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1.
Vaccine ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39004526

RESUMO

Cervical cancer is a major cause of morbidity and mortality globally with a disproportionate impact on women in low- and middle-income countries. In 2021, the World Health Organization (WHO) called for increased vaccination, screening, and treatment to eliminate cervical cancer. However, even with widespread rollout of human papillomavirus (HPV) prophylactic vaccines, millions of women who previously acquired HPV infections will remain at risk for progression to cancer for decades to come. The development and licensing of an affordable, accessible therapeutic HPV vaccine, designed to clear or control carcinogenic HPV and/or to induce regression precancer could significantly contribute to the elimination efforts, particularly benefiting those who missed out on the prophylactic vaccine. One barrier to development of such vaccines is clarity around the regulatory pathway for licensure. In Washington, D.C. on September 12-13, 2023, a meeting was convened to provide input and guidance on trial design with associated ethical and regulatory considerations. This report summarizes the discussion and conclusions from the meeting. Expert presentation topics included the current state of research, potential regulatory challenges, WHO preferred product characteristics, modeling results of impact of vaccine implementation, epidemiology and natural history of HPV infection, immune responses related to viral clearance and/or precancer regression including potential biomarkers, and ethical considerations. Panel discussions were held to explore specific trial design recommendations to support the licensure process for two vaccine indications: (1) treatment of prevalent HPV infection or (2) treatment of cervical precancers. Discussion covered inclusion/exclusion criteria, study endpoints, sample size and power, safety, study length, and additional data needed, which are reported here. Further research of HPV natural history is needed to address identified gaps in regulatory guidance, especially for therapeutic vaccines intended to treat existing HPV infections.

2.
Prev Med Rep ; 35: 102368, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37680853

RESUMO

The 12th HPV Prevention and Control meeting was held on June 2-3, 2022, in Antwerp, Belgium. This technical meeting focused on several topics. This report summarises the discussions and lessons learned on two topics: an update on one-dose HPV vaccination studies and humoral immune responses upon HPV vaccination. Long-term follow-up studies from Costa Rica (eleven years) and India (ten years) report stable levels of antibodies after a single HPV vaccination. High vaccine effectiveness against incident persistent HPV 16/18 infection was seen in India (95.4%, 85.0-99.9) ten years postvaccination and in Kenya (97.5%, 81.7-99.7) eighteen months postvaccination, an important observation in a setting with a higher HPV prevalence. The potential impact of HPV vaccination using a one-dose schedule in India was modelled and showed that implementation of one-dose schedule can contribute towards achieving WHO Cervical Cancer elimination goals. These data support the WHO SAGE recommendations for adopting a one-dose schedule for females aged 9-20 years. Immunobridging studies were discussed during the meeting. General agreement was reached that when thoughtfully applied, they can support and accelerate the expanded use of HPV vaccine with new vaccine schedules, age cohorts, or vaccine formulations. Internationally standardised measurements of HPV immune responses important for the progress of HPV vaccinology field. Humoral immune responses upon HPV vaccination plateau at 24 months regardless of number of doses, therefore, data should be analysed after at least 24 months of follow-up to bridge studies accurately.

3.
Elife ; 122023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37070731

RESUMO

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally.


Assuntos
COVID-19 , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/diagnóstico , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Detecção Precoce de Câncer
4.
Vaccine ; 40(41): 5843-5855, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-36008233

RESUMO

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Adolescente , Detecção Precoce de Câncer , Feminino , Humanos , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Saúde Pública , Encaminhamento e Consulta , Neoplasias do Colo do Útero/diagnóstico , Organização Mundial da Saúde
5.
Mol Pharm ; 19(7): 2549-2563, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35583476

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by increased levels of desmoplasia that contribute to reduced drug delivery and poor treatment outcomes. In PDAC, the stromal content can account for up to 90% of the total tumor volume. The complex interplay between stromal components, including pancreatic cancer-associated fibroblasts (PCAFs), and PDAC cells in the tumor microenvironment has a significant impact on the prognoses and thus needs to be recapitulated in vitro when evaluating various treatment strategies. This study is a systematic evaluation of photodynamic therapy (PDT) in 3D heterotypic coculture models of PDAC with varying ratios of patient-derived PCAFs that simulate heterogeneous PDAC tumors with increasing stromal content. The efficacy of antibody-targeted PDT (photoimmunotherapy; PIT) using cetuximab (a clinically approved anti-EGFR antibody) photoimmunoconjugates (PICs) of a benzoporphyrin derivative (BPD) is contrasted with that of liposomal BPD (Visudyne), which is currently in clinical trials for PDT of PDAC. We demonstrate that both Visudyne-PDT and PIT were effective in heterotypic PDAC 3D spheroids with a low stromal content. However, as the stromal content increases above 50% in the 3D spheroids, the efficacy of Visudyne-PDT is reduced by up to 10-fold, while PIT retains its efficacy. PIT was found to be 10-, 19-, and 14-fold more phototoxic in spheroids with 50, 75, and 90% PCAFs, respectively, as compared to Visudyne-PDT. This marked difference in efficacy is attributed to the ability of PICs to penetrate and distribute homogeneously within spheroids with a higher stromal content and the mechanistically different modes of action of the two formulations. This study thus demonstrates how the stromal content in PDAC spheroids directly impacts their responsiveness to PDT and proposes PIT to be a highly suited treatment option for desmoplastic tumors with particularly high degrees of stromal content.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Fotoquimioterapia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Microambiente Tumoral , Verteporfina , Neoplasias Pancreáticas
6.
Cancer Epidemiol Biomarkers Prev ; 31(5): 1052-1057, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35244674

RESUMO

BACKGROUND: It is unknown whether reactivation of human papillomavirus (HPV) after latency occurs in the anus. We measured incidence and predictors of incident anal HPV in sexually inactive gay and bisexual men (GBM) as a surrogate of HPV reactivation. METHODS: The Study of the Prevention of Anal Cancer collected data on sexual behavior, anal cytology, HPV DNA, histology and HPV serology. HPV incidence during periods when zero sexual partners were reported in the last six months at both the current and previous annual visit ("no sexual activity") was analyzed by Cox regression using the Wei-Lin-Weissfeld method to determine univariable predictors. RESULTS: Of 617 men enrolled, 525 had results for ≥2 visits, of whom 58 (11%) had ≥ one period of "no sexual activity". During sexually inactive periods, there were 29 incident high risk HPV infections in 20 men, which occurred more commonly in older men (Ptrend = 0.010), HIV-positive men (HR = 3.12; 95% CI, 0.91-16.65), longer duration of HIV (Ptrend = 0.028), history of AIDS defining illness (P = 0.010), lower current (P = 0.010) and nadir CD4 count (P = 0.014). For 18 of 29 infections with available results, 12 men remained type-specific HRHPV L1 seronegative. None were consistently seropositive. A new diagnosis of HSIL occurred in only two men, caused by an HPV type other than the incident type. CONCLUSIONS: Our findings suggest that in sexually inactive GBM, anal HRHPV incidence is relatively common, and is associated with increasing age and immune dysfunction, a pattern consistent with HPV reactivation. IMPACT: Reactivation of anal HPV may occur.


Assuntos
Alphapapillomavirus , Doenças do Sistema Imunitário , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Idoso , Canal Anal , Biomarcadores , Feminino , Humanos , Masculino , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Comportamento Sexual
7.
Prev Med ; 156: 106960, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35065979

RESUMO

The global confrontation with COVID-19 has not only diverted current healthcare resources to deal with the infection but has also resulted in increased resources in the areas of testing and screening, as well as educating most of the global public of the benefits of vaccination. When the COVID-19 pandemic eventually recedes, the opportunity must not be missed to ensure that these newly created resources are maintained and redeployed for use in testing and immunisation against other vaccine-preventable infectious diseases. A notable example is infection by human papillomavirus (HPV), the commonest sexually transmitted human virus and the leading cause of a variety of cancers in both men and women, such as cervical, head and neck, anal, vaginal, vulvar and penile cancers. The most important is cervical cancer, the objective of the global elimination goals targeting the vaccination of young female and male adolescents, screening all women and treatment of all infected women. As the campaigns to control SARS-CoV-2, the eradication of HPV-induced cancers also relies on effective prevention and control programs. The lessons learned and the technical, logistical and human resources which have been established to combat COVID-19 by vaccination and testing must be applied to the eradication of other infections which affect the global population. This commentary summarizes the opportunities that the COVID-19 pandemic has created for HPV prevention and control, lists the already available tools for HPV control, and emphasizes the potential public health threats amidst the ongoing COVID-19 pandemic.


Assuntos
Alphapapillomavirus , COVID-19 , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Adolescente , COVID-19/prevenção & controle , Feminino , Humanos , Masculino , Pandemias/prevenção & controle , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/uso terapêutico , SARS-CoV-2 , Neoplasias do Colo do Útero/diagnóstico , Vacinação
8.
Curr Opin Virol ; 51: 106-110, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34628358

RESUMO

The ability to establish long term persistent infection is a feature of human papillomaviruses. The available evidence is that this ability is a consequence of a complex local immune milieu whereby innate immune receptors and signalling pathway cascades are inhibited by HPV early proteins resulting in failure of dendritic cell maturation, antigen processing and presentation and activation of cytotoxic antigen specific T cell responses. The development of cutaneous and mucosal infection models with the mouse papillomavirus MmuPV1 and the access to multiple gene deficient strains is providing the frame work to dissect the mechanisms underlying these complex host virus interactions.


Assuntos
Interações entre Hospedeiro e Microrganismos/imunologia , Evasão da Resposta Imune , Papillomaviridae/imunologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Infecção Persistente/virologia , Animais , Apresentação de Antígeno , Células Dendríticas , Humanos , Infecção Persistente/imunologia , Linfócitos T
9.
BMC Proc ; 15(Suppl 7): 16, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384438

RESUMO

For more than a decade human papillomavirus (HPV) vaccine have been implemented in most high-income countries, and more recently also in several low- and middle-income countries. The vaccines are safe and their impact and effectiveness in preventing HPV vaccine type infection and associated diseases has been thoroughly established. Currently, the primary recommended cohorts for immunisation are adolescents, 9-15 years of age but HPV is an ubiquitous infection that is mainly (but not exclusively) sexually transmitted. Sexually active adults remain susceptible to infection and continued transmission of the virus, representing a reservoir of infection in the population. A recent meeting, conducted by the HPV Prevention and Control Board (HPV-PCB), reviewed the current status of HPV vaccination of adults, discussed limitations, challenges and benefits of HPV vaccination of adults, evaluated the effectiveness of HPV vaccination after treatment of post cervical cancer and precancerous lesions, and discussed the potential impact of adult vaccination on cervical cancer elimination strategies in light of the current and future HPV vaccine shortage. HPV-PCB is an independent multidisciplinary board of international experts that disseminates relevant information on HPV to a broad array of stakeholders and provides guidance on strategic, technical and policy issues in the implementation of HPV prevention and control programs. The HPV-PCB concluded that, given the current data available on adult HPV vaccination and the ongoing vaccine supply constraints, it is too early to implement routine vaccination of adults. Many research gaps need to be filled before we have a better understanding of the efficacy and broader public health impact of HPV vaccination in adult women.

11.
Vaccine ; 39(32): 4419-4422, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34183205

RESUMO

BACKGROUND: Recommendations for human papillomavirus vaccination have relied on immunogenicity studies and efficacy results derived from adult women. Insufficient information exists regarding HPV effectiveness in vaccinated girls as they become sexually active, regardless of dose scheme. We aimed to compare the prevalence of high-risk HPV between unvaccinated and vaccinated young women eight years after immunization. METHODS: After eight years, we recontacted women who received two-dose of bivalent or three-dose-either bivalent or quadrivalent-, HPV vaccine when aged 9-10 years-old as part of a clinical trial. Additionally, we recruited a contemporaneous unvaccinated woman group for comparison. Only those sexually active were included. High-risk HPV DNA was determined in urine samples and compared across groups. RESULTS: The prevalence of HPV16/18 types was 6.8% (95 %CI 3.2-14.1%) in the unvaccinated (n = 6/88), 1.1% (95 %CI 0.2-5.8%) in the three-dose (n = 1/93), and 0.0% (95 %CI 0.0-7.0%) in the two-dose group (n = 0/51). CONCLUSION: HPV vaccination, with two-dose of bivalent or three-dose schemes-either with the bivalent or quadrivalent vaccine-, was associated with a lower prevalence of HPV16/18 types eight years after primary immunization.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adulto , Criança , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Prevalência , Vacinação
12.
Prev Med ; 144: 106321, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33678229

RESUMO

Prophylactic HPV vaccination has been a great public health success. For >20 years, clinical trials were conducted with the 2-, 4-, and/or 9-valent vaccines in young-adult females, mid-adult women, males, and adolescents. In all studies, the vaccines were highly efficacious, immunogenic, and well tolerated. Following vaccine licensure and utilization in national vaccine programs globally (real-world settings primarily in high income countries), numerous studies demonstrated that the vaccines continue to have an excellent safety profile and have dramatically reduced the incidence of genital warts, HPV vaccine-type prevalence, and precancerous lesions. Thirty-eight clinical trials with the currently licensed HPV vaccines are ongoing. Key questions being addressed in new trials include: efficacy against persistent infection and immunogenicity of a 1-dose regimen; efficacy of 3 doses in 20-45-year-old females; use in postpartum women and immunocompromised individuals (HIV, liver and kidney transplants); dose sparing via intradermal administration; use in combination with a PD1 monoclonal antibody in patients with cervical cancer; impact on recurrent disease in women undergoing cervical conization; persistence of protection; and use to prevent oropharyngeal cancer. Additional clinical research that should be conducted includes: long-term follow-up, particularly of 1- and 2-dose regimens; further evaluation of flexible 2-dose regimens; immunogenicity of 1- or 2-dose regimens in persons ≥15 years old and immunocompromised populations; safety and immunogenicity of 1 or 2 doses in children <9 years old; assessment of the vaccine in the prevention of transmission; interchangeability with newer HPV vaccines; additional concomitant use studies; and prevention of penile cancer and recurrent respiratory papillomatosis.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Infecções Respiratórias , Neoplasias do Colo do Útero , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Saúde Pública , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem
13.
Vaccine ; 39(16): 2224-2236, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33744051

RESUMO

BACKGROUND: The extent of cross-protection provided by currently licensed bivalent and quadrivalent HPV vaccines versus direct protection against HPV 31-, 33-, 45-, 52-, and 58-related disease is debated. A systematic literature review was conducted to establish the duration and magnitude of cross-protection in interventional and observational studies. METHODS: PubMed and Embase databases were searched to identify randomized controlled trials (RCT) and observational studies published between 2008 and 2019 reporting on efficacy and effectiveness of HPV vaccines in women against non-vaccine types 31, 33, 45, 52, 58, and 6 and 11 (non-bivalent types). Key outcomes of interest were vaccine efficacy against 6- and 12-month persistent infection or genital lesions, and type-specific genital HPV prevalence or incidence. RCT data were analyzed for the according-to-protocol (bivalent vaccine) or negative-for-14-HPV-types (quadrivalent vaccine) efficacy cohorts. RESULTS: Data from 23 RCTs and 33 observational studies evaluating cross-protection were extracted. RCTs assessed cross-protection in post-hoc analyses of small size subgroups. Among fully vaccinated, baseline HPV-naïve women, the bivalent vaccine showed statistically significant cross-protective efficacy, although with wide confidence intervals, against 6-month and 12-month persistent cervical infections and CIN2+ only consistently for HPV 31 and 45, with the highest effect observed for HPV 31 (range 64.6% [95% CI: 27.6 to 83.9] to 79.1% [97.7% CI: 27.6 to 95.9] for 6-month persistent infection; maximal follow-up 4.7 years). No cross-protection was shown in extended follow-up. The quadrivalent vaccine efficacy reached statistical significance for HPV 31 (46.2% [15.3-66.4]; follow-up: 3.6 years). Similarly, observational studies found consistently significant effectiveness only against HPV 31 and 45 with both vaccines. CONCLUSIONS: RCTs and observational studies show that cross-protection is inconsistent across non-vaccine HPV types and is largely driven by HPV 31 and 45. Furthermore, existing data suggest that it wanes over time; its long-term durability has not been established.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Proteção Cruzada , Feminino , Humanos , Infecções por Papillomavirus/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Vaccine ; 39(16): 2214-2223, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33658126

RESUMO

INTRODUCTION: Studies on the cross-protective effect of HPV bivalent and quadrivalent vaccines demonstrated inconsistent findings against additional HPV types covered by the nonavalent vaccine. The objective of this study was to conduct a systematic literature review to assess the consistency and durability of the cross-protective neutralizing antibody immune responses of the currently licensed bivalent and quadrivalent vaccines to non-vaccine HPV types targeted by the nonavalent vaccine (HPV 6, 11, 31, 33, 45, 52, and 58). METHODS: PubMed and EMBASE databases were searched from 2008 to 2019 to identify studies reporting antibody/immune response after vaccination with either the bivalent, quadrivalent, or nonavalent vaccine. Key outcomes were seroconversion, seropositivity or geometric mean titers against HPV types 6, 11, 31, 33, 45, 52, and 58. RESULTS: Eighteen publications met inclusion criteria, reporting on 14 interventional and five observational studies. Across all studies, immune responses to non-vaccine high-risk HPV types after bivalent vaccination were higher than baseline or quadrivalent vaccine. Nonavalent vaccine elicited near total seroconversion to HPV types 31, 33, 45, 52, and 58, with seropositivity remaining near 100% up to 24 months post-dose 1. In contrast, bivalent and quadrivalent vaccination resulted in lower seroconversion levels for non-vaccine types, which waned over time. CONCLUSIONS: The cross-protection antibody/immune response among participants having received all three doses of bivalent or quadrivalent vaccine is not comparable to the specific response elicited by HPV vaccine types. Even in cases where a statistically significant cross-reactive immunological response is reported, long-term data on the duration of the response beyond two years are very limited. Further, the lack of a standard for assays limits comparability of results between studies.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Anticorpos Neutralizantes , Proteção Cruzada , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Humanos , Infecções por Papillomavirus/prevenção & controle , Vacinas Combinadas
15.
Br J Cancer ; 124(4): 831-841, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33257839

RESUMO

BACKGROUND: The host adaptive immune response helps determine which cervical HPV infections persist and progress to precancer and cancer, and systematic characterisation of T-cell infiltration would help inform key steps in cervical carcinogenesis. METHODS: A systematic review and meta-analysis were conducted of infiltrating T-cells in normal cervix, low-grade lesions, high-grade lesions, and invasive cancers including epithelial, stromal, and total tissue and the following markers: CD3, CD4, CD8, FoxP3, CD25, and the CD4:CD8 ratio. An additional qualitative review summarised longitudinal data on associations between infiltrating T-cells and cervical disease persistence, regression, progression, or prognosis. RESULTS: There were fewer CD3+, CD4+, and CD8+ cells in cervical lesions and more cells in cancers compared to normal epithelium. FoxP3 and CD25+ regulatory T-cell infiltration is high in persistent and precancerous lesions, and longitudinal data show improved outcomes with lower regulatory T-cell levels. CONCLUSIONS: Successful immune evasion may reduce T-cell infiltration in HPV infected and precancerous epithelium, while invasive cancers are highly immunogenic, and regulatory T-cell infiltration increases with cervical disease progression. Understanding these factors may have prognostic value and could aid in novel treatment development and clinical guidelines, but published data are highly heterogeneous and leave important gaps to be filled by future studies.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Infecções por Papillomavirus/imunologia , Linfócitos T/imunologia , Neoplasias do Colo do Útero/imunologia , Carcinogênese/imunologia , Carcinogênese/patologia , Feminino , Humanos , Linfócitos do Interstício Tumoral/patologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Linfócitos T/patologia , Neoplasias do Colo do Útero/patologia
17.
Expert Rev Vaccines ; 18(12): 1309-1316, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31847625

RESUMO

Introduction: The randomized control trials (RCTs) that resulted in licensure of HPV VLP vaccines used a traditional prime, prime-boost schedule for a subunit protein vaccine. These vaccines delivered predominantly to 9-14-year-old females with this schedule have been shown to be highly effective against vaccine HPV-type disease (CIN and genital warts) and infection. A two-dose prime-boost schedule is immunologically non-inferior to 3 doses in 9-14-year-olds and is currently widely adopted. However, even with a reduced dosage schedule, these vaccines are expensive to buy and expensive and logistically complex to deliver especially in low resource countries that bear the major burden of cervical cancer the most prevalent of HPV caused cancers.Areas covered: Observational studies and post hoc analysis of RCTs show that 1 dose, although immunologically inferior to 2 and 3 doses, is as effective at preventing persistent infection with vaccine HPV types at least for 7-10 years. To address the issue of alternative dosage schedules that include 1 dose either as a single dose or extended 1 + 1 with the second dose 3-5 years post-first dose are under investigation in RCTs.Expert opinion: Since, in the short term, vaccine supplies are constrained and will impact on the ability of countries to implement HPV vaccine programs: the challenges and opportunities of the alternative approaches in this scenario are discussed.


Assuntos
Esquemas de Imunização , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Humanos , Neoplasias/prevenção & controle , Infecções por Papillomavirus/complicações , Resultado do Tratamento
18.
J Infect Dis ; 219(1): 41-49, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085139

RESUMO

Background: There are limited data regarding the duration of immunity induced by different human papillomavirus (HPV) vaccination schedules and the immunogenicity of a booster dose of both bivalent HPV vaccine (bHPV) or quadrivalent HPV vaccine (qHPV). Methods: Follow-up of a nonrandomized clinical trial to evaluate the 5-year antibody persistence of the bHPV in girls (age, 9-10 years) and women (age, 18-24 years). Noninferiority of the 2-dose versus 3-dose schedule among girls was evaluated at months 54 (n = 639) and 64 (n = 990). Girls vaccinated with a 2-dose schedule of bHPV or qHPV received a booster dose of either vaccine at month 61. Immunogenicity was measured using a virus-like particle-based enzyme-linked immunosorbent assay. Geometric mean titers (GMTs) for HPV16/18 were estimated after stratification by vaccination schedule and age group. Results: At months 54 and 64, the 2-dose schedule remained noninferior to the 3-dose schedule. GMTs remained above natural infection levels across all age groups up to 64 months. After the booster, anti-HPV16/18 GMTs increased exponentially with the same pattern, regardless of vaccine administered. No safety concerns were identified with the booster dose. Conclusions: A 2-dose schedule is highly immunogenic in girls, suggesting a high immune memory. Thus, a booster dose is likely to be unprofitable, considering the low global immunization coverage. Clinical Trials Registration: NCT01717118.


Assuntos
Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Imunização Secundária , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vacinação , Adolescente , Anticorpos Antivirais/sangue , Criança , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Esquemas de Imunização , Ensaios Clínicos Controlados não Aleatórios como Assunto , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/sangue , Adulto Jovem
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