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1.
Cell Mol Life Sci ; 81(1): 141, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485766

RESUMO

Human papillomavirus (HPV) infection is a primary cause of cervical and head-and-neck cancers. The HPV genome enters the nucleus during mitosis when the nuclear envelope disassembles. Given that lamins maintain nuclear integrity during interphase, we asked to what extent their loss would affect early HPV infection. To address this question, we infected human cervical cancer cells and keratinocytes lacking the major lamins with a HPV16 pseudovirus (HP-PsV) encoding an EGFP reporter. We found that a sustained reduction or complete loss of lamin B1 significantly increased HP-PsV infection rate. A corresponding greater nuclear HP-PsV load in LMNB1 knockout cells was directly related to their prolonged mitotic window and extensive nuclear rupture propensity. Despite the increased HP-PsV presence, EGFP transcript levels remained virtually unchanged, indicating an additional defect in protein turnover. Further investigation revealed that LMNB1 knockout led to a substantial decrease in autophagic capacity, possibly linked to the persistent activation of cGAS by cytoplasmic chromatin exposure. Thus, the attrition of lamin B1 increases nuclear perviousness and attenuates autophagic capacity, creating an environment conducive to unrestrained accumulation of HPV capsids. Our identification of lower lamin B1 levels and nuclear BAF foci in the basal epithelial layer of several human cervix samples suggests that this pathway may contribute to an increased individual susceptibility to HPV infection.


Assuntos
Lamina Tipo B , Infecções por Papillomavirus , Feminino , Humanos , Lamina Tipo B/genética , Lamina Tipo B/metabolismo , Infecções por Papillomavirus/genética , Membrana Nuclear/metabolismo , Mitose , Cromossomos/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo
2.
Genes Dev ; 31(2): 172-183, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28143833

RESUMO

Senescence is a form of cell cycle arrest induced by stress such as DNA damage and oncogenes. However, while arrested, senescent cells secrete a variety of proteins collectively known as the senescence-associated secretory phenotype (SASP), which can reinforce the arrest and induce senescence in a paracrine manner. However, the SASP has also been shown to favor embryonic development, wound healing, and even tumor growth, suggesting more complex physiological roles than currently understood. Here we uncover timely new functions of the SASP in promoting a proregenerative response through the induction of cell plasticity and stemness. We show that primary mouse keratinocytes transiently exposed to the SASP exhibit increased expression of stem cell markers and regenerative capacity in vivo. However, prolonged exposure to the SASP causes a subsequent cell-intrinsic senescence arrest to counter the continued regenerative stimuli. Finally, by inducing senescence in single cells in vivo in the liver, we demonstrate that this activates tissue-specific expression of stem cell markers. Together, this work uncovers a primary and beneficial role for the SASP in promoting cell plasticity and tissue regeneration and introduces the concept that transient therapeutic delivery of senescent cells could be harnessed to drive tissue regeneration.


Assuntos
Plasticidade Celular/fisiologia , Senescência Celular/fisiologia , Regeneração/fisiologia , Via Secretória/fisiologia , Animais , Biomarcadores/metabolismo , Plasticidade Celular/genética , Células Cultivadas , Senescência Celular/genética , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Feminino , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento/genética , Queratinócitos/citologia , Queratinócitos/fisiologia , Fígado/citologia , Fígado/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Fenótipo , Regeneração/genética , Via Secretória/genética , Células-Tronco/metabolismo
3.
Microb Pathog ; 193: 106764, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38944216

RESUMO

Cervical cancer (CC) is the fourth most common cancer among female patients. The primary cause of all types of cervical cancer is human papillomavirus (HPV), which was projected to account for 5,70,000 reported cases in 2018. Two HPV strains (16 and 18) account for 70 % of cervical abnormalities and precancerous cervical cancers. CC is one of the main causes of the 17 % cancer-related death rate among Indian women between the ages of 30 and 69 is CC. The side effects of the currently approved treatments for cervical cancer could endanger the lives of women affected by the illness. Thus, probiotics may be extremely important in the management of CC. Numerous studies on probiotics and their potential for use in cancer diagnosis, prevention, and treatment have been conducted. This review describes the enhancement of the immune system, promotion of a balanced vaginal microbiome, and decreased risk of secondary infections, which have anti-inflammatory effects on the body. Probiotics have the potential to reduce inflammation, thereby adversely affecting cancer cell growth and metastasis. During the course of antibiotic therapy, they support a balanced vaginal microbiome. Oncogenic virus inactivation is possible with probiotic strains. In postmenopausal women, the use of vaginal probiotics helps lessen menopausal symptoms caused by Genitourinary Syndrome of Menopause (GSM). The antitumor effects of other medications can be enhanced by them as potential agents, because they can both promote the growth of beneficial bacteria and reduce the quantity of potentially harmful bacteria. The development of tumors and the proliferation of cancer cells may be indirectly affected by the restoration of the microbial balance. Probiotics may be able to prevent and treat cervical cancer, as they seem to have anticancer properties. To identify probiotics with anticancer qualities that can supplement and possibly even replace traditional cancer treatments, further investigation is required, including carefully planned clinical trials.


Assuntos
Infecções por Papillomavirus , Probióticos , Neoplasias do Colo do Útero , Humanos , Probióticos/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Feminino , Infecções por Papillomavirus/complicações , Vagina/microbiologia , Microbiota , Papillomaviridae
4.
Histopathology ; 84(1): 124-135, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37691383

RESUMO

While lung cancer is one of the most common malignancies routinely encountered by pathologists, benign pulmonary neoplasms are quite rare. However, it is important for pathologists to be familiar with the typical diagnostic features of benign lung tumors to avoid confusing them with malignant morphological mimics. There have also been intriguing discoveries in the genetics of benign pulmonary neoplasms in the past decade. This review will cover several of the most common benign lung tumors, including the diagnostic categories of pulmonary adenomas, bronchial papillomas, and benign mesenchymal tumors, with discussion of the current classification, differential diagnosis, and current knowledge regarding genetic drivers.


Assuntos
Adenoma , Neoplasias Brônquicas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Brônquicas/patologia , Adenoma/patologia
5.
Histopathology ; 85(3): 383-396, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38923027

RESUMO

Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplastic entities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed.


Assuntos
Neoplasias da Mama , Esclerose , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Feminino , Esclerose/patologia , Diagnóstico Diferencial , Mama/patologia , Doenças Mamárias/patologia , Doenças Mamárias/diagnóstico
6.
BMC Cancer ; 24(1): 375, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528459

RESUMO

INTRODUCTION: Cervical cancer is a major public health issue in Uganda, with high incidence due to limited screening especially in rural areas. In 2019, HPV DNA testing using GeneXpert was rolled out to improve screening access. Assessing progress and challenges since its introduction is important. AIM: To determine genotype distribution and explore health worker experiences with HPV screening using GeneXpert in Uganda. METHODS: We conducted a retrospective cohort study where HPV screening data from 66 GeneXpert labs from March 2021-May 2023 country wide was analyzed. We used descriptive statistics to provide percentages and proportions from the data. Seven focus group discussions and five interviews were done with health workers to understand experiences. RESULTS: We extracted 24,497 HPV tests that were done, and 39.1% were HPV positive. Other high-risk HPV genotypes were the most common at 65%, followed by HPV 16 (17%) and HPV 18/45 (18%). 15% of the HPV positive cases had more than one genotype. Qualitative findings showed inconsistent health worker knowledge, high workload, and complex care seeking behaviors as main challenges. It also revealed low community awareness, care seeking from traditional healers, CONCLUSION: HPV DNA testing has been expanding since its rollout, but the yield of HPV cases is lower than expected, signaling need to address supply-side challenges. Limited information on HPV among health workers especially community health workers, demand-side barriers like myths, medical pluralism and social norms must also be tackled through trainings of health workers and awareness campaigns engaging communities. Although access to GeneXpert services has increased, health system weaknesses pose bottlenecks to screening HPV. Targeted interventions are required to strengthen HPV diagnosis, prevent cervical cancer and save lives.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Papillomavirus Humano , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Uganda/epidemiologia , Estudos Retrospectivos , Papillomaviridae/genética , DNA , Detecção Precoce de Câncer/efeitos adversos
7.
BMC Cancer ; 24(1): 807, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971725

RESUMO

BACKGROUND: In 2020, uterine cervical cancer (UCC) was the 12th most common cancer among women in France and the 4th worldwide. French health authorities wanted to increase Human Papilloma Virus (HPV) vaccination and screening rates. There were still many barriers to these measures among young women, their families, and health professionals and teachers. Between 2014 and 2019, international studies found inconsistent effects of HPV vaccination on UCC screening. In 2022, a survey was conducted among women aged 25 to 40 in the Nord-Pas-de-Calais region to assess participation 1) in HPV vaccination and its barriers, 2) in UCC screening as a function of HPV vaccination status. METHODS: Data were collected using an anonymous online questionnaire distributed by QR code in 80 general practices randomly selected in the Nord-Pas-de-Calais region between January and June 2022. Results were analyzed bivariately using the Chi2 test, multivariately when numbers allowed, and in age subgroups (sensitivity analysis). RESULTS: 407 complete questionnaires (for 602 participating women) were analyzed. In our sample, 41% of women aged 25 to 40 in the Nord-Pas-de-Calais region were vaccinated against HPV viruses in 2022. The risk factors for non-vaccination, after multivariable adjustment, were: the periods of eligibility for vaccination in the early days of French vaccination (2007-2012: odds ratio OR = 0.04 [95% CI, 0.02-0.09]; 2012-2017: OR = 0.5 [0.3-0.8]), information received from non-medical sources (OR = 0.3 [0.2-0.6]), and absence of information about vaccination (OR = 0.12 [0.05-0.27]). In our sample, 90% of women were screened for UCC. In bivariate analysis, women at risk of not being screened were those who were youngest, had been vaccinated against HPV, were not heterosexual, lived alone, had gynecological follow-up by their general practitioner, and did not have regular gynecological follow-up. Sensitivity analysis showed that the only risk factor significantly correlated with non-screening regardless of age group was lack of regular gynecological follow-up. CONCLUSIONS: Participation in HPV vaccination and UCC screening is improved by medical education and gynecological follow-up. This multicenter study, limited by the relative youth of vaccination in France, should be repeated after 2037 to assess the possible effect of vaccination on screening.


Assuntos
Detecção Precoce de Câncer , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Vacinação , Humanos , Feminino , Adulto , Estudos Transversais , França/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Inquéritos e Questionários , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos
8.
Virol J ; 21(1): 182, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123176

RESUMO

BACKGROUND: Human papillomavirus (HPV) is among the leading cause of sexually transmitted infections, particularly prevalent among sexually active individuals. While many HPV infections clear up over time, some may progress to various cancers such as anal cancer, cervical cancer and, vaginal cancer. This study examines the prevalence of different HPV genotypes, classified as high-risk (HR) and low-risk (LR), among females of various age groups who visited the laboratory in Karaj. MATERIAL AND METHODS: Genital specimens were gathered from the individuals involved in the study and subjected to DNA extraction (DNA/RNA extraction AmpliSense, Moscow, Russia) followed by amplification using Real-Time PCR. HR- and LR-HPV genotypes were identified using the GenoFlow HPV Array test kit (GenoFlow; DiagCor Bioscience, Hong Kong) and homemade HPV genotyping kit. Demographic information such as age, was examined alongside statistical virological data. RESULTS: Overall, 367 (17%) out of the 2109 (100%) female cases tested positive for HPV. Among these, 219 (46.2%) were classified as low-risk, 44 (9.3%) as potentially high-risk, and 211 (44.5%) as high-risk. The highest percentage of positive test results was detected in individuals under 30 years old (35%) and those aged 40-50 (18%). Individuals in the < 30 age group were primarily infected with HR genotypes. The most commonly identified genotypes overall were HPV-16 (11.7%), HPV-54 (10.3%), HPV-56 (8.4%), HPV-40 (8.1%). The lowest frequency was observed for HPV-70, HPV-71, HPV-82, and HPV-90, each recorded in only a single case. CONCLUSION: Our results highlight the notable occurrence of HPV among females who visited the laboratory in Karaj, especially in the < 30 age group. Identifying HPV-16 as the most prevalent genotype in our examination highlights the necessity of tailored interventions for specific age ranges. While HPV-16 is covered by vaccination programs, HPV-54 and HPV-56 are not, emphasizing the need for effective screening and preventive plans to manage the consequences of HPV-related diseases in future.


Assuntos
Genótipo , Papillomavirus Humano , Infecções por Papillomavirus , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Alphapapillomavirus , DNA Viral/genética , Papillomavirus Humano/classificação , Papillomavirus Humano/genética , Papillomavirus Humano/isolamento & purificação , Irã (Geográfico)/epidemiologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Prevalência
9.
Cell Commun Signal ; 22(1): 107, 2024 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341592

RESUMO

Cervical cancer (CC) is a common gynecologic malignancy, accounting for a significant proportion of women death worldwide. Human papillomavirus (HPV) infection is one of the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible for disease expansion. Circular RNAs (circRNAs), which are known as a particular subset of non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported to be involved in the progression of diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs are in strong correlation with CC pathogenesis through regulating substantial signaling pathways. Also, these RNA molecules can be considered as promising biomarkers and therapeutic targets for CC diagnosis/prognosis and treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/ß-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, as well as angiogenesis and metastasis, by which circRNAs interfere with CC development. Then, diagnostic, prognostic, and therapeutic potentials of these ncRNA molecules will be highlighted in depth.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , RNA Circular/genética , Infecções por Papillomavirus/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/genética
10.
J Surg Oncol ; 129(6): 1025-1033, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38305061

RESUMO

Previously reported upgrade rates for benign breast intraductal papilloma (IDP) are widely variable. However, many previous studies have failed to consider radiologic-pathologic discordance of lesions. This review aims to synthesize malignant upgrade data for benign, concordant IDP at surgical excision. Thirteen studies were included in our meta-analysis. The pooled estimate for percentage underestimation of carcinoma was 1.4% (95% CI: 0.8%-2.0%). We conclude that these lesions can be safely managed by active surveillance.


Assuntos
Neoplasias da Mama , Papiloma Intraductal , Humanos , Papiloma Intraductal/patologia , Papiloma Intraductal/cirurgia , Papiloma Intraductal/diagnóstico por imagem , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/diagnóstico por imagem
11.
Exp Mol Pathol ; 138: 104915, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38964052

RESUMO

A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as Epstein-Barr virus (EBV) testing by EBER-ISH. CD5 and c-KIT (CD117) IHC was done to evaluate for possible thymic origin in all virus-negative cases. Whole exome sequencing, followed by MSA, was used to identify UV signature mutations indicative of cutaneous origin. HPV was identified in 12 of 22 tumors (54.5%), favoring an oropharyngeal origin, and closely associated with nonkeratinizing tumor morphology (Fisher's exact test; p = 0.0002). One tumor with indeterminant morphology had discordant HPV and p16 status (p16+/HPV-). All tumors were EBV-negative. Diffuse expression of CD5 and c-KIT was identified in 1 of 10 virus-negative SCCUPs (10%), suggesting a possible ectopic thymic origin rather than a metastasis. A UV mutational signature, indicating cutaneous origin, was identified in 1 of 10 (10%) virus-negative SCCUPs. A cutaneous auricular primary emerged 3 months after treatment in this patient. Primary tumors became clinically apparent in 2 others (1 hypopharynx, 1 hypopharynx/larynx). Thus, after follow-up, 6 tumors remained unclassifiable as to the possible site of origin (27%). Most SCCUPs of the neck in our series were HPV-associated and thus likely of oropharyngeal origin. UV signature mutation analysis and additional IHC for CD5 and c-KIT for possible thymic origin may aid in further classifying virus-negative unknown primaries. Close clinical inspection of hypopharyngeal mucosa may also be helpful, as a subset of primary tumors later emerged at this site.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Primárias Desconhecidas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Neoplasias Primárias Desconhecidas/virologia , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/genética , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/genética , Proteínas Proto-Oncogênicas c-kit/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/patogenicidade , Imuno-Histoquímica , Biomarcadores Tumorais/genética , Mutação , Idoso de 80 Anos ou mais , Adulto , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Papillomaviridae/isolamento & purificação , Sequenciamento do Exoma , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética
12.
J Med Primatol ; 53(1): e12690, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38345331

RESUMO

BACKGROUND: Cervical cancer is an abnormal growth of cervical tissue epithelial cells due to persistent human papilloma virus (HPV) infection. Cynomolgus monkeys (Macaca fascicularis) can be naturally and spontaneously infected with M. fascicularis Papillomavirus Type 3 (MfPV3), a virus that is phylogenetically closely related to human oncogenic HPV (HPV-16 and HPV-34), and therefore a potentially beneficial for modeling HPV disease. This study aims to evaluate the expression of the integrin alpha 6 (ITGα6) receptor in cynomolgus monkeys spontaneously infected with MfPV3, which this receptor also found in human infected with HPV. METHODS: The study was done on archived Formalin-fixed Paraffin-Embedded (FFPE) samples of uterine and cervix tissue of cynomolgus monkeys. Immunohistochemistry was also performed to quantify the expression levels of ITGα6. RESULTS: The results showed 80% of the samples positive Cervical Intraepithelial Neoplasia (CIN) and increased expression of ITGα6 significantly in Positive-MfPV3 group than negative-MfPV3 group. CONCLUSIONS: This indicated the potential of cynomolgus monkeys as a spontaneous oncogenesis model of PV infection type.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Animais , Colo do Útero/metabolismo , Macaca fascicularis , Infecções por Papillomavirus/veterinária , Neoplasias do Colo do Útero/química , Neoplasias do Colo do Útero/metabolismo , Papillomaviridae , Integrinas/análise
13.
Pathobiology ; : 1-12, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39191209

RESUMO

INTRODUCTION: Although urothelial papilloma (UP) is an indolent papillary neoplasm that can mimic the morphology of low-grade papillary urothelial carcinoma (PUC), there is no immunomarker to differentiate reliably these two entities. In addition, the molecular characteristics of UP are not fully understood. METHODS: We conducted an in-depth proteomic analysis of papillary urothelial lesions (n = 31), including UP and PUC along with normal urothelium. Protein markers distinguishing UP and PUC were selected with machine learning analysis, followed by internal and external validation using immunohistochemistry. RESULTS: In the proteomic analysis, UP and PUC showed overlapping proteomic profiles. We identified EHD4 and KRT18 as candidate diagnostic biomarkers of UP. Through immunohistochemical validation in two independent cohorts (n = 120), KRT18 was suggested as a novel UP diagnostic marker, able to differentiate UP from low-grade PUC. We also found that 3.5% of patients with UP developed urothelial carcinoma in subsequent resections, supporting the malignant potential of UP. KRT18 downregulation was significantly associated with UPs subsequently progressing to urothelial carcinoma, following their initial diagnosis. CONCLUSION: This is the first study that successfully revealed UPs comprehensive proteomic landscape, while it also identified KRT18 as a potential diagnostic biomarker of UP.

14.
BMC Infect Dis ; 24(1): 369, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565994

RESUMO

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection and the leading cause of cervical cancer. The HPV vaccine is a safe and effective way to prevent HPV infection. In Zambia, the vaccine is given during Child Health Week to girls aged 14 years who are in and out of school in two doses over two years. The focus of this evaluation was to establish the cost to administer a single dose of the vaccine as well as for full immunisation of two doses. METHODS: This work was part of a broader study on assessing HPV programme implementation in Zambia. For HPV costing aspect of the study, with a healthcare provider perspective and reference year of 2020, both top-down and micro-costing approaches were used for financial costing, depending on the cost data source, and economic costs were gathered as secondary data from Expanded Programme for Immunisation Costing and Financing Project (EPIC), except human resource costs which were gathered as primary data using existing Ministry of Health salary scales and reported time spent by different health cadres on activities related to HPV vaccination. Data was collected from eight districts in four provinces, mainly using a structured questionnaire, document reviews and key informant interviews with staff at national, provincial, district and health facility levels. Administrative coverage rates were obtained for each district. RESULTS: Findings show that schools made up 53.3% of vaccination sites, community outreach sites 30.9% and finally health facilities 15.8%. In terms of coverage for 2020, for the eight districts sampled, schools had the highest coverage at 96.0%. Community outreach sites were at 6.0% of the coverage and health facilities accounted for only 1.0% of the coverage. School based delivery had the lowest economic cost at USD13.2 per dose and USD 28.1 per fully immunised child (FIC). Overall financial costs for school based delivery were US$6.0 per dose and US$12.4 per FIC. Overall economic costs taking all delivery models into account were US$23.0 per dose and US$47.6 per FIC. The main financial cost drivers were microplanning, supplies, service delivery/outreach and vaccine co-financing; while the main economic cost drivers were human resources, building overhead and vehicles. Nurses, environmental health technicians and community-based volunteers spent the most time on HPV related vaccination activities compared to other cadres and represented the greatest human resource costs. CONCLUSIONS: The financial cost of HPV vaccination in Zambia aligns favourably with similar studies conducted in other countries. However, the economic costs appear significantly higher than those observed in most international studies. This discrepancy underscores the substantial strain placed on healthcare resources by the program, a burden that often remains obscured. While the vaccine costs are currently subsidized through the generous support of Gavi, the Vaccine Alliance, it's crucial to recognize that these expenses pose a considerable threat to long-term sustainability. Consequently, countries such as Zambia must proactively devise strategies to address this challenge.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Criança , Feminino , Humanos , Zâmbia , Infecções por Papillomavirus/complicações , Vacinação , Papillomavirus Humano , Neoplasias do Colo do Útero/complicações , Análise Custo-Benefício , Programas de Imunização
15.
Rev Med Virol ; 33(1): e2337, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35194874

RESUMO

The majority of sexually active individuals becomes infected with human papillomavirus (HPV) at least once in their lifetime. Pathways for HPV transmission vary across different mucosal sites per individual. They include autoinoculation within one host, direct transmission between individuals (including perinatal transmission and transmission during sexual activity), and indirect transmission through contact with hands. The authors aim to clarify the prevalence and route of transmission per anatomic site, inter- and intra-individually, using a narrative review of the literature. In conclusion, transmission of HPV to the oral cavity and oropharynx is hypothesised to occur mainly through sexual contact. Transmission of particles through saliva has not been proven and daily living activities are not a documented source of HPV infection. Oropharyngeal HPV related cancer survivors and their partners do not show increased risk of infection during sexual intercourse. Transmission of HPV to the oral cavity (autoinoculation with fingers or transmission through saliva in deep kissing) is probably of limited importance.


Assuntos
Carcinoma , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Papillomavirus Humano , Transmissão Vertical de Doenças Infecciosas , Boca , Neoplasias Orofaríngeas/epidemiologia , Prevalência , Fatores de Risco , Papillomaviridae
16.
Curr Oncol Rep ; 26(8): 967-976, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38861124

RESUMO

PURPOSE OF REVIEW: Squamous cell carcinoma of the anus (SCCA) is an HPV-associated malignancy that has limited treatment options. Immunotherapy has expanded these options and here we review current and emerging immunotherapeutic approaches. RECENT FINDINGS: Multiple studies of single-agent anti-PD1/PD-L1 immunotherapy have demonstrated a modest response rate of approximately 10% to 15%. While a minority of patients (~5%) with SCCA experience durable complete responses, most advanced SCCAs are resistant to anti-PD1/PD-L1 monotherapy. Given the need for more broadly effective immunotherapies, novel strategies, such as adaptive cell therapies and therapeutic vaccination, are being explored. To reduce the recurrence risk of localized high-risk SCCA, strategies combining immunotherapy with chemoradiation are also being investigated. While a small subset of patients with SCCA have prolonged responses to PD1-directed immunotherapy, the majority do not derive clinical benefit, and new immunotherapeutic strategies are needed. Better understanding of the immune microenvironment and predictive biomarkers could accelerate therapeutic advances.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias do Ânus/terapia , Neoplasias do Ânus/imunologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Microambiente Tumoral/imunologia , Antígeno B7-H1/antagonistas & inibidores
17.
Acta Obstet Gynecol Scand ; 103(1): 165-175, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37840151

RESUMO

INTRODUCTION: Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways-one involving high-risk human papilloma virus infection (HPV-associated), and the other without HPV infection (HPV-independent) often involving TP53 mutation. HPV-associated VSCC generally has a better progression-free survival than HPV-independent VSCC. The aim of this study was to determine TP53 mutation status using immunohistochemistry, compare different methods of HPV detection and correlate both with survival in a retrospective cohort of 123 patients with VSCC. MATERIAL AND METHODS: Immunohistochemistry for p53, Ki67 and p16INK4A (a surrogate marker for HPV infection) was performed on formalin-fixed paraffin-embedded tissues from a cohort of surgically treated VSCC patients to identify molecular subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR and HPV mRNA in situ hybridization (ISH). The Pearson chi-square test and multivariable Cox regression model were used to investigate the association of different parameters with progression-free survival and disease-specific survival (DSS), and Kaplan-Meier curves were used to show the association of different parameters with survival. RESULTS: The results of p53 and p16INK4A immunohistochemistry confirmed three VSCC subtypes associated with different prognosis. The TP53 mutation status was identified as an independent prognostic factor of worse progression-free survival (p = 0.024) after adjustment for FIGO stage. p16INK4A immunohistochemistry, mRNA ISH, and DNA PCR had excellent concordance in terms of HPV detection. According to the multivariable Cox regression model, the presence of hrHPV mRNA correlated significantly with increased progression-free survival (p = 0.040) and DSS (p = 0.045), after adjustment for other confounders. CONCLUSIONS: p53 and p16INK4A immunohistochemistry stratify VSCC cohort into three subtypes with TP53mutated patients having the worst prognosis. The detection of hrHPV mRNA by ISH was an independent predictor of increased survival. Thus, the combined detection of p53 and HPV mRNA might improve risk stratification in VSCC.


Assuntos
Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias Vulvares , Feminino , Humanos , Prognóstico , Papillomavirus Humano , Estudos Retrospectivos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteína Supressora de Tumor p53/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Vulvares/patologia , DNA , RNA Mensageiro , Vulva/química , Vulva/metabolismo , Vulva/patologia , Papillomaviridae/genética
18.
BMC Womens Health ; 24(1): 76, 2024 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-38281960

RESUMO

BACKGROUND: Screening participation at recommended intervals is a crucial component of cervical cancer prevention effectiveness. However, little is known regarding the rate of re-screening in a Sub-Saharan context. This study aimed to estimate the re-screening rate of women in a semi-rural after an initial HPV-based screening and identify factors that influence adherence. METHODS: This cohort study at the Annex Regional Hospital of Dschang enrolled women screened for cervical cancer over 5 years ago and due for re-screening. Women who initially tested HPV-positive (n = 132) and a random sample of HPV-negative women (n = 220) participated in a telephone survey between October 2021 and March 2022 to assess re-screening participation and reasons. Sociodemographic factors were collected, and associations with rescreening were evaluated. RESULTS: A total of 352 participants aged under 50 years (mean age 37.4 years) were contacted, and 203 (58.0%) completed the survey. The proportion of women who complied with the screening recommendation was 34.0% (95% CI 27.5% - 40.5%), The weighted re-screening proportion was 28.4%. Age, marital status, education level, type of employment, and place of residence were not associated with the rate of re-screening. Main reported barriers to re-screening were lack of information (39.0%), forgetfulness (39.0%), and impression of being in good health (30.0%). Women who remembered the recommended screening interval were 2 to 3 times more likely to undergo re-screening (aOR (adjusted odds ratio) = 2.3 [1.2-4.4], p = 0.013). Human papilloma virus- positive status at the initial screening was also associated with the re-screening((aOR) (95% CI): 3.4 (1.8-6.5). CONCLUSION: Following an initial Human Papilloma Virus-based screening campaign in the West Region of Cameroon, one third of women adhered to re-screening within the recommended timeframe. Existing screening strategies would benefit from developing better information approaches to reinforce the importance of repeated cervical cancer screening.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Idoso , Adulto , Neoplasias do Colo do Útero/prevenção & controle , Estudos de Coortes , Detecção Precoce de Câncer , Saúde da População Rural , Camarões , Infecções por Papillomavirus/prevenção & controle , Papillomaviridae , Programas de Rastreamento
19.
BMC Womens Health ; 24(1): 139, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395851

RESUMO

BACKGROUND: Human papillomavirus (HPV) is associated with cervical cancer and cervical dysplasia worldwide. Data on HPV prevalence in a region is important because it serves as a predictor of the likelihood of the population in that particular region acquiring cervical cancer. Moreover, with the availability of effective vaccines, the public health system must be aware of the preponderance of HPV to implement the vaccine. The present study was designed to understand the prevalence of HPV and associated factors among the women of South Andaman Island. METHODS: A cross-sectional study was conducted among married women of reproductive age (18-59 years) from South Andaman District from 2018 to 2022. Cervical scrapes were collected from participants after obtaining informed written consent for HPV molecular testing (HPV DNA) such as PCR assay. Demographic data was collected using a standard questionnaire and statistical analyses were performed to determine the associated factors. RESULTS: The study showed prevalence of HPV as 5.9%(95% CI: 3.9-7.9) and prevalence of HR-HPV16 was 4.1% (95% CI 2.6 - 5.5) and HR-HPV18 prevalence was 1.8(95% CI: 0.6-3). The independent factors associated the HPV positivity were age above 55 years, menopause, post-menopausal bleeding, blood-stained vaginal discharge and loss of weight. Age was associated with all HPV infections among the South Andaman women. CONCLUSIONS: HPV 16 was reported as the predominant high risk HPV type circulating among women of South Andaman. Cervical cancer and precancerous lesions were significantly associated with HPV positivity and High risk HPV 16. Based on the knowledge of the risk factors associated with HPV, implementation of stronger public health awareness and prophylactic HPV vaccination is crucial among the women of this remote island.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Estudos Transversais , Papillomavirus Humano 16/genética , Fatores de Risco , Índia/epidemiologia , Papillomaviridae/genética , Prevalência , Vacinas contra Papillomavirus/uso terapêutico
20.
BMC Womens Health ; 24(1): 116, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347568

RESUMO

BACKGROUND: The present study aimed to evaluate the long-term oncological and obstetric outcomes following the loop electrosurgical excision procedure (LEEP) in patients with cervical intraepithelial neoplasia (CIN) and investigate the risk factors for recurrence and preterm birth. METHODS: This retrospective cohort study included patients who underwent LEEP for CIN 2-3 between 2011 and 2019. Demographic information, histopathological findings, postoperative cytology, and human papillomavirus (HPV) status were collected and analyzed. The Cox proportional hazards model and Kaplan-Meier curves with the log-rank test were used for risk factor analysis. RESULTS: A total of 385 patients treated with the LEEP were analyzed. Treatment failure, including recurrence or residual disease following surgery, was observed in 13.5% of the patients. Positive surgical margins and postoperative HPV detection were independent risk factors for CIN1 + recurrence or residual disease (HR 1.948 [95%CI 1.020-3.720], p = 0.043, and HR 6.848 [95%CI 3.652-12.840], p-value < 0.001, respectively). Thirty-one patients subsequently delivered after LEEP, and the duration between LEEP and delivery was significantly associated with preterm-related complications, such as a short cervix, preterm labor, and preterm premature rupture of the membrane (p = 0.009). However, only a history of preterm birth was associated with preterm delivery. CONCLUSIONS: Positive HPV status after LEEP and margin status were identified as independent risk factors for treatment failure in patients with CIN who underwent LEEP. However, combining these two factors did not improve the prediction accuracy for recurrence.


Assuntos
Infecções por Papillomavirus , Nascimento Prematuro , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Gravidez , Feminino , Recém-Nascido , Humanos , Estudos Retrospectivos , Margens de Excisão , Papillomavirus Humano , Eletrocirurgia/métodos , Infecções por Papillomavirus/complicações , Nascimento Prematuro/epidemiologia , Displasia do Colo do Útero/patologia , Recidiva Local de Neoplasia/cirurgia
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