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BPV-2 infection can cause bladder infections in cattle that, when associated with bracken fern consumption, can progress to cancerous bladder tumors and also present as bovine enzootic hematuria (BEH). This study aimed to evaluate the prolonged natural BPV-2 infection in the blood and urine of cattle, excluding bracken fern consumption. Thirteen Girolando papillomatosis-affected cattle with no bracken fern contact history were monitored for 20 months. Blood, urine, and wart samples were collected for BPV-2 detection and clinical laboratory analyses. All animals showed the presence of BPV-2 in papillomas and blood, and 92.85% showed BPV-2 in urine, suggesting viral dissemination in the urinary tract. Despite all animals being infected with BPV-2, none showed BEH signs during the study. Thus, it was observed that BPV-2 infection alone didn't induce BEH over 20 months, implying a complex interaction with environmental factors or genetic predisposition. This underlines bracken fern consumption's critical role in urinary bladder carcinogenesis. The study underscores BEH's pathogenesis complexity, advocating longitudinal studies to comprehend BPV-2's role fully.
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Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.
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Neoplasias da Mama , Infecções por Papillomavirus , Humanos , Brasil/epidemiologia , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias da Mama/virologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Papillomaviridae , Carga ViralRESUMO
Background and purpose: The employment of yeasts for biomedical purposes has become increasingly frequent for the delivery of prophylactic and therapeutic products. Its structural components, such as ß-glucans, mannan, and chitin, can be explored as immunostimulators that show safety and low toxicity. Besides, this system minimizes antigen degradation after administration, facilitating the delivery to the target cells. Review approach: This review sought to present molecules derived from yeast, called yeast shells (YS), and their applications as carrier vehicles for drugs, proteins, and nucleic acids for immunotherapy purposes. Furthermore, due to the diversity of information regarding the production and immunostimulation of these compounds, a survey of the protocols and immune response profiles generated was presented. Key results: The use of YS has allowed the development of strategies that combine efficiency and effectiveness in antigen delivery. The capsular structure can be recognized and phagocytized by dendritic cells and macrophages. In addition, the combination with different molecules, such as nanoparticles or even additional adjuvants, improves the cargo loading, enhancing the system. Activation by specific immune pathways can also be achieved by different administration routes. Conclusion: Yeast derivatives combined in different ways can increase immunostimulation, enhancing the delivery of medicines and vaccine antigens. These aspects, combined with the simplicity of the production steps, make these strategies more accessible to be applied in the prevention and treatment of various diseases.
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Breast cancer is the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. Despite the detection of HPV in breast carcinomas, the virus's activity against this type of cancer remains controversial. HPV infection promotes remodeling of the host's immune response, resulting in an immunosuppressive profile. This study assessed the individual role of HPV oncogenes in the cell line MDA-MB-231 transfected with the E5, E6, and E7 oncogenes and co-cultured with peripheral blood mononuclear cells. Immunophenotyping was conducted to evaluate immune system modulation. There was an increase in CD4+ T cell numbers when compared with non-transfected and transfected MDA-MB-231, especially in the Treg profile. Pro-inflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17, were impaired by transfected cells, and a decrease in the cytolytic activity of the CD8+ and CD56+ lymphocytes was observed in the presence of HPV oncogenes, mainly with E6 and E7. The E6 and E7 oncogenes decrease monocyte expression, activating the expected M1 profile. In the monocytes found, a pro-inflammatory role was observed according to the cytokines released in the supernatant. In conclusion, the MDA-MB-231 cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.
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Neoplasias da Mama , Citocinas , Humanos , Feminino , Citocinas/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/virologia , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Transfecção , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/genética , Papillomaviridae/imunologia , Papillomavirus HumanoRESUMO
In the last decades, technological advances for RNA manipulation enabled and expanded its application in vaccine development. This approach comprises synthetic single-stranded mRNA molecules that direct the translation of the antigen responsible for activating the desired immune response. The success of RNA vaccines depends on the delivery vehicle. Among the systems, yeasts emerge as a new approach, already employed to deliver protein antigens, with efficacy demonstrated through preclinical and clinical trials. ß-glucans and mannans in their walls are responsible for the adjuvant property of this system. Yeast ß-glucan capsules, microparticles, and nanoparticles can modulate immune responses and have a high capacity to carry nucleic acids, with bioavailability upon oral immunization and targeting to receptors present in antigen-presenting cells (APCs). In addition, yeasts are suitable vehicles for the protection and specific delivery of therapeutic vaccines based on RNAi. Compared to protein antigens, the use of yeast for DNA or RNA vaccine delivery is less established and has fewer studies, most of them in the preclinical phase. Here, we present an overview of the attributes of yeast or its derivatives for the delivery of RNA-based vaccines, discussing the current challenges and prospects of this promising strategy.
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Improving antigen presentation is crucial for the success of immunization strategies. Yeasts are classically used as biofactories to produce recombinant proteins and are efficient vehicles for antigen delivery, in addition to their adjuvant properties. Despite the absence of epidemic outbreaks, several vaccine approaches continue to be developed for Zika virus infection. The development of these prophylactic strategies is fundamental given the severity of clinical manifestations, mainly due to viral neurotropism. The present study aimed to evaluate in vivo the immune response induced by P. pastoris recombinant strains displaying epitopes of the envelope (ENV) and NS1 ZIKV proteins. Intramuscular immunization with heat-attenuated yeast enhanced the secretion of IL-6, TNF-α, and IFN-γ, in addition to the activation of CD4+ and CD8+ T cells, in BALB/c mice. P. pastoris displaying ENV epitopes induced a more robust immune response, increasing immunoglobulin production, especially IgG isotypes. Both proposed vaccines showed the potential to induce immune responses without adverse effects, confirming the safety of administering P. pastoris as a vaccine vehicle. Here, we demonstrated, for the first time, the evaluation of a vaccine against ZIKV based on a multiepitope construct using yeast as a delivery system and reinforcing the applicability of P. pastoris as a whole-cell vaccine.
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Prophylactic vaccines against human papillomavirus (HPV) have proven efficacy in those who have not been infected by the virus. However, they do not benefit patients with established tumors. Therefore, the development of therapeutic options for HPV-related malignancies is critical. Third-generation vaccines based on nucleic acids are fast and simple approaches to eliciting adaptive immune responses. However, techniques to boost immunogenicity, reduce degradation, and facilitate their capture by immune cells are frequently required. One option to overcome this constraint is to employ delivery systems that allow selective antigen absorption and help modulate the immune response. This review aimed to discuss the influence of these different systems on the response generated by nucleic acid vaccines. The results indicate that delivery systems based on lipids, polymers, and microorganisms such as yeasts can be used to ensure the stability and transport of nucleic acid vaccines to their respective protein synthesis compartments. Thus, in view of the limitations of nucleic acid-based vaccines, it is important to consider the type of delivery system to be used-due to its impact on the immune response and desired final effect.
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In the context of vaccine development, improving antigenic presentation is critical for the activation of specific immune responses and the success of immunization, in addition to selecting an appropriate target. In this sense, different strategies have been developed and improved. Among them is the use of yeast cells as vehicles for the delivery of recombinant antigens. These vaccines, named whole yeast vaccines (WYVs), can induce humoral and cellular immune responses, with the additional advantage of dispensing with the use of adjuvants due to the immunostimulatory properties of their cell wall components. However, there are some gaps in the methodologies for obtaining and validating recombinant strains and vaccine formulations. The standardization of these parameters is an important factor for WYVs approval by regulatory agencies and, consequently, their licensing. This review aimed to provide an overview of the main parameters to consider when developing a yeast-based vaccine, addressing some available tools, and highlighting the main variables that can influence the vaccine production process.
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This study evaluated the presence of Human Papillomavirus (HPV) DNA in the cervix and peripheral blood of women with cervical intraepithelial neoplasia (CIN I, II, and III) and healthy individuals. Overall, 139 paired peripheral blood and cervix samples of healthy women and women with CIN I, II, and III (n = 68) were tested for HPV DNA by using standard procedures. Polymerase chain reaction (PCR) sequencing determined HPV types. Quantification of HPV16 E6 and E2 genes was performed to determine viral load and physical state. HPV DNA was detected in the cervix (21.1% in healthy individuals; 48.8-55.5% in CIN patients), blood (46.4% in healthy individuals; 44.1-77.7% in CIN patients) and paired peripheral blood and cervix samples (24% in healthy individuals; 32.5-44.4% in CIN patients). The most frequent types found in the cervix were HPV16, 18, 31, 33, 58, and 70, while HPV16, 18, 33, 58, and 66 were the most frequent types found in the blood. HPV DNA in the cervix was associated with previous sexually transmitted infections (STIs) (p = 0.023; OR: 2.978; CI:1.34-7.821), HPV DNA in the blood (p = 0.000; OR: 8.283; CI:3.700-18.540), and cervical lesions (CIN I/II or III) (p = 0.007). Binomial logistic regression showed that HPV DNA in the blood (p = 0.000; OR: 9.324; CI:3.612-24.072) and cervical lesions (p = 0.011; OR: 3.622; CI:1.338-9.806) were associated with HPV DNA in the cervix. However, we did not find an association between HPV DNA in the blood and cervical lesions (p = 0.385). Our results showed that only HPV DNA found in the cervix was associated with cervical lesions.
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The current pandemic called COVID-19 caused by the SARS-CoV-2 virus brought the need for the search for fast alternatives to both control and fight the SARS-CoV-2 infection. Therefore, a race for a vaccine against COVID-19 took place, and some vaccines have been approved for emergency use in several countries in a record time. Ongoing prophylactic research has sought faster, safer, and precise alternatives by redirecting knowledge of other vaccines, and/or the development of new strategies using available tools, mainly in the areas of genomics and bioinformatics. The current review highlights the development of synthetic antigen vaccines, focusing on the usage of bioinformatics tools for the selection and construction of antigens on the different vaccine constructions under development, as well as strategies to optimize vaccines for COVID-19.
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COVID-19 , Vacinas contra COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Vacinas Sintéticas/genéticaRESUMO
The emergence and rapid spread of Zika virus (ZIKV) in the Americas has prompted the development of in vitro and in vivo models to understand several aspects of ZIKV biology and boost the development of vaccines and antivirals. In vitro model studies include reverse genetics systems, two-dimensional (2D) cell models, such as primary cells and cell lines, and ex vivo three-dimensional (3D) models derived from skin, brain and placenta. While these models are cost-effective and allow rigorous control of experimental variables, they do not always recapitulate in vivo scenarios. Thus, a number of in vivo models have been developed, including mosquitoes (Aedes sp. and Culex sp.), embryonated chicken eggs, immunocompetent and immunodeficient mice strains, hamsters, guinea pigs, conventional swine and non-human primates. In this review, we summarize the main research systems that have been developed in recent years and discuss their advantages, limitations and main applications.
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Modelos Animais de Doenças , Interações Hospedeiro-Patógeno , Modelos Teóricos , Infecção por Zika virus/patologia , Infecção por Zika virus/virologia , Zika virus/fisiologia , Zika virus/patogenicidade , Aedes , Animais , Pesquisa Biomédica/métodos , Galinhas , Cricetinae , Culex , Cobaias , Camundongos , Primatas , SuínosRESUMO
PURPOSE: Evaluate the presence of human papillomavirus (HPV) in biopsies of Brazilian patients with lung cancer and also the expression of the E6 and E7 oncoproteins. HPV is widely known as an important condition for cervical cancer although evidence today shows it is associated with several other types of cancer and may also be involved in lung cancer development. However, there are some divergences regarding the presence and activity of HPV in lung carcinogenesis. METHODS: The detection of HPV was performed by PCR, followed by genotype and immunohistochemical evaluation of E6 and E7 HPV type specific, from 63 patients. RESULTS: HPV was found to be present in 33 of the 63 samples, and types 16 and 18 were detected with frequencies of 81% (27/33) and 19% (6/33), respectively. About the presence of the virus in different histological types of tumors, HPV was detected in squamous cell carcinoma (39.39%), followed by adenocarcinoma (33.33%) and small cell carcinoma (18.18%) and large cell carcinoma (9.1%). The presence of the E6 (antibody anti-HPV 16 and anti-HPV 18) and E7 (antibody anti-HPV 16 and anti-HPV 18) oncoproteins was detected by immunohistochemical stain technique in 28/33 samples and 25/33 samples, respectively. CONCLUSIONS: Our results suggest that the lung tumor patients have high prevalence of HPV and the virus is not only present but also active in tumor cells. Therefore, the HPV is probably playing a role in lung carcinogenesis.
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Neoplasias Pulmonares/etiologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/classificação , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Adulto JovemRESUMO
The immune system is composed of immune as well as non-immune cells. As this system is a well-established component of human papillomavirus- (HPV)-related carcinogenesis, high risk human papillomavirus (hrHPV) prevents its routes and mechanisms in order to cause the persistence of infection. Among these mechanisms are those originated from stromal cells, which include the cancer-associated fibroblasts (CAFs), the myeloid-derived suppressor cells (MDSCs) and the host infected cells themselves, i.e. the keratinocytes. These types of cells play central role since they modulate immune cells activities to create a prosperous milieu for cancer development, and the knowledge how such interactions occur are essential for prognostic assessment and development of preventive and therapeutic approaches. Nevertheless, the precise mechanisms are not completely understood, and this lack of knowledge precluded the development of entirely efficient immunotherapeutic strategies for HPV-associated tumors. As a result, an intense work for attaining how host immune response works, and developing of effective therapies has been applied in the last decade. Based on this, this review aims to discuss the major mechanisms of immune and non-immune cells modulated by hrHPV and the potential and existing immunotherapies involving such mechanisms in HPV-related cancers. It is noticed that the combination of immunotherapies has been demonstrated to be essential for obtaining better results, especially because the possibility of increasing the modulating capacity of the HPV-tumor microenvironment has been shown to be central in strengthening the host immune system.
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Neoplasias/etiologia , Neoplasias/patologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Células Estromais/metabolismo , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Humanos , Evasão da Resposta Imune , Imunoterapia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Mastócitos/imunologia , Mastócitos/metabolismo , Mastócitos/patologia , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Células Estromais/patologia , Microambiente Tumoral/imunologiaRESUMO
The modulation of the host innate immune system is a well-established carcinogenesis feature of several tumors, including human papillomavirus- (HPV-) related cancers. This virus is able to interrupt the initial events of the immune response, including the expression of Toll-like receptors (TLRs), cytokines, and inflammation. Both TLRs and cytokines play a central role in HPV recognition, cell maturation and differentiation as well as immune signalling. Therefore, the imbalance of this sensitive control of the immune response is a key factor for developing immunotherapies, which strengthen the host immune system to accomplish an efficient defence against HPV and HPV-infected cells. Based on this, the review is aimed at exposing the HPV immune evasion mechanisms involving TLRs and cytokines and at discussing existing and potential immunotherapeutic TLR- and cytokine-related tools.
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Citocinas/metabolismo , Imunoterapia/métodos , Neoplasias/imunologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/imunologia , Receptores Toll-Like/metabolismo , Animais , Transformação Celular Neoplásica , Humanos , Evasão da Resposta Imune , Neoplasias/virologia , Infecções por Papillomavirus/virologiaRESUMO
INTRODUCTION: Cervical cancer and cervical intraepithelial neoplasia (CIN) are well-known outcomes of a human papillomavirus (HPV) infection. Viral oncogenes expressions like E6, E7, and, recently recognized E5, lead to HPV-related malignant progression. Although HPV prevention by powerful vaccines against most frequent and oncogenic genotypes is feasible, current treatment against cervical neoplasia is distant from an ideal one. In addition, late diagnosis is commonly associated with a poor prognosis. On top of that, radiotherapy, chemotherapy, or surgery are less effective in high-grade lesions. Areas covered: Due to their peculiarities, HPV oncogenes represent an excellent target for cancer immunotherapy. Safety, efficacy, and potential immunogenicity are features achieved by DNA vaccines targeting HPV. The literature search has indicated that genetic immunotherapy is becoming a pharmacological tool and therapeutic option against cervical disease, as more and more DNA vaccines are reaching clinical trial phases. Expert commentary: Among some of the promising results, a phase II randomized trial showed a clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN patients. The concept of a synergic combination of anti-HPV DNA vaccines with radiotherapy, chemotherapy, sophisticated delivery methods, immunomodulators or immune adjuvants opens a new and interesting perspective in cervical malignancy treatment.
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Vacinas Anticâncer/administração & dosagem , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Animais , Vacinas Anticâncer/imunologia , Feminino , Humanos , Imunoterapia/métodos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologia , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/virologiaRESUMO
The immune response is a key factor in the fight against HPV infection and related cancers, and thus, HPV is able to promote immune evasion through the expression of oncogenes. In particular, the E5 oncogene is responsible for modulation of several immune mechanisms, including antigen presentation and inflammatory pathways. Moreover, E5 was suggested as a promising therapeutic target, since there is still no effective medical therapy for the treatment of HPV-related pre-neoplasia and cancer. Indeed, several studies have shown good prospective for E5 immunotherapy, suggesting that it could be applied for the treatment of pre-cancerous lesions. Thus, insofar as the majority of cervical, oropharyngeal and anal cancers are caused by high-risk HPV (hrHPV), mainly by HPV16, the aim of this review is to discuss the immune pathways interfered by E5 oncoprotein of hrHPV highlighting the various aspects of the potential immunotherapeutic approaches.
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Evasão da Resposta Imune , Imunomodulação , Proteínas Oncogênicas Virais/imunologia , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/fisiologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Animais , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunoterapia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/terapia , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Replicação ViralRESUMO
Lung cancer is the most common cause of cancer deaths worldwide. Although tobacco smoking is considered to be the main risk factor and the most well-established risk factor for lung cancer, a number of patients who do not smoke have developed this disease. This number varies between 15 % to over one-half of lung cancer cases, and the deaths from lung cancer in non-smokers are increasing every year. There are many other agents that are thought to be etiological, including diesel exhaust exposure, metals, radiation, radon, hormonal factors, cooking oil, air pollution and infectious diseases, such as human papillomavirus (HPV). Studies in various parts of the world have detected HPV DNA at different rates in lung tumors. However, the role of HPV in lung cancer is still unclear. Thus, in this review, we investigated some molecular mechanisms of HPV protein activity in host cells, the entry of HPV into lung tissue and the possible route used by the virus to reach the lung cells.
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Transformação Celular Viral , Neoplasias Pulmonares/virologia , Papillomaviridae/fisiologia , Transformação Celular Viral/genética , Humanos , Pulmão/patologia , Pulmão/virologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Infecções por Papillomavirus/complicações , Internalização do VírusRESUMO
BACKGROUND/AIM: Host molecules disturbed by human papillomavirus (HPV) oncoproteins have been shown to be potential biomarkers of cervical carcinogenesis and represent an alternative or supplementary aid to cytological testing and HPV detection. The miR-203 and one of its targets, ΔNp63, are known to be host molecules that interact with each other to control the proliferation and differentiation of keratinocytes; both have been found to be dysregulated in many cancers. As the role of p63 and miR-203 in cervical carcinogenesis is not yet well-understood, we have, thus, decided to evaluate the changes of expression of both in cervical carcinogenesis. MATERIALS AND METHODS: This study was carried out by obtaining quantitative polymerase chain reaction (qPCR) data from cervical biopsies. RESULTS: miR-203 and ΔNp63 displayed a similar expression pattern across cervical tissues and both targets showed statistically significant differences between low-grade squamous intraepithelial lesion (LSIL) x high-grade squamous intraepithelial lesion (HSIL); HSIL x Cancer. Additionally, we did not observe an inverse correlation between ΔNp63 mRNA and miR-203 levels as expected but, rather, a positive correlation between cervical tissues. CONCLUSION: Although preliminary, the expression levels of ΔNp63 mRNA and miR-203 seem to be promising for cervical cancer screening. In addition, positive correlation between miR-203 and ΔNp63 expression suggests the possible existence of some indirect pathways. However, further studies are needed to clarify the role of ΔNp63 and miR-203 in cervical carcinogenesis and, thus, determine how they can be applied in new strategies for diagnosis.
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Biomarcadores Tumorais/biossíntese , Proteínas de Membrana/biossíntese , MicroRNAs/biossíntese , Lesões Intraepiteliais Escamosas Cervicais/genética , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/genética , Carcinogênese/genética , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , MicroRNAs/genética , Gradação de Tumores , Papillomaviridae/patogenicidade , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
We performed an association between high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and single or multiple vaccine-target as well as non-vaccine target Human papillomavirus (HPV) types. Using bead-based HPV genotyping, 594 gynecological samples were genotyped. An association between squamous intraepithelial lesion (SIL) and presence of HPV16, 18, 31, 58 and 56 types were calculated. The risk was estimated by using odds ratio (OR) and 95% of confidence intervals (CI). A total of 370 (62.3%) women were HPV positive. Among these, 157 (42.7%) presented a single HPV infection, and 212 (57.3%) were infected by more than one HPV type. HPV31 was the most prevalent genotype, regardless single and multiple HPV infections. Single infection with HPV31 was associated with LSIL (OR=2.32; 95%CI: 1.01 to 5.32; p=0.04); HPV31 was also associated with LSIL (OR=3.28; 95%CI: 1.74 to 6.19; p= 0.0002) and HSIL (OR=3.82; 95%CI: 2.10 to 6.97; p<0.001) in multiple HPV infections. Risk to harbor cervical lesions was observed in multiple HPV infections with regard to the HPV56 (OR=5.39; 95%CI: 2.44 to 11.90; p<0.001for LSIL; OR=5.37; 95%CI: 2.71 to 10.69; p<0.001) and HPV58 (OR=3.29; 95%CI: 1.34 to 8.09; p=0.0091 for LSIL; OR=3.55; 95%CI: 1.56 to 8.11; p=0.0026) genotypes. In addition, women coinfected with HPV16/31/56 types had 6 and 5-fold increased risk of HSIL (OR=6.46; 95%CI: 1.89 to 22.09; p=0.002) and LSIL (OR=5.22; 95%CI: 1.10 to 24.70; p=0.03), respectively. Multiple HPV infections without HPV16/18 has 2-fold increased risk of HSIL (OR=2.57; 95%CI: 1.41 to 4.70; p=0.002) and LSIL OR=2.03; 95%CI: 1.08 to 3.79; p=0.02). The results of this study suggest that single and multiple vaccine target as well as non-vaccine target HPV types are associated with LSIL and HSIL. These finding should be taken into consideration in the design of HPV vaccination strategies.
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Papillomaviridae/fisiologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/imunologia , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/virologia , Adulto , Brasil , Feminino , Humanos , Fatores de Risco , Lesões Intraepiteliais Escamosas Cervicais/imunologia , Lesões Intraepiteliais Escamosas Cervicais/virologiaRESUMO
This study showed the prevalence of human papillomavirus (HPV) variants as well as nucleotide changes within L1 gene and LCR of the HPV16, HPV31, and HPV58 found in cervical lesions of women from North-East Brazil.