RESUMO
Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Infecções por Papillomavirus , Humanos , China/epidemiologia , Estudos Soroepidemiológicos , Masculino , Feminino , Anticorpos Antivirais/sangue , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Adulto , Pessoa de Meia-Idade , Anticorpos Neutralizantes/sangue , Adulto Jovem , Idoso , Adolescente , Criança , Imunoglobulina G/sangue , Pré-Escolar , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Papillomaviridae/imunologia , Papillomaviridae/genética , Papillomaviridae/classificação , Testes de Neutralização , Vacinação/estatística & dados numéricos , Idoso de 80 Anos ou mais , Lactente , Papillomavirus HumanoRESUMO
Cervical cancer is a significant health concern for women worldwide, with human papillomavirus (HPV) being the primary cause. This study aimed to assess Saudi women's awareness and knowledge of HPV, determine their information sources, and evaluate their intention to receive the HPV vaccine. A questionnaire-based survey was conducted among 654 Saudi females aged 18 to 60 years from January to May 2023. The results revealed that 60.85% of the participants had heard about HPV, but only 8.25% had received the HPV vaccination. Despite the low vaccination rate, 71.11% of the respondents expressed willingness to receive the vaccine. Educational level was the significant predictor of the vaccine awareness and acceptance. The internet and social media were the most prevalent sources of information about HPV. The study highlights the need for additional education about HPV-related diseases and vaccination among Saudi women. Although there is a high level of HPV vaccine acceptance, the lack of knowledge suggests that targeted educational interventions are necessary to increase awareness and promote vaccination uptake. These findings can inform public health strategies to reduce the burden of cervical cancer in Saudi Arabia through improved HPV vaccination coverage and education.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Aceitação pelo Paciente de Cuidados de Saúde , Neoplasias do Colo do Útero , Humanos , Feminino , Vacinas contra Papillomavirus/administração & dosagem , Infecções por Papillomavirus/prevenção & controle , Arábia Saudita , Adulto , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Inquéritos e Questionários , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Vacinação/psicologia , Vacinação/estatística & dados numéricos , Papillomaviridae/imunologia , Papillomavirus HumanoRESUMO
Objective: The objective of the study is to validate a new human papillomavirus (HPV) L1 high-risk specific serological assay in a case-control study. Methods: Serum samples of 138 patients (cervical intraepithelial neoplasia (CIN) 1, 2, and 3 and cervical cancer), 21 vaccinees, and 246 female controls were tested for the presence of HPV L1 high-risk specific antibodies. Results: HPV L1 high-risk antibodies were detected in 100% of the CIN1 and 2, 86.6% of the CIN3 and 82.4% of the cervical cancer cases, 100% of the vaccinees, and 3.9% of the female controls. Area under the curve (AUC) was calculated with 0.91 for controls versus CIN2+, 0.923 for controls versus CIN1+, and 0.968 for controls versus CIN1/2. Conclusion: The HPV L1 high-risk specific serological lateral flow rapid test shows promising data in the field of early detection of HPV high-risk induced cervical cancer and its precursor lesions. This easy-to-use, robust, and affordable approach could offer a chance to reach women in low- or middle-income countries (LMICs) that could not be reached by HPV molecular testing-based cervical cancer screening programs.
Assuntos
Anticorpos Antivirais , Detecção Precoce de Câncer , Infecções por Papillomavirus , Sensibilidade e Especificidade , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/diagnóstico , Estudos de Casos e Controles , Adulto , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Anticorpos Antivirais/sangue , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/diagnóstico , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Proteínas Oncogênicas Virais/imunologia , Proteínas do Capsídeo/imunologia , Adulto Jovem , Papillomaviridae/imunologia , Papillomaviridae/isolamento & purificação , IdosoRESUMO
Human Papillomavirus (HPV), an extensive family of DNA viruses, manifests as a persistent global health challenge. Persistent HPV infection is now firmly established as a significant aetiological factor for a spectrum of malignancies. In this review, we examine the latest insights into HPV biology and its intricate relationship with the host. We delve into the complex dynamics of co-infections involving HPV alongside other viruses, such as HIV, EBV, and HSV, as well as the burgeoning role of the microbiome in cancer development. We also explore recent advancements in understanding the specific contributions of HPV in the development of various cancers, encompassing cancers of the anogenital region, head and neck, as well as breast, lung, and prostate. Moreover, we focus on the current preventive strategies, including vaccination and screening methods, and therapeutic interventions that range from traditional approaches like surgery and chemotherapy to emerging modalities such as targeted therapies and immunotherapies. Additionally, we provide a forward-looking view on the future directions of HPV research, highlighting potential areas of exploration to further our understanding and management of HPV and its associated cancers. Collectively, this review is positioned to deepen readers' understanding of HPV biology and its complex interplay with cancer biology. It presents innovative strategies for the prevention, management, and therapeutic intervention of HPV-associated malignancies.
Assuntos
Neoplasias , Papillomaviridae , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/etiologia , Neoplasias/virologia , Papillomaviridae/fisiologia , Papillomaviridae/imunologia , Coinfecção , Interações Hospedeiro-Patógeno/imunologia , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/uso terapêutico , Animais , Papillomavirus HumanoRESUMO
Validation of bioanalytical methods is crucial, especially in the pharmaceutical industry, to determine their suitability for specific purposes and the accuracy of analytical results. The pseudovirion-based neutralization assay (PBNA) is considered the gold standard for detecting and quantifying neutralizing antibodies against human papillomavirus in vaccine development for disease prevention. This paper introduces an improved triple-color PBNA method, capable of simultaneous detection of two or three human papillomavirus (HPV types for use in the development of a 14-valent HPV vaccine candidate. The primary objective was to comprehensively validate the triple-color PBNA method for general vaccine immunogenicity assays. Results show that the method has good specificity, accuracy, precision, linearity, robustness, and applicability. This innovative triple-color PBNA offers an improved approach for large-scale immunogenicity assessment in vaccine development. This study lays a solid foundation that can serve as a guiding paradigm for assessing vaccine responses in preclinical and clinical phases, providing valuable insights to the field.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Testes de Neutralização , Vacinas contra Papillomavirus , Humanos , Testes de Neutralização/métodos , Vacinas contra Papillomavirus/imunologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Vacinas Sintéticas/imunologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Imunogenicidade da Vacina , Papillomaviridae/imunologia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Patient-centered communication has emerged as a potent strategy for increasing vaccine uptake. Drawing on evidence-based paths established from previous studies, our study examines the relationship between patient-centered communication, HPV knowledge and perceived HPV vaccine effectiveness. We also explored the sociodemographic factors impacting patient-centered communication, HPV knowledge and perceived HPV vaccine effectiveness. METHODS: We analyzed data from the Health Information National Trends Survey (HINTS) 5, Cycle 1, ran Structural equation modeling (SEM) to test the pathways in our conceptual framework. RESULTS: Our sample comprised 2522 adults aged 18-79 (mean age 47.98 years) who were predominantly Non-Hispanic White (67.65%), female (53.31%), and heterosexual (95.12%). The model fit statistics for the final structural model indicated a good fit [RMSEA= 0.039, CFI=0.99 TLI= 0.99, and SRMR =0.070]. The path linking patient-centered communication to HPV knowledge (ß=0.011, p<0.05), and the knowledge-mediated path linking patient-centered communication to HPV vaccine effectiveness (ß=0.007, p<0.05) were found to be statistically significant. CONCLUSION: HPV researchers must delve deeper into patient-centered communication practices to improve vaccine uptake. Tailoring conversations to individual needs and preferences is key to enhancing HPV knowledge, and ultimately improve perceptions of HPV vaccine effectiveness and increase its acceptability.
Assuntos
Comunicação , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Vacinas contra Papillomavirus/administração & dosagem , Feminino , Infecções por Papillomavirus/prevenção & controle , Adulto , Pessoa de Meia-Idade , Masculino , Adolescente , Adulto Jovem , Idoso , Assistência Centrada no Paciente , Seguimentos , Análise de Classes Latentes , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Prognóstico , Vacinação/psicologia , Papillomaviridae/imunologia , Inquéritos e QuestionáriosRESUMO
Human papillomavirus (HPV) has been linked to the development of various cancers, including head and neck, cervical, vaginal, penile, and anal cancers. The development of therapeutic vaccines against HPV-positive tumors is crucial for protecting individuals already infected with HPV, preventing tumor progression, and effectively treating the disease. The HPV therapeutic peptide-based vaccines demonstrate specificity and safety advantages by targeting specific epitopes while minimizing the risk of allergic or autoimmune reactions. However, HPV therapeutic peptide-based vaccines typically lack immunogenicity and frequently fail to induce effective immune responses. Therefore, there is a need for more effective approaches to improve the immunogenicity of HPV peptide-based vaccines. Here, we review relevant research and possible uses for increasing the immunogenicity and therapeutic efficacy of HPV peptide-based vaccines through combined therapy and improved delivery strategies. Additional research is necessary to validate the application of combination therapy and delivery strategy modifications as standard treatment approaches for HPV therapeutic peptide-based vaccines.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vacinas de Subunidades Antigênicas , Humanos , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/terapia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Terapia Combinada/métodos , Papillomaviridae/imunologia , Imunogenicidade da VacinaRESUMO
Most national prophylactic HPV vaccination programs started in approximately 2008, with either the bivalent Cervarix HPV16/18 or quadrivalent Gardasil (HPV6/11/16/18) vaccines, which were then followed by introduction of the nonavalent Gardasil 9 (HPV6/11/16/18/ 31/33/45/52/58) vaccine from 2015. Since that time, these products have demonstrated their ability to prevent infection with vaccine-covered HPV types and subsequent development of HPV-related cervical and genital pathologies. The data indicate that vaccination of young girls prior to sexual debut is more effective than vaccination of older HPV+ve women. Although some studies have shown a decline in the prevalence of vaccine-covered HPV types, there are national and regional differences in overall vaccine efficacy. Furthermore, several recently published studies show an increase in the prevalence of non-vaccine-covered HPV types in vaccinated populations, which is indicative of HPV type-replacement. It is also notable that vaccine-related changes in HPV type prevalence spread between vaccinated and unvaccinated women at the same geographical location-presumably via sexual transmission. In conclusion, it is not yet clear what effect dissemination of vaccine-associated changes in HPV type prevalence will have on vaccine efficacy and cervical pathology, particularly in mixed populations of vaccinated and unvaccinated women. However, it is very clear these observations do underscore the need for long-term continuation of cervical screening combined with regular reassessment of testing practices.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Prevalência , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , Colo do Útero/virologia , Colo do Útero/patologia , Vacinação , Papillomaviridae/imunologia , Papillomaviridae/classificação , Papillomaviridae/genética , Adolescente , Eficácia de VacinasRESUMO
Propensity to develop cervical cancer (CC) in human papilloma virus (HPV) infected individual could potentially involve the impaired immune functioning. Several stages of HPV surveillance by immune cells in tumor micro-environment (TME) is regulated mainly by transforming growth factor-beta (TGF-ß) and is crucial for the establishment of CC. The role of TGF-ß in the initiation and progression of CC is very complex and involve different suppressor of mothers against decapentaplegic homolog (SMAD) dependent and SMAD independent signaling mechanism(s). This review summarizes the handling of HPV by immune cells such as T lymphocytes, B lymphocytes, natural killer cells (NK), dendritic cells (DC), monocytes, macrophages, myeloid derived suppressor cells (MDSC) and their regulation by TGF-ß. The hijack mechanisms adapted by HPV to evade this surveillance process is discussed. Biomarkers indicating the stages of CC and immune checkpoints that can be targeted for improved outcome are included for immune-based theragnostics. This review also addresses the direct actions of TGF-ß on CC cells and tumor/immune cell interactions. Therapies focused on targeting TGF-ß using small molecule inhibitors, monoclonal antibodies and TGF-ß chimeric antigen receptor (CAR)T cells are collated to understand the current strategies related to TGF-ß in the management of CC.
Assuntos
Infecções por Papillomavirus , Fator de Crescimento Transformador beta , Microambiente Tumoral , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/imunologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/imunologia , Microambiente Tumoral/imunologia , Feminino , Infecções por Papillomavirus/imunologia , Animais , Papillomaviridae/imunologiaRESUMO
Oral HPV infection is the main risk factor for the development of oropharyngeal carcinoma. Men who have sex with men (MSM), especially if living with HIV (PLWH), are at increased risk of infection and consequently of cancer development. Aim of this study is to evaluate the impact of nonavalent vaccine on oral HPV infection in a cohort of MSM and transgender women (TGW). This prospective study included all MSM and TGW who started nonavalent HPV vaccination from May 2019 to September 2021. Oral rinse was collected before each vaccine administration and after six months of follow up. Descriptive statistics were used. Kaplan Meier probability curves and Cox regression models for HPV acquisition and clearance were calculated. The analysis included 211 individuals (202 MSM and 9 TGW). PLWH were 138 (65.4%). Baseline oral rinse was positive in 30 subjects (14.2%). Positivity rate did not change over time (p = 0.742), even when restricting the analysis only to high-risk genotypes (p = 0.575) and to genotypes covered by vaccine (p = 0.894). The risk to acquire HPV infection was 12.8% at one year and 33.4% at two years after vaccination. The probability to clear the infection was 67.6% at one year and 87.9% at two years. HIV infection had no impact on vaccine efficacy. Age above 45 years was the only factor associated to HPV acquisition (aHR 4.06, 95% CI 1.03-15.98, p = 0.045). Prevalence of oral HPV infection was higher in PLWH, but HIV had no impact on viral clearance or acquisition after vaccination.
Assuntos
Homossexualidade Masculina , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Pessoas Transgênero , Humanos , Masculino , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Pessoas Transgênero/estatística & dados numéricos , Adulto , Homossexualidade Masculina/estatística & dados numéricos , Feminino , Vacinas contra Papillomavirus/administração & dosagem , Pessoa de Meia-Idade , Vacinação/estatística & dados numéricos , Adulto Jovem , Papillomaviridae/genética , Papillomaviridae/imunologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Fatores de Risco , Boca/virologiaRESUMO
The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Vacinas contra Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/imunologia , Feminino , Desenvolvimento de Vacinas , Adjuvantes Imunológicos , Animais , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologia , Papillomaviridae/imunologia , Eficácia de VacinasRESUMO
OBJECTIVES: This study aimed to assess current vaccination rates among health care workers at risk for occupational human papillomavirus (HPV) exposure and explore factors that influence decisions about HPV vaccination. DESIGN: Using a mixed-methods design, this study included a questionnaire and qualitative focus groups. SETTING: The study took place at an academic medical center. PARTICIPANTS: Participants were 37 health care professionals in occupations at risk for workplace HPV exposure. MAIN OUTCOME MEASURES: The primary qualitative outcome measured was HPV vaccination status. The primary qualitative outcomes assessed were perceptions of occupational HPV exposure risk, protective measures, and HPV vaccination. RESULTS: Most participants were female (86.5%, n = 32) and younger than 35 years (51.4%; n = 19) and therefore would have been eligible to receive the HPV vaccine series as a teenager or young adult. Nearly two-thirds (67.6%; n = 25) of participants had received the HPV vaccine; of those, half were vaccinated as teenagers (52%; n = 13). One-third (n = 4) of those vaccinated as adults reported vaccination due to workplace HPV exposure. Focus groups revealed themes consistent with the Health Belief Model. Most participants recognized their risk of aerosolized HPV exposure in the workplace but felt uneducated about occupational exposure risk and protective measures. Many participants recognized risk of exposure through surgical smoke but perceived that risk was stratified by medical specialty, proximity to surgical field, and personal protective equipment use. Many participants had some level of concern for head and neck lesions with exposure to aerosolized HPV. Most participants recognized the need to protect themselves against workplace HPV exposure. Those who were vaccinated felt that they were better protected against HPV exposure. Almost all participants said that they had not received formal education on workplace HPV exposure risk. Many participants voiced perceived barriers to HPV vaccination. CONCLUSION: Health care workers encounter the HPV virus in a myriad of fields and procedures. Our mixed-methods study demonstrated that at-risk health care workers feel uninformed about their risk of HPV exposure in the workplace, availability of HPV vaccination, and appropriate protective equipment recommendations.
Assuntos
Grupos Focais , Pessoal de Saúde , Exposição Ocupacional , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vacinação , Humanos , Feminino , Masculino , Adulto , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/psicologia , Pessoal de Saúde/psicologia , Pessoal de Saúde/estatística & dados numéricos , Exposição Ocupacional/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Inquéritos e Questionários , Vacinação/psicologia , Vacinação/estatística & dados numéricos , Percepção , Pesquisa Qualitativa , Pessoa de Meia-Idade , Papillomaviridae/patogenicidade , Papillomaviridae/imunologia , Conhecimentos, Atitudes e Prática em Saúde , Papillomavirus HumanoRESUMO
Background: Women living with HIV/AIDS (WLHA) have an increased prevalence of high-risk HPV infection (HR-HPV) and cervical intraepithelial neoplasia (CIN) and a greater risk of cervical cancer despite access to a new generation of antiretroviral therapy. The aim of this study is to evaluate the concentrations of different cytokines involved in the local immune response in WLHA, which is fundamental for understanding the pathogenesis of HPV-related cancer in this population. Methods: IL-1ß, IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, IP-10, GM-CSF, and MIP-1α were investigated in the cervicovaginal lavage (CVL) of 106 WLHA attending at Hospital Universitario Professor Edgard Santos in Salvador, Bahia, Brazil, during the period December 2019 to April 2023 by Luminex®. All participants were also tested for Chlamydia trachomatis and Neisseria gonorrhoeae and underwent colposcopy, Pap smear, and Nugent score. HIV plasma viral load (VL) and CD4 cell count were performed for all WLHA. Results: In this study, 22.6% (24/106) of WLHA were infected with HR-HPV. A higher proportion of patients with HR-HPV (66.7%) had detectable levels of IL-10 than those negative ones (40.2%, p = 0.02). More premenopausal women had either IL-6 (51.4%) or IP-10 (58.3%) than those in menopausal status (26.5% for IL-6 and 32.4% for IP-10, p = 0.013 and p = 0.011, respectively). Vaginosis was negatively associated with detection of IP-10 (24.2% vs. 61.4%, p < 0.001) and INF-γ (39.4% vs. 68.6%, p = 0.005). A positive association was detected for IL-1ß (66.7 vs. 37.1%, p = 0.005) and IL-10 (63.6% vs. 37.1%, p = 0.01). VL and CD4 were not associated with the studied cytokines. Conclusion: We demonstrated a positive association between IL-10 and HPV infection in CVL, suggesting the predominance of the Th2 response in HIV/HPV co-infected patients. However, further studies with longer follow-up will be needed to evaluate the association of IL-10 with HPV infection, CIN, and cervical cancer in WLHA.
Assuntos
Citocinas , Infecções por HIV , Infecções por Papillomavirus , Humanos , Feminino , Infecções por HIV/imunologia , Infecções por HIV/complicações , Citocinas/metabolismo , Infecções por Papillomavirus/imunologia , Adulto , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Papillomaviridae/imunologia , Colo do Útero/imunologia , Colo do Útero/virologia , Colo do Útero/metabolismo , Brasil/epidemiologia , Carga Viral , Vagina/imunologia , Vagina/virologia , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologia , Papillomavirus HumanoAssuntos
Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Índia , Vacinas contra Papillomavirus/administração & dosagem , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinação/psicologia , Papillomaviridae/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Papillomavirus HumanoRESUMO
Neutralizing antibodies (NAbs) are considered the primary mechanism of vaccine-mediated protection against human papillomaviruses (HPV), the causative agent of cervical cancer. However, the minimum level of NAb needed for protection is currently unknown. The HPV pseudovirion-based neutralization assay (PBNA) is the gold standard method for assessing HPV antibody responses but is time-consuming and labor-intensive. With the development of higher valency HPV vaccines, alternative serological assays with the capacity for multiplexing would improve efficiency and output. Here we describe a multiplex bead-based immunoassay to characterize the antibody responses to the seven oncogenic HPV types (HPV16/18/31/33/45/52/58) contained in the current licensed nonavalent HPV vaccine. This assay can measure antibody isotypes and subclasses (total IgG, IgM, IgA1-2, IgG1-4), and can be adapted to measure other antibody features (e.g., Fc receptors) that contribute to vaccine immunity. When tested with serum samples from unvaccinated and vaccinated individuals, we found high concordance between HPV-specific IgG using this multiplex assay and NAbs measured with PBNA. Overall, this assay is high-throughput, sample-sparing, and time-saving, providing an alternative to existing assays for the measurement and characterization of HPV antibody responses.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Imunoglobulina G , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Anticorpos Antivirais/sangue , Imunoensaio/métodos , Feminino , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Imunoglobulina G/sangue , Papillomaviridae/imunologia , Papillomavirus HumanoRESUMO
BACKGROUND/AIM: Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is clinically and immunologically distinct from HPV-negative HNSCC. Herein, we investigated the presence of tumor antigens HPV E6/E7 and wild-type p53-specific T-cell responses, and the impact of immune checkpoint blockade in patients with HPV-positive HNSCC. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) from patients with HPV-positive HNSCC were stimulated with HPV E6/E7 or wild-type p53-derived peptide mixture and evaluated using the interferon-γ enzyme-linked immunosorbent spot assay. Flow cytometry was performed to analyze the proportion of T-cell subsets and T cells expressing immune checkpoint molecules. RESULTS: HPV E6/E7-specific T cells were detected in 22 (95.7%) of 23 patients, whereas wild-type p53-specific T cells were detected in 3 (15.0%) of 20 patients. Seven (43.8%) of 16 patients exhibited wild-type p53-specific T-cell responses, as determined using whole proteins instead of peptides. Immune checkpoint blockade enhanced wild-type p53-specific T-cell responses in 9 (45.0%) of 20 patients. Flow cytometric analysis of PBMCs revealed that responders exhibiting enhanced wild-type p53-specific T-cell responses following immune checkpoint blockade had a significantly higher proportion of Ki-67+CD4+ T cells, Ki-67+CD8+ T cells, regulatory T cells, PD-1+CD4+ T cells, and TIM-3+CD4+ T cells than non-responders. CONCLUSION: Our findings indicate that tumor antigen-specific T cells are present in the peripheral blood of patients with HPV-positive HNSCC. Blockade of checkpoint pathways can enhance T-cell responses in certain patients, probably via activated T cells, Tregs, and/or exhausted CD4+ T cells.
Assuntos
Neoplasias de Cabeça e Pescoço , Inibidores de Checkpoint Imunológico , Infecções por Papillomavirus , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/virologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Antígenos de Neoplasias/imunologia , Proteínas Oncogênicas Virais/imunologia , Proteína Supressora de Tumor p53/imunologia , Adulto , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Papillomaviridae/imunologia , Linfócitos T/imunologia , Papillomavirus HumanoRESUMO
Cervical cancer, along with other sexual and reproductive health and rights (SRHR) conditions, poses a significant burden in the Kingdom of Saudi Arabia (KSA). Despite the availability of effective preventive methods such as vaccinations, particularly against the Human Papillomavirus (HPV), awareness about such preventive methods and HPV vaccination remains alarmingly low in the KSA, even with governmental effort and support. While many women are aware of the risks, the uptake of the HPV vaccine remains below 10% (7.6%) at the country level. This highlights the urgent need for Knowledge, Attitude, and Practice (KAP) at the community level to raise awareness, dispel misconceptions, and empower women to embrace vaccinations. Additionally, there is a need to revitalize the cancer registry system to better track and monitor cervical cancer cases. This short communication aims to map these barriers while identifying opportunities for impactful research. Drawing from the scientific literature, government reports, and expert insights, we highlight the challenges surrounding the tackling of HPV. By exploring diverse sources of knowledge, this paper not only highlights current obstacles but also proposes actionable solutions for future interventions.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Vacinação , Humanos , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinas contra Papillomavirus/administração & dosagem , Feminino , Infecções por Papillomavirus/prevenção & controle , Arábia Saudita/epidemiologia , Vacinação/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde , Papillomaviridae/imunologiaRESUMO
Human papillomavirus (HPV) is a circular, double-stranded DNA virus and recognized as the most prevalent sexually transmitted infectious agent worldwide. The HPV life cycle encompasses three primary stages. First, the virus infiltrates the basal cells of the stratified epidermis. Second, there is a low-level expression of viral genes and preservation of the viral genome in the basal layer. Lastly, productive replication of HPV occurs in differentiated cells. An effective immune response, involving various immune cells, including innate immunity, keratinocytes, dendritic cells, and natural killer T cells, is instrumental in clearing HPV infection and thwarting the development of HPV-associated tumors. Vaccines have demonstrated their efficacy in preventing genital warts, high-grade precancerous lesions, and cancers in females. In males, the vaccines can also aid in preventing genital warts, anal precancerous lesions, and cancer. This comprehensive review aims to provide a thorough and detailed exploration of HPV infections, delving into its genetic characteristics, life cycle, pathogenesis, and the role of high-risk and low-risk HPV strains. In addition, this review seeks to elucidate the intricate immune interactions that govern HPV infections, spanning from innate immunity to adaptive immune responses, as well as examining the evasion mechanisms used by the virus. Furthermore, the article discusses the current landscape of HPV vaccines and common treatments, contributing to a holistic understanding of HPV and its associated diseases.
Assuntos
Papillomaviridae , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Feminino , Papillomaviridae/imunologia , Papillomaviridae/genética , Cobertura Vacinal , Neoplasias/imunologia , Neoplasias/terapia , Masculino , Imunidade Inata , Imunidade AdaptativaRESUMO
Loss of heterozygosity (LOH) has been reported to occur in HLA regions in cervical intraepithelial neoplasia (CIN) and cervical cancer. However, the details of how this is related to the progression of CIN have been unclear. In this study, we examined the human papillomavirus (HPV) antigen-presenting capacity of people with CIN and the significance of LOH of HLA class I in the progression of CIN. It was shown that differences in antigen-presenting capacity among each case depended on HLA types, not HPV genotypes. Focusing on the HLA type, there was a positive correlation between antigen-presenting capacity against HPV and the frequency of allelic loss. Furthermore, the lost HLA-B alleles had a higher HPV antigen-presenting capacity than intact alleles. In addition, frequency of LOH of HLA class I was significantly higher in advanced CIN (CIN2-3) than in cervicitis or early-stage CIN (CIN1): around half of CIN2-3 had LOH of any HLA class I. Moreover, the antigen-presenting capacity against E5, which is the HPV proteins that facilitate viral escape from this immune surveillance by suppressing HLA class I expression, had the most significant impact on the LOH in HLA-B. This study suggests that HPV evades immune surveillance mechanisms when host cells lose the capacity for antigen presentation by HLA class I molecules, resulting in long-term infection and progression to advanced lesions.
Assuntos
Antígenos de Histocompatibilidade Classe I , Perda de Heterozigosidade , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Feminino , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/genética , Apresentação de Antígeno/imunologia , Adulto , Alelos , Papillomaviridae/imunologia , Vigilância Imunológica , Pessoa de Meia-Idade , GenótipoRESUMO
The design of prophylactic and diagnostic tools specific to animal papillomaviruses is hampered by the difficulties of viral in vitro manipulation and by the scarce availability of dedicated biotechnological tools. This paper reports the production of Ovine Papillomavirus 3 (OaPV3)-based virus-like particles (OaPV3-VLPs) in the baculovirus system and their use to investigate host humoral immune response through the establishment of an indirect ELISA test., Polyclonal sera and monoclonal antibodies were generated against OaPV3-VLPs, and their isotype and reactivity were determined. Additionally, antibodies allowed OaPV3 detection in ovine squamous cell carcinoma (SCC) samples by immunohistochemistry. Results encourage the standardization of OaPV3-specific prophylactic and serological diagnostic tools, and open new perspectives for the study of host-viral interaction and SCC development.