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1.
Urologiia ; (5): 61-66, 2020 Nov.
Artigo em Russo | MEDLINE | ID: mdl-33185349

RESUMO

INTRODUCTION: The involvement of human papillomavirus (HPV) in male infertility is becoming increasingly evident. There are no approved treatment for male infertility associated with human papillomavirus infection (HPV). RESEARCH OBJECTIVE: To study the effectiveness of interferon therapy (recombinant interferon -2b with an antioxidant complex of vitamins E and C) in the treatment of male infertility associated with HPV MATERIALS AND METHODS: An analysis of the results of a survey of 103 patients aged 28 to 46 years with a diagnosis of infertility associated with HPV was carried out. Ejaculate was assessed in accordance with the WHO recommendations (2010); the amplification method of DNA diagnostics, polymerase chain reaction (PCR), was used to identify the type of virus. The material for the study was ejaculate. Depending on the therapy, the patients were divided into two groups: the 1st control group (n=54) - were under observation. Group 2 (n=49) - received treatment with recombinant interferon -2b with an antioxidant complex of vitamins E and C (Viferon), (rectal suppositories), which was prescribed at a dosage of 3,000,000 IU per rectum 2 times a day with an interval of 12 hours for 20 days. The observation period is 1 year. The end point of the study was the onset of pregnancy. RESULTS: When comparing the characteristics of the groups obtained, no statistically significant difference was found. Almost all of the studied patients had various types of pathospermia. When identifying the virus, 6, 16, 18, 31, 33 types of HPV were most often detected in the ejaculate. The most common disorder in the studied groups is asthenozoospermia. The association of several types of virus had a statistically significant weak inverse correlation with morphological changes in the ejaculate, in comparison with the ejaculate where one type of virus was detected (r=0.257, p=0.0853). The more types of the virus were registered in the ejaculate in associative relationships, the more the expression of morphological changes in the ejaculate. CONCLUSIONS: Male infertility may be due to the presence of HPV in the ejaculate. The more types of HPV present in the ejaculate, the lower the total sperm motility. For the treatment of infertility caused by PVI, it is recommended to use recombinant interferon -2b with an antioxidant complex of vitamins E and C.


Assuntos
Infertilidade Masculina , Papillomaviridae , Infecções por Papillomavirus , Adulto , Feminino , Humanos , Infertilidade Masculina/tratamento farmacológico , Interferons , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , Gravidez , Motilidade Espermática , Espermatozoides
3.
BMC Infect Dis ; 20(1): 801, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121447

RESUMO

BACKGROUND: According to the 2006 American Society for Colposcopy and Cervical Pathology guidelines, positive CIN2 p16 in women over the age of 25 should be managed with excisional treatment. However, excisional treatment is associated with physical, psychological and obstetric morbidity and can have a negative impact on sexual function. In our study we sought to identify a clear management strategy, addressing the impact of routine use of p16 immunohistochemistry in this population and identify appropriate criteria for patient selection with the aim of reducing over-treatment. METHOD: We studied the medical records of 130 patients who had undergone laser therapy for CIN2. Each patient underwent colposcopy, biopsy and HPV test and were tested for p16 protein,. Patients were divided based on HPV infection into: single infections, multiple infections. All patients underwent ZTA laser therapy with follow-up (2-year follow-up). STATISTICAL ANALYSIS: Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p < 0.05 were considered statistically significant. RESULTS: Single infections had a histological regression of 61.8% (21/34) and a histological persistence rate of 35.3% (12/34), which was greater than the multiple infection rate. The common characteristic that the women with persistence and progression had was the dimension of the lesion and the genotype 16. Ten cases of histological persistence and the only case of progression had one lesion greater than three quarters of the cervix. CONCLUSIONS: With the progress of our understanding of the natural history of infection from human papillomavirus and the increasing use of colposcopy, thanks to the addition of HPV genotyping and the technique of immunohistochemistry, conservative management of these lesions is now possible.


Assuntos
Neoplasia Intraepitelial Cervical/complicações , Neoplasia Intraepitelial Cervical/terapia , Tratamento Conservador/métodos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/terapia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Colposcopia , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Progressão da Doença , Feminino , Seguimentos , Genótipo , Humanos , Imuno-Histoquímica , Terapia a Laser , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/virologia
4.
Crit Rev Oncol Hematol ; 156: 103116, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33115701

RESUMO

OBJECTIVES: to provide accurate information about the global prevalence of human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (OPSCC). MATERIAL AND METHODS: a systematic review was performed using three main electronic databases. Studies were independently assessed by two reviewers based on established eligibility criteria, to identify the prevalence of HPV-driven OPSCC following criteria defined by the American Society of Clinical Oncology. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Statistical software MedCalc was used to perform meta-analyses. RESULTS: from 2215 records found, 15 were included, reporting data from 6009 patients (time period range: 1980-2016), distributed in 11 countries. Eleven studies were considered as presenting low risk, and four as moderate risk of bias. Using proportion meta-analysis, pooled prevalence of HPV-driven OPSCC was 44.8 % (95 %CI: 36.4-53.5 %; i2 = 97.6 %), with the highest rates in New Zealand (74.5 %; 95 %CI: 60.9-85.3 %), and the lowest in Brazil (11.1 %; 95 %CI: 4.5-21.5 %). HPV prevalence was similar between males (45.7 %; 95 %CI: 36.5-55.0 %; i2 = 96.4 %) and females (42.2 %; 95 %CI: 34.3-50.5 %; i2 = 85.4 %). Mean/median age ranged from 59.1-67.1 years in the HPV-negative group, and from 55.7-63.5 years in the HPV-positive group. There was an overall discordance between testing by p16 (49.4 %; 95 %CI, 38.2-60.5 %; i2 = 96.2 %) and p16+ISH/PCR (44.7 %; 95 %CI, 33.5-56.2 %; i2 = 96.4 %). CONCLUSION: Overall pooled prevalence of HPV-driven OPSCC was approximately 45 %, with similar distribution among males and females. Double p16/HPV-DNA/RNA testing may be considered to increase specificity and prognostic accuracy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Papillomaviridae , Infecções por Papillomavirus , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Prevalência
5.
MMWR Morb Mortal Wkly Rep ; 69(37): 1283-1287, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32941412

RESUMO

Human papillomavirus (HPV) causes most cervical cancers and some cancers of the penis, vulva, vagina, oropharynx, and anus. Cervical precancers can be detected through screening. HPV vaccination with the 9-valent HPV vaccine (9vHPV) can prevent approximately 92% of HPV-attributable cancers (1).* Previous studies have shown lower incidence of HPV-associated cancers in non-Hispanic American Indian and Alaska Native (AI/AN) populations compared with other racial subgroups (2); however, these rates might have been underestimated as a result of racial misclassification. Previous studies have shown that cancer registry data corrected for racial misclassification resulted in more accurate cancer incidence estimates for AI/AN populations (3,4). In addition, regional variations in cancer incidence among AI/AN populations suggest that nationally aggregated data might not adequately describe cancer outcomes within these populations (5). These variations might, in part, result from geographic disparities in the use of health services, such as cancer screening or vaccination (6). CDC analyzed data for 2013-2017 from central cancer registries linked with the Indian Health Service (IHS) patient registration database to assess the incidence of HPV-associated cancers and to estimate the number of cancers caused by HPV among AI/AN populations overall and by region. During 2013-2017, an estimated 1,030 HPV-associated cancers were reported in AI/AN populations. Of these cancers, 740 (72%) were determined to be attributable to HPV types targeted by 9vHPV; the majority were cervical cancers in females and oropharyngeal cancers in males. These data can help identify regions where AI/AN populations have disproportionately high rates of HPV-associated cancers and inform targeted regional vaccination and screening programs in AI/AN communities.


Assuntos
Nativos do Alasca/estatística & dados numéricos , Índios Norte-Americanos/estatística & dados numéricos , Neoplasias/etnologia , Neoplasias/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/etnologia , Feminino , Humanos , Incidência , Masculino , Sistema de Registros , Estados Unidos/epidemiologia
6.
BMC Infect Dis ; 20(1): 642, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873233

RESUMO

BACKGROUND: Evidence suggested that vaginal microbiome played a functional role in the progression of cervical lesions in female infected by HPV. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of high risk HPV (hr-HPV). METHODS: From January 15, 2017 to December 31, 2017, 310,545 female aged at least 30 years old had been recruited for cervical cancer screening from 9 clinical research centers in Central China. All the recruited participants received hr-HPV genotyping for cervical cancer screening and vaginal microenvironment test by a high vaginal swab. Colposcopy-directed biopsy was recommended for female who were infected with HPV 16 and HPV 18, and other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results ≥ ASCUS among them were referred to colposcopy directly, and cervical tissues were taken for pathology examination to make clear the presence or absence of other cervical lesions. RESULTS: Among 310,545 female, 6067 (1.95%) were tested with positive HPV 16 and HPV 18, 18,297 (5.89%) were tested with other positive hr-HPV genotypes, cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3 and invasive cervical cancer (ICC) were detected in 861 cases, 377 cases, 423 cases, and 77 cases, respectively. Candida albicans and Gardnerella were not associated with the detection of cervical lesions. Positive trichomonas vaginitis (TV) was correlated with hr-HPV infection (p < 0.0001). Co-infection with TV increased the risk of CIN 1 among female infected with hr-HPV (OR 1.18, 95% CI: 1.42-2.31). Co-infection with TV increased the risk of CIN 2-3 among female infected with HPV 16 (OR 1.71, 95% CI: 1.16-2.53). CONCLUSIONS: Co-infection of TV and HPV 16 is a significant factor for the detection of cervical lesions.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Coinfecção/complicações , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Infecções por Papillomavirus/complicações , Vaginite por Trichomonas/complicações , Trichomonas vaginalis/isolamento & purificação , Neoplasias do Colo do Útero/epidemiologia , Adulto , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Coinfecção/diagnóstico , Colposcopia , Estudos Transversais , Citodiagnóstico , Detecção Precoce de Câncer/métodos , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Vaginite por Trichomonas/diagnóstico , Vaginite por Trichomonas/parasitologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia
7.
J Exp Clin Cancer Res ; 39(1): 200, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967703

RESUMO

BACKGROUND: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas. METHODS: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC. RESULTS: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation. CONCLUSIONS: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Neoplasias de Cabeça e Pescoço/patologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Pneumonia Viral/complicações , Serina Endopeptidases/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estudos de Casos e Controles , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pandemias , Infecções por Papillomavirus/virologia , Pneumonia Viral/virologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Taxa de Sobrevida
8.
PLoS Pathog ; 16(8): e1008792, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813746

RESUMO

Tumor suppressors can exert pro-proliferation functions in specific contexts. In the beta human papillomavirus type 38 (HPV38) experimental model, the viral proteins E6 and E7 promote accumulation of a wild-type (WT) p53 form in human keratinocytes (HKs), promoting cellular proliferation. Inactivation of p53 by different means strongly decreases the proliferation of HPV38 E6/E7 HKs. This p53 form is phosphorylated at S392 by the double-stranded RNA-dependent protein kinase PKR, which is highly activated by HPV38. PKR-mediated S392 p53 phosphorylation promotes the formation of a p53/DNMT1 complex, which inhibits expression of integrin alpha 1 (ITGA1), a repressor of epidermal growth factor receptor (EGFR) signaling. Ectopic expression of ITGA1 in HPV38 E6/E7 HKs promotes EGFR degradation, inhibition of cellular proliferation, and cellular death. Itga1 expression was also inhibited in the skin of HPV38 transgenic mice that have an elevated susceptibility to UV-induced skin carcinogenesis. In summary, these findings reveal the existence of a specific WT p53 form that displays pro-proliferation properties.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Proliferação de Células , Queratinócitos/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/complicações , Proteínas Repressoras/metabolismo , Neoplasias Cutâneas/etiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Células Cultivadas , Regulação para Baixo , Humanos , Queratinócitos/imunologia , Queratinócitos/virologia , Camundongos , Camundongos Transgênicos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/isolamento & purificação , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/virologia , Proteínas Repressoras/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteína Supressora de Tumor p53/genética
9.
HNO ; 68(9): 657-661, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32767069

RESUMO

Surgical therapy, regardless of the procedure, remains of great importance for today's treatment of oropharyngeal carcinomas, despite advances in radiation and immunotherapy. The individual treatment plan should be defined in discussion with the patient and in an interdisciplinary tumor conference, taking into account the likelihood of achieving of tumor-free resection margins and an acceptable postoperative quality of life. With regard to conventional and possibly also open surgical procedures, a good overview of the surgical site-particularly in the case of more extensive carcinomas and challenging patient anatomy-and simplified reconstructability of the defect region are decisive aspects. Endoscopically, microsurgically, or even robot-assisted minimally invasive procedures have the advantage of precise and gentle removal of tumor tissue with improved maintenance of function. Overall, selection of the appropriate surgical procedure remains an individual decision based on tumor size, the facilities at the tumor center, and the surgeon's experience. The extent of surgical intervention, also with regard to simultaneous neck dissection, depends on tumor stage. In the case of oropharyngeal carcinomas, there will be an increasing distinction between human papillomavirus (HPV)-negative and HPV-positive tumors in the future; however, the therapeutic strategy is currently identical. Upcoming clinical trials will show whether treatment de-escalation is appropriate depending on HPV infection status.


Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Procedimentos Cirúrgicos Robóticos , Humanos , Esvaziamento Cervical , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Qualidade de Vida
10.
Andrologia ; 52(9): e13791, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32790205

RESUMO

Male infertility is linked to some viral infections including human papillomavirus (HPV), herpes simplex viruses (HSV) and human immunodeficiency viruses (HIVs). Almost nothing is known about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effect on fertility. The possible risk factors of coronavirus disease 2019 (COVID-19) infection on fertility comes from the abundance of angiotensin-Converting Enzyme-2 (ACE2), receptor entry of the virus, on testes, a reduction in important sex hormone ratios and COVID-19-associated fever. Recent studies have shown a gender difference for COVID-19 rates and comorbidity. In this review, we will discuss the potential effect of COVID-19 on male fertility and talk about what needs to be done by the scientific community to tackle our limited understanding of the disease. On the other side, we will focus on what is known so far about the risk of COVID-19 on pregnancy, neonatal health and the vertical transfer of the virus between mothers and their neonates. Finally, because reproduction is a human right and infertility is considered a health disease, we will discuss how assisted reproductive clinics can cope with the pandemic and what guidelines they should follow to minimise the risk of viral transmission.


Assuntos
Infecções por Coronavirus/complicações , Transmissão Vertical de Doença Infecciosa , Infertilidade Masculina/virologia , Pneumonia Viral/complicações , Complicações Infecciosas na Gravidez/virologia , Saúde Reprodutiva , Betacoronavirus/isolamento & purificação , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/transmissão , Infecções por HIV/virologia , Herpes Simples/complicações , Herpes Simples/transmissão , Herpes Simples/virologia , Humanos , Infertilidade Masculina/patologia , Masculino , Pandemias , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/transmissão , Infecções por Papillomavirus/virologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Gravidez , Fatores de Risco , Glicoproteína da Espícula de Coronavírus/metabolismo , Testículo/metabolismo , Testículo/patologia
11.
Medicine (Baltimore) ; 99(27): e21005, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629719

RESUMO

INTRODUCTION: Mild local hyperthermia at 44°C has been proven efficacious in the treatment of cutaneous warts induced by human papillomavirus (HPV), while its effect on cervical intraepithelial neoplasia (CIN) caused by high risk type of HPVs has not been reported. PATIENT CONCERNS: Three patients with low grade CIN and positive high risk HPV types (HPV 16, 31, 52, 56, 58) are reported in this study. DIAGNOSIS: The diagnosis was based on identification of HPV types and abnormal cytological findings. INTERVENTIONS: The 3 patients were treated with local hyperthermia from ceramic heating (surface temperature, 44°C) to cervix. The treatment was delivered once a day for 3 consecutive days, plus two similar treatments 10 ± 3 days later, with each session lasting 30 minutes. HPV and cytology test were performed 3 months thereafter. OUTCOMES: All the 3 patients recovered to normal cytological findings. Two of the patients were negative for HPV, the remaining patient with pre-treatment HPV 56 and 58 positivity changed to HPV58 positive alone. CONCLUSION: This pilot observation inspires that mild local hyperthermia be recommended as a new method in the treatment of CIN patients with persistent HPV infection, once validated by qualified RCT.


Assuntos
Neoplasia Intraepitelial Cervical/terapia , Hipertermia Induzida/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/virologia
12.
J Laryngol Otol ; 134(6): 533-540, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32616096

RESUMO

OBJECTIVE: To evaluate the effect of definitive radiotherapy dose on survival in patients with human papillomavirus positive oropharyngeal carcinoma. METHODS: Human papillomavirus positive oropharyngeal carcinoma patients staged T1-3 and N0-2c, who received definitive radiotherapy (fraction sizes of 180 cGy to less than 220 cGy), were identified from the National Cancer Database 2010-2014 and stratified by radiation dose (50 Gy to less than 66 Gy, or 66 Gy or more). RESULTS: A total of 2173 patients were included, of whom 124 (6 per cent) received a radiation dose of 50 Gy to less than 66 Gy. With a median follow up of 33.8 months, patients had a 3-year overall survival rate of 88.6 per cent (95 per cent confidence interval = 87.1-90.1 per cent). On multivariate Cox analysis, a radiotherapy dose of 50 Gy to less than 66 Gy (hazard ratio = 0.95, 95 per cent confidence interval = 0.52-1.74, p = 0.86) was not a predictor of increased mortality risk. CONCLUSION: Human papillomavirus positive oropharyngeal carcinoma patients had excellent outcomes with definitive radiotherapy doses of 50 Gy to less than 66 Gy. These results further support patients enrolling into clinical trials for radiation dose de-escalation.


Assuntos
Carcinoma/radioterapia , Neoplasias Orofaríngeas/mortalidade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/virologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Radioterapia/métodos , Taxa de Sobrevida
13.
HNO ; 68(9): 688-694, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32638060

RESUMO

The incidence of human papillomavirus (HPV)-positive oropharyngeal carcinomas is increasing worldwide. Due to a markedly different response to treatment compared to HPV-negative oropharyngeal carcinomas, determining the ideal therapeutic approach can be challenging. Particularly in never-smokers, HPV-positive oropharyngeal carcinomas respond well to primary radiation therapy; at the same time recent studies indicate comparable survival after primary surgery. For stage I tumors according to TNM­8, retrospective analyses show very good oncologic outcomes after surgery alone, and no added benefit of adjuvant radio- or chemotherapy. Results of prospective treatment deintensification trials are expected in the coming years. Minimally invasive transoral surgical approaches for selected oropharyngeal cancers can improve preservation of postoperative function and quality of life. For both HPV-positive and HPV-negative oropharyngeal carcinomas, salvage surgery is the treatment of choice for resectable recurrent locoregional disease and resectable distant metastases.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Procedimentos Cirúrgicos Robóticos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/virologia , Humanos , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Terapia de Salvação
14.
Life Sci ; 256: 118026, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32615187

RESUMO

AIM: We aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection. MATERIALS AND METHODS: Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated. CONCLUSION: Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina/genética , Genes MHC da Classe II/genética , Infecções por Papillomavirus/complicações , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Regulação para Baixo , Matriz Extracelular/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Estadiamento de Neoplasias , Infecções por Papillomavirus/genética , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia , Transcriptoma , Regulação para Cima , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
15.
BMC Womens Health ; 20(1): 139, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615963

RESUMO

BACKGROUND: Although human papillomavirus (HPV) infection has been regarded as the cause of cervical cancer in over 99% of cases, only a small fraction of HPV-infected women develop this malignancy. Emerging evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains undetermined. METHODS: The current study included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to compute odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models. RESULTS: HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls (1.63 vs. 1.23, P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed (Ptrend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant. CONCLUSIONS: In women who test HPV positive, the increase of mtCN in cervical exfoliated cells is associated with cervical cancer. This suggests a potential role of mtCN in cervical carcinogenesis.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/epidemiologia , China/epidemiologia , DNA Viral/genética , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
16.
Pol Merkur Lekarski ; 48(285): 157-161, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32564038

RESUMO

Social trends, a new style of modern young woman, which includes the polygamy of sexual relationships, increases the incidence and probability of infection caused by sexually transmitted pathogens, including the human papillomavirus. In women entered into motherhood with chronic papillomavirus carrier, pregnancy is accompanied with an increase in obstetrics and perinatal complications. The inability to use antiviral therapy due to its embryo- and fetotoxic effects requires searching for safe agents for timely and effective preconceptional and prenatal preparation for the fetal infection prevention. AIM: The aim of the study was to evaluate a reduce level of obstetrics and perinatal complications in pregnant women infected with the human papillomavirus by using adequate preconceptional and prenatal preparation. MATERIALS AND METHODS: The immune status assessment was provided in 89 women who were chronic carriers of papillomavirus infection by determining the T and B lymphocyte levels, the concentration of proinflammatory (IL-2, IL-6, TNF-α) and anti-inflammatory (IL-4, IL-10) factors and the follow-up analysis of the pregnancy course and childbirth. RESULTS: Pregnancy course in women who are chronic carriers of human papillomavirus infection is accompanied by the high incidence of perinatal complications such as placental dysfunction, polyhydramnios, gestosis, premature membrane rupture, preterm labour, oligohydramnios, and fetal growth retardation syndrome. Chronic carriage of human papillomavirus infection leads to decrease in the CD3+, CD4+, and CD19+ levels associated with an increased CD8+ level and activation of proinflammatory cytokines (IL-2, IL-6, TNF-α) against the background of a decrease in their anti-inflammatory concentration analogues (IL-4, IL- 10) during pregnancy, which, in turn, creates favourable conditions for viral reactivation and subsequently causes reproductive complications and losses. CONCLUSIONS: The use of Proteflazid which contain a complex of plant flavonoids with a direct antiviral effect on human papillomavirus, for the purpose of preconceptional and prenatal preparation in women who are chronic carriers of human papillomavirus infection, contributes to the pregnant woman's immune balance restoration and significant perinatal complication reduction.


Assuntos
Trabalho de Parto Prematuro , Infecções por Papillomavirus , Complicações Infecciosas na Gravidez , Feminino , Humanos , Recém-Nascido , Trabalho de Parto Prematuro/prevenção & controle , Infecções por Papillomavirus/complicações , Parto , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/terapia
17.
PLoS One ; 15(6): e0233974, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542012

RESUMO

BACKGROUND: The surrogate immunohistochemical marker, p16INK4a, is used in clinical practice to determine the high-risk human papillomavirus (HPV) status of oropharyngeal squamous cell carcinomas (OPSCC). With a specificity of 83%, this will misclassify some patients compared with direct HPV testing. Patients who are p16INK4a-positive but HPV DNA-negative, or RNA-negative, may be unsuitable for treatment de-escalation aimed at reducing treatment-related side effects. We aimed to identify cost-effective serum markers to improve decision making for patients at risk of misclassification by p16INK4a alone. METHODS: Serum proteins from pre-treatment samples of 36 patients with OPSCC were identified and quantified using label-free mass spectrometry-based proteomics. HPV-status was determined using p16INK4a/HPV DNA and E6/E7 mRNA. Serum protein expressions were compared between groups of patients according to HPV status, using the unpaired t-test with a Benjamini-Hochberg correction. ROC curves (AUC) were calculated with SPSS (v25). RESULTS: Of 174 serum proteins identified, complement component C7 (C7), apolipoprotein F (ApoF) and galectin-3-Binding Protein (LGALS3BP) significantly differed between HPV-positive and -negative tumors (AUC ranging from 0.84-0.87). ApoF levels were more than twice as high in the E6/E7 mRNA HPV-positive group than HPV-negative. CONCLUSIONS: Serum C7, ApoF and LGALS3BP levels discriminate between HPV-positive and HPV-negative OPSCC. Further studies are needed to validate these host immunity-related proteins as markers for HPV-associated OPSCC.


Assuntos
Antígenos de Neoplasias/sangue , Apolipoproteínas/sangue , Biomarcadores Tumorais/sangue , Complemento C7/análise , Neoplasias Orofaríngeas/sangue , Neoplasias Orofaríngeas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Inibidor p16 de Quinase Dependente de Ciclina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue
18.
Cancer ; 126(15): 3426-3437, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32478895

RESUMO

BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT-hypo) during the COVID-19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT-hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT-acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005-2017 were included. Locoregional control (LRC) and distant control (DC) after RT-hypo, RT-acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT-hypo, RT-acc, and CCRT, respectively) and 1045 HPV- HNSCC cases (with 263, 451, and 331 receiving RT-hypo, RT-acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy-alone patients were older. The median follow-up was 4.6 years. RT-hypo, RT-acc, and CCRT produced comparable 3-year LRC and DC for HPV+ T1-2N0-N2a disease (seventh edition of the TNM system [TNM-7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1-T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1-2N2c/T3N0-N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT-hypo or RT-acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV- HNSCC, 3-year LRC and DC were similar with RT-hypo, RT-acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT-hypo and RT-acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT-acc (62%) but not RT-hypo (80%) or CCRT (92%; RT-hypo vs CCRT: P = .270; RT-acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT-hypo or RT-acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT-hypo be considered in place of CCRT for HPV+ T1-T3N0-N2c (TNM-7) HNSCCs, HPV- T1-T2N0 HNSCCs, and select stage III HNSCCs during the COVID-19 outbreak.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Hipofracionamento da Dose de Radiação , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/epidemiologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/virologia , Pandemias , Infecções por Papillomavirus/complicações , Pneumonia Viral/epidemiologia , Radioterapia de Intensidade Modulada , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Resultado do Tratamento
19.
Int J Gynecol Cancer ; 30(8): 1097-1100, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32487685
20.
Acta Cytol ; 64(5): 442-451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32599588

RESUMO

INTRODUCTION: Persistent infection with high-risk human papillomavirus (HPV) types is associated with high-grade intraepithelial lesions (HSILs) and invasive cervical cancer. The host immune response plays a key role in whether HPV clears or persists. Most studies on local immune response to HPV collect cervical mucus in order to quantify secreted cytokines; however, cells located inside the tissue can release different cytokines associated with HPV infection. OBJECTIVE: This study compared the cytokine levels in cervical biopsy specimens of women with abnormal colposcopic findings according to the histopathological results: low-grade intraepithelial lesion (LSIL), HSIL, and no intraepithelial lesion (NSIL). METHODS: A cross-sectional study enrolling 141 cervical biopsy specimens examined the cytokine profile for interleukin (IL-) 2, IL-4, IL-10, IL-12, IL-17, and IL-23 and interferon-γ, using the Luminex assay/ELISA. Differences in cytokine levels among the cervical lesion groups were assessed using the Kruskal-Wallis test. RESULTS: The 141 specimens included 90 HSILs, 22 LSILs, and 29 NSILs. IL-2 levels were significantly higher in NSIL samples than in LSIL or in HSIL samples (p = 0.0001) and IL-23 levels were significantly higher in NSIL than in HSIL samples (p = 0.003). CONCLUSIONS: Our study shows that in samples from the lesion site point, 2 important pro-inflammatory cytokines, IL-2 and IL-23, are downregulated in HPV lesions.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Interleucina-23/metabolismo , Interleucina-2/metabolismo , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/patologia , Adulto , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/virologia , Estudos Transversais , Regulação para Baixo , Feminino , Humanos , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia
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