarinen
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | | | | | | | | | | | | | | | | | | | | | | | | | - Gary Dubin
- Takeda Pharmaceuticals International, Zurich, Switzerland
| | - Joakim Dillner
- Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
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14
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Sundström K, Herweijer E, Sparén P, Ploner A. Reply to Ryser et al. Int J Cancer 2017; 141:416-418. [DOI: 10.1002/ijc.30757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 04/05/2017] [Indexed: 11/08/2022]
Affiliation(s)
- Karin Sundström
- Department of Laboratory Medicine; Karolinska Institutet; Stockholm Sweden
| | - Eva Herweijer
- Department of Medical Epidemiology and Biostatistics; Karolinska Institutet; Stockholm Sweden
| | - Pär Sparén
- Department of Medical Epidemiology and Biostatistics; Karolinska Institutet; Stockholm Sweden
| | - Alexander Ploner
- Department of Medical Epidemiology and Biostatistics; Karolinska Institutet; Stockholm Sweden
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15
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Brief Report: Antibody Responses to Quadrivalent HPV Vaccination in HIV-Infected Young Women as Measured by Total IgG and Competitive Luminex Immunoassay. J Acquir Immune Defic Syndr 2017; 75:241-245. [PMID: 28291048 DOI: 10.1097/qai.0000000000001355] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
We compared antibody responses of HIV-infected young women to the human papillomavirus (HPV) 6, 11, 16, and 18 vaccine using total immunoglobulin (Ig) G Luminex immunoassay (LIA) and competitive Luminex immunoassay (cLIA) assays. HPV18 seropositivity after HPV vaccination as measured with IgG LIA remained high (98%) 48 weeks after vaccination, in contrast with seropositivity as measured with cLIA (73%). Seropositivity rates at week 48 as measured by both IgG LIA and cLIA remained high for HPV6, 11, and 16 (93.5%-100%). These results suggest that the lower rate of seropositivity to HPV18 when cLIA vs. IgG LIA is used is a function of the assay and does not imply lower vaccine immunogenicity.
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16
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Cameron RL, Kavanagh K, Pan J, Love J, Cuschieri K, Robertson C, Ahmed S, Palmer T, Pollock KGJ. Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009-2013. Emerg Infect Dis 2016; 22:56-64. [PMID: 26692336 PMCID: PMC4696690 DOI: 10.3201/eid2201.150736] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Prevalence was reduced, and early evidence indicates herd immunity. In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009–2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous cervical disease. By linking vaccination, cervical screening, and HPV testing data, over the study period we found a decline in HPV types 16 and 18, significant decreases in HPV types 31, 33, and 45 (suggesting cross-protection), and a nonsignificant increase in HPV 51. In addition, among nonvaccinated women, HPV types 16 and 18 infections were significantly lower in 2013 than in 2009. Our results preliminarily indicate herd immunity and sustained effectiveness of the bivalent vaccine on virologic outcomes at the population level.
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17
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Badiga S, Chambers MM, Huh W, Eltoum IEA, Piyathilake CJ. Expression of p16 INK4A in cervical precancerous lesions that is unlikely to be preventable by human papillomavirus vaccines. Cancer 2016; 122:3615-3623. [PMID: 27479745 DOI: 10.1002/cncr.30229] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 06/22/2016] [Accepted: 07/11/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND Whether higher grade cervical intraepithelial neoplasia (CIN grade 2 or greater [CIN ≥ 2]) that develops because of human papillomavirus (HPV) genotypes not included in vaccines may progress to cervical cancer is largely unknown. The objectives of this study were to document expression of the cyclin-dependent kinase inhibitor 2A (p16) tumor-suppressor protein p16INK4A as a biomarker of cervical carcinogenesis or of malignant potential and to evaluate whether its expression differs between lesions associated with vaccine and nonvaccine high-risk (HR) human papillomavirus (HPV) genotypes. METHODS The study population consisted of 371 women who had not received HPV vaccines. Women were categorized into vaccine and nonvaccine HR-HPV genotypes and lesions associated with those types. Logistic regression analyses were used to determine the association between positive expression p16INK4A and the risk of being diagnosed with CIN 2 or CIN 3. Differences in the proportion of CIN ≥2 lesions that were positive for p16INK4A expression by vaccine-related or nonvaccine-related HR-HPV genotype were determined using the Pearson chi-square test. RESULTS Specimens that were positive for p16INK4A expression were 5.3 and 16.6 times more likely to be diagnosed as CIN 2 and CIN 3 lesions, respectively, compared to CIN 1 lesions. CIN ≥ 2 lesions that were negative for the bivalent and 9-valent HR-HPV genotypes had similar rates of positive p16INK4A expression compared with lesions that were positive for those HR-HPV genotypes. CONCLUSIONS Lesions that may develop because of HR-HPV genotypes not included in HPV vaccines are likely to have similar malignant potential, suggesting that well developed screening programs combined with nonvaccine-based approaches may be needed to manage the residual risk of developing cervical cancer in the post-HPV vaccination era. Cancer 2016;122:3615-23. © 2016 American Cancer Society.
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Affiliation(s)
- Suguna Badiga
- Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Michelle M Chambers
- Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Warner Huh
- Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Isam-Eldin A Eltoum
- Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Chandrika J Piyathilake
- Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama
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18
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Gender-neutrality, herd effect and resilient immune response for sustainable impact of HPV vaccination. Curr Opin Obstet Gynecol 2016; 27:326-32. [PMID: 26308204 DOI: 10.1097/gco.0000000000000208] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW This review summarize the impact of various strategies of human papillomavirus (HPV) vaccination, such as vaccinating only girls or both girls and boys. RECENT FINDINGS Slow and inefficient implementation of HPV vaccination programmes has delayed the impact of the first human cancer vaccine. Vaccinating only girls, with a rather low coverage, has led to a limited herd effect and, thus, not full use of the HPV vaccine potential. SUMMARY Gender-neutral vaccination based on comparative effectiveness research will hopefully soon tackle the whole spectrum of HPV cancers in both sexes. The remaining challenges are how to ensure resilience of HPV vaccine-induced immunity and herd effect to guarantee population-level impact of HPV vaccination, and how to guard against HPV type replacement.
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19
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Blackadar CB. Historical review of the causes of cancer. World J Clin Oncol 2016; 7:54-86. [PMID: 26862491 PMCID: PMC4734938 DOI: 10.5306/wjco.v7.i1.54] [Citation(s) in RCA: 155] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 10/31/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
In the early 1900s, numerous seminal publications reported that high rates of cancer occurred in certain occupations. During this period, work with infectious agents produced only meager results which seemed irrelevant to humans. Then in the 1980s ground breaking evidence began to emerge that a variety of viruses also cause cancer in humans. There is now sufficient evidence of carcinogenicity in humans for human T-cell lymphotrophic virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human papillomavirus, Epstein-Barr virus, and human herpes virus 8 according to the International Agency for Research on Cancer (IARC). Many other causes of cancer have also been identified by the IARC, which include: Sunlight, tobacco, pharmaceuticals, hormones, alcohol, parasites, fungi, bacteria, salted fish, wood dust, and herbs. The World Cancer Research Fund and the American Institute for Cancer Research have determined additional causes of cancer, which include beta carotene, red meat, processed meats, low fibre diets, not breast feeding, obesity, increased adult height and sedentary lifestyles. In brief, a historical review of the discoveries of the causes of human cancer is presented with extended discussions of the difficulties encountered in identifying viral causes of cancer.
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20
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Abstract
The hallmarks of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was clear there must be opportunities to intervene early in carcinogenesis. A vast array of molecular information has since been uncovered, with much of this stemming from studies of existing cancer or cancer models. Here, examples of how an understanding of cancer biology has informed cancer prevention studies are highlighted and emerging areas that may have implications for the field of cancer prevention research are described. A note of caution accompanies these examples, in that while there are similarities, there are also fundamental differences between the biology of premalignant lesions or premalignant conditions and invasive cancer. These differences must be kept in mind, and indeed leveraged, when exploring potential cancer prevention measures.
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Affiliation(s)
- Bríd M Ryan
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA..
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21
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Vacuna frente al virus del papiloma humano. Eficacia y seguridad. Enferm Infecc Microbiol Clin 2015; 33:342-54. [DOI: 10.1016/j.eimc.2015.03.018] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Accepted: 03/27/2015] [Indexed: 11/30/2022]
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22
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O'Keefe EB, Meltzer JP, Bethea TN. Health disparities and cancer: racial disparities in cancer mortality in the United States, 2000-2010. Front Public Health 2015; 3:51. [PMID: 25932459 PMCID: PMC4398881 DOI: 10.3389/fpubh.2015.00051] [Citation(s) in RCA: 152] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 03/11/2015] [Indexed: 01/05/2023] Open
Abstract
Declining cancer incidence and mortality rates in the United States (U.S.) have continued through the first decade of the twenty-first century. Reductions in tobacco use, greater uptake of prevention measures, adoption of early detection methods, and improved treatments have resulted in improved outcomes for both men and women. However, Black Americans continue to have the higher cancer mortality rates and shorter survival times. This review discusses and compares the cancer mortality rates and mortality trends for Blacks and Whites. The complex relationship between socioeconomic status and race and its contribution to racial cancer disparities is discussed. Based on current trends and the potential and limitations of the patient protection and affordable care act with its mandate to reduce health care inequities, future trends, and challenges in cancer mortality disparities in the U.S. are explored.
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Affiliation(s)
- Eileen B O'Keefe
- Department of Health Sciences, Boston University , Boston, MA , USA
| | - Jeremy P Meltzer
- Department of Health Sciences, Boston University , Boston, MA , USA
| | - Traci N Bethea
- Slone Epidemiology Center, Boston University , Boston, MA , USA
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23
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Potter RC, Flagg EW, Datta SD, Saraiya M, Copeland G. Monitoring the impact of human papillomavirus vaccines on high-grade pre-invasive cervical lesions: designing a framework of linked immunization information system and cancer registry data in Michigan. Vaccine 2015; 33:1400-5. [PMID: 25573038 PMCID: PMC6921485 DOI: 10.1016/j.vaccine.2014.12.063] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 12/17/2014] [Accepted: 12/23/2014] [Indexed: 11/30/2022]
Abstract
State immunization and cancer registries contain data that, if linked, could be used to monitor the impact of human papillomavirus (HPV) vaccine on cervical cancer and precancer. Michigan is uniquely positioned to examine these outcomes using two population-based resources: the state-wide cancer registry and immunization information system (IIS). We assessed the feasibility of identifying females in the IIS who had continuous Michigan residence and linking them to the cancer registry. We considered continuous residence necessary for future studies of vaccine impact to avoid misclassifying those who may have been immunized while residing out-of-state and whose immunization therefore may not have been reported in Michigan. We identified females with 1976-1996 birthdates in the IIS and used probabilistic linkage software to match them with Michigan birth records. A stratified random sample of IIS-birth matches was provided to a commercial locator service to identify females with continuous Michigan residence. Cervical carcinoma in situ cases diagnosed in 2006 among females aged 10 through 30 years were also matched with the birth records; cancer registry-birth matches were merged with the IIS-birth matches using the birth record identifier. Overall, 68% of the 1274,282 IIS and 61% of the 1358 cancer registry records could be matched with birth records. Among the sample of IIS-birth matches, most (86%) were continuous residents. Seventy percent or more of cancer registry-birth matches merged with IIS-birth matches for cases born after 1984. This is the first effort in the U.S. to show that linking records across IIS and cancer registries is practical and reasonably efficient. The increasing proportion of matches between the registries and live birth file with birth year, and the use of population-based data, strengthen the utility of this approach. Future steps include use of this method to examine incidence of cervical cancer precursors in HPV immunization-eligible females.
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Affiliation(s)
- Rachel C Potter
- Michigan Department of Community Health, Division of Immunization, 201 Townsend, PO Box 30195, Lansing, MI 48909, United States.
| | - Elaine W Flagg
- Surveillance and Data Management Branch, Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, NE MS E-02, Atlanta, GA 30333, United States.
| | - S Deblina Datta
- Surveillance and Data Management Branch, Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, NE MS E-02, Atlanta, GA 30333, United States.
| | - Mona Saraiya
- Epidemiology and Applied Research Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 4770 Buford Hwy, NE MS K-40, Atlanta, GA 30341, United States.
| | - Glenn Copeland
- Michigan Department of Community Health, Division for Vital Records and Health Statistics, 201 Townsend, PO Box 30195, Lansing, MI 48909, United States.
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24
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Lehtinen M, Apter D, Baussano I, Eriksson T, Natunen K, Paavonen J, Vänskä S, Bi D, David MP, Datta S, Struyf F, Jenkins D, Pukkala E, Garnett G, Dubin G. Characteristics of a cluster-randomized phase IV human papillomavirus vaccination effectiveness trial. Vaccine 2015; 33:1284-90. [PMID: 25593103 DOI: 10.1016/j.vaccine.2014.12.019] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Revised: 12/08/2014] [Accepted: 12/11/2014] [Indexed: 11/18/2022]
Abstract
High-risk human papillomaviruses (hrHPV) cause anogenital and oropharyngeal cancers. HPV-16/18 virus-like particle vaccine formulated with an AS04 adjuvant is very efficacious against hrHPV associated precancers but the herd effects of different vaccination scenarios are not known. Our cluster randomized trial (NCT00534638) assesses the overall and herd effects of vaccinating girls vs. girls and boys. In two school-years (2007-2008 and 2008-2009) we invited 80,272 1992-1995 born early adolescents to a CRT in 33 communities a priori stratified by low, intermediate and high HPV-16/18 seroprevalence. In 11 Arm A communities 90% of participating girls and boys were assigned to receive HPV-16/18 vaccine, in 11 Arm B communities 90% of girls were assigned to receive HPV-16/18 vaccine - boys were assigned to receive hepatitis B-virus (HBV) vaccine, and in 11 Arm C communities all were assigned to receive HBV-vaccine. Prevalence of HPV in vaccinated and unvaccinated girls is studied at age 18.5 years. Recruitment resulted in equal enrolment of four birth cohorts (born 1992-1995) comprising altogether 32,175 (40% response) early adolescents: 20,514 girls (50.5-53.0% response by arm) and 11,661 boys (21.9-31.6%% response by arm). At the age of 15 years, 79.3% of the vaccinees completed a questionnaire. Among them >98% were living at, and during the week-ends 1.3-1.6% stayed outside, the study site communities. Smoking habit and alcohol consumption were similar in the different trial arms, also mean-age of menarche (12.4 years) and 1st ejaculation (12.6 years), and sexual behaviour (among those <25%, who had had sexual debut) did not differ by arm: mean-age at the sexual debut 14.3 and 14.4 in girls and boys, and proportions of those with multiple (≥5) life-time sexual partners (6.5-7.5%) at the age of 15 years. Uniform residential, life-style and sexual behaviour characteristics indicate successful randomization/enrolment of the CRT. Our CRT will verify modelled predictions on up to 31% herd effect of vaccinating both girls and boys with moderate vaccine coverage - quantifying overall effectiveness of different strategies which will soon guide how to implement HPV vaccination.
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Affiliation(s)
| | - Dan Apter
- Family Federation of Finland, Helsinki and Oulu, Finland
| | | | | | | | | | | | - Dan Bi
- GSK Vaccines, Wavre, Belgium
| | | | | | | | - David Jenkins
- DDL Diagnostic Laboratory, Rijswijk, The Netherlands
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25
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Sankaranarayanan R, Qiao YL, Keita N. The next steps in cervical screening. WOMEN'S HEALTH (LONDON, ENGLAND) 2015; 11:201-12. [PMID: 25776294 DOI: 10.2217/whe.14.70] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Cervical cancer is fourth most common cancer among women with four-fifths of the global burden in low- and middle-income countries (LMICs). Persistent infection with one of the high-risk types of human papillomaviruses (HPV), particularly HPV 16/18, is the central cause of cervical neoplasia. Progress in developing feasible, alternative screening methods in LMICs and HPV vaccines have further improved cervical cancer prevention prospects. While existing screening programs in high-income countries should be re-organized, in view of the downstream effects of national HPV vaccination programs, LMICs should introduce national programs to vaccinate single year cohorts of girls aged 9-13 years with two or three doses and screen 30-35-year-old women with HPV testing to pragmatically decrease their high disease burden.
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26
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AlObaid A, Al-Badawi IA, Al-Kadri H, Gopala K, Kandeil W, Quint W, Al-Aker M, DeAntonio R. Human papillomavirus prevalence and type distribution among women attending routine gynecological examinations in Saudi Arabia. BMC Infect Dis 2014; 14:643. [PMID: 25496614 PMCID: PMC4272558 DOI: 10.1186/s12879-014-0643-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 11/19/2014] [Indexed: 01/08/2023] Open
Abstract
Background Cervical cancer (CC) is caused by persistent infection with high-risk (HR) human papillomavirus (HPV) types. In Saudi Arabia which has a population of 6.5 million women over the age of 15 years, approximately 152 new cases of CC are diagnosed and 55 women die from the disease annually. Nevertheless current epidemiological data for HPV in this population are limited. This study evaluated the prevalence and type distribution of HPV and documented the awareness of HPV infection and health-related behavior among Saudi and non-Saudi women attending routine examination. Methods This was an observational, epidemiological cross-sectional study conducted between April 2010 and December 2011 at three hospitals in Saudi Arabia. Cervical samples from women aged ≥15 years, who were attending routine gynecological examinations were collected and tested for HPV-DNA by polymerase chain reaction and typed using the SPF10 DEIA/LiPA25 system. Two questionnaires on health-related behavior and awareness of HPV infection were completed. Results A total of 417 women, mean age (standard deviation) 41.9 (±10.4) years, were included in the final analysis, of whom 77% (321/417) were Saudi nationals. HPV-DNA was detected in 9.8% women (41/417, 95% confidence interval [CI]: 7.1-13.1). The prevalence of any HR-HPV by age was: 25–34 years: 3.0%; 35–44 years: 4.5%; 45–54 years: 3.2%; >55 years: 10.9%. The most prevalent HR-HPV-types were: HPV-68/73 (5 cases); HPV-18 (4 cases); HPV-16 (3 cases). The most prevalent low risk (LR) types were HPV-6 (4 cases); HPV-42, HPV-53 and HPV-54 (2 cases each). The prevalence of HPV was higher among non-Saudi nationals vs. Saudi nationals (16.7% vs. 7.8%, P = 0.0234). No statistically significant risk factors were identified: 32.2% (101/314) women were aware of HPV and 89.9% (285/317) showed an interest in HPV vaccination. Conclusion The overall prevalence of HPV was 9.8% in Saudi Arabia, but was higher in women over 55 years, as well as in non-Saudi nationals. These data provide a reference for public health authorities and may also help in determining future policies for the prevention of CC. Clinical trial registration NCT01213459 Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0643-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Abdulaziz AlObaid
- King Fahd Medical City, P.O. Box 59046, Riyadh, 11525, Saudi Arabia.
| | - Ismail A Al-Badawi
- King Faisal Specialist Hospital & Research Centre, P.O. Box 3354, Riyadh, 11211, MBC-52, Saudi Arabia.
| | - Hanan Al-Kadri
- Department of Obstetrics and Gynecology, King Abdulaziz Medical City, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, P.O Box 22490, Riyadh, 11426, Saudi Arabia.
| | - Kusuma Gopala
- GlaxoSmithKline Pharmaceuticals Ltd, Bangalore, India.
| | | | - Wim Quint
- DDL Diagnostic Laboratory, Rijswijk, the Netherlands.
| | - Murad Al-Aker
- King Faisal Specialist Hospital & Research Centre, P.O. Box 3354, Riyadh, 11211, MBC-52, Saudi Arabia. .,Sydney Gynecologic Oncology Group, Royal Prince Alfred Hospital, Sydney, Australia.
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De Vincenzo R, Conte C, Ricci C, Scambia G, Capelli G. Long-term efficacy and safety of human papillomavirus vaccination. Int J Womens Health 2014; 6:999-1010. [PMID: 25587221 PMCID: PMC4262378 DOI: 10.2147/ijwh.s50365] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV) vaccines and their safety profile. Two prophylactic HPV vaccines - bivalent (bHPV) and quadrivalent (qHPV) - are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman's sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs), serious AEs, and discontinuations due to a serious AE reported in clinical studies are similar between the two vaccines and their control groups. In particular, no increased risk of autoimmune disease has been shown among HPV-vaccinated subjects in long-term observation studies. As these are crucial topics in HPV vaccination, it is important to establish systems for continued monitoring of vaccine immunogenicity, efficacy, and safety over time.
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Affiliation(s)
- Rosa De Vincenzo
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy
| | - Carmine Conte
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy
| | - Caterina Ricci
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy
| | - Giovanni Scambia
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy
| | - Giovanni Capelli
- Department of Human Sciences, Society and Health, University of Cassino and Southern Lazio, Cassino, Italy
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Isidean SD, Tota JE, Gagnon JA, Franco EL. Human papillomavirus vaccines: key factors in planning cost-effective vaccination programs. Expert Rev Vaccines 2014; 14:119-33. [PMID: 25266065 DOI: 10.1586/14760584.2015.964213] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Prophylactic HPV vaccines hold tremendous potential for reducing cervical and non-cervical HPV-related disease burden worldwide. To maximize on this potential, policy officials will need to carefully consider available evidence, existing uncertainties and the cost-effectiveness of mass HPV vaccination programs in the context of their respective nations and/or regions. Proper harmonization of primary prevention strategies with secondary prevention efforts will also be important. Decisions following such considerations may ultimately depend on programmatic objectives, infrastructure and available resources. Continued research and surveillance surrounding HPV vaccination will be essential for filling current knowledge gaps, and forcing ongoing reconsiderations of selected immunization strategies.
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Affiliation(s)
- Sandra D Isidean
- Department of Epidemiology, Biostatistics, and Occupational Health, Division of Cancer Epidemiology, McGill University, 546 Pine Avenue West, Montreal, QC H2W1S6, Canada
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Lehtinen M, Nieminen P, Apter D, Paavonen J. Prevention of HPV disease burden. WOMENS HEALTH 2014; 10:341-3. [PMID: 25259894 DOI: 10.2217/whe.14.35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Matti Lehtinen
- School of Health Sciences, University of Tampere, Finland
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Couto E, Sæterdal I, Juvet LK, Klemp M. HPV catch-up vaccination of young women: a systematic review and meta-analysis. BMC Public Health 2014; 14:867. [PMID: 25149765 PMCID: PMC4159543 DOI: 10.1186/1471-2458-14-867] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Accepted: 08/18/2014] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND While prophylactic human papilloma virus (HPV) vaccination is considered effective in young girls, it is unclear whether a catch-up vaccination of older girls would be beneficial. We, therefore, aimed to examine the potential health impact of a HPV catch-up vaccination of girls who were too old at the time of vaccine introduction, hence aged 16 and older. METHODS We systematically searched the literature for randomized clinical trials (RCTs) that examined the effect of HPV vaccines on overall mortality, cancer mortality and incidence, high-grade cervical intraepithelial neoplasia grade 2 and higher (CIN2+), vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VaIN) grade 2 and higher lesions (VIN2+ and VaIN2+, respectively) genital warts (condyloma). We considered all lesions and those associated with HPV type(s) included in the vaccines. RCTs reporting on serious adverse events were also eligible. Selected publications were assessed for potential risk of bias, and we ascertained the overall quality of the evidence for each outcome using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were performed, assuming both random and fixed effects, to estimate risk ratios (RR) and corresponding 95% confidence intervals (CI), using intention-to-treat and per-protocol populations. RESULTS We included 46 publications reporting on 13 RCTs. Most of the RCTs had a maximum follow-up period of four years. We identified no RCT reporting on the effect of HPV catch vaccination on overall and cancer related mortality, and on cervical cancer incidence. We found a borderline protective effect of a HPV catch-up vaccination on all CIN2+, with a pooled RR of 0.80 (95% CI: 0.62-1.02) for a follow-up period of 4 years. A HPV catch-up vaccination was associated with a reduction in VIN2+ and VaIN2+ lesions, and condyloma. No difference in risk of serious adverse events was seen in vaccinated participants versus unvaccinated women (pooled RR of 0.99 (0.91-1.08)). CONCLUSIONS This systematic review indicates that a HPV catch-up vaccination could be beneficial, however the long-term effect of such a vaccination, and its effect on cervical cancer incidence and mortality is still unclear.
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Affiliation(s)
- Elisabeth Couto
- Norwegian Knowledge Center for the Health Services, Health Economic and Drug Unit, St Olavsplass, PO Box 7004, 0130 Oslo, Norway
| | - Ingvil Sæterdal
- Norwegian Knowledge Center for the Health Services, Health Economic and Drug Unit, St Olavsplass, PO Box 7004, 0130 Oslo, Norway
| | - Lene Kristine Juvet
- Norwegian Knowledge Center for the Health Services, Health Economic and Drug Unit, St Olavsplass, PO Box 7004, 0130 Oslo, Norway
| | - Marianne Klemp
- Norwegian Knowledge Center for the Health Services, Health Economic and Drug Unit, St Olavsplass, PO Box 7004, 0130 Oslo, Norway
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Lessons learned from HPV vaccine delivery in low-resource settings and opportunities for HIV prevention, treatment, and care among adolescents. J Acquir Immune Defic Syndr 2014; 66 Suppl 2:S209-16. [PMID: 24918597 DOI: 10.1097/qai.0000000000000175] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Human papillomavirus (HPV) vaccines to prevent cervical cancer have become available in recent years and presented a new challenge to health systems, since they prevent a sexually transmitted virus and are most effective if they are delivered to young adolescent girls, a group not widely served by other health programs. Demonstration and pilot HPV vaccination programs undertaken in the past 7-8 years in low-resource settings have produced lessons that may be more broadly applied to other adolescent health interventions, particularly to those that attempt to reduce human immunodeficiency virus (HIV) infection. METHODS A systematic literature review was undertaken to identify formal and informal evaluations of HPV vaccine use in low- and middle-income countries. Special attention was devoted to the detailed evaluations carried out on large demonstration projects in India, Peru, Uganda, and Vietnam. RESULTS These lessons fall into 2 main categories: service delivery operations and community outreach and mobilization. Operational issues included venue and timing of vaccinations, definition of target population, micro-planning and coordination, integration with other services, and training. Community issues included consent, messages and channels, endorsement and support, and timing of mobilization efforts. DISCUSSION Careful planning, good coordination across sectors and levels, and sensitive attention to the expressed needs for information and preferences for communication channels among youth, parents, and communities more broadly were among the key lessons that are relevant for HIV interventions, but many of the smaller details were also important. CONCLUSIONS Applying or adapting these lessons to adolescent HIV services could accelerate effective program design and enhance success.
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Baldur-Felskov B, Dehlendorff C, Munk C, Kjaer SK. Early Impact of Human Papillomavirus Vaccination on Cervical Neoplasia--Nationwide Follow-up of Young Danish Women. J Natl Cancer Inst 2014; 106:djt460. [DOI: 10.1093/jnci/djt460] [Citation(s) in RCA: 139] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
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Basu P, Banerjee D, Singh P, Bhattacharya C, Biswas J. Efficacy and safety of human papillomavirus vaccine for primary prevention of cervical cancer: A review of evidence from phase III trials and national programs. South Asian J Cancer 2014; 2:187-92. [PMID: 24455618 PMCID: PMC3889021 DOI: 10.4103/2278-330x.119877] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
The Human Papillomavirus (HPV) vaccines have been widely introduced in the national immunization programs in most of the medium and high income countries following endorsement from national and international advisory bodies. HPV vaccine is unique and its introduction is challenging in many ways – it is the first vaccine developed to prevent any cancer, the vaccine is gender specific, it targets adolescent females who are difficult to reach by any health intervention programs. It is not unusual for such a vaccine to face scepticism and reservations not only from lay public but also from professionals in spite of the clinical trial results convincingly and consistently proving their efficacy and safety. Over the last few years millions of doses of the HPV vaccine have been administered round the world and the efficacy and safety data have started coming from the real life programs. A comprehensive cervical cancer control program involving HPV vaccination of the adolescent girls and screening of the adult women has been proved to be the most cost-effective approach to reduce the burden of cervical cancer. The present article discusses the justification of HPV vaccination in the backdrop of natural history of cervical cancer, the mechanism of action of the vaccines, efficacy and safety data from phase III randomized controlled trials as well as from the national immunization programs of various countries.
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Affiliation(s)
- Partha Basu
- Department of Gynaecologic Oncology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India
| | - Dipanwita Banerjee
- Department of Gynaecologic Oncology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India
| | - Priyanka Singh
- Department of Gynaecologic Oncology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India
| | - Chandrani Bhattacharya
- Department of Gynaecologic Oncology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India
| | - Jaydip Biswas
- Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India
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Sui S, Jiao Z, Niyazi M, Sulaiya S, Lu P, Qiao YL. Genotype Distribution and Behavioral Risk Factor Analysis of Human Papillomavirus Infection in Uyghur Women. Asian Pac J Cancer Prev 2013; 14:5861-5. [DOI: 10.7314/apjcp.2013.14.10.5861] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Abstract
Human papillomavirus (HPV) is the most common sexually transmitted infectious agent; its 14 oncogenic types are causally associated with 5-10% of all cancers. The major structural HPV protein self-assembles into immunogenic virus-like particles. Two licensed HPV vaccines--the bivalent vaccine comprising HPV types 16 and 18, and the quadrivalent vaccine comprising HPV types 6, 11, 16 and 18--have proven to be safe and efficacious against 6-month-persistent cervical infections of HPV16 and HPV18 and associated precancerous lesions, and both have efficacies of 90-100%. Among baseline HPV-negative adolescent females, vaccine efficacies against the immediate precursor of cervical cancer (intraepithelial neoplasia grade 3) irrespective of HPV type are 93.2% and 43.0% for the bivalent and quadrivalent vaccines, respectively. The quadrivalent vaccine is efficacious (>75% vaccine efficacy) against any of the more-severe precursors of vulval, vaginal and anal cancers. A strong increase in vaccine efficacy with increasing severity of the precancerous lesion is explained by accumulation of the most-oncogenic HPV types 16 and 18 in these lesions. Therefore, prophylactic HPV vaccination will exceed the best results from screening for cancer. With the extremely efficacious prophylactic HPV vaccines, the focus of organized intervention (vaccination and screening) programmes should, however, shift from reducing the HPV disease burden to controlling the prevalence of oncogenic HPV (and nononcogenic HPV) types. Eradication of the major oncogenic HPV types should be pursued.
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Affiliation(s)
- Matti Lehtinen
- University of Tampere, School of Health Sciences, Kalevantie 4, FI-33014 Tampere, Finland.
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Abstract
Recent guidelines from multiple organizations stress screening initiation no earlier than the age of 21 years and increased screening intervals for women aged 21 to 29 years. Primary prevention with human papillomavirus vaccination has the potential to significantly affect the development of high-grade cervical lesions, including cancer, and will likely affect screening guidelines in the future.
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Affiliation(s)
- Lori A Boardman
- Department of Clinical Sciences, University of Central Florida College of Medicine, Orlando, FL 32827, USA.
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