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Akumbom AM, Bergman AJ, Strickler H, Budhathoki C, Nkimbeng M, Grant R, Reynolds NR, Talaat KR. Understanding human papillomavirus vaccine response and efficacy in people living with HIV: A systematic mixed studies review and meta-analysis. PLOS GLOBAL PUBLIC HEALTH 2024; 4:e0003931. [PMID: 39705286 PMCID: PMC11661617 DOI: 10.1371/journal.pgph.0003931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 10/21/2024] [Indexed: 12/22/2024]
Abstract
Coinfection with human papillomavirus (HPV) and HIV compounds the risks of developing cervical, anal, and HPV-associated oral neoplasia. Safe prophylactic vaccines are available to prevent HPV infections in people with HIV(PWH). Yet, vaccine efficacy and duration of protection remain questionable. Historically, the efficacy of vaccines has been suboptimal in PWH compared to people without HIV (PWoH).A systematic review of HPV vaccine trials in PWH was conducted using PRISMA guidelines. Outcomes of interest were vaccine efficacy, immunogenicity, and predictors of HPV vaccine efficacy. A secondary outcome was to assess age and sex differences. Efficacy was reviewed as cervical/anal/oral lesions or neoplasia, and incident or persistent HPV infection following vaccination. A random effects meta-analysis was performed comparing geometric mean titer (GMT) in PWH to PWoH. Twenty-eight studies out of 988 were eligible for inclusion in our study, and qualitatively synthesized. Eight of these studies were meta-analyzed. GMT results of HPV16 and HPV18 genotypes were significantly lower in PWH; Hedges's g -0.434 (95% CI: -0.823, -0.046) and Hedges's g -0.57 (95% CI: -0.72, -0.43), respectively. The mean difference in GMT for HPV18 between PWH and PWoH was -536.23 (95% CI: -830.66, -241.81); approximately 22 times higher than HPV18 seropositivity cut-offs, assuming milli-Merck Units per milliliter. Risk factors for incident or persistent infections in PWH included: failure to seroconvert after vaccination, baseline CD4+ T-cell count <500 cells/mm3, early age of sexual debut, HIV viral load ≥ 400 copies/mL. There was a trend towards decreased HPV vaccine efficacy in studies that included enrollees with a history of AIDS or AIDS-defining illness.Applying existing evidence of HPV vaccine efficacy on meaningful clinical outcomes in PWH is questionable. This could be influenced by the diversity of eligibility criteria across clinical trials of HPV vaccine efficacy. Precision medicine may offer novel alternatives for evaluating HPV vaccine efficacy in PWH.
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Affiliation(s)
- Alvine M. Akumbom
- Center for Infectious Disease and Nursing Innovation, Johns Hopkins School of Nursing, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Alanna J. Bergman
- University of Virginia School of Nursing, Charlottesville, Virginia, United States of America
| | - Howard Strickler
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America
| | - Chakra Budhathoki
- Center for Infectious Disease and Nursing Innovation, Johns Hopkins School of Nursing, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Manka Nkimbeng
- Division of Health Policy and Management, University of Minnesota School of Public Health, Minneapolis, Minnesota, United States of America
| | - Raeven Grant
- David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, Los Angeles, California, United States of America
| | - Nancy R. Reynolds
- Center for Infectious Disease and Nursing Innovation, Johns Hopkins School of Nursing, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Kawsar R. Talaat
- Department of International Health, Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
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Losada C, Samaha H, Scherer EM, Kazzi B, Khalil L, Ofotokun I, Rouphael N. Efficacy and Durability of Immune Response after Receipt of HPV Vaccines in People Living with HIV. Vaccines (Basel) 2023; 11:1067. [PMID: 37376456 DOI: 10.3390/vaccines11061067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/24/2023] [Accepted: 05/31/2023] [Indexed: 06/29/2023] Open
Abstract
People living with HIV (PLH) experience higher rates of HPV infection as well as an increased risk of HPV-related disease, including malignancies. Although they are considered a high-priority group for HPV vaccination, there are limited data regarding the long-term immunogenicity and efficacy of HPV vaccines in this population. Seroconversion rates and geometric mean titers elicited by vaccination are lower in PLH compared to immunocompetent participants, especially in individuals with CD4 counts below 200 cells/mm3 and a detectable viral load. The significance of these differences is still unclear, as a correlate of protection has not been identified. Few studies have focused on demonstrating vaccine efficacy in PLH, with variable results depending on the age at vaccination and baseline seropositivity. Although waning humoral immunity for HPV seems to be more rapid in this population, there is evidence that suggests that seropositivity lasts at least 2-4 years following vaccination. Further research is needed to determine the differences between vaccine formulations and the impact of administrating additional doses on durability of immune protection.
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Affiliation(s)
- Cecilia Losada
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA
| | - Hady Samaha
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA
| | - Erin M Scherer
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA
| | - Bahaa Kazzi
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA
| | - Lana Khalil
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA
| | - Ighovwerha Ofotokun
- Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, GA 30322, USA
| | - Nadine Rouphael
- The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, GA 30030, USA
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Staadegaard L, Rönn MM, Soni N, Bellerose ME, Bloem P, Brisson M, Maheu-Giroux M, Barnabas RV, Drolet M, Mayaud P, Dalal S, Boily MC. Immunogenicity, safety, and efficacy of the HPV vaccines among people living with HIV: A systematic review and meta-analysis. EClinicalMedicine 2022; 52:101585. [PMID: 35936024 PMCID: PMC9350866 DOI: 10.1016/j.eclinm.2022.101585] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 07/08/2022] [Accepted: 07/08/2022] [Indexed: 01/21/2023] Open
Abstract
Background Vaccines have been demonstrated to protect against high-risk human papillomavirus infection (HPV), including HPV-16/18, and cervical lesions among HIV negative women. However, their efficacy remains uncertain for people living with HIV (PLHIV).We systematically reviewed available evidence on HPV vaccine on immunological, virological, or other biological outcomes in PLHIV. Methods We searched five electronic databases (PubMed, Medline and Embase, clinicaltrials.gov and the WHO clinical trial database) for longitudinal prospective studies reporting immunogenicity, virological, cytological, histological, clinical or safety endpoints following prophylactic HPV vaccination among PLHIV. We included studies published by February 11th, 2021. We summarized results, assessed study quality, and conducted meta-analysis and subgroup analyses, where possible. Findings We identified 43 publications stemming from 18 independent studies (Ns =18), evaluating the quadrivalent (Ns =15), bivalent (Ns =4) and nonavalent (Ns =1) vaccines. A high proportion seroconverted for the HPV vaccine types. Pooled proportion seropositive by 28 weeks following 3 doses with the bivalent, quadrivalent, and nonavalent vaccines were 0.99 (95% confidence interval: 0.95-1.00, Ns =1), 0.99 (0.98-1.00, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-16 and 0.99 (0.96-1.00, Ns =1), 0.94 (0.91-0.96, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-18, respectively. Seropositivity remained high among people who received 3 doses despite some declines in antibody titers and lower seropositivity over time, especially for HPV-18, for the quadrivalent than the bivalent vaccine, and for HIV positive than negative individuals. Seropositivity for HPV-18 at 29-99 weeks among PLHIV was 0.72 (0.66-0.79, Ns =8) and 0.96 (0.92-0.99, Ns =2) after 3 doses of the quadrivalent and bivalent vaccine, respectively and 0.94 (0.90-0.98, Ns =3) among HIV-negative historical controls. Evidence suggests that the seropositivity after vaccination declines over time but it can lasts at least 2-4 years. The vaccines were deemed safe among PLHIV with few serious adverse events. Evidence of HPV vaccine efficacy against acquisition of HPV infection and/or associated disease from the eight trials available was inconclusive due to the low quality. Interpretation PLHIV have a robust and safe immune response to HPV vaccination. Antibody titers and seropositivity rates decline over time but remain high. The lack of a formal correlate of protection and efficacy results preclude definitive conclusions on the clinical benefits. Nevertheless, given the burden of HPV disease in PLHIV, although the protection may be shorter or less robust against HPV-18, the robust immune response suggests that PLHIV may benefit from receiving HPV vaccination after acquiring HIV. Better quality studies are needed to demonstrate the clinical efficacy among PLHIV. Funding World Health Organization. MRC Centre for Global Infectious Disease Analysis, Canadian Institutes of Health Research, UK Medical Research Council (MRC).
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Affiliation(s)
- Lisa Staadegaard
- Department of Infectious Diseases Epidemiology, Imperial College, London, United Kingdom
| | - Minttu M. Rönn
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, United States
| | - Nirali Soni
- Department of Infectious Diseases Epidemiology, Imperial College, London, United Kingdom
- Medical Research Council Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom
| | - Meghan E. Bellerose
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, United States
| | - Paul Bloem
- World Health Organization, Geneva, Switzerland
| | - Marc Brisson
- Laval University, Québec, Canada
- Centre de recherche du CHU de Québec-Université Laval, Canada
| | - Mathieu Maheu-Giroux
- Department of Epidemiology and Biostatistics, School of Population and Global Health, McGill University, Montreal, Canada
| | - Ruanne V. Barnabas
- Department of Global Health, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, United States
| | - Melanie Drolet
- Centre de recherche du CHU de Québec-Université Laval, Canada
| | - Philippe Mayaud
- Faculty of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Shona Dalal
- World Health Organization, Geneva, Switzerland
| | - Marie-Claude Boily
- Department of Infectious Diseases Epidemiology, Imperial College, London, United Kingdom
- Medical Research Council Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom
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Donkoh ET, Dassah ET, Owusu-Dabo E. Optimization of a protocol for the evaluation of antibody responses to human papillomavirus (HPV) vaccination in low-resource settings. BMC Womens Health 2022; 22:234. [PMID: 35710373 PMCID: PMC9204889 DOI: 10.1186/s12905-022-01821-y] [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: 09/22/2021] [Accepted: 06/06/2022] [Indexed: 11/25/2022] Open
Abstract
Introduction Available human papillomavirus (HPV) vaccines could have an important primary role in cervical cancer prevention once their long-term immunogenicity and safety are evaluated at the population level. The aim of this study was to optimize an assay to be used in evaluating the long-term durability of HPV vaccine response following a pilot vaccination of adolescent girls in Ghana. Methods A rapid, high-throughput, indirect enzyme-linked immunosorbent assay (ELISA) was optimized for the detection and quantitation of anti-HPV L1 (late expression protein: types 6, 11, 16 and 18) immunoglobulin G (IgG) in human serum (n = 89). The utility of the assay was demonstrated using serum collected from a cohort of pre-adolescent girls (n = 49) previously vaccinated with a quadrivalent vaccine and non-immune serum obtained from age-matched controls (n = 40). Results The assay showed good discrimination of antibody levels between cases and control sera: seroprevalence of anti-HPV IgG antibodies was significantly higher among vaccinated than unvaccinated girls for both HPV-16 (63.3% vs. 12.5%; p < 0.001) and HPV-18 (34.7% vs. 20.0%; p = 0.042), respectively. Thirty-six months after receiving the third dose of vaccine, significantly higher mean anti-HPV-16 (0.618 vs. 0.145), anti-HPV-18 (0.323 vs. 0.309), and anti-HPV-6 (1.371 vs. 0.981) antibody levels were measured, compared to unvaccinated girls (all p < 0.05). A correlation between optical density and antibody activity indicated assay sensitivity to increasing levels of antibody activity. Conclusion We have successfully optimized and implemented a robust and sensitive assay for the evaluation of antibody responses among immunized adolescent girls for monitoring future large-scale HPV vaccination studies in low-income settings. Our results demonstrated greater immunoglobulin G antibody activity within serum drawn from adolescent girls immunized 36 months prior. Supplementary Information The online version contains supplementary material available at 10.1186/s12905-022-01821-y.
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Affiliation(s)
- Emmanuel Timmy Donkoh
- Center for Research in Applied Biology, University of Energy and Natural Resources, Sunyani, Ghana.
| | - Edward Tieru Dassah
- Department of Population, Family and Reproductive Health, School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Ellis Owusu-Dabo
- Department of Global and International Health, School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
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Kuguyo O, Dube Mandishora RS, Thomford NE, Makunike-Mutasa R, Nhachi CFB, Matimba A, Dandara C. High-risk HPV genotypes in Zimbabwean women with cervical cancer: Comparative analyses between HIV-negative and HIV-positive women. PLoS One 2021; 16:e0257324. [PMID: 34582476 PMCID: PMC8478215 DOI: 10.1371/journal.pone.0257324] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 08/30/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND High-risk human papillomavirus HPV (HR-HPV) modifies cervical cancer risk in people living with HIV, yet African populations are under-represented. We aimed to compare the frequency, multiplicity and consanguinity of HR-HPVs in HIV-negative and HIV-positive Zimbabwean women. METHODS This was a cross-sectional study consisting of women with histologically confirmed cervical cancer attending Parirenyatwa Group of Hospitals in Harare, Zimbabwe. Information on HIV status was also collected for comparative analysis. Genomic DNA was extracted from 258 formalin fixed paraffin embedded tumour tissue samples, and analysed for 14 HR-HPV genotypes. Data was analysed using Graphpad Prism and STATA. RESULTS Forty-five percent of the cohort was HIV-positive, with a median age of 51 (IQR = 42-62) years. HR-HPV positivity was detected in 96% of biospecimens analysed. HPV16 (48%), was the most prevalent genotype, followed by HPV35 (26%), HPV18 (25%), HPV58 (11%) and HPV33 (10%), irrespective of HIV status. One third of the cohort harboured a single HPV infection, and HPV16 (41%), HPV18 (21%) and HPV35 (21%) were the most prevalent. HIV status did not influence the prevalence and rate of multiple HPV infections (p>0.05). We reported significant (p<0.05) consanguinity of HPV16/18 (OR = 0.3; 95% CI = 0.1-0.9), HPV16/33 (OR = 0.3; 95% CI = 0.1-1.0), HPV16/35 (OR = 3.3; 95% CI = 2.0-6.0), HPV35/51 (OR = 6.0; 95%CI = 1.8-15.0); HPV39/51 (OR = 6.4; 95% CI = 1.8-15), HPV31/52 (OR = 6.2; 95% CI = 1.8-15), HPV39/56 (OR = 11 95% CI = 8-12), HPV59/68 (OR = 8.2; 95% CI = 5.3-12.4), HPV66/68 (OR = 7; 95% CI = 2.4-13.5), independent of age and HIV status. CONCLUSION We found that HIV does not influence the frequency, multiplicity and consanguinity of HR-HPV in cervical cancer. For the first time, we report high prevalence of HPV35 among women with confirmed cervical cancer in Zimbabwe, providing additional evidence of HPV diversity in sub-Saharan Africa. The data obtained here probes the need for larger prospective studies to further elucidate HPV diversity and possibility of selective pressure on genotypes.
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Affiliation(s)
- Oppah Kuguyo
- Department of Clinical Pharmacology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
- Division of Human Genetics, Department of Pathology, Pharmacogenomics and Drug Metabolism Group, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
| | - Racheal S. Dube Mandishora
- Faculty of Health Sciences, Department of Medical Microbiology Unit, University of Zimbabwe College of Health Sciences, Harare Zimbabwe University of Zimbabwe, Medical Microbiology Unit, Harare, Zimbabwe
- Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer, Lyon, France
| | - Nicholas Ekow Thomford
- Division of Human Genetics, Department of Pathology, Pharmacogenomics and Drug Metabolism Group, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
- Department of Medical Biochemistry, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, PMB, Ghana
| | - Rudo Makunike-Mutasa
- Department of Pathology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
| | - Charles F. B. Nhachi
- Department of Clinical Pharmacology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
| | - Alice Matimba
- Advanced Courses and Scientific Conferences, Wellcome Genome Campus, Hinxton, United Kingdom
| | - Collet Dandara
- Division of Human Genetics, Department of Pathology, Pharmacogenomics and Drug Metabolism Group, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa
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Focal Epithelial Hyperplasia. Viruses 2021; 13:v13081529. [PMID: 34452393 PMCID: PMC8402694 DOI: 10.3390/v13081529] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/28/2021] [Accepted: 07/29/2021] [Indexed: 01/18/2023] Open
Abstract
Focal epithelial hyperplasia (FEH) or Heck’s disease is a rare, benign, oral condition that is associated with infection by human papillomavirus type 13, 32 or both. The whiteish to mucosal-colored, soft, papular or nodular elevated lesions in the oral cavity are normally asymptomatic but can grow to a size or at a location where treatment is needed. The diagnosis is often based on clinical presentation and histopathology, and the HPV genotype can be determined using PCR utilizing specific primers or DNA sequencing. While FEH was reported to often affect several members of the same family and exist primarily among indigenous populations around the world, the number of reported cases within the European region is increasing. This contemporary review summarizes the main findings in relation to HPV genotypes, impact of superinfection exclusion and vaccination, transmission, diagnosis, geographical and ethnical distribution, comorbidities and treatment of FEH with an emphasis on including the most recent case reports within the field. Furthermore, we describe for the first time a FEH lesion infected with the low-risk HPV90.
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Shin MB, Liu G, Mugo N, Garcia PJ, Rao DW, Broshkevitch CJ, Eckert LO, Pinder LF, Wasserheit JN, Barnabas RV. A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities. Front Public Health 2021; 9:670032. [PMID: 34277540 PMCID: PMC8281011 DOI: 10.3389/fpubh.2021.670032] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 05/19/2021] [Indexed: 12/14/2022] Open
Abstract
The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.
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Affiliation(s)
- Michelle B. Shin
- School of Nursing, University of Washington, Seattle, WA, United States
| | - Gui Liu
- Department of Epidemiology, University of Washington, Seattle, WA, United States
| | - Nelly Mugo
- Department of Global Health, University of Washington, Seattle, WA, United States
- Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya
| | - Patricia J. Garcia
- Department of Global Health, University of Washington, Seattle, WA, United States
- School of Public Health, Cayetano Heredia University, Lima, Peru
| | - Darcy W. Rao
- Department of Epidemiology, University of Washington, Seattle, WA, United States
- Department of Global Health, University of Washington, Seattle, WA, United States
| | - Cara J. Broshkevitch
- Department of Global Health, University of Washington, Seattle, WA, United States
| | - Linda O. Eckert
- Department of Global Health, University of Washington, Seattle, WA, United States
- Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, United States
| | - Leeya F. Pinder
- Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, United States
- Department of Obstetrics and Gynecology, University of Zambia, Lusaka, Zambia
| | - Judith N. Wasserheit
- Department of Epidemiology, University of Washington, Seattle, WA, United States
- Department of Global Health, University of Washington, Seattle, WA, United States
- Department of Medicine, University of Washington, Seattle, WA, United States
| | - Ruanne V. Barnabas
- Department of Epidemiology, University of Washington, Seattle, WA, United States
- Department of Global Health, University of Washington, Seattle, WA, United States
- Department of Medicine, University of Washington, Seattle, WA, United States
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
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Sias C, Guarrasi V, Minosse C, Lapa D, Nonno FD, Capobianchi MR, Garbuglia AR, Del Porto P, Paci P. Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity. Front Microbiol 2020; 11:603657. [PMID: 33324386 PMCID: PMC7723855 DOI: 10.3389/fmicb.2020.603657] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 11/03/2020] [Indexed: 12/21/2022] Open
Abstract
Non-nonavalent vaccine (9v) Human papillomavirus (HPV) types have been shown to have high prevalence among HIV-positive women. Here, 1444 cervical samples were tested for HPV DNA positivity. Co-infections of the 9v HPV types with other HPV types were evaluated. The HPV81 L1 and L2 genes were used to investigate the genetic variability of antigenic epitopes. HPV-positive samples were genotyped using the HPVCLART2 assay. The L1 and L2 protein sequences were analyzed using a self-optimized prediction method to predict their secondary structure. Co-occurrence probabilities of the 9v HPV types were calculated. Non9v types represented 49% of the HPV infections; 31.2% of the non9v HPV types were among the low-grade squamous intraepithelial lesion samples, and 27.3% among the high-grade squamous intraepithelial lesion samples, and several genotypes were low risk. The co-occurrence of 9v HPV types with the other genotypes was not correlated with the filogenetic distance. HPV81 showed an amino-acid substitution within the BC loop (N75Q) and the FGb loop (T315N). In the L2 protein, all of the mutations were located outside antigenic sites. The weak cross-protection of the 9v types suggests the relevance of a sustainable and effective screening program, which should be implemented by HPV DNA testing that does not include only high-risk types.
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Affiliation(s)
- Catia Sias
- Laboratory of Virology, Lazzaro Spallanzani National Institute for Infectious Diseases, IRCCS, Rome, Italy
| | - Valerio Guarrasi
- Dipartimento di Ingegneria Informatica, Automatica e Gestionale “A. Ruberti”, Sapienza Università di Roma, Rome, Italy
| | - Claudia Minosse
- Laboratory of Virology, Lazzaro Spallanzani National Institute for Infectious Diseases, IRCCS, Rome, Italy
| | - Daniele Lapa
- Laboratory of Virology, Lazzaro Spallanzani National Institute for Infectious Diseases, IRCCS, Rome, Italy
| | - Franca Del Nonno
- Laboratory of Pathology, Lazzaro Spallanzani National Institute for Infectious Diseases, IRCCS, Rome, Italy
| | - Maria Rosaria Capobianchi
- Laboratory of Virology, Lazzaro Spallanzani National Institute for Infectious Diseases, IRCCS, Rome, Italy
| | - Anna Rosa Garbuglia
- Laboratory of Virology, Lazzaro Spallanzani National Institute for Infectious Diseases, IRCCS, Rome, Italy,*Correspondence: Anna Rosa Garbuglia,
| | - Paola Del Porto
- Department of Biology and Biotechnology “C. Darwin”, Sapienza University, Rome, Italy
| | - Paola Paci
- Dipartimento di Ingegneria Informatica, Automatica e Gestionale “A. Ruberti”, Sapienza Università di Roma, Rome, Italy
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Moscicki AB, Karalius B, Tassiopoulos K, Yao TJ, Jacobson DL, Patel K, Purswani M, Seage GR. Human Papillomavirus Antibody Levels and Quadrivalent Vaccine Clinical Effectiveness in Perinatally Human Immunodeficiency Virus-infected and Exposed, Uninfected Youth. Clin Infect Dis 2020; 69:1183-1191. [PMID: 30927547 DOI: 10.1093/cid/ciy1040] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Persons who are infected with human immunodeficiency virus (HIV) are at high risk of human papillomavirus (HPV)-associated cancers. The objectives are to compare antibody titers to HPV 6, 11, 16, and 18 and rate of abnormal cytology between perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth. METHODS This is a prospective observational cohort study of HPV4 vaccinated youth performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Seroconversion and geometric mean titer (GMT) against HPV types 6, 11, 16, and 18 were calculated. Vaccine effectiveness included rates of abnormal cervical cytology and genital warts. RESULTS Seroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62% of 310 vaccinated PHIV youth compared to 94%, 96%, 99%, and 87% of 148 vaccinated PHEU youth, respectively (P < .05 for all comparisons). GMTs were lower in the PHIV vs PHEU within each category of HPV4 doses received. Higher GMTs were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination, as well as shorter duration between last vaccine dose and antibody specimen. Abnormal cytology occurred in 33 of 56 PHIV and 1 of 7 PHEU sexually active vaccinated females, yielding incidence rates per 100 person-years of 15.0 (10.9 to 20.6) and 2.9 (0.4 to 22.3), respectively. CONCLUSION Antibody titers to HPV4 were lower for all serotypes in PHIV compared to PHEU youth. Protection against abnormal cytology was also diminished in sexually active PHIV females.
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Affiliation(s)
- Anna-Barbara Moscicki
- Department of Pediatrics, Division of Adolescent Medicine, University of California, Los Angeles
| | - Brad Karalius
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Katherine Tassiopoulos
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Tzy-Jyun Yao
- Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Denise L Jacobson
- Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Kunjal Patel
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Murli Purswani
- Division of Pediatric Infectious Disease, Bronx-Lebanon Hospital Center, Icahn School of Medicine at Mount Sinai, New York
| | - George R Seage
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
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Hayashi A, Matsumoto K, Mitsuishi T. Three cases of recalcitrant cutaneous warts treated with quadrivalent human papillomavirus (HPV) vaccine: the HPV type may not determine the outcome. Br J Dermatol 2020; 182:1285-1287. [DOI: 10.1111/bjd.18645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- A. Hayashi
- Department of Dermatology Ube‐kohsan Central Hospital Ube‐city Yamaguchi Japan
| | - K. Matsumoto
- Department of Dermatology Ube‐kohsan Central Hospital Ube‐city Yamaguchi Japan
| | - T. Mitsuishi
- Department of Dermatology Tokyo Women's Medical University Yachiyo Medical Center Yachiyo Chiba Prefecture Japan
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Nailescu C, Nelson RD, Verghese PS, Twombley KE, Chishti AS, Mills M, Mahan JD, Slaven JE, Shew ML. Human Papillomavirus Vaccination in Male and Female Adolescents Before and After Kidney Transplantation: A Pediatric Nephrology Research Consortium Study. Front Pediatr 2020; 8:46. [PMID: 32154194 PMCID: PMC7045870 DOI: 10.3389/fped.2020.00046] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 01/28/2020] [Indexed: 01/10/2023] Open
Abstract
Background: Kidney transplant (KT) recipients have higher incidence of malignancies, including Human Papillomavirus (HPV)-associated cancers. Thus, HPV vaccines may have an important role in preventing HPV-related disease in this population; however, immunogenicity and safety data are lacking. Objective: To examine the immunological response and tolerability to HPV vaccination in pediatric KT recipients compared to future KT candidates. Methods: The quadrivalent HPV vaccine was administered to girls and boys age 9-18 recruited from seven centers part of the Pediatric Nephrology Research Consortium. Subjects were recruited for three groups: (1) CKD: chronic kidney disease stages 3, 4, and 5 not on dialysis; (2) Dialysis; (3) KT recipients. The outcome consisted of antibody concentrations against HPV 6, 11, 16, and 18. Geometric mean titers (GMTs) and seroconversion rates were compared. Vaccine tolerability was assessed. Results: Sixty-five participants were recruited: 18 in the CKD, 18 in the dialysis, and 29 into the KT groups. KT patients had significantly lower GMTs after vaccination for all serotypes. The percentages of subjects who reached seroconversion were overall lower for the KT group, reaching statistical significance for HPV 6, 11, and 18. Comparing immunosuppressed subjects (anyone taking immunosuppression medications, whether KT recipient or not) with the non-immunosuppressed participants, the former had significantly lower GMTs for all the HPV serotypes and lower seroconversion rates for HPV 6, 11, and 18. KT females had higher GMTs and seroconversion rates for certain serotypes. There were no adverse events in either group. Conclusions: HPV vaccine was well-tolerated in this population. Pediatric KT recipients had in general lower GMTs and seroconversion rates compared to their peers with CKD or on dialysis. Immunosuppression played a role in the lack of seroconversion. Our results emphasize the importance of advocating for HPV vaccination prior to KT and acknowledge its safety post transplantation. Future studies are needed to investigate the effect of a supplemental dose of HPV vaccine in KT recipients who do not seroconvert and to evaluate the long-term persistence of antibodies post-KT.
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Affiliation(s)
- Corina Nailescu
- Department of Pediatrics, Indiana University, Riley Hospital for Children, Indianapolis, IN, United States
| | - Raoul D Nelson
- Department of Pediatrics, University of Utah, Primary Children's Hospital, Salt Lake City, UT, United States
| | - Priya S Verghese
- Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, United States
| | - Katherine E Twombley
- Department of Pediatrics, Medical University of South Carolina Children's Hospital, Charleston, SC, United States
| | - Aftab S Chishti
- Department of Pediatrics, Kentucky Children's Hospital, University of Kentucky, Lexington, KY, United States
| | - Michele Mills
- Department of Pediatrics, C. S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, United States
| | - John D Mahan
- Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, United States
| | - James E Slaven
- Department of Biostatistics, Indiana University, Indianapolis, IN, United States
| | - Marcia L Shew
- Department of Pediatrics, Indiana University, Riley Hospital for Children, Indianapolis, IN, United States
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12
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Bergman H, Buckley BS, Villanueva G, Petkovic J, Garritty C, Lutje V, Riveros‐Balta AX, Low N, Henschke N, Cochrane Gynaecological, Neuro‐oncology and Orphan Cancer Group. Comparison of different human papillomavirus (HPV) vaccine types and dose schedules for prevention of HPV-related disease in females and males. Cochrane Database Syst Rev 2019; 2019:CD013479. [PMID: 31755549 PMCID: PMC6873216 DOI: 10.1002/14651858.cd013479] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Uptake of human papillomavirus (HPV) vaccine remains low in many countries, although the bivalent and quadrivalent HPV vaccines given as a three-dose schedule are effective in the prevention of precancerous lesions of the cervix in women. Simpler immunisation schedules, such as those with fewer doses, might reduce barriers to vaccination, as may programmes that include males. OBJECTIVES To evaluate the efficacy, immunogenicity, and harms of different dose schedules and different types of HPV vaccines in females and males. SEARCH METHODS We conducted electronic searches on 27 September 2018 in Ovid MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library), and Ovid Embase. We also searched the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov (both 27 September 2018), vaccine manufacturer websites, and checked reference lists from an index of HPV studies and other relevant systematic reviews. SELECTION CRITERIA We included randomised controlled trials (RCTs) with no language restriction. We considered studies if they enrolled HIV-negative males or females aged 9 to 26 years, or HIV-positive males or females of any age. DATA COLLECTION AND ANALYSIS We used methods recommended by Cochrane. We use the term 'control' to refer to comparator products containing an adjuvant or active vaccine and 'placebo' to refer to products that contain no adjuvant or active vaccine. Most primary outcomes in this review were clinical outcomes. However, for comparisons comparing dose schedules, the included RCTs were designed to measure antibody responses (i.e. immunogenicity) as the primary outcome, rather than clinical outcomes, since it is unethical to collect cervical samples from girls under 16 years of age. We analysed immunogenicity outcomes (i.e. geometric mean titres) with ratios of means, clinical outcomes (e.g. cancer and intraepithelial neoplasia) with risk ratios or rate ratios and, for serious adverse events and deaths, we calculated odds ratios. We rated the certainty of evidence with GRADE. MAIN RESULTS We included 20 RCTs with 31,940 participants. The length of follow-up in the included studies ranged from seven months to five years. Two doses versus three doses of HPV vaccine in 9- to 15-year-old females Antibody responses after two-dose and three-dose HPV vaccine schedules were similar after up to five years of follow-up (4 RCTs, moderate- to high-certainty evidence). No RCTs collected clinical outcome data. Evidence about serious adverse events in studies comparing dose schedules was of very low-certainty owing to imprecision and indirectness (three doses 35/1159; two doses 36/1158; 4 RCTs). One death was reported in the three-dose group (1/898) and none in the two-dose group (0/899) (low-certainty evidence). Interval between doses of HPV vaccine in 9- to 14-year-old females and males Antibody responses were stronger with a longer interval (6 or 12 months) between the first two doses of HPV vaccine than a shorter interval (2 or 6 months) at up to three years of follow-up (4 RCTs, moderate- to high-certainty evidence). No RCTs collected data about clinical outcomes. Evidence about serious adverse events in studies comparing intervals was of very low-certainty, owing to imprecision and indirectness. No deaths were reported in any of the studies (0/1898, 3 RCTs, low-certainty evidence). HPV vaccination of 10- to 26-year-old males In one RCT there was moderate-certainty evidence that quadrivalent HPV vaccine, compared with control, reduced the incidence of external genital lesions (control 36 per 3081 person-years; quadrivalent 6 per 3173 person-years; rate ratio 0.16, 95% CI 0.07 to 0.38; 6254 person-years) and anogenital warts (control 28 per 2814 person-years; quadrivalent 3 per 2831 person-years; rate ratio 0.11, 95% CI 0.03 to 0.38; 5645 person-years). The quadrivalent vaccine resulted in more injection-site adverse events, such as pain or redness, than control (537 versus 601 per 1000; risk ratio (RR) 1.12, 95% CI 1.06 to 1.18, 3895 participants, high-certainty evidence). There was very low-certainty evidence from two RCTs about serious adverse events with quadrivalent vaccine (control 12/2588; quadrivalent 8/2574), and about deaths (control 11/2591; quadrivalent 3/2582), owing to imprecision and indirectness. Nonavalent versus quadrivalent vaccine in 9- to 26-year-old females and males Three RCTs were included; one in females aged 9- to 15-years (n = 600), one in females aged 16- to 26-years (n = 14,215), and one in males aged 16- to 26-years (n = 500). The RCT in 16- to 26-year-old females reported clinical outcomes. There was little to no difference in the incidence of the combined outcome of high-grade cervical epithelial neoplasia, adenocarcinoma in situ, or cervical cancer between the HPV vaccines (quadrivalent 325/6882, nonavalent 326/6871; OR 1.00, 95% CI 0.85 to 1.16; 13,753 participants; high-certainty evidence). The other two RCTs did not collect data about clinical outcomes. There were slightly more local adverse events with the nonavalent vaccine (905 per 1000) than the quadrivalent vaccine (846 per 1000) (RR 1.07, 95% CI 1.05 to 1.08; 3 RCTs, 15,863 participants; high-certainty evidence). Comparative evidence about serious adverse events in the three RCTs (nonavalent 243/8234, quadrivalent 192/7629; OR 0.60, 95% CI 0.14 to 2.61) was of low certainty, owing to imprecision and indirectness. HPV vaccination for people living with HIV Seven RCTs reported on HPV vaccines in people with HIV, with two small trials that collected data about clinical outcomes. Antibody responses were higher following vaccination with either bivalent or quadrivalent HPV vaccine than with control, and these responses could be demonstrated to have been maintained for up to 24 months in children living with HIV (low-certainty evidence). The evidence about clinical outcomes and harms for HPV vaccines in people with HIV is very uncertain (low- to very low-certainty evidence), owing to imprecision and indirectness. AUTHORS' CONCLUSIONS The immunogenicity of two-dose and three-dose HPV vaccine schedules, measured using antibody responses in young females, is comparable. The quadrivalent vaccine probably reduces external genital lesions and anogenital warts in males compared with control. The nonavalent and quadrivalent vaccines offer similar protection against a combined outcome of cervical, vaginal, and vulval precancer lesions or cancer. In people living with HIV, both the bivalent and quadrivalent HPV vaccines result in high antibody responses. For all comparisons of alternative HPV vaccine schedules, the certainty of the body of evidence about serious adverse events reported during the study periods was low or very low, either because the number of events was low, or the evidence was indirect, or both. Post-marketing surveillance is needed to continue monitoring harms that might be associated with HPV vaccines in the population, and this evidence will be incorporated in future updates of this review. Long-term observational studies are needed to determine the effectiveness of reduced-dose schedules against HPV-related cancer endpoints, and whether adopting these schedules improves vaccine coverage rates.
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Affiliation(s)
- Hanna Bergman
- CochraneCochrane ResponseSt Albans House57‐59 HaymarketLondonUKSW1Y 4QX
| | - Brian S Buckley
- CochraneCochrane ResponseSt Albans House57‐59 HaymarketLondonUKSW1Y 4QX
- University of PhillipinesDepartment of SurgeryManilaPhilippines
| | - Gemma Villanueva
- CochraneCochrane ResponseSt Albans House57‐59 HaymarketLondonUKSW1Y 4QX
| | - Jennifer Petkovic
- CochraneCochrane ResponseSt Albans House57‐59 HaymarketLondonUKSW1Y 4QX
- University of OttawaBruyère Research Institute43 Bruyère StAnnex E, room 312OttawaONCanadaK1N 5C8
| | - Chantelle Garritty
- CochraneCochrane ResponseSt Albans House57‐59 HaymarketLondonUKSW1Y 4QX
- Ottawa Hospital Research InstituteOttawa Methods Centre, Clinical Epidemiology ProgramOttawaOntarioCanadaK1H 8L1
| | - Vittoria Lutje
- Liverpool School of Tropical MedicineDepartment of Clinical SciencesPembroke PlaceLiverpoolUKL3 5QA
| | | | - Nicola Low
- University of BernInstitute of Social and Preventive Medicine (ISPM)Finkenhubelweg 11BernSwitzerlandCH‐3012
| | - Nicholas Henschke
- CochraneCochrane ResponseSt Albans House57‐59 HaymarketLondonUKSW1Y 4QX
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Mavundza EJ, Wiyeh AB, Mahasha PW, Halle-Ekane G, Wiysonge CS. A systematic review of immunogenicity, clinical efficacy and safety of human papillomavirus vaccines in people living with the human immunodeficiency virus. Hum Vaccin Immunother 2019; 16:426-435. [PMID: 31448991 PMCID: PMC7062428 DOI: 10.1080/21645515.2019.1656481] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/26/2019] [Accepted: 08/09/2019] [Indexed: 02/07/2023] Open
Abstract
The human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide. People living with the human immunodeficiency virus (HIV) are at high risk of HPV infection. This systematic review evaluates the immunogenicity, clinical efficacy, and safety of prophylactic HPV vaccines in people living with HIV. We registered the protocol for this review in the International Prospective Register of Systematic Reviews (CRD42018109898) and prepared the review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Five randomized trials with 1042 participants are included in this review. One trial with 120 participants compared the bivalent HPV vaccine to placebo, three trials with 830 participants compared the quadrivalent vaccine to placebo, and another trial with 92 participants compared the quadrivalent to the bivalent vaccine. There was low to moderate certainty evidence suggesting that seroconversion was higher among participants in the vaccine arms compared to the placebo arms for both vaccines. In one study with very low certainty evidence, participants who received the bivalent vaccine had higher anti-HPV-18 geometric mean titers (GMTs) compared to those who received the quadrivalent vaccine, despite little difference in anti-HPV-16 GMTs between the two vaccines. There were no differences in the incident and persistent HPV infections in both groups. None of the studies reported data on the incidence of precancerous lesions, or cancer. There were no reports of serious adverse events following vaccination in any of the trials. None of the included studies assessed the effects of HPV vaccines in adolescents living with HIV. Very limited evidence suggests lower immunogenicity of HPV vaccines in HIV positive compared to HIV-negative people. Finally, the long-term effect of the HPV vaccine in the incidence of cervical precancerous lesions and cervical cancer needs to be monitored. There is an urgent need for more high-quality randomized controlled trials that can address these gaps.
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Affiliation(s)
- Edison J. Mavundza
- Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa
| | - Alison B. Wiyeh
- Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa
| | - Phetole W. Mahasha
- 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, Stellenbosch University, Cape Town, 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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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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15
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The Host-Microbe Interplay in Human Papillomavirus-Induced Carcinogenesis. Microorganisms 2019; 7:microorganisms7070199. [PMID: 31337018 PMCID: PMC6680694 DOI: 10.3390/microorganisms7070199] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 07/09/2019] [Accepted: 07/11/2019] [Indexed: 02/06/2023] Open
Abstract
Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women. In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries. The majority of these cancers are caused by the infection with carcinogenic strains of human papillomavirus (HPV), which is also causally implicated in the development of other malignancies, including cancer of the anus, penis cancer and head and neck cancer. HPV is by far the most common sexually transmitted infection worldwide, however, most infected people do not develop cancer and do not even have a persistent infection. The development of highly effective HPV vaccines against most common high-risk HPV strains is a great medical achievement of the 21st century that could prevent up to 90% of cervix cancers. In this article, we review the current understanding of the balanced virus-host interaction that can lead to either virus elimination or the establishment of persistent infection and ultimately malignant transformation. We also highlight the influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis.
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16
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Lacey CJ. HPV vaccination in HIV infection. ACTA ACUST UNITED AC 2019; 8:100174. [PMID: 31252073 PMCID: PMC6603434 DOI: 10.1016/j.pvr.2019.100174] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 06/23/2019] [Accepted: 06/24/2019] [Indexed: 02/07/2023]
Abstract
Persons with HIV are at increased risk of HPV infection, HPV disease, and HPV-related cancers compared to HIV negative persons. In persons with HIV, immune responses to vaccination are often sub-optimal, and while these improve with ART, they often remain lower and decline more rapidly than in HIV-negative individuals. Although the evidence base to support the immunogenicity of HPV vaccines in HIV + ve persons is reasonable, the evidence base to support the efficacy of HPV vaccines in HIV + ve individuals is inconsistent. There is one study in HIV + ve men who have sex with men (MSM) which showed no effect, and two other studies, one in HIV + ve women and one in HIV + ve adolescents that showed reduced effectiveness. All these effectiveness studies used Gardasil 4 (G4). Two studies in HIV + ve persons have shown superior immunogenicity of Cervarix (which uses a TLR4 agonist adjuvant) compared to G4. Studies of Hepatitis B vaccines in HIV + ve persons have shown that either (i) increased number of doses (ii) increased vaccine dose, or (iii) TLR agonist adjuvanted vaccines, all produce increased immunogenicity compared to standard vaccine regimes. Therefore, questions remain as to optimal HPV vaccine regimes in HIV and further clinical trials with different HPV vaccine regimes are needed.
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17
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Stankiewicz Karita HC, Hauge K, Magaret A, Mao C, Schouten J, Grieco V, Xi LF, Galloway DA, Madeleine MM, Wald A. Effect of Human Papillomavirus Vaccine to Interrupt Recurrence of Vulvar and Anal Neoplasia (VIVA): A Trial Protocol. JAMA Netw Open 2019; 2:e190819. [PMID: 30977845 PMCID: PMC6481452 DOI: 10.1001/jamanetworkopen.2019.0819] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
IMPORTANCE Human papillomavirus (HPV), particularly HPV type 16, causes most anal and vulvar high-grade squamous intraepithelial lesions (HSIL), which are precursors to cancer. After initial treatment of HSIL, more than 30% of patients will have disease recurrence, with even higher recurrence among HIV-positive individuals and men who have sex with men. Recurrences can be debilitating and lead to significant morbidity and medical expense. Observational studies suggest a possible therapeutic benefit of the licensed HPV vaccines in reducing recurrent lesions in previously infected persons. OBJECTIVE To test whether the licensed prophylactic HPV vaccine (Gardasil-9) can reduce the risk of HSIL recurrence by 50% in previously unvaccinated individuals recently treated for anal or vulvar HSIL. DESIGN, SETTING, AND PARTICIPANTS This is a trial protocol for a randomized, double-blind, placebo-controlled, proof-of-concept clinical trial. Eligible participants are aged 27 to 69 at study start and have not received prior HPV vaccination, have had anal or vulvar HSIL diagnosed on or after January 1, 2014, and have no evidence of HSIL recurrence at screening. Persons infected with HIV are eligible for the study provided they are receiving antiretroviral therapy. Target enrollment is 345 individuals. The primary outcome is time to histopathologically confirmed recurrence of HSIL. Differences in the risk for recurrence of HSIL will be evaluated using Cox proportional hazard models. Additional analyses include (1) frequency of HSIL recurrence; (2) role of HPV antibodies in deterring recurrence; (3) role of HPV persistence in recurrence, as measured by HPV genotype or HPV-16 variant lineage determined using swab samples collected at months 0, 18, and 36; and (4) incidence of adverse events. The study will be conducted at the University of Washington Virology Research Clinic from 2017 through 2022. Participants will be followed up for up to 36 months in the clinic, and up to 42 months by telephone. DISCUSSION Management of persistent or rapidly recurring anogenital HSIL remains challenging. Results from this study will provide evidence on whether incorporating the nonavalent HPV vaccine into routine care can decrease recurrence of anal and vulvar HSIL. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03051516.
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Affiliation(s)
| | - Kirsten Hauge
- Department of Medicine, University of Washington, Seattle
| | - Amalia Magaret
- Department of Biostatistics, University of Washington, Seattle
- Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Laboratory Medicine, University of Washington, Seattle
| | - Constance Mao
- Department of Obstetrics and Gynecology, University of Washington, Seattle
| | - Jeffrey Schouten
- Department of Medicine, University of Washington, Seattle
- Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Surgery, University of Washington, Seattle
| | - Verena Grieco
- Department of Pathology, University of Washington, Seattle
| | - Long Fu Xi
- Department of Epidemiology, University of Washington, Seattle
| | - Denise A Galloway
- Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Margaret M Madeleine
- Department of Epidemiology, University of Washington, Seattle
- Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Anna Wald
- Department of Medicine, University of Washington, Seattle
- Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Laboratory Medicine, University of Washington, Seattle
- Department of Epidemiology, University of Washington, Seattle
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Abstract
Human papillomavirus (HPV) is the first identified necessary cause of human cancers and is associated with nearly 100% of all cervical cancers. Compared to the general female populations, HIV+ women have higher prevalence and incidence of cervical HPV infections, higher risks of persistent HPV infections and subsequent cervical intraepithelial lesions, and a higher incidence of cervical cancer. Although the wide use of combined antiretroviral therapy (cART) has improved the immune function and the longevity of HIV+ women, the incidence of cervical cancer in HIV+ women has not declined. For HIV+ women who follow routine cervical cancer screenings, their incidence of cervical cancer is comparable to that in HIV-negative women. Thus, adherence to the recommended cervical cancer screening is still critical for HIV+ women to prevent cervical cancer. Prophylactic HPV vaccines may also benefit HIV+ women, but prospective studies are needed to determine the effectiveness of HPV vaccination on reducing cervical cancer incidence in HIV+ women.
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Affiliation(s)
- Ping Du
- Department of Medicine, Department of Public Health Sciences, Penn State Hershey College of Medicine, 90 Hope Drive, Suite 2200, A210, Hershey, PA, USA.
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19
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Gilca V, Sauvageau C, Panicker G, De Serres G, Ouakki M, Unger ER. Immunogenicity and safety of a mixed vaccination schedule with one dose of nonavalent and one dose of bivalent HPV vaccine versus two doses of nonavalent vaccine - A randomized clinical trial. Vaccine 2018; 36:7017-7024. [PMID: 30314913 PMCID: PMC6497054 DOI: 10.1016/j.vaccine.2018.09.057] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 09/17/2018] [Accepted: 09/22/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Limited data is available on the use of different HPV vaccines in the same subjects. We evaluated the immunogenicity and safety of a mixed vaccination schedule with one dose of nonavalent (9vHPV) and one dose of bivalent vaccine (2vHPV) administered in different order versus two doses of 9vHPV vaccine. METHODS 371 girls and boys aged 9-10 years were randomized (1:1) to receive (I) two doses of 9vHPV or (II) a mixed schedule of 2vHPV + 9vHPV or 9vHPV + 2vHPV with a 6 month interval. Antibodies to HPV were tested by ELISA in blood samples collected one or six months post-first dose and one month post-second dose. RESULTS Post-first dose of 9vHPV 99.4-100% of subjects were seropositive to 9 HPV types included in the vaccine. GMTs varied from 5.0 to 73.6 IU(AU)/ml depending on HPV type. Post-first dose of 2vHPV all subjects were seropositive to HPV16 and 18 (GMTs 16.7 and 11.7 IU/ml, respectively) and 50.0-76.7% were seropositive to 7 types not included in 2vHPV (GMTs varied from 0.3 to 17.5 AU/ml depending on type). Post-second dose all subjects, regardless of the study group, were seropositive to 9 HPV types included in 9vHPV. Anti-HPV16 and 18 GMTs were higher in subjects with the mixed schedule and for the other 7 HPV types higher in subjects who received two doses of 9vHPV vaccine. A higher proportion of subjects who received 2vHPV reported local or systemic adverse events than those who received 9vHPV as the first dose. Post-second dose there were no differences in reported adverse events between the two vaccines. CONCLUSIONS The results show the mixed HPV vaccination schedules used in this study are immunogenic and have an acceptable safety profile. Although the seroprotective threshold of antibodies remains unknown the 100% seropositivity to all 9 HPV types included in 9vHPV and the increase of GMTs observed in all study groups post-second dose administration are reassuring and suggest protection might be achieved regardless of the schedule used. CLINICAL TRIALS REGISTRATION Clinicaltrials.gov NCT02567955.
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Affiliation(s)
- Vladimir Gilca
- Quebec Public Health Institute, Quebec, Canada; Laval University Research Hospital Center, Quebec, Canada.
| | - Chantal Sauvageau
- Quebec Public Health Institute, Quebec, Canada; Laval University Research Hospital Center, Quebec, Canada
| | | | - Gaston De Serres
- Quebec Public Health Institute, Quebec, Canada; Laval University Research Hospital Center, Quebec, Canada
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Mugo NR, Eckert L, Magaret AS, Cheng A, Mwaniki L, Ngure K, Celum C, Baeten JM, Galloway DA, Wamalwa D, Wald A. Quadrivalent HPV vaccine in HIV-1-infected early adolescent girls and boys in Kenya: Month 7 and 12 post vaccine immunogenicity and correlation with immune status. Vaccine 2018; 36:7025-7032. [PMID: 30297124 DOI: 10.1016/j.vaccine.2018.09.059] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 09/20/2018] [Accepted: 09/22/2018] [Indexed: 12/17/2022]
Abstract
INTRODUCTION In sub-Saharan Africa, a generation of HIV-1-infected children is approaching the age of sexual debut and becoming at risk for HPV infection and its sequelae. We assessed safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in HIV-1-infected adolescents. METHODS In an open-label trial among Kenyan, HIV-1-infected adolescents aged 9-14 years, we administered the qHPV vaccine at 0, 2 and 6 months and measured antibody titers to HPV-16, 18, 6 and 11 at month 7 and 12 post-vaccination. Measures of immunogenic response from HIV-1-negative historical cohorts from Africa and HIV-1 positive adolescent cohorts from the USA were used for comparison. RESULTS We enrolled 100 girls and 80 boys with a median age of 12 years and median baseline CD4 cell count of 684 (IQR 478, 935) cells/µL. One hundred and fifty four (86%) were receiving antiretroviral therapy for a median of 4.5 (IQR 2.3, 6.3) years; 110 (71%) had <400 copies of plasma HIV-1 RNA/mL. Of 189 enrolled children, 179 received all three doses. Two hundred and eighty five (64%) of 445 adverse events were injection site reactions; none were greater than grade 2. Of 6 Serious Adverse Events (SAEs), none were considered vaccine related. Seroconversion to HPV-18, 16, 11, 6 at month 7 occurred in 93.3%, 98.3%, 97.2% and 99.6% of vaccine recipients; similar rates have been reported in historical controls. The mean log10 HPV antibody titer measured at month 7 increased with each log10 increase in CD4 by 1.4 (95% CI: 1.1-1.7) for HPV-18; 1.2 (0.9-1.4) for HPV-16; 1.1 (0.8-1.3) for HPV-11; 0.7 (0.5-1.0) for HPV-6 (all p < 0.0001). CONCLUSION Almost all Kenyan HIV-1-infected adolescents mounted an immune response comparable to other immunized populations. HPV antibody titers were higher in those with preserved CD4 cell counts. Longer term-follow up will determine sustainability of the immune response. ClinicalTrials.gov number, NCT00557245.
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Affiliation(s)
- Nelly R Mugo
- Kenya Medical Research Institute, Center for Clinical Research, Kenya; Department of Global Health, University of Washington, Seattle, WA, USA; Partners in Health Research and Development, Kenya.
| | - Linda Eckert
- Department of Obstetrics and Gynaecology, University of Washington, WA, USA
| | - Amalia S Magaret
- Department of Laboratory Medicine, University of Washington, Seattle, WA, USA; Department of Biostatistics, University of Washington, Seattle, WA, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Anqi Cheng
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | | | - Kenneth Ngure
- Department of Global Health, University of Washington, Seattle, WA, USA; Jomo Kenyatta University of Agriculture and Technology, Kenya
| | - Connie Celum
- Department of Global Health, University of Washington, Seattle, WA, USA; Departments of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Jared M Baeten
- Department of Global Health, University of Washington, Seattle, WA, USA; Departments of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA
| | | | | | - Anna Wald
- Department of Laboratory Medicine, University of Washington, Seattle, WA, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Departments of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA
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Geretti AM, Brook G, Cameron C, Chadwick D, French N, Heyderman R, Ho A, Hunter M, Ladhani S, Lawton M, MacMahon E, McSorley J, Pozniak A, Rodger A. British HIV Association Guidelines on the Use of Vaccines in HIV-Positive Adults 2015. HIV Med 2018; 17 Suppl 3:s2-s81. [PMID: 27568789 DOI: 10.1111/hiv.12424] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Anna Maria Geretti
- Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
| | | | | | | | | | | | | | | | | | - Mark Lawton
- Royal Liverpool University Hospital, Liverpool, UK
| | - Eithne MacMahon
- Guy's & St Thomas' NHS Foundation Trust, London, UK.,King's College London, London, UK
| | | | - Anton Pozniak
- Chelsea and Westminster Hospital, NHS Foundation Trust, London, UK
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Kim SC, Feldman S, Moscicki AB. Risk of human papillomavirus infection in women with rheumatic disease: cervical cancer screening and prevention. Rheumatology (Oxford) 2018; 57:v26-v33. [PMID: 30137592 PMCID: PMC6099129 DOI: 10.1093/rheumatology/kex523] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2017] [Revised: 12/06/2017] [Indexed: 01/06/2023] Open
Abstract
Human Papillomavirus (HPV) is the most common sexually transmitted infection in the USA, with over 14 million people acquiring HPV each year. HPV is also the cause of most anogenital cancers. About 90% of HPV infections spontaneously resolve over 3 years. However, about 10% remain as persistent infection defined as repeatedly detected in cervical samples. As HPV is controlled by local and systemic immune responses, individuals with immunosuppression are at risk for cervical cancer. It is hypothesized that immunosuppressed individuals are more likely to have HPV persistence, which is necessary for malignant transformation. Accordingly, women with rheumatic diseases such as SLE and RA are likely vulnerable to HPV infection and the progression of cervical disease. The HPV vaccine, given as a series of vaccinations, is safe and effective that can prevent HPV infection and cervical cancer. There is no contraindication to HPV vaccination for women to age 26 with rheumatic disease, as it is not live. As in the general population, timing is key for the efficacy of the HPV vaccine as the goal is to vaccinate prior to sexual debut and exposure to HPV. There are no formal recommendations for cervical cancer screening in women with rheumatic disease but recommendations for the HIV-positive population can be adopted, meaning to screen with a Pap test annually for three consecutive years and if all normal, to extend the interval to every 3 years with the option of co-testing with HPV at 30 years and older.
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Affiliation(s)
- Seoyoung C Kim
- Division of Pharmacoepidemiology and Pharmacoeconomics
- Division of Rheumatology, Immunology and Allergy, Department of Medicine
| | - Sarah Feldman
- Department of Obstetrics Gynecology & Reproductive Biology, Brigham and Women’s Hospital, Boston, MA
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23
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Immunogenicity and Safety of the Quadrivalent Human Papillomavirus Vaccine in Girls Living With HIV. Pediatr Infect Dis J 2018; 37:595-597. [PMID: 29278613 DOI: 10.1097/inf.0000000000001874] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
We evaluated quadrivalent human papillomavirus vaccine seroresponses among 35 girls living with HIV (9-13 years of ages) and compared with data on girls without HIV, as part of a subgroup analysis. The quadrivalent human papillomavirus vaccine was safe and well tolerated. However, antibody response was significantly lower in girls living with HIV relative to girls without HIV. HIV virologic suppression predicted better antibody response.
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Weinberg A, Huang S, Moscicki AB, Saah A, Levin MJ. Persistence of memory B-cell and T-cell responses to the quadrivalent HPV vaccine in HIV-infected children. AIDS 2018; 32:851-860. [PMID: 29424778 PMCID: PMC5869173 DOI: 10.1097/qad.0000000000001773] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children. METHODS Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose. RESULTS HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs. HPV18. These HPV T-cell responses correlated with HIV disease characteristics at the study visits. Global T-cell function declined over time as measured by nonspecific mitogenic stimulation. B-cell memory was similar across treatment groups and HPV genotypes. There was a decline in HPV-specific B-cell memory over time that reached statistical significance for HPV16 in the four-dose group. CONCLUSION B-cell and T-cell memory did not significantly differ after either three or four doses of QHPV in HIV-infected children. The clinical consequences of decreasing global T-cell function and HPV B-cell memory over time in HIV-infected children requires further investigation.
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Affiliation(s)
- Adriana Weinberg
- Section of Pediatric Infectious Diseases, Departments of Pediatrics and Medicine, and Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Sharon Huang
- Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts
| | - Anna-Barbara Moscicki
- Department of Pediatrics, University of California Los Angeles, Los Angeles, California
| | | | - Myron J Levin
- Section of Pediatric Infectious Diseases, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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25
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Zurek Munk-Madsen M, Toft L, Kube T, Richter R, Ostergaard L, Søgaard OS, Tolstrup M, Kaufmann AM. Cellular immunogenicity of human papillomavirus vaccines Cervarix and Gardasil in adults with HIV infection. Hum Vaccin Immunother 2017; 14:909-916. [PMID: 29172992 PMCID: PMC5893199 DOI: 10.1080/21645515.2017.1407896] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Human papillomavirus (HPV) infection is a frequent cause of malignant and non-malignant disease, in particular among persons with HIV. HPV serotype-specific anti L1 antibodies protect against HPV infection but little is known about prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk individuals. We recently showed that both HPV vaccines (Gardasil® and Cervarix®) induce solid, serological immune responses in HIV-infected persons. This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV-vaccine recipients, T cell responses being critical for B cell activation and antibody-isotype switching. Thirty HIV-infected patients on long-term antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45) and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and IFNγ was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells (CD154+/IL-2+ or CD154+/ IFNγ+) were determined. Both HPV-vaccines significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory despite HIV-induced immune compromisation.
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Affiliation(s)
- Maria Zurek Munk-Madsen
- a Clinic for Gynecology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin , Germany.,b Department of Infectious Diseases , Aarhus University Hospital , Aarhus , Denmark
| | - Lars Toft
- b Department of Infectious Diseases , Aarhus University Hospital , Aarhus , Denmark
| | - Tina Kube
- a Clinic for Gynecology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin , Germany
| | - Rolf Richter
- a Clinic for Gynecology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin , Germany
| | - Lars Ostergaard
- b Department of Infectious Diseases , Aarhus University Hospital , Aarhus , Denmark
| | - Ole S Søgaard
- b Department of Infectious Diseases , Aarhus University Hospital , Aarhus , Denmark
| | - Martin Tolstrup
- b Department of Infectious Diseases , Aarhus University Hospital , Aarhus , Denmark
| | - Andreas M Kaufmann
- a Clinic for Gynecology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin , Germany
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Poljak M, Šterbenc A, Lunar MM. Prevention of human papillomavirus (HPV)-related tumors in people living with human immunodeficiency virus (HIV). Expert Rev Anti Infect Ther 2017; 15:987-999. [PMID: 29027811 DOI: 10.1080/14787210.2017.1392854] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION In comparison to their HIV-negative counterparts, people living with HIV (PLWH) have a higher prevalence of human papillomavirus (HPV) infection in various anatomical sites coupled with increased HPV persistence, higher risk of HPV-related tumors, and faster disease progression. Areas covered: Gender-neutral prevention strategies for HPV-related cancers in PLWH discussed: ABC approach, HPV vaccination, antiretroviral treatment (ART), anal cancer screening, and smoking cessation. Gender specific strategies: cervical cancer screening reduces the incidence and mortality of cervical cancer and circumcision might reduce the risk of HPV infections in men. Expert commentary: HPV-related cancer incidence has not declined (e.g. cervical cancer) and has even increased (e.g. anal cancer) in the ART era, demanding an effective HPV prevention strategy. HPV vaccination should be introduced into national prevention programs worldwide immediately because current prophylactic vaccines are safe, tolerable, and immunogenic in PLWH. HPV vaccine efficacy trials in PLWH are essential to determine the most appropriate immunization schedule. The population most at risk of anal cancer is HIV-positive men who have sex with men, who are not protected by herd immunity if only the female population is vaccinated. Unvaccinated PLWH need enhanced surveillance for early detection of HPV-related cancers and their precursors.
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Affiliation(s)
- Mario Poljak
- a Institute of Microbiology and Immunology, Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia
| | - Anja Šterbenc
- a Institute of Microbiology and Immunology, Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia
| | - Maja M Lunar
- a Institute of Microbiology and Immunology, Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia
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Camacho-Gonzalez AF, Chernoff MC, Williams PL, Chahroudi A, Oleske JM, Traite S, Chakraborty R, Purswani MU, Abzug MJ, the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 Study Team. Sexually Transmitted Infections in Youth With Controlled and Uncontrolled Human Immunodeficiency Virus Infection. J Pediatric Infect Dis Soc 2017; 6:e22-e29. [PMID: 27440505 PMCID: PMC5907850 DOI: 10.1093/jpids/piw039] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 06/16/2016] [Indexed: 11/12/2022]
Abstract
BACKGROUND Sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), disproportionately affect adolescents and young adults (AYAs) ages 13-24 years. Sexually transmitted infections likewise are a risk factor for HIV acquisition and transmission; however, there is a lack of data on STI acquisition in HIV-infected AYAs. METHODS We determined the incidence of STIs in HIV-infected AYAs 12.5 <25 years of age in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 observational cohort study. Univariate and multivariable logistic regression models were used to evaluate the association of HIV control (mean viral load <500 copies/mL and CD4+ T cells >500 cells/mm3 in the year preceding STI diagnosis) and other risk factors with STI occurrence. RESULTS Of 1201 enrolled subjects, 1042 participants met age criteria and were included (49% male, 61% black, 88% perinatally infected; mean age 18.3 years). One hundred twenty participants had at least 1 STI on study, of whom 93 had their first lifetime STI (incidence rate = 2.8/100 person-years). For individual STI categories, 155 incident category-specific events were reported; human papillomavirus (HPV) and chlamydial infections were the most common. In the multivariable model, having an STI was associated with older age (adjusted odds ratio [aOR] = 1.13; 95% confidence interval [CI], 1.05-1.22), female sex (aOR = 2.65; 95% CI, 1.67-4.21), nonperinatal HIV acquisition (aOR = 2.33; 95% CI, 1.29-4.22), and uncontrolled HIV infection (aOR = 2.05; 95% CI, 1.29-3.25). CONCLUSIONS Sexually transmitted infection acquisition in HIV-infected AYAs is associated with older age, female sex, nonperinatal HIV acquisition, and poorly controlled HIV infection. Substantial rates of STIs among HIV-infected AYAs support enhanced preventive interventions, including safe-sex practices and HPV vaccination, and antiretroviral adherence strategies.
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Affiliation(s)
- Andres F Camacho-Gonzalez
- Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Division of Pediatric Infectious Diseases
- Ponce Family and Youth Clinic, Grady Infectious Diseases Program, Grady Health Systems, Atlanta, Georgia,
| | - Miriam C Chernoff
- Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Paige L Williams
- Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Ann Chahroudi
- Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Division of Pediatric Infectious Diseases
- Ponce Family and Youth Clinic, Grady Infectious Diseases Program, Grady Health Systems, Atlanta, Georgia,
| | - James M Oleske
- Department of Pediatrics, Division of Allergy, Immunology, Infectious Diseases and Pulmonology, Rutgers New Jersey Medical School, Newark;
| | - Shirley Traite
- Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Rana Chakraborty
- Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Division of Pediatric Infectious Diseases
- Ponce Family and Youth Clinic, Grady Infectious Diseases Program, Grady Health Systems, Atlanta, Georgia,
| | - Murli U Purswani
- Department of Pediatrics, Division of Pediatric Infectious Diseases, Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, New York, and
| | - Mark J Abzug
- Department of Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Division of Pediatric Infectious Diseases, Aurora
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Ghebre RG, Grover S, Xu MJ, Chuang LT, Simonds H. Cervical cancer control in HIV-infected women: Past, present and future. Gynecol Oncol Rep 2017; 21:101-108. [PMID: 28819634 PMCID: PMC5548335 DOI: 10.1016/j.gore.2017.07.009] [Citation(s) in RCA: 105] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 07/18/2017] [Indexed: 01/17/2023] Open
Abstract
Since the initial recognition of acquired immunodeficiency syndrome (AIDS) in 1981, an increased burden of cervical cancer was identified among human immunodeficiency virus (HIV)-positive women. Introduction of antiretroviral therapy (ART) decreased risks of opportunistic infections and improved overall survival. HIV-infected women are living longer. Introduction of the human papillomavirus (HPV) vaccine, cervical cancer screening and early diagnosis provide opportunities to reduce cervical cancer associated mortality. In line with 2030 Sustainable Development Goals to reduce mortality from non-communicable diseases, increased efforts need to focus on high burden countries within sub-Saharan Africa (SSA). Despite limitations of resources in SSA, opportunities exist to improve cancer control. This article reviews advancements in cervical cancer control in HIV-positive women.
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Affiliation(s)
- Rahel G. Ghebre
- University of Minnesota Medical School, Minneapolis, MN, USA
- Human Resources for Health, Rwanda
- School of Medicine, Yale University, CT, USA
| | - Surbhi Grover
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Melody J. Xu
- Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA
| | - Linus T. Chuang
- Department of Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Hannah Simonds
- Division of Radiation Oncology, Tygerberg Hospital/University of Stellenbosch, Stellenbosch, South Africa
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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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Howitt BE, Herfs M, Tomoka T, Kamiza S, Gheit T, Tommasino M, Delvenne P, Crum CP, Milner D. Comprehensive Human Papillomavirus Genotyping in Cervical Squamous Cell Carcinomas and Its Relevance to Cervical Cancer Prevention in Malawian Women. J Glob Oncol 2017; 3:227-234. [PMID: 28717764 PMCID: PMC5493214 DOI: 10.1200/jgo.2015.001909] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
PURPOSE Cervical squamous cell carcinoma (SCC) continues to be a significant cause of cancer morbidity and is the third leading cause of cancer-related death in women worldwide. In sub-Saharan Africa, cervical cancer is not only the most common female cancer but also the leading cause of cancer-related deaths in women. Malawi, in particular, has the highest burden of cervical cancer. With the increasing use of human papillomavirus (HPV) vaccination, documenting the prevalent HPV types in those high-risk populations is necessary to both manage expectations of HPV vaccination and guide future vaccine development. MATERIALS AND METHODS In this study, we performed HPV typing on 474 cervical SCC samples and analyzed the potential impact of HPV vaccination in this population. RESULTS Ninety-seven percent of tumors were positive for at least one HPV type, and 54% harbored more than one HPV type. HPV 16 was the most common type (82%), followed by HPV 18 (34%), HPV 35 (24%), and HPV 31 (12%). A vaccine against HPV 16 and 18 would ideally prevent 53% of cervical SCC, and the nonavalent HPV vaccine (covering HPV 16, 18, 31, 33, 45, 52, and 58) would prevent 71% of cervical SCC in Malawi (assuming 100% vaccine efficacy). The main reason for a lack of coverage was high prevalence of HPV 35, which was also present as a single infection in a small subset of patients. CONCLUSION Although any HPV vaccination in this population would likely prevent a significant proportion of cervical cancer, the nonavalent vaccine would provide better coverage. Furthermore, investigation of the role of HPV 35 in this population, including possible cross-protection with other HPV types, should be pursued.
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Affiliation(s)
- Brooke E. Howitt
- Brooke E. Howitt, Christopher P. Crum, and Danny Milner, Brigham and Women’s Hospital, Boston, MA; Michael Herfs and Philippe Delvenne, University of Liege, Liege, Belgium; Tamiwe Tomoka, Steve Kamiza, and Danny Milner, Malawi College of Medicine, Blantyre, Malawi; and Tarik Gheit and Massimo Tommasino, International Agency for Research on Cancer, Lyon, France
| | - Michael Herfs
- Brooke E. Howitt, Christopher P. Crum, and Danny Milner, Brigham and Women’s Hospital, Boston, MA; Michael Herfs and Philippe Delvenne, University of Liege, Liege, Belgium; Tamiwe Tomoka, Steve Kamiza, and Danny Milner, Malawi College of Medicine, Blantyre, Malawi; and Tarik Gheit and Massimo Tommasino, International Agency for Research on Cancer, Lyon, France
| | - Tamiwe Tomoka
- Brooke E. Howitt, Christopher P. Crum, and Danny Milner, Brigham and Women’s Hospital, Boston, MA; Michael Herfs and Philippe Delvenne, University of Liege, Liege, Belgium; Tamiwe Tomoka, Steve Kamiza, and Danny Milner, Malawi College of Medicine, Blantyre, Malawi; and Tarik Gheit and Massimo Tommasino, International Agency for Research on Cancer, Lyon, France
| | - Steve Kamiza
- Brooke E. Howitt, Christopher P. Crum, and Danny Milner, Brigham and Women’s Hospital, Boston, MA; Michael Herfs and Philippe Delvenne, University of Liege, Liege, Belgium; Tamiwe Tomoka, Steve Kamiza, and Danny Milner, Malawi College of Medicine, Blantyre, Malawi; and Tarik Gheit and Massimo Tommasino, International Agency for Research on Cancer, Lyon, France
| | - Tarik Gheit
- Brooke E. Howitt, Christopher P. Crum, and Danny Milner, Brigham and Women’s Hospital, Boston, MA; Michael Herfs and Philippe Delvenne, University of Liege, Liege, Belgium; Tamiwe Tomoka, Steve Kamiza, and Danny Milner, Malawi College of Medicine, Blantyre, Malawi; and Tarik Gheit and Massimo Tommasino, International Agency for Research on Cancer, Lyon, France
| | - Massimo Tommasino
- Brooke E. Howitt, Christopher P. Crum, and Danny Milner, Brigham and Women’s Hospital, Boston, MA; Michael Herfs and Philippe Delvenne, University of Liege, Liege, Belgium; Tamiwe Tomoka, Steve Kamiza, and Danny Milner, Malawi College of Medicine, Blantyre, Malawi; and Tarik Gheit and Massimo Tommasino, International Agency for Research on Cancer, Lyon, France
| | - Philippe Delvenne
- Brooke E. Howitt, Christopher P. Crum, and Danny Milner, Brigham and Women’s Hospital, Boston, MA; Michael Herfs and Philippe Delvenne, University of Liege, Liege, Belgium; Tamiwe Tomoka, Steve Kamiza, and Danny Milner, Malawi College of Medicine, Blantyre, Malawi; and Tarik Gheit and Massimo Tommasino, International Agency for Research on Cancer, Lyon, France
| | - Christopher P. Crum
- Brooke E. Howitt, Christopher P. Crum, and Danny Milner, Brigham and Women’s Hospital, Boston, MA; Michael Herfs and Philippe Delvenne, University of Liege, Liege, Belgium; Tamiwe Tomoka, Steve Kamiza, and Danny Milner, Malawi College of Medicine, Blantyre, Malawi; and Tarik Gheit and Massimo Tommasino, International Agency for Research on Cancer, Lyon, France
| | - Danny Milner
- Brooke E. Howitt, Christopher P. Crum, and Danny Milner, Brigham and Women’s Hospital, Boston, MA; Michael Herfs and Philippe Delvenne, University of Liege, Liege, Belgium; Tamiwe Tomoka, Steve Kamiza, and Danny Milner, Malawi College of Medicine, Blantyre, Malawi; and Tarik Gheit and Massimo Tommasino, International Agency for Research on Cancer, Lyon, France
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Levin MJ, Huang S, Moscicki AB, Song LY, Read JS, Meyer WA, Saah AJ, Richardson K, Weinberg A. Four-year persistence of type-specific immunity after quadrivalent human papillomavirus vaccination in HIV-infected children: Effect of a fourth dose of vaccine. Vaccine 2017; 35:1712-1720. [PMID: 28238631 DOI: 10.1016/j.vaccine.2017.02.021] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 02/02/2017] [Accepted: 02/09/2017] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Although HIV-infected children are recommended to receive quadrivalent human papillomavirus vaccine (QHPV) there is limited information on their response to QHPV. This study in HIV-infected children, evaluated the magnitude and duration of immune responses to QHPV. This report describes type-specific serum antibody responses over a 4-to-5year period after either 3 or 4 doses of QHPV. DESIGN/METHODS HIV-infected children, ages 7-to-11years, received 3 doses of QHPV (n=96) or placebo (n=30). At 72weeks QHPV recipients received a fourth dose (n=84), while placebo recipients began the 3-dose QHPV schedule (n=27). HPV serotype-specific antibody was determined, by competitive Luminex immunoassay (cLIA) and IgG Luminex immunoassay, at 2, 3.5, and 4-to-5years after the last dose of QHPV in each treatment arm. RESULTS At 4-to-5years after the last dose of QHPV, antibody titers were significantly higher in 4-dose than in 3-dose group. However, the proportion of vaccinees with a seroresponse in the cLIA assay was not different between the two groups (86-93% for HPV types 6, 11, and 16, and 64% for HPV type 18). These results were very similar to the seroresponse rate in these HIV-infected children at 1month after completing vaccination. CONCLUSIONS Children with well-controlled HIV infection who receive 3 doses of the QHPV vaccine maintain seropositivity and antibody levels that are generally similar to children of the same age who are not HIV-infected. Antibody titer correlated strongly with low log HIV RNA, low CD8%, and high CD4%. Additionally, a fourth dose of vaccine in HIV-infected children produces a marked rise in antibody characteristic of an anamnestic response and persistence of high antibody levels. Study identification: IMPAACT P1085 (V501-021). CLINICALTRIALS.GOV identifier: NCT01206556.
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Affiliation(s)
- Myron J Levin
- Section of Pediatric Infectious Diseases, Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States.
| | - Sharon Huang
- Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA 02115, United States
| | - Anna-Barbara Moscicki
- Department of Pediatrics, University of California Los Angeles, Los Angeles, CA 19954, United States
| | - Lin-Ye Song
- Formerly Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA 02115, United States; Office of Science, Food & Drug Administration; Silver Spring, MD 20993, United States
| | - Jennifer S Read
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, United States
| | | | | | - Kelly Richardson
- Section of Pediatric Infectious Diseases, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States
| | - Adriana Weinberg
- Section of Pediatric Infectious Diseases, Departments of Pediatrics, Medicine, and Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States
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Endo F, Tabata T, Sadato D, Kawamura M, Ando N, Oboki K, Ukaji M, Kobayashi K, Kobayashi Y, Ikeda T, Shibasaki F. Development of a simple and quick immunochromatography method for detection of anti-HPV-16/-18 antibodies. PLoS One 2017; 12:e0171314. [PMID: 28158224 PMCID: PMC5291722 DOI: 10.1371/journal.pone.0171314] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2016] [Accepted: 01/19/2017] [Indexed: 12/20/2022] Open
Abstract
Immunochromatography (IC) is widely used to detect target molecules in biological fluids. Since this method can be performed without a special technique or device, IC is a convenient way to assess the existence of antibodies or pathogens such as viruses and bacteria, simply and quickly. In this study, we established an IC method to detect serum antibodies against oncogenic human papillomavirus (HPV)-16 and HPV-18 L1 proteins using recombinant L1 proteins produced by silkworms as antigens. Infection of oncogenic HPVs is a major risk factor of cervical cancer, which is one of the most common cancers in women worldwide. We first measured blood sera of two groups by magnetic beads enzyme-linked immunosorbent assay (MB-ELISA). For the first group, sera were collected prospectively from young women who planned to receive HPV vaccination. The second group consisted of children under 20 years of age, non-vaccinated healthy women, vaccinated healthy women, dysplasia, cervical intraepithelial neoplasia III, and cervical cancer patients. We confirmed that standard vaccination doses significantly increased serum HPV antibody concentrations, and the level was sustained at least more than 30 months after vaccination. In contrast, an increase in antibody concentration was not observed in patients with precancerous cervical changes and cervical cancer. We next measured the samples in both groups using the IC method we originally developed, and found that the measurement values of IC highly correlated with those of MB-ELISA. The simple and quick IC method would be a useful tool for rapid monitoring of L1 specific antibody levels in a non-laboratory environment. With less than one drop of serum, our IC can easily detect serum HPV-16/-18 antibodies within 15 minutes, without the need for electronic devices or techniques.
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Affiliation(s)
- Fumiko Endo
- Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-Kitazawa, Setagaya-ku, Tokyo, Japan
| | - Tsutomu Tabata
- Department of Obstetrics and Gynecology, Faculty of Medicine, Mie University, 2–174 Edobashi, Tsu-city, Mie, Japan
| | - Daichi Sadato
- Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-Kitazawa, Setagaya-ku, Tokyo, Japan
- Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, Japan
| | - Machiko Kawamura
- Department of Pediatrics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, Japan
| | - Noriyuki Ando
- Josei-Kokoro-Clinic, 1-1-9 Machiya, Arakawa-ku, Tokyo, Japan
| | - Keisuke Oboki
- Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-Kitazawa, Setagaya-ku, Tokyo, Japan
- * E-mail: (FS); (KO)
| | - Masako Ukaji
- Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-Kitazawa, Setagaya-ku, Tokyo, Japan
| | | | | | - Tomoaki Ikeda
- Department of Obstetrics and Gynecology, Faculty of Medicine, Mie University, 2–174 Edobashi, Tsu-city, Mie, Japan
| | - Futoshi Shibasaki
- Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-Kitazawa, Setagaya-ku, Tokyo, Japan
- * E-mail: (FS); (KO)
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Verma M, Erwin S, Abedi V, Hontecillas R, Hoops S, Leber A, Bassaganya-Riera J, Ciupe SM. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa. PLoS One 2017; 12:e0168133. [PMID: 28060843 PMCID: PMC5218576 DOI: 10.1371/journal.pone.0168133] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Accepted: 11/24/2016] [Indexed: 02/07/2023] Open
Abstract
Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.
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Affiliation(s)
- Meghna Verma
- Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America
| | - Samantha Erwin
- Department of Mathematics, Virginia Tech, Blacksburg, VA, United States of America
| | - Vida Abedi
- Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America
| | - Raquel Hontecillas
- Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America
| | - Stefan Hoops
- Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America
| | - Andrew Leber
- Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America
| | - Josep Bassaganya-Riera
- Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States of America
| | - Stanca M Ciupe
- Department of Mathematics, Virginia Tech, Blacksburg, VA, United States of America
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Esser S, Kreuter A, Oette M, Gingelmaier A, Mosthaf F, Sautter-Bihl ML, Jongen J, Brockmeyer NH, Eldering G, Swoboda J, Postel N, Degen O, Schalk H, Jessen A, Knechten H, Thoden J, Stellbrink HJ, Schafberger A, Wieland U. German-Austrian guidelines on anal dysplasia and anal cancer in HIV-positive individuals: prevention, diagnosis, and treatment. J Dtsch Dermatol Ges 2016; 13:1302-19. [PMID: 26612810 DOI: 10.1111/ddg.12726] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Stefan Esser
- University Hospital Essen, HPSTD Outpatient Clinic, Department of Dermatology and Venereology, Essen, Germany
| | - Alexander Kreuter
- HELIOS St. Elisabeth Hospital Oberhausen, Department of Dermatology, Venereology, and Allergology, Oberhausen, Germany
| | - Mark Oette
- Augustinerinnen Hospital, Department of General Medicine, Gastroenterology; and Infectious Diseases, Cologne, Germany
| | - Andrea Gingelmaier
- Ludwig-Maximilians-University, University Hospital Munich, Department of Gynecology, Munich, Germany
| | - Franz Mosthaf
- Medical Specialist Practice for Hematology, Oncology, and Infectious Diseases, Karlsruhe, Germany
| | | | | | - Norbert H Brockmeyer
- Ruhr-University, St. Josef Hospital, Department of Dermatology, Venereology, and Allergology, Center for Sexual Health und Medicine, Bochum, Germany
| | | | | | | | - Olaf Degen
- University Hospital Hamburg-Eppendorf, Outpatient Clinic Center for Infectious Diseases, Hamburg, Germany
| | - Horst Schalk
- Medical Practice Center of General Medicine, Vienna, Austria
| | | | - Heribert Knechten
- Medical Practice for Internal Medicine and Infectious Diseases, Aachen, Germany
| | - Jan Thoden
- Medical Group Practice for Internal Medicine and Rheumatology, Freiburg, Germany
| | | | | | - Ulrike Wieland
- University Köln, Institute of Virology, National Reference Center for Papilloma and Polyomavirus, Cologne, Germany
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35
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MacIntyre CR, Shaw P, Mackie FE, Boros C, Marshall H, Barnes M, Seale H, Kennedy SE, Moa A, Hayen A, Chughtai AA, O'Loughlin EV, Stormon M. Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children. Vaccine 2016; 34:4343-50. [PMID: 27406936 DOI: 10.1016/j.vaccine.2016.06.049] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Revised: 06/14/2016] [Accepted: 06/15/2016] [Indexed: 12/31/2022]
Abstract
AIM The aim of this study was to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. METHODS A multi-centre clinical trial was conducted in three paediatric hospitals in Australia. Unvaccinated children 5-18years of age attending one of three paediatric hospitals with a range of specified conditions associated with immunosuppression were included. Quadrivalent HPV vaccine (Gardasil) was given to the participants and serum anti-HPV antibody levels were measured at baseline (before first dose), 7 and 24months after the first dose of vaccine. RESULTS Fifty-nine participants were enrolled across the three paediatric hospitals and among those one was seropositive to types 6, 11 and 16 at baseline. Seven months after the first dose, seroconversion rates were 93.3%, 100%, 100% and 88.9% for type 6, 11, 16 and 18 respectively. The corresponding rates at 24month follow up were 82.2%, 91.1%, 91.1% and 68.9%. The greatest increase in geometric mean titre (GMT) was for type 16, followed by type 11. GMTs declined over the following months, but remained more than fourfold higher for all serotypes compared to baseline titres at 24months post vaccination. Injection site erythema, pain and swelling were commonly reported local adverse events and were less common after each dose. Few participants reported systemic adverse events, and minor disease flare occurred in two participants. One child developed a squamous cell oral carcinoma during follow up, but tissue was unable to be tested for HPV. CONCLUSION Immunosuppressed children had an adequate immunogenic response to Quadrivalent HPV vaccine regardless of age and the cause of immunosuppression. HPV related cancers occur at higher frequency and earlier in immunosuppressed patients, so early vaccination and optimal scheduling should be further studied in such children. CLINICAL TRIAL REGISTRATION NCT02263703 (ClinicalTrials.gov).
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Affiliation(s)
- C Raina MacIntyre
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia; College of Public Service and Community Solutions, Arizona State University, USA.
| | - Peter Shaw
- Dept Gastroenterology Children's Hospital at Westmead, Hawkesbury Rd, Westmead NSW 2145, Australia
| | - Fiona E Mackie
- Nephrology, Sydney Children's Hospital, Randwick, High St, Randwick NSW 2031, Australia; School of Women's & Children's Health, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Christina Boros
- The Women's and Children's Hospital and Robinson Research Institute and School of Medicine, The University of Adelaide, 55 King William Road, North Adelaide 5006, Australia
| | - Helen Marshall
- The Women's and Children's Hospital and Robinson Research Institute and School of Medicine, The University of Adelaide, 55 King William Road, North Adelaide 5006, Australia
| | - Michelle Barnes
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Holly Seale
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Sean E Kennedy
- Nephrology, Sydney Children's Hospital, Randwick, High St, Randwick NSW 2031, Australia; School of Women's & Children's Health, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Aye Moa
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Andrew Hayen
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Abrar Ahmad Chughtai
- School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Edward V O'Loughlin
- Dept Gastroenterology Children's Hospital at Westmead, Hawkesbury Rd, Westmead NSW 2145, Australia
| | - Michael Stormon
- Dept Gastroenterology Children's Hospital at Westmead, Hawkesbury Rd, Westmead NSW 2145, Australia
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36
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Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids. Br J Cancer 2016; 114:409-16. [PMID: 26867163 PMCID: PMC4815771 DOI: 10.1038/bjc.2015.462] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 11/15/2015] [Accepted: 11/26/2015] [Indexed: 12/15/2022] Open
Abstract
Background: Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. Methods: We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. Results: HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. Conclusions: We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx.
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37
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Chapman-Davis E, Dockery LE, Griffith K, Stroup C. Update on human papillomavirus vaccination: Where are we now? World J Obstet Gynecol 2016; 5:5-15. [DOI: 10.5317/wjog.v5.i1.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 10/16/2015] [Accepted: 11/25/2015] [Indexed: 02/05/2023] Open
Abstract
Infection with human papillomavirus (HPV) is the major cause of pre-invasive and invasive lesions of the urogenital tract, resulting in morbidity and mortality worldwide. HPV-related infection is responsible for most cases of cervical cancer, a leading cause of cancer death in women worldwide. Developed countries have screening programs in place to detect precancerous lesions at early stages; in resource-limited settings however, HPV related diseases are often identified in advanced stages. This is due to limitations in the availability and roll out of effective screening programs. The relatively recent availability of the HPV vaccine has provided a new public health opportunity to decrease the incidence of HPV-related disease. The high mortality rates seen in developing countries could be reduced through effective implementation of HPV vaccination programs. Large trials have proven the efficacy of bivalent, quadrivalent vaccine and most recently 9-valent vaccine. Uptake in vaccination remains low due to multiple barriers including lack of education, lack of access, and costs. New strategies are being assessed to increase access, increase knowledge and reduce costs that may result in feasible vaccination programs worldwide. The goal of this article is to review the effectiveness and safety of the current HPV vaccines available, vaccine delivery strategies, cost effectiveness, and efforts to improve the acceptability. A literature search was conducted through PubMed using the terms “HPV vaccination, and safety, and males, and acceptability and strategies, and cost effectiveness,”focusing on articles published between 2006 and 2015. The most relevant and larger scale trials were evaluated for discussion.
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38
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Esser S, Kreuter A, Oette M, Gingelmaier A, Mosthaf F, Sautter-Bihl ML, Jongen J, Brockmeyer NH, Eldering G, Swoboda J, Postel N, Degen O, Schalk H, Jessen A, Knechten H, Thoden J, Stellbrink HJ, Schafberger A, Wieland U. Deutsch-Österreichische S2k-Leitlinie: anale Dysplasien und Analkarzinome bei HIV-Infizierten: Prävention, Diagnostik und Therapie. J Dtsch Dermatol Ges 2015. [DOI: 10.1111/ddg.60_12726] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Stefan Esser
- Universitätsklinikum Essen, HPSTD-Ambulanz; Klinik für Dermatologie und Venerologie; Essen Deutschland
| | - Alexander Kreuter
- HELIOS St. Elisabeth Klinik Oberhausen; Klinik für Dermatologie, Venerologie und Allergologie; Oberhausen Deutschland
| | - Mark Oette
- Augustinerinnen Hospital, Klinik für Allgemeinmedizin; Gastroenterologie und Infektiologie; Köln Deutschland
| | - Andrea Gingelmaier
- Ludwig-Maximilians-Universität, Universitätsklinikum München; Klinik für Gynäkologie; München Deutschland
| | - Franz Mosthaf
- Facharztpraxis für Hämatologie; Onkologie und Infektiologie; Karlsruhe Deutschland
| | - Marie-Luise Sautter-Bihl
- Städtische Klinikum Karlsruhe; Klinik für Radioonkologie und Strahlentherapie; Karlsruhe Deutschland
| | | | - Norbert H. Brockmeyer
- Ruhr-Universität, St. Josef Krankenhaus, Klinik für Dermatologie; Venerologie und Allergologie, Zentrum für sexuelle Gesundheit und Medizin; Bochum Deutschland
| | | | | | | | - Olaf Degen
- Universitätsklinikum Hamburg-Eppendorf; Ambulanzzentrum Bereich Infektiologie; Hamburg Deutschland
| | - Horst Schalk
- Gruppenpraxis für Allgemeinmedizin; Wien Österreich
| | | | | | - Jan Thoden
- Gemeinschaftspraxis für Innere Medizin und Rheumatologie; Freiburg Deutschland
| | | | | | - Ulrike Wieland
- Universität Köln, Institut für Virologie; Nationales Referenzzentrum für Papillom- und Polyomaviren; Köln Deutschland
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Abstract
The development of efficacious prophylactic human papillomavirus vaccines provided an opportunity for the primary prevention of related infections and diseases. Certain oncogenic human papillomaviruses that preferentially infect the genital epithelium cause cervical cancer and a substantial proportion of anal, penile, vaginal, vulvar and oropharyngeal cancers. Following extensive clinical trials demonstrating their efficacy and safety, two vaccines have been in global use for over 6 years. This review summarises the accumulated evidence regarding their high level of efficacy, safety in population usage, reductions in genital warts, infections and cervical disease following their adoption, and facilitators and barriers to achieving high vaccination coverage. The review also discusses practical issues and frequently asked questions regarding duration of effect, vaccination of women treated for cervical disease and alternate vaccination schedules, as well as the need to review cervical screening strategies in the post- vaccination environment.
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Affiliation(s)
- Julia M L Brotherton
- National HPV Vaccination Program Register, VCS Inc, East Melbourne, Victoria, Australia
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40
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Brotherton JM. Human papillomavirus vaccination. Br J Hosp Med (Lond) 2014; 75 Suppl 11:C165-8. [PMID: 25381861 DOI: 10.12968/hmed.2014.75.sup11.c165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Julia Ml Brotherton
- Medical Director of the National HPV Vaccination Program Register, Victorian Cytology Service, East Melbourne, Victoria 8002, Australia and Honorary Senior Fellow, School of Global and Population Health, University of Melbourne, Victoria, Australia
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41
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Neutralizing and cross-neutralizing antibody titres induced by bivalent and quadrivalent human papillomavirus vaccines in the target population of organized vaccination programmes. Vaccine 2014; 32:5357-62. [DOI: 10.1016/j.vaccine.2014.07.014] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2014] [Revised: 05/11/2014] [Accepted: 07/08/2014] [Indexed: 01/26/2023]
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42
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Seitz H, Müller M. Current perspectives on HPV vaccination: a focus on targeting the L2 protein. Future Virol 2014. [DOI: 10.2217/fvl.14.44] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
ABSTRACT: Thirty years ago, human papillomavirus types 16 and 18 were isolated from cervical carcinomas, and it has been almost 10 years since the introduction of the first prophylactic virus-like particle (VLP) vaccine. The VLP vaccines have already impacted the reduction of pre-malignant lesions and genital warts, and it is expected that vaccination efforts will successfully lower the incidence of cervical cancer before the end of the decade. Here we summarize the historical developments leading to the prophylactic HPV vaccines and discuss current advances of next-generation vaccines that aim to overcome certain limitations of the VLP vaccines, including their intrinsic narrow range of protection, stability and production/distribution costs.
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Affiliation(s)
- Hanna Seitz
- National Institutes of Health, NCI/CCR/LCO, 37 Convent Drive, Bethesda, MD 20892, USA
| | - Martin Müller
- Deutsches Krebsforschungszentrum, F035, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
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Toft L, Tolstrup M, Müller M, Sehr P, Bonde J, Storgaard M, Østergaard L, Søgaard OS. Comparison of the immunogenicity of Cervarix® and Gardasil® human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults. Hum Vaccin Immunother 2014; 10:1147-54. [PMID: 24553190 DOI: 10.4161/hv.27925] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Individuals infected with human immunodeficiency virus (HIV) have excess risk of developing human papillomavirus (HPV)-related disease. A substantial fraction of HPV-associated cancers is caused by HPV serotypes not included in the currently available vaccines. Among healthy women, both Cervarix(®) (HPV-16/18, GlaxoSmithKline Biologicals, GSK) and Gardasil(®) (HPV-6/11/16/18, Merck) have demonstrated partial cross-protection against certain oncogenic non-vaccine HPV-types. Currently, there are no available data on vaccine-induced cross-protection in men and little is known about cross-reactive immunity after HPV-vaccination of HIV-infected individuals. In an investigator-initiated trial, we randomized 91 HIV-positive men and women to receive vaccination with Cervarix(®) or Gardasil(®). The HPV-DNA status of the participants was determined with pcr before and after immunization. Cross-reactive antibody responses against HPV-31, HPV-33, and HPV-45 were evaluated for up to 12 months using a pseudovirion-based neutralization assay (PBNA). Geometric mean antibody titers (GMTs) were compared among vaccine groups and genders at 7 and 12 months.: Both vaccines induced anti-HPV-31, -33, and -45 neutralizing antibodies in participants who were seronegative and HPV-DNA negative for those types at study entry. Geometric mean antibody titers were comparable between vaccine groups. Interestingly, anti-HPV-31 and -33 antibody titers were higher among women compared with men at 7 and 12 months.: In conclusion, both licensed HPV-vaccines induced cross-neutralizing antibodies against frequent oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults, and women had greater serological responses against HPV-31 and -33 compared with men.
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Affiliation(s)
- Lars Toft
- Department of Infectious Diseases; Aarhus University Hospital; Aarhus, Denmark
| | - Martin Tolstrup
- Department of Infectious Diseases; Aarhus University Hospital; Aarhus, Denmark
| | - Martin Müller
- Research Program Infection and Cancer; German Cancer Research Center; Heidelberg, Germany
| | - Peter Sehr
- Chemical Biology Core Facility; European Molecular Biology Laboratory; Heidelberg, Germany
| | - Jesper Bonde
- Department of Pathology; Copenhagen University Hospital; Hvidovre, Denmark; Clinical Research Centre; Copenhagen University Hospital; Hvidovre, Denmark
| | - Merete Storgaard
- Department of Infectious Diseases; Aarhus University Hospital; Aarhus, Denmark
| | - Lars Østergaard
- Department of Infectious Diseases; Aarhus University Hospital; Aarhus, Denmark
| | - Ole S Søgaard
- Department of Infectious Diseases; Aarhus University Hospital; Aarhus, Denmark
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Murall CL, McCann KS, Bauch CT. Revising ecological assumptions about Human papillomavirus interactions and type replacement. J Theor Biol 2014; 350:98-109. [PMID: 24412334 DOI: 10.1016/j.jtbi.2013.12.028] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Revised: 12/12/2013] [Accepted: 12/29/2013] [Indexed: 12/25/2022]
Abstract
The controversy over whether vaccine-targeted HPV types will be replaced by other oncogenic, non-vaccine-targeted types remains unresolved. This is in part because little is known about the ecology of HPV types. Patient data has been interpreted to suggest independence or facilitative interactions between types and therefore replacement is believed to be unlikely. With a novel mathematical model, we investigated which HPV type interactions and their immune responses gave qualitatively similar patterns frequently observed in patients. To assess the possibility of type replacement, vaccination was added to see if non-vaccine-targeted types increased their 'niche'. Our model predicts that independence and facilitation are not necessary for the coexistence of types inside hosts, especially given the patchy nature of HPV infection. In fact, independence and facilitation inadequately represented co-infected patients. We found that some form of competition is likely in natural co-infections. Hence, non-vaccine-targeted types that are not cross-reactive with the vaccine could spread to more patches and can increase their viral load in vaccinated hosts. The degree to which this happens will depend on replication and patch colonization rates. Our results suggest that independence between types could be a fallacy, and so without conclusively untangling HPV within-host ecology, type replacement remains theoretically viable. More ecological thinking is needed in future studies.
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Affiliation(s)
- Carmen Lía Murall
- Department of Integrative Biology, University of Guelph, Canada; Department of Mathematics and Statistics, University of Guelph, Canada.
| | - Kevin S McCann
- Department of Integrative Biology, University of Guelph, Canada
| | - Chris T Bauch
- Department of Applied Mathematics, University of Waterloo, Canada
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Toft L, Tolstrup M, Storgaard M, Ostergaard L, Søgaard OS. Vaccination against oncogenic human papillomavirus infection in HIV-infected populations: review of current status and future perspectives. Sex Health 2014; 11:511-23. [PMID: 25218800 DOI: 10.1071/sh14015] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Accepted: 08/05/2014] [Indexed: 12/30/2022]
Abstract
UNLABELLED Background Men and women with HIV infection are at increased risk of developing cancers associated with human papillomavirus (HPV). The two licensed prophylactic HPV vaccines protect against de novo infection with HPV-16 and HPV-18, which cause the majority of HPV-associated cancers. Currently, no vaccine efficacy data are available for persons with HIV infection. Nevertheless, some countries have implemented specific HPV vaccination recommendations for HIV-positive populations. To specifically recommend prophylactic HPV vaccination in people with HIV, the vaccines must be safe and immunogenic in immunosuppressed people at a high risk of HPV infection. This review aims to summarise the current knowledge from published HPV vaccine trials in HIV-infected populations, to compile scheduled and ongoing HPV vaccine trials with HIV-positive study populations and to extrapolate the relevant knowledge about HPV vaccine efficacy in HIV-negative populations to an HIV context. METHODS The databases PubMed, Scopus and ClinicalTrials.gov were searched for peer-reviewed articles and scheduled or ongoing clinical HPV vaccine trials enrolling HIV-positive persons. RESULTS Current data indicate that prophylactic HPV vaccines are safe and immunogenic in different HIV-positive populations (children, female adolescents, adults). Increased immunogenicity has been reported in persons on antiretroviral therapy compared with antiretroviral-naïve persons, whereas no clear association has been found between CD4(+) cell count at immunisation and vaccine response. Several scheduled and ongoing HPV vaccine trials aim to determine vaccine efficacy against disease endpoints in HIV-infected study populations. CONCLUSION Prophylactic HPV vaccination appears safe, immunogenic and, by extrapolation, likely to reduce HPV-associated cancer development among persons with HIV infection.
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Affiliation(s)
- Lars Toft
- Department of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, Denmark
| | - Martin Tolstrup
- Department of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, Denmark
| | - Merete Storgaard
- Department of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, Denmark
| | - Lars Ostergaard
- Department of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, Denmark
| | - Ole S Søgaard
- Department of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, Denmark
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Toft L, Storgaard M, Müller M, Sehr P, Bonde J, Tolstrup M, Østergaard L, Søgaard OS. Comparison of the immunogenicity and reactogenicity of Cervarix and Gardasil human papillomavirus vaccines in HIV-infected adults: a randomized, double-blind clinical trial. J Infect Dis 2013; 209:1165-73. [PMID: 24273179 DOI: 10.1093/infdis/jit657] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND We compared the immunogenicity and reactogenicity of Cervarix or Gardasil human papillomavirus (HPV) vaccines in adults infected with the human immunodeficiency virus (HIV). METHODS This was a double-blind, controlled trial randomizing HIV-positive adults to receive 3 doses of Cervarix or Gardasil at 0, 1.5, and 6 months. Immunogenicity was evaluated for up to 12 months. Neutralizing anti-HPV-16/18 antibodies were measured by pseudovirion-based neutralization assay. Laboratory tests and diary cards were used for safety assessment. The HPV-DNA status of the participants was determined before and after immunization. RESULTS Ninety-two participants were included in the study. Anti-HPV-18 antibody titers were higher in the Cervarix group compared with the Gardasil group at 7 and 12 months. No significant differences in anti-HPV-16 antibody titers were found among vaccine groups. Among Cervarix vaccinees, women had higher anti-HPV-16/18 antibody titers compared to men. No sex-specific differences in antibody titers were found in the Gardasil group. Mild injection site reactions were more common in the Cervarix group than in the Gardasil group (91.1% vs 69.6%; P = .02). No serious adverse events occurred. CONCLUSIONS Both vaccines were immunogenic and well tolerated. Compared with Gardasil, Cervarix induced superior vaccine responses among HIV-infected women, whereas in HIV-infected men the difference in immunogenicity was less pronounced.
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Affiliation(s)
- Lars Toft
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
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Siberry GK, Abzug MJ, Nachman S, Brady MT, Dominguez KL, Handelsman E, Mofenson LM, Nesheim S, National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Diseases Society of America, Pediatric Infectious Diseases Society, American Academy of Pediatrics. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. Pediatr Infect Dis J 2013; 32 Suppl 2:i-KK4. [PMID: 24569199 PMCID: PMC4169043 DOI: 10.1097/01.inf.0000437856.09540.11] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- George K Siberry
- 1National Institutes of Health, Bethesda, Maryland 2University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado 3State University of New York at Stony Brook, Stony Brook, New York 4Nationwide Children's Hospital, Columbus, Ohio 5Centers for Disease Control and Prevention, Atlanta, Georgia
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Kumar D, Unger ER, Panicker G, Medvedev P, Wilson L, Humar A. Immunogenicity of quadrivalent human papillomavirus vaccine in organ transplant recipients. Am J Transplant 2013; 13:2411-7. [PMID: 23837399 PMCID: PMC4583130 DOI: 10.1111/ajt.12329] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Revised: 04/15/2013] [Accepted: 05/13/2013] [Indexed: 01/25/2023]
Abstract
Solid organ transplant recipients are at risk of morbidity from human papillomavirus (HPV)-related diseases. Quadrivalent HPV vaccine is recommended for posttransplant patients but there are no data on vaccine immunogenicity. We determined the immunogenicity of HPV vaccine in a cohort of young adult transplant patients. Patients were immunized with three doses of quadrivalent HPV vaccine containing viral types 6, 11, 16 and 18. Immunogenicity was determined by type-specific viral-like protein ELISA. Four weeks after the last dose of vaccine, a vaccine response was seen in 63.2%, 68.4%, 63.2% and 52.6% for HPV 6, 11, 16 and 18, respectively. Factors that led to reduced immunogenicity were vaccination early after transplant (p = 0.019), having a lung transplant (p = 0.007) and having higher tacrolimus levels (p = 0.048). At 12 months, there were significant declines in antibody titer for all HPV types although the number of patients who remained seropositive did not significantly differ. The vaccine was safe and well tolerated. We show suboptimal immunogenicity of HPV vaccine in transplant patients. This is important for counseling patients who choose to receive this vaccine. Further studies are needed to determine an optimal HPV vaccine type and schedule for this population.
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Affiliation(s)
- D. Kumar
- Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada,Corresponding author: Deepali Kumar,
| | - E. R. Unger
- Chronic Viral Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA
| | - G. Panicker
- Chronic Viral Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA
| | - P. Medvedev
- Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada
| | - L. Wilson
- Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada
| | - A. Humar
- Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada
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Hawkes D, Lea CE, Berryman MJ. Answering human papillomavirus vaccine concerns; a matter of science and time. Infect Agent Cancer 2013; 8:22. [PMID: 23758825 PMCID: PMC3691750 DOI: 10.1186/1750-9378-8-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 06/05/2013] [Indexed: 01/30/2023] Open
Abstract
Since the introduction of the HPV vaccine, questions have been asked about its efficacy in preventing cancer linked with HPV. Concerns about the HPV vaccine safety profile have also been raised. This paper highlights the rapidly growing body of evidence (including clinical trials and post-marketing surveillance) illustrating both the safety of the HPV vaccine, through a detailed investigation of reported adverse events, and its efficacy in reducing both HPV infections rates and the resulting drop in cervical lesions, which have been demonstrated to be good predictors of cervical cancer risk.
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Affiliation(s)
- David Hawkes
- The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia.
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