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2.
HNO ; 68(2): 80-86, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31915881

RESUMO

BACKGROUND: The incidence of HPV-associated squamous cell carcinoma of the head and neck region (HNSCC) has increased dramatically in recent years. Despite a similar localization (oropharyngeal squamous cell epithelia) to smoking- and alcohol-associated cancers, HPV-associated carcinomas are considered to represent a distinct entity. Reasons for the different therapeutic responses of the two tumor entities are not yet fully understood. METHODS AND OBJECTIVE: This review investigates the importance of tumor-infiltrating lymphocytes in HPV+ and HPV- HNSCC by means of articles and publications concerning the tumor micromilieu, effects on prognosis, and patients' therapeutic responses. RESULTS: HNSCC patients with a positive HPV status and increased frequencies of CD8+ T cells (CD, cluster of differentiation) demonstrated an improved therapeutic response and improved outcomes. Decreased expression of the EGF (epidermal growth factor) receptor correlates with increased TH1 cytokine secretion by CD4+ T cells, which, in their role as T helper cells, can activate macrophages, dendritic cells, and cytotoxic T cells, amongst others. Regulatory T cells (Treg) execute an immune-suppressive effect in the tumor micromilieu through different metabolic and signaling pathways (IL[interleukin]­4, IL-10, TGF­ß ["transforming growth factor­ß"]). CONCLUSION: The importance of the adaptive immune response for treatment response and patients' prognosis has been supported by different investigations. Understanding the immunological processes in the tumor environment plays an important role for the development of new treatment approaches.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Linfócitos do Interstício Tumoral , Infecções por Papillomavirus , Linfócitos T CD8-Positivos , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Infecções por Papillomavirus/complicações
3.
Oral Dis ; 26(1): 72-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31670871

RESUMO

OBJECTIVES: The objective of this study was to report the integrated observations of high-risk HPV-related oral squamous carcinoma (OSCC) at our national referral center for cancer, the Dharmais National Cancer Hospital (DNCH), Jakarta, from 2003 to 2013. MATERIALS AND METHODS: Seventy-eight formalin-fixed paraffin-embedded specimens obtained from OSCC cases were collected from 2003 to 2013 DNCH archives and were included in this high-risk HPV (HR-HPV) study. Seventy-nine DNA samples from the normal oral mucosa of healthy individuals were obtained from the Oral Biology Laboratory DNA archives from 2001 to 2005. Glyceraldehyde 3-phosphate dehydrogenase was used as a control to ensure the DNA integrity for the subsequent HPV DNA PCR detection. High-risk HPV16/18 DNA amplification was conducted by nested PCR using two pairs of primers that were designed specifically to identify the region of gene L1 HPV16 and the HPV16/18 region. RESULTS AND CONCLUSIONS: A high prevalence of HPV16/18 was detected in OSCC cases (17.9%). HPV18 occurred more often than HPV16 (86%) among OSCC patients who were HPV positive. This result supports high HPV18 prevalence among Indonesian cervical cancer patients studied in 1995 and 2006. The prevalence of high-risk HPV remains low in the normal Indonesian population (3.8%), but HPV16 is consistently more frequently detected in non-cancer populations.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias Bucais/virologia , Infecções por Papillomavirus/epidemiologia , Adulto , Carcinoma de Células Escamosas/epidemiologia , DNA Viral/isolamento & purificação , Feminino , Técnicas de Genotipagem , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Infecções por Papillomavirus/complicações , Prevalência
4.
Acta Cytol ; 64(1-2): 63-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30889579

RESUMO

The association between high-risk genotypes of human papillomavirus (hr-HPV) and cervical cancer is well established. As hr-HPV testing is rapidly becoming a part of routine cervical cancer screening, either in conjunction with cytology or as primary testing, the management of hr-HPV-positive women has to be tailored in a way that increases the detection of cervical abnormalities while decreasing unnecessary colposcopic biopsies or other invasive procedures. In this review, we discuss the overall utility and strategies of hr-HPV testing, as well as the advantages and limitations of potential triage strategies for hr-HPV-positive women, including HPV genotyping, p16/Ki-67 dual staining, and methylation assays.


Assuntos
Citodiagnóstico/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Detecção Precoce de Câncer/métodos , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Triagem , Neoplasias do Colo do Útero/complicações
5.
Int J Cancer ; 146(3): 731-738, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30963559

RESUMO

HPV73 is classified as possibly oncogenic. It is neither routinely evaluated in HPV screening, nor covered by any of the prophylactic vaccines. We sought to investigate the carcinogenic characteristics of HPV73. Molecular studies were performed on eight cervix cancer biopsy specimens containing HPV73 from a cross-sectional cancer cohort of 590 women referred to the National Cancer Institute in Rio de Janeiro, Brazil. Transcriptional activity of HPV73 was evaluated by detection of spliced transcripts of E6/E6* and E1^E4 in cDNA created from RNA isolated from fresh tissue. Disruption of viral E1 and E2 genes in the tumor DNA was assessed by overlapping PCR amplification. Evaluation of viral integration was performed using a customized capture panel and next-generation sequencing, and an in-house bioinformatic pipeline. HPV73 E6/E6* transcripts were found in 7/7 specimens with available RNA, and three also had HPV73 E1^E4 transcripts. Disruption of E1 and E2 genes was observed in 4/8 specimens. Integration of HPV73 sequences into the cancer cell genomes was identified in all cervix cancer tissues. These results provide evidence that HPV73 is an oncogenic virus that can cause invasive cervix cancer. With current molecular screening and HPV vaccination, not all cervix cancers will be prevented.


Assuntos
Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Brasil , Estudos Transversais , DNA de Neoplasias/genética , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Reação em Cadeia da Polimerase/métodos , RNA Viral/genética , Integração Viral/genética
6.
Int J Radiat Oncol Biol Phys ; 106(1): 146-156, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521718

RESUMO

PURPOSE: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) commonly affects people of working age, yet there is limited data regarding the return-to-work experience in this cohort. This study aimed to investigate the proportion of survivors currently working after completion of radiation therapy and to explore potential facilitators and barriers to working after treatment. METHODS: A cross-sectional, single-institutional study was undertaken at the Peter MacCallum Cancer Centre, a comprehensive cancer center in Melbourne, Victoria, Australia. Eligible participants were 18 to 65 years old at diagnosis, were employed at or within the 3 months before diagnosis, and had completed curative treatment for HPV-associated OPC ≥4 months before enrollment. Participants completed a paper-based survey to assess baseline demographics, employment status, and quality of life (QOL; Functional Assessment of Cancer Therapy Head and Neck). Open-ended questions explored factors affecting return to work. Associations between current employment status and various disease, treatment, and demographic variables and with QOL were examined. Free-text items were analyzed by summarizing content analysis. RESULTS: Of 93 participants approached, 68 responded (73.1%). Mean age was 54.1 years (range, 39-64 years), and 89.7% were male. Most participants (67.6%) had stage II disease and were treated with chemoradiation (85.3%). Mean time after treatment was 2.6 years (range, 0.3-9.1 years). Fifty-eight of 68 participants (85.3%) were working at enrollment; median time to return to work was 6.0 months (interquartile range, 4-10 months); 45 (77.6%) were in the same role and 35 (60.3%) worked the same number of hours. Ten participants were not working, 3 had retired, 5 reported persistent and significant treatment toxicity preventing employment. Survivors currently working reported higher physical, functional, and global QOL scores. Access to leave and support from treating doctors were facilitators for return to work, whereas fatigue was frequently reported as a barrier to returning to work. CONCLUSION: With time, the majority of participants with HPV-associated OPC will return to work after radiation therapy. Attention to symptom management and support from the workplace may enable more successful return to work.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Emprego/estatística & dados numéricos , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/complicações , Qualidade de Vida , Retorno ao Trabalho/estatística & dados numéricos , Adulto , Sobreviventes de Câncer/psicologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/estatística & dados numéricos , Estudos Transversais , Fadiga/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Pesquisa Qualitativa , Aposentadoria/estatística & dados numéricos , Retorno ao Trabalho/psicologia , Licença Médica/estatística & dados numéricos , Apoio Social , Inquéritos e Questionários , Fatores de Tempo , Vitória , Tolerância ao Trabalho Programado , Local de Trabalho
7.
Bratisl Lek Listy ; 120(11): 832-838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31747763

RESUMO

Head and neck squamous cell carcinomas (HNSCC) are a highly heterogenous disease which can be induced by two main carcinogens - tobacco and/or alcohol, or by HR HPV infection. This work examined 60 paraffin-embedded biopsies of head and neck carcinomas after histological verification. HPV infection, including its specific types in various HNSCC areas, was studied using multiplex qPCR. Expression levels of p16INK4A and p53 were detected by subsequent IHC analysis as being potential diagnostic markers. Based on the assumption that patients with HNSCC could benefit from anti-EGFR therapy (cetuximab), but the predictors are not yet defined, analyses of point mutations of ras genes (Kras, Nras) were carried out using multiplex qPCR and sequence analysis of the Braf gene. All statistical data were processed by Chí-x2 test.HPV infection was detected in 23.34 % of cases with HNSCC, of which 100 % were HPV 16, which is the most frequently infection found in the oropharyngeal region. Using IHC analysis, a positive expression of P16INK4A was detected in 100 % of HPV-positive HNSCC while this expression was discovered to be highly correlated with HPV infection. Furthermore, a correlation between p53 and HPV-negative HNSCC was proved. The mutation incidence was the highest in the Kras gene (codon 12 and codon 146), Nras (codon 12) and Braf. A correlation between tumor location in the oropharyngeal region and Kras mutations was proved. The HPV infection correlated with Kras mutations in case of codon 146 but on the grounds of low amount of output data, these figures could be irrelevant. In one case, c.1808 G>A, protein 603 Arg>Gln mutation was found in the Braf gene but its correlation with head and neck carcinomas has not been described yet (Tab. 2, Fig. 2, Ref. 24). Keywords: head and neck carcinomas, biopsy, HPV types, PCR, p16INK4A, p53, molecular predictors, Kras, Nras, Braf.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , GTP Fosfo-Hidrolases/genética , Neoplasias de Cabeça e Pescoço/virologia , Papillomavirus Humano 16 , Humanos , Imuno-Histoquímica , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética
8.
HNO ; 67(12): 912-917, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31701169

RESUMO

At this year's Annual Meeting of the American Society for Clinical Oncology (ASCO), the keyword search "HPV-associated head and neck cancer" resulted in 920 hits-74% of the hits on human papillomavirus (HPV). This underlines the relevance of the topic. The spectrum ranged from validation and separation of the prognostic groups of patients with HPV-associated oropharyngeal carcinoma (OPSCC) according to TNM 8, to the characterization of new tumor markers and tumor mutational burden for possible de-escalation strategies to avoid toxicity of standard multimodal treatments. It has been shown that the separation of p16-positive OPSCC into Union for International Cancer Control (UICC) stages I and II with the current TNM 8 classification without further markers is not sufficiently successful to justify de-escalation strategies. Following publication of the results of the De-ESCALaTE- and RTOG-1016 trials in 2018, which confirm the current standard of care for p16-positive OPSCC, no further phase III studies on de-escalation were presented. In a presented prospective phase II study (NCT02281955), the radiotherapy dose was reduced to cumulative 60 Gy, whereby the simultaneous chemotherapy regimen with cisplatin 30 mg/m2 weekly is not standard of care and could be administered as an alternative to cisplatin cetuximab. Some work dealt with the oral and intestinal microbiota as prognostic markers or their treatment-related changes, particularly under immunotherapy. Modification seems to have a positive impact on the success of therapy. However, robust data are still lacking for the various modified treatments for HPV-associated OPSCC, which are needed before their implementation in daily practice.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Congressos como Assunto , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Oncologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Estados Unidos
9.
Anticancer Res ; 39(11): 6307-6316, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704861

RESUMO

BACKGROUND/AIM: Oropharyngeal squamous cell carcinoma (OPSCC) could be clinically undetectable despite the relatively large size of lymph node metastases. Here, we aimed to elucidate the correlation of p16 expression with epithelial-to-mesenchymal transition (EMT) markers. PATIENTS AND METHODS: Radically resected 121 OPSCC and 270 non-OPSCC tissue samples were included in the analysis, and p16, Twist, and Snail/Slug immunohistochemistry was performed. RESULTS: Compared to non-OPSCCs, OPSCCs were significantly associated with lymphovascular invasion, lymph node metastasis, larger maximal diameter of metastatic foci in the lymph nodes, and p16 expression. In addition, p16 expression correlated with high Twist and Snail/Slug expression. CONCLUSION: Expression of EMT markers, such as Twist and Snail/Slug, is related to p16 expression in OPSCC. This might indicate that HPV infection in OPSCCs alters the expression of EMT markers and results in metastases.


Assuntos
Carcinoma de Células Escamosas/secundário , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Transição Epitelial-Mesenquimal , Linfonodos/patologia , Proteínas Nucleares/metabolismo , Neoplasias Orofaríngeas/patologia , Fatores de Transcrição da Família Snail/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Intervalo Livre de Progressão , Carga Tumoral
10.
Medicine (Baltimore) ; 98(44): e17800, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689859

RESUMO

RATIONALE: Human papillomavirus (HPV)-related oropharyngeal cancer is becoming more common, the primary cancer AQ4 usually occult and appearing only as cystic cervical lymph node (LN) metastasis. Distinguishing between a benign cystic lesion and cystic LN metastasis is challenging given their similar radiologic and histologic appearances. PATIENT CONCERNS: A 54-year-old man presented with a bulging cystic mass measuring 6.4cm on the right side of neck. DIAGNOSES: Postexcision diagnosis was second branchial cleft cyst. After 2 years, the cystic mass recurred, and HPV-related tonsillar squamous cell carcinoma with cystic metastatic LNs was confirmed after wide tonsillectomy and neck dissection. The previous cystic lesion proved to be a cystic metastatic LN from the same malignancy with additional p16 immunostain. INTERVENTIONS: The patient was treated with adjuvant concurrent chemoradiation therapy. OUTCOMES: The patient was followed up in the outpatient department with no evidence of recurrence after 1 year. LESSONS: When an adult has a cystic mass in the upper neck, we must rigorously exclude it as a cystic metastatic LN of occult HPV-related oropharyngeal cancer. Additional p16 staining might be helpful.


Assuntos
Branquioma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Metástase Linfática/diagnóstico , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Orofaríngeas/diagnóstico , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/virologia , Diagnóstico Diferencial , Humanos , Linfonodos/patologia , Linfonodos/virologia , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Pescoço/virologia , Esvaziamento Cervical , Neoplasias Císticas, Mucinosas e Serosas/secundário , Neoplasias Císticas, Mucinosas e Serosas/virologia , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/virologia , Neoplasias Orofaríngeas/secundário , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias Tonsilares/diagnóstico , Neoplasias Tonsilares/patologia , Neoplasias Tonsilares/virologia
11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 666-671, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762235

RESUMO

OBJECTIVE: To explore the dynamic changes of human papillomavirus (HPV) type 16 E5 gene in the development of cervical cancer and the significance of E5 mRNA in early screening of cervical cancer. METHODS: Paraffin specimens of cervical lesions were collected from 49 cases (HPV positive) during September 2015 to December 2017 According to the standard of FIGO, all cervical lesions were diagnosed as: 13 cases of cervicitis, cervical intraepithelial neoplasia disorders (CIN) Ⅰ in 5 cases, CIN Ⅱ in 18 cases, CIN Ⅲ in 5 cases, 8 cases of cervical cancer. Real-time fluorescence quantitative PCR was used to detect the integrity of E5 gene and the mRNA expression levels of E5, E6 and E 7in cervical tissues. RESULTS: All the 49 cases showed positive HPV16 infection. E5 genetic integrity in CINⅠwas higher than that in cervical inflammation, CIN Ⅱand cervical cancer (P < 0.05), which was also higher than that in CIN Ⅲ, but without statistically significance (P>0.05). The mRNA levels of E5, E6, E7 were the highest in CIN Ⅲ. Compared with E6 and E7, E5 presented superior expression in all types of cervical lesions (P < 0.05), while E 6and E7 mRNA expressions only increased in CIN Ⅲ and cervical cancer. CONCLUSION: In the patients with HPV16 infection, the integrity of E5 gene in cervical tissues may be related to the occurrence and development of cervical diseases. E5 gene is expected to be the target gene for early screening of cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/virologia , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia , Neoplasia Intraepitelial Cervical/patologia , Feminino , Papillomavirus Humano 16 , Humanos , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia
12.
Br J Radiol ; 92(1104): 20190466, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31600090

RESUMO

OBJECTIVE: One approach to reduce treatment-related morbidity for human papilloma virus (HPV)-associated tonsil cancer is omitting radiotherapy to the contralateral neck. Pathologic risk factors for early contralateral neck disease, however, are poorly understood. We report on the risk contralateral neck failures from the time of pre-operative diagnostic imaging to time of planning for adjuvant radiation in a single institution series of HPV-associated tonsillar cancer patients undergoing surgery followed by radiotherapy (RT). METHODS: Retrospective analysis of 123 patients with T1-T3 HPV-positive tonsillar squamous cell carcinoma treated between 2010 and 2016 with transoral robotic surgery and selective ipsilateral neck dissection followed by adjuvant RT. Contralateral neck recurrence was classified as the detection of a pathologic node in the contralateral neck prior to initiation of adjuvant RT. RESULTS: Seven patients (5.7%) developed contralateral neck disease/failure between the time of pre-operative diagnostic neck imaging and time of planning of adjuvant radiation. Increased ratio of positive/resected nodes [odds ratio (OR) 1.073, p = 0.005] was significantly associated with increased risk of contralateral neck recurrence, with a trend found for close/positive margins (OR 5.355, p = 0.06), tumor size (OR 2.046, p = 0.09), and total number of nodes positive (OR 1.179, p = 0.062). CONCLUSIONS: Patients who develop very early contralateral neck disease, between completion of ipsilateral neck dissection and the initiation of radiotherapy, have a higher ratio of positive nodes to total nodes resected in the ipsilateral neck. These findings suggest that proper selection of patients for omission of treatment of the contralateral, node-negative neck should be made with this in mind, with future studies needed to document the impact on toxicity and disease outcomes from such an approach. ADVANCES IN KNOWLEDGE: Pathologic risk factors in the dissected, ipsilateral neck in patients with tonsil cancer may inform the risk of contralateral neck failure. Patient selection for future, prospective efforts to examine sparing of the contralateral neck need to be based with these risk factors in mind.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Segunda Neoplasia Primária/etiologia , Infecções por Papillomavirus/complicações , Neoplasias Tonsilares/radioterapia , Neoplasias Tonsilares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Razão de Chances , Papillomaviridae , Período Pós-Operatório , Radioterapia Adjuvante/métodos , Radioterapia de Intensidade Modulada , Análise de Regressão , Estudos Retrospectivos , Risco , Neoplasias Tonsilares/patologia , Neoplasias Tonsilares/virologia , Carga Tumoral
13.
Bull Cancer ; 106(11): 1008-1022, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31606139

RESUMO

With more than 3300 new cases and almost 2500 deaths each year, cervical cancer (CC) ranks second among female cancers in Moroccan women. The majority of cases occurs in women aged 50 and over. In absence of a national cancer registry, data published in Morocco are limited to the number of cases recorded in some oncology centers, so the incidence of this cancer is likely much higher than estimated. A Moroccan national program against CC based on the practice of visual inspection after application of acetic acid was set up in 2010, allowing both screening and possibly immediate treatment of (pre)cancerous lesions. However, this program has not been implemented in all regions of the country. The CC develops slowly and most often without any symptoms, and so it is diagnosed at an advanced stage of the disease. Virtually, all CC are associated with persistent infection of high risk human papillomavirus (HPV), particularly HPV16 and 18. For more than ten years, two prophylactic vaccines targeting these two HPV genotypes have been marketed. They have proved their excellent immunogenicity and efficacy and they are well tolerated. However, HPV vaccine is not yet recommended by health authorities in Morocco. In this literature review, we focused on the current situation of CC, the prevalence of HPV infection and the prevention strategies against CC in Morocco.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Lesões Pré-Cancerosas/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Ácido Acético/administração & dosagem , Adulto , Algoritmos , Coinfecção/epidemiologia , Detecção Precoce de Câncer/métodos , Feminino , Infecções por HIV/epidemiologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Incidência , Indicadores e Reagentes/administração & dosagem , Pessoa de Meia-Idade , Marrocos/epidemiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/virologia , Prevenção Primária , Sistema de Registros/estatística & dados numéricos , Gestão de Riscos , Prevenção Secundária , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
14.
Medicine (Baltimore) ; 98(39): e17293, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574850

RESUMO

Human papillomavirus (HPV) infection is the leading cause of cervical cancer and precancerous lesions. Knowledge regarding the prevalence and genotype distribution of HPV in women is important to establish strategies for cervical cancer screening and HPV vaccination. This study aimed to evaluate the characteristics of HPV infection in Taizhou, China. HPV genotype of 10,733 women who visited Taizhou People's Hospital from November 2016 to October 2018 was determined using a PCR and hybridization-based detection test. The prevalence of overall, high risk (HR), and low risk (LR) HPV infections was 34.58%, 29.92%, and 10.12%, respectively. Of HPV-positive cases, 2417 (65.13%) were infected with a single HPV genotype and 1294 (34.87%) were infected with multiple HPV genotypes. HPV-52 was the most prevalent genotype (6.21%), followed by HPV-16 (5.33%), HPV-53 (4.03%), HPV-58 (3.89%), and HPV-81 (3.75%). The highest prevalence of HPV infection was found in women aged ≥60 years (40.72%). Furthermore, the prevalence of HPV increased with the severity of cervical lesions. In conclusions, the prevalence and genotype distribution of HPV varied with age and cervical lesions. The findings might serve as a potential reference for guiding cervical cancer screening and vaccine-based HPV prevention in Taizhou.


Assuntos
Detecção Precoce de Câncer/métodos , Genótipo , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Prevalência , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem
15.
Int J Med Sci ; 16(8): 1096-1101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523171

RESUMO

Objective: Efficient and highly predictive biomarkers reflecting the prognosis of persistent atypical squamous cells of unknown significance(ASCUS) and low grade squamous intraepithelial lesion(LSIL)s are unavailable and need to be developed urgently. We aimed to develop a predictive model for diagnosis of cervical intraepithelial neoplasia(CIN)2+ by analyzing the immunocytochemical expression of the HPV L1 capsid protein in patients with persistent ASCUS and LSIL with a high risk of HPV infection. Methods: Cervical cytology samples comprising (70 ASCUS and 215 LSIL Pap smears) were analyzed. Immunocytochemical identification of the HPV L1 capsid protein in cervical cytology samples was performed. Expression levels of HPV L1 capsid protein in cervical cytology samples were measured, and the correlation between HPV L1 expression and cervical pathologic diagnosis was evaluated. The risk for CIN2+ was calculated using the results of immunocytochemistry and the HPV DNA test. Results: Negative results for HPV L1 immunochemistry test were more frequently observed in CIN2+, and expression of the HPV L1 capsid protein was higher in CIN1 or cervicitis (Fisher's exact test, p<0.05). Diagnosis rates for CIN2+ were highest for the combination of HPV L1 capsid protein immunocytochemistry, cytology and HPV test when compared with other combinations (Akaike information criterion (AIC): 191.7, Schwarz criterion(SC): 206.3, p<0.001). Conclusion: Absence of HPV L1 capsid expression and presence of HPV type 16 or 18 infection are reliable predictors of progression to CIN2+ in patients showing persistent ASCUS and LSIL.


Assuntos
Células Escamosas Atípicas do Colo do Útero/virologia , Biomarcadores Tumorais/análise , Proteínas do Capsídeo/análise , Neoplasia Intraepitelial Cervical/virologia , Proteínas Oncogênicas Virais/análise , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Células Escamosas Atípicas do Colo do Útero/metabolismo , Células Escamosas Atípicas do Colo do Útero/patologia , Proteínas do Capsídeo/metabolismo , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Prognóstico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Adulto Jovem
16.
Pan Afr Med J ; 33: 124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31558923

RESUMO

Introduction: high risk HPV is the perpetrator of cervical cancer disease, however screening and vaccination is not included in cervical cancer prevention program within public hospitals in Kenya. This descriptive study assessed the association of specific microbial STI and socio-demographic characteristics and practices with cervical cytomorphologic presentations in regards to pre cervical cancer grades amongst health seeking patients attending the reproductive health clinic of Nakuru County referral hospital, a public hospital under newly devolved health services governance. Methods: a total of 142 patients (AGC/AIS, n=8; HSIL, n=59; LSIL, n=35; controls, n=40) whose median age ranged between 20-70 years were purposively sampled. A structured questionnaire with closed and open ended entries was administered and STI screening including Pap smear examination for cytomorphological profiling done according to revised 2014 Bethesda classification. Associations were established using chi-square and multivariate logistic regression model to determine prediction of cervical atypia manifestations. Results: a majority of the study participants had only primary education or no education in AGC/AIS (63%) and HSIL (73%) relative to LSIL (49%) and controls (53%) (P=0.017). Koilocyte rates were higher in AGC/AIS (25%), HSIL (52%) and LSIL (77%) compared controls (12.5%) (P<0.0001). ASCUS predominated in HSIL (61%) and LSIL (86%), while almost all AGC/AIS had AGCUS (88%). HR HPV 16/18 infection rates were higher in AGC/AIS (100%), HSIL (80%) and LSIL (83%) relative to controls (10%) (P<0.0001), and was associated with higher risk of having AGC/AIS (OR, 2.0; 95% CI, 1.940-1.947; P<0.0001); HSIL, (OR, 36.3; 95% CI, 9.5-139.5; P<0.0001); and LSIL (OR, 50.1; 95% CI, 12.0-209.0; P<0.0001). Conclusion: altogether, pre-cervical cancer in Kenyan women is characterized by koilocytosis and ASCUS probably from the high rates of HPV 16/18 infections. Promoting cancer education and screening for high risk HPV infections and pre-cancerous lesions will improve women's reproductive health.


Assuntos
Colo do Útero/patologia , Programas de Rastreamento/métodos , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Escolaridade , Feminino , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Quênia , Pessoa de Meia-Idade , Teste de Papanicolaou/métodos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Inquéritos e Questionários , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/métodos , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-31514378

RESUMO

Chlamydia trachomatis (Ct) and human papillomavirus (HPV) are the most prevalent sexually transmitted infections throughout the world. Despite the serious complications associated with chronic Ct infections in sexually active women, a screening program is not yet available in Italy. Moreover, HPV/Ct co-infections are also known to occur frequently, increasing the risk of HPV-induced carcinogenesis. The aim of this study was to evaluate the prevalence of Ct infections, the distribution of Ct serovars, and the incidences of Ct/HPV co-infections among women with a recent history of abnormal cervical cytology. Cervical samples were collected from 199 women referred for a gynecological visit following an abnormal Pap test results. All samples were tested for the presence of Ct and HPV DNA using real-time PCR assays; Ct typing of positive samples was performed by PCR-RFLP (restriction fragment length polymorphism) targeting the ompA gene. A high percentage of these women (12.8% and 21.7% with or without abnormal cytology on "retesting", respectively) were found to be Ct positive. Serovar F was the most prevalent type in Ct positive women, followed by E and K. Ct/HPV co-infections were detected in 7% (14/199) of enrolled women, with HPV-16, HPV-51, and HPV-52 being most frequently identified in co-infections. This study provides new epidemiological data on the prevalence of Ct and associated HPV infection in women with a recent history of abnormal cervical cytology in Italy, where notification of cases is not mandatory.


Assuntos
Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/isolamento & purificação , Infecções por Papillomavirus/complicações , Displasia do Colo do Útero/microbiologia , Adulto , Chlamydia trachomatis/genética , Coinfecção , Feminino , Papillomavirus Humano 16/genética , Humanos , Incidência , Itália/epidemiologia , Programas de Rastreamento , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Sorogrupo , Doenças Sexualmente Transmissíveis/epidemiologia
18.
Int J Mol Sci ; 20(16)2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31405112

RESUMO

Carcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant efficacy, but also considerable toxicity. This study addresses the chemopreventive effect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16-/-, n = 10, parecoxib-treated); II (HPV16-/- n = 11, untreated); III (HPV16+/-, n = 11, parecoxib-treated) and IV (HPV16+/-, n = 11, untreated). Parecoxib (5.0 mg/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+/- treated animals (0% versus 64% in HPV16+/- untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+/- treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn't modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive effects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.


Assuntos
Anticarcinógenos/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Papillomavirus Humano 16/isolamento & purificação , Isoxazóis/uso terapêutico , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/virologia , Animais , Anticarcinógenos/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Feminino , Papillomavirus Humano 16/genética , Isoxazóis/efeitos adversos , Camundongos , Camundongos Transgênicos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Pele/efeitos dos fármacos , Pele/patologia , Pele/virologia , Neoplasias Cutâneas/patologia
19.
BMC Cancer ; 19(1): 845, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455277

RESUMO

BACKGROUND: The rise in cervical cancer trends in the past two decades has coincided with the human immunodeficiency virus (HIV) epidemic especially in the sub-Saharan African region. Young people (15 to 24 years old) are associated with many risk factors such as multiple sexual partners, early sexual debut, and high HIV incidences, which increase the chances of developing cervical cancer. The National Cancer Prevention and Control Strategy for Zimbabwe (2014-2018) highlights that no cancer communication strategy focusing on risk factors as primary cancer prevention. Therefore, the study aims to determine the knowledge, attitude and practices of young people in Zimbabwe on cervical cancer, screening, human papillomavirus (HPV) and vaccination. METHODS: A cross-sectional survey assessing young people's knowledge, attitude and practices concerning cervical cancer was conducted in five provinces in Zimbabwe. A total of 751 young people were recruited through a three-stage cluster design from high schools and universities. Knowledge, attitudes and practices were assessed using questions based and adapted from the concepts of the Health Belief Model (HBM) and the Cervical Cancer Measuring tool kit-United Kingdom (UK). RESULTS: Most young people, 87.47% (656/750) claimed to know what the disease called cervical cancer is, with a mean score of 89.98% [95% CI 73.71.11-96.64] between high school and 86.72% [95% CI 83.48-89.40] among university students. There was no significant difference in mean scores between high school and university students (p = 0.676). A risk factor knowledge proficiency score of ≥13 out of 26 was achieved in only 13% of the high school respondents and 14% of the university respondents with a broad range of misconceptions about cervical cancer risk factors in both females and males. There was not much difference on comprehensive knowledge of cervical cancer and its risk factors between female and male students, with the difference in knowledge scores among high school (p = 0.900) and university (p = 0.324) students not statistically significant. In contrast, 43% of respondents heard of cervical cancer screening and prevention, and 47% knew about HPV transmission and prevention. Parents' educational level, province and smoking, were some of the factors associated with knowledge of and attitude towards cervical among high school and university students. CONCLUSION: This study revealed that young people in Zimbabwe have an idea about cervical cancer and the seriousness thereof, but they lack adequate knowledge of risk factors. Cervical cancer education and awareness emphasising causes, risk factors and care-seeking behaviours should be commissioned and strengthen at the community, provincial and national level. Developing a standard cervical cancer primary prevention tool that can be integrated into schools can be a step towards addressing health inequity.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Programas de Rastreamento , Razão de Chances , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vigilância em Saúde Pública , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Adulto Jovem , Zimbábue/epidemiologia
20.
Yi Chuan ; 41(8): 725-735, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447423

RESUMO

Oropharyngeal cancer is one type of head and neck squamous cell carcinoma that is commonly associated with human papillomavirus (HPV) infection. Its incidence is increasing year by year. However, in the clinical treatment, it is found that the overall prognosis of HPV positive oropharyngeal cancer patients is better than that of HPV negative patients. But till now, the underlying mechanism that leads to this phenomenon has not been fully elucidated. This research analyzed the immune cell infiltration and function, as well as neoantigen loads between HPV positive and negative patients by bioinformatic analysis using the TCGA database, and found that the overall survival rate of HPV positive patients was significantly higher than those in the HPV negative group. Analysis of the relative abundance of immune cells in tumor tissues showed that CD8 + T cells in HPV positive patients were significantly increased compared to those in HPV negative patients, and the expression levels of effector molecules, like IFN-γ and Granzyme B, were significantly upregulated. Meanwhile, the analysis of tumor neoantigen load (TNB) showed that the TNB of HPV positive patients was lower than that of the HPV negative group. This study provides some basic theoretical support for the treating HPV-related oropharyngeal cancer.


Assuntos
Antígenos de Neoplasias/análise , Linfócitos T CD8-Positivos/citologia , Neoplasias Orofaríngeas/diagnóstico , Infecções por Papillomavirus/diagnóstico , Humanos , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Prognóstico
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