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1.
BMC Infect Dis ; 21(1): 278, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740909

RESUMO

BACKGROUND: The causative agent of cervical cancer referred to as Human papillomavirus (HPV) remains a real public health problem. Many countries in West Africa, such as Togo have no data on the high-risk HPV (HR-HPV) infection and genotypes distribution. In order to fill the knowledge gap in the field in Togo, the main objective of this study was to determine the prevalence of pre-cancerous lesions of the cervix and HR-HPV genotypes among Togolese women. METHODS: Samples were collected from 240 women by introducing a swab in the cervix. Then, the screening of precancerous cervical lesions using the visual inspection with acetic acid and lugol (VIA / VIL) was conducted. The HR-HPV genotypes were characterised by real-time multiplex PCR. RESULTS: Out of 240 women recruited, 128 (53.3%) were infected by HR-HPV. The most common genotypes were HPV 56 (22.7%), followed by HPV 51 (20.3%), HPV 31 (19.5%), HPV 52 (18.8%) and HPV 35 (17.2%). The least common genotypes were HPV 33 (2.3%) and HPV 16 (2.3%). Among the women, 1.3% (3/240) were positive to VIA/VIL. CONCLUSION: This study allowed HR-HPV genotypes to be characterised for the first time in Lomé, Togo. This will help in mapping the HR-HPV genotypes in West Africa.


Assuntos
Alphapapillomavirus/genética , Infecções por Papillomavirus/patologia , Adulto , Alphapapillomavirus/isolamento & purificação , Colo do Útero/virologia , Estudos Transversais , DNA Viral/genética , DNA Viral/metabolismo , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Infecções por Papillomavirus/epidemiologia , Fatores de Risco , Togo/epidemiologia
2.
BMC Cancer ; 21(1): 232, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676451

RESUMO

BACKGROUND: There is currently a lack of information on full anogenital evaluation of women with a previous history of anogenital neoplasia. METHODS: Retrospective analysis of the Homerton Anogenital Neoplasia Service records from January 2012 to March 2017, to identify all new referrals of women with previous anogenital neoplasia, who had had at least one complete examination of all anogenital sites. Multizonal anogenital disease (MZD) was defined as the presence of high-grade squamous intraepithelial lesions (HSIL)/carcinoma concurrently at two or more of the following sites/zones: perianus, anal canal, vulva, vagina or cervix. RESULTS: 253 women were included, mean age was 47 (SD=15) years and median duration of follow-up was 12 (IQR=21) months. Fifty-six women (22%) were diagnosed with MZD at first assessment and/or during follow-up. Current smokers (RR=1.84, 95% CI 1.21-2.79, p=0.004) and women on immunodulators/immunosuppressive drugs (RR=2.57, 95% CI 1.72-3.86, p<0.001) had an increased risk for MZD. The risk was lower for women without a previous history of anogenital high-grade lesions/cancer compared to those with this history (RR=0.06, 95% CI 0.01-0.45, p=0.006). CONCLUSIONS: Multizonal assessment was important to diagnose occult areas of disease and should be especially considered in current smokers, pharmacologically immunocompromised and those with a previous history of anogenital HSIL/cancer.


Assuntos
Neoplasias do Ânus/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias dos Genitais Femininos/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Infecções por Papillomavirus/diagnóstico , Adulto , Canal Anal/diagnóstico por imagem , Canal Anal/patologia , Canal Anal/virologia , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/virologia , Biópsia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Colo do Útero/virologia , Colposcopia , Feminino , Seguimentos , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/virologia , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Centros de Atenção Terciária/estatística & dados numéricos , Vagina/diagnóstico por imagem , Vagina/patologia , Vagina/virologia , Vulva/diagnóstico por imagem , Vulva/patologia , Vulva/virologia
3.
Arch Virol ; 166(4): 1157-1161, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33550506

RESUMO

Numerous raised plaques were observed on the feet of a red-billed gull (Chroicocephalus novaehollandiae scopulinus) that had been found dead. The plaques consisted of thickened epidermis with cell changes indicative of papillomavirus (PV) infection prominent within affected areas. Evidence suggesting progression to neoplasia was visible in one lesion. A DNA sequence that was most similar, but only 68.3% identical, to duck PV type 3 was amplified from the papillomas, suggesting a novel PV type. Lesions containing PV DNA have only previously been reported in three avian species. This is the first evidence that PVs could cause neoplasia in birds.


Assuntos
Doenças das Aves/virologia , Carcinoma in Situ/veterinária , Charadriiformes/virologia , Papiloma/veterinária , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/veterinária , Animais , Doenças das Aves/patologia , Proteínas do Capsídeo/genética , Carcinoma in Situ/patologia , Carcinoma in Situ/virologia , DNA Viral/genética , Pé/patologia , Pé/virologia , Papiloma/patologia , Papiloma/virologia , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Filogenia
4.
Arch Gynecol Obstet ; 303(4): 1049-1056, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33624123

RESUMO

PURPOSE: This study was aimed to quantify genomic DNA breakages in the cervical epithelium cells of patients diagnosed with different grades of cervical lesions using a quick test based on chromatin dispersion after controlled protein depletion. The association between the progressive stages of cervical dysplasia and the levels of DNA damage, taking into account the presence of papillomavirus human (HPV) infection, was investigated. METHODS: A hospital-based unmatched case-control study was conducted during 2018 with a sample of 78 women grouped according to histological diagnosis as follows: 23 women with low grade-squamous intraepithelial lesion (LG-SIL), 34 women with high grade- squamous intraepithelial lesion (HG-SIL), and three women with cervical carcinoma (CC). In parallel, 15 women without cervical lesions were included as a Control cohort. DNA damage levels in cervical epithelial cells were assessed using the chromatin dispersion test (CDT) and controlled in parallel with DNA breakage detection coupled with florescent in situ hybridization (DBD‒FISH) using whole genomic DNA probes. RESULTS: CDT produces different morphotypes in the cervical epithelium that can be associated with the level of DNA breakage revealed with DBD‒FISH. A significant increase of DNA damage was correlated with the histological progression of the patients and human papillomavirus (HPV) infection. CONCLUSION: The CDT is a simple, accurate and inexpensive morphological bioassay to identify different levels DNA damage that can be associated with the level of abnormal cells present in the cervical epithelium in patients who commonly present HPV infection.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Cromatina , Células Epiteliais/patologia , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Adulto Jovem
5.
Viruses ; 13(1)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33418959

RESUMO

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is driven by human papillomavirus (HPV) low-risk strains and is associated with significant morbidity. While previous studies of 2D cultures have shed light on disease pathogenesis and demonstrated the utility of personalized medicine approaches, monolayer cultures lack the 3D tissue architecture and physiology of stratified, sequentially differentiated mucosal epithelium important in RRP disease pathogenesis. Herein we describe the establishment of JoRRP-derived primary cell populations that retain HPV genomes and viral gene expression in culture. These were directly compared to cells from matched adjacent non-diseased tissue, given the known RRP patient-to-patient variability. JoRRP papilloma versus control cells displayed decreased growth at subconfluency, with a switch to increased growth after reaching confluency, suggesting relative resistance to cell-cell contact and/or differentiation. The same papilloma cells grown as 3D organotypic rafts harbored hyperproliferation as compared to controls, with increased numbers of proliferating basal cells and inappropriately replicating suprabasal cells, mimicking phenotypes in the patient biopsies from which they were derived. These complementary model systems provide novel opportunities to elucidate disease mechanisms at distinct stages in JoRRP progression and to identify diagnostic, prognostic and therapeutic factors to personalize patient management and treatment.


Assuntos
Alphapapillomavirus/genética , Alphapapillomavirus/isolamento & purificação , Células Epiteliais/virologia , Infecções por Papillomavirus/virologia , Infecções Respiratórias/patologia , Humanos , Técnicas de Cultura de Órgãos , Infecções por Papillomavirus/patologia , Fenótipo , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Infecções Respiratórias/virologia , Fatores de Risco
6.
Viruses ; 13(1)2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374445

RESUMO

There are >200 different types of human papilloma virus (HPV) of which >51 infect genital epithelium, with the ~14 of these classed as high-risk being more commonly associated with cervical cancer. During development of the disease, high-risk types have an increased tendency to develop a truncated non-replicative life cycle, whereas low-risk, non-cancer-associated HPV types are either asymptomatic or cause benign lesions completing their full replicative life cycle. HPVs can also be present as non-replicative so-called "latent" infections and they can also show superinfection exclusion, where cells with pre-existing infections with one type cannot be infected with a different HPV type. Thus, the HPV repertoire and replication status present in an individual can form a complex dynamic meta-community which changes with respect to both time and exposure to different HPV types. In light of these considerations, it is not clear how current prophylactic HPV vaccines will affect this system and the potential for iatrogenic outcomes is discussed in light of recent outcome data.


Assuntos
Proteínas do Capsídeo/imunologia , Proteínas Oncogênicas Virais/imunologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Superinfecção/virologia , Latência Viral , Feminino , Humanos , Incidência , Neoplasias/etiologia , Papillomaviridae/classificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prevalência , Lesões Intraepiteliais Escamosas Cervicais/etiologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Vacinação , Latência Viral/imunologia , Replicação Viral
7.
Med Clin North Am ; 104(6): 1063-1078, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33099451

RESUMO

The most effective strategy for cervical cancer prevention involves vaccination to prevent human papillomavirus (HPV) infections during adolescence followed by screening to detect HPV infections during adulthood. HPV vaccination before sexual debut can prevent HPV infections, precancers, and cancers. HPV vaccination of sexually active populations does not prevent cancer. Screening with HPV testing is the most effective method of detecting precancers and cancers between ages 25 and 65. Ensuring adequate screening around the age of menopause may be the key to preventing cervical cancer among elderly women. Most cervical cancers at all ages occur among unscreened or underscreened women.


Assuntos
Neoplasias do Colo do Útero/prevenção & controle , Detecção Precoce de Câncer , Feminino , Humanos , Teste de Papanicolaou , Papillomaviridae/imunologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/prevenção & controle , Atenção Primária à Saúde , Estados Unidos , Neoplasias do Colo do Útero/patologia , Vacinação
8.
Anticancer Res ; 40(11): 6355-6366, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109573

RESUMO

BACKGROUND/AIM: p16 and PTEN are tumor suppressor genes. Loss of these molecules in oral squamous cell carcinoma (OSCC) has been studied worldwide. In this study, we explored whether p16 cooperates with inactive PTEN during the pathogenesis of OSCC, especially in regard to tumor aggressiveness and proliferation. MATERIALS AND METHODS: Immunocytochemistry and western blot analysis were used to examine the levels of p16 and PTEN. Sequencing analysis was performed to identify mutations in the PTEN gene and HPV infection. Fluorescence in situ hybridization was used to examine the presence of the PTEN locus. RESULTS: PTEN analysis showed high positivity in T4 samples. HPV-positive tumors correlated with tabagism, tumor size 3 and 4, disease stages 3 and 4, presence of lymph node metastasis (N1) and poor differentiation. Immunoexpression of p16 was strongly correlated with the presence of HPV. CONCLUSION: PTEN demonstrated a higher reactivity in advanced disease stages and p16 was strongly associated with HPV. Viral presence decreases tumor aggressiveness. Patients with advanced stage lesions demonstrated lower survival rate.


Assuntos
Carcinoma de Células Escamosas/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias Bucais/genética , PTEN Fosfo-Hidrolase/genética , Adulto , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Hibridização in Situ Fluorescente , Perda de Heterozigosidade/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia
9.
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
10.
APMIS ; 128(12): 637-646, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32911563

RESUMO

High-risk HPVs (HR-HPVs) are DNA viruses considered as primary etiologic factors in malignancies of the low female genital tract. Their presence has also been documented in oropharyngeal and laryngeal cancers. However, HPV infection is considered a necessary but not sufficient cause of tumoral development; meantime, increasing evidences on the tumorigenic role of cancer stem cells (CSCs) have been documented in the literature. CSCs represent a small subpopulation of neoplastic cells with self-renewal potential, capable of maintaining tumor growth and cell differentiation, also involved in metastatic process, recurrence, and resistance to chemotherapeutic agents. In the present study, performed on KB cell lines, we evaluated the tumor forming potential of CSCs, and their relationship with the HPV infection status. We started our study by identifying the most aggressive cell line on the minimal number of cells being able of growth in vivo in a model of athymic nude mice (BALB/c nu/nu). We used an oral-derived KB cell line separated in the KB-CD133+ and KB-CD133- populations, by using immunomagnetic beads and fluorescence-activated cell sorting (FACS). The separated populations were injected in athymic nude mice (BALB/c nu/nu). Xenograft tumors have been analyzed for tumor size, CD133 expression by immunohistochemistry (IHC) and for DNA HR-HPV integration by in situ hybridization (ISH), comparing CD133-enriched xenograft tumors versus the CD133 non-enriched ones. On standard conditions, the KB cell line has a poor population of glycosylated CD133 marker (<5.0%) when investigated with antibodies versus CD133, and more specifically its glycosylated epitope (AC133). Enriched CD133 KB cells possess a higher capacity of tumor growth in xenograft models of nude mice when compared to KB CD133-negative cells. We observed that the AC133 epitope, extensively used to purifying hematopoietic stem cells, is able to select an epithelial subpopulation of cancer stem cells with aggressive behavior. We retain that CD133 may be a useful target in anticancer strategies including pharmacological and immunological therapies.


Assuntos
Antígeno AC133/metabolismo , Papillomavirus Humano 18/fisiologia , Células-Tronco Neoplásicas/metabolismo , Infecções por Papillomavirus/metabolismo , Antígeno AC133/genética , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/patologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia
11.
BMC Infect Dis ; 20(1): 683, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948142

RESUMO

BACKGROUND: External genital lesions (EGL) are the most common sexually transmitted infections (STIs). We aimed to evaluate the prevalence, determinants and sex differences in EGL among young adults from Brazil. METHODS: Overall, 7694 participants (aged 16 to 25 years) underwent an interview, genital examination and sampling for HPV genotyping. RESULTS: The prevalence of EGL was 4.08% (234) and is more frequent in men (5.72%) than women (2.31%) (p <  0.001). Genital lesions were significantly associated with male sex, infection by high-risk and multiple HPV types, having more than two sexual partners in the last year, smoking status and the presence of other STI. While alcohol use was associated with a higher prevalence of EGL in women, same-sex sexual relationship increase the prevalence in men. In the EGL group, 67.79% (p = 0.032) were positive for HPV infection and the types HPV6 and HPV11 were the most prevalent ones. CONCLUSION: The prevalence of EGL in young adults was consistently high, and most cases were associated with genital HPV infection and STIs. Although men have a higher prevalence, both sexes share most genital lesion determinants. The promotion of sexual education and vaccination especially focus in young men, who are usually outside the targets of primary health care programmes, can prevent EGL in Brazilian young adults.


Assuntos
Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Doenças Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Estudos Transversais , Feminino , Genitália/patologia , Genitália/virologia , Papillomavirus Humano 11/patogenicidade , Humanos , Masculino , Prevalência , Fatores de Risco , Fatores Sexuais , Parceiros Sexuais , Doenças Sexualmente Transmissíveis/patologia , Adulto Jovem
12.
Biol Res ; 53(1): 33, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758292

RESUMO

Cervical cancer is a common and fatal malignancy of the female reproductive system. Human papillomavirus (HPV) is the primary causal agent for cervical cancer, but HPV infection alone is insufficient to cause the disease. Actually, most HPV infections are sub-clinical and cleared spontaneously by the host immune system; very few persist and eventually develop into cervical cancer. Therefore, other host or environmental alterations could also contribute to the malignant phenotype. One of the candidate co-factors is the ß-catenin protein, a pivotal component of the Wnt/ß-catenin signaling pathway. ß-Catenin mainly implicates two major cellular activities: cell-cell adhesion and signal transduction. Recent studies have indicated that an imbalance in the structural and signaling properties of ß-catenin leads to various cancers, such as cervical cancer. In this review, we will systematically summarize the role of ß-catenin in cervical cancer and provide new insights into therapeutic strategies.


Assuntos
Carcinogênese , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt , beta Catenina/fisiologia , Feminino , Humanos
13.
Acta otorrinolaringol. esp ; 71(4): 212-218, jul.-ago. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194985

RESUMO

ANTECEDENTES Y OBJETIVO: Diferentes estudios realizados en poblaciones con una elevada incidencia de infección por HPV han encontrado una ausencia de capacidad pronóstica de la afectación ganglionar clínica (cN+) en los pacientes con carcinomas de orofaringe HPV-positivos. El objetivo del presente estudio fue evaluar la capacidad pronóstica de la afectación ganglionar en pacientes con carcinomas de orofaringe en función del estatus HPV en una población oncológica con una baja incidencia de infección por HPV. MATERIAL Y MÉTODOS: Estudio retrospectivo de una cohorte de 420 pacientes con carcinomas de orofaringe tratados durante el periodo 1990-2016 de los cuales se dispuso de información del estatus HPV. RESULTADOS: Un 14,8% de los pacientes incluidos en el estudio presentaron tumores HPV-positivos. En relación con los pacientes sin afectación ganglionar (cN0), la afectación ganglionar en el momento del diagnóstico (cN+) disminuyó de forma significativa la supervivencia específica de los pacientes con carcinomas de orofaringe HPV-negativos. Por el contrario, no aparecieron diferencias en la supervivencia para los pacientes con tumores HPV-positivos en función de la presencia de afectación ganglionar. El antecedente de consumo de tóxicos no modificó la ausencia de significado pronóstico de la afectación ganglionar para los pacientes con tumores HPV-positivos. CONCLUSIONES: La afectación regional en el momento del diagnóstico no es una variable con capacidad pronóstica para los pacientes con carcinomas de orofaringe HPV-positivos


BACKGROUND AND OBJECTIVE: Different studies performed in populations with a high incidence of HPV infection have found no prognostic capacity of clinical nodal involvement (cN+) in patients with HPV-positive oropharyngeal carcinomas. The objective of this study was to assess the prognostic ability of nodal involvement in patients with oropharyngeal carcinomas according to HPV status in a cancer population with a low incidence of HPV infection. MATERIAL AND METHODS: Retrospective study of a cohort of 420 patients with oropharyngeal carcinomas treated during the period 1990-2016 for whom information on HPV status was available. RESULTS: 14.8% of the patients included in the study had HPV-positive tumours. In relation to patients without nodal involvement (cN0), nodal involvement at diagnosis (cN+) significantly decreased the specific survival of patients with HPV-negative oropharyngeal carcinomas. Conversely, no differences in survival were found for patients with HPV-positive tumours according to the presence of nodal involvement. A history of toxic consumption did not change the absence of prognostic significance of nodal involvement for patients with HPV-positive tumours. CONCLUSIONS: Regional involvement at the time of diagnosis is not a prognostic variable for patients with HPV-positive oropharyngeal carcinomas


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Orofaríngeas/virologia , Carcinoma/virologia , Infecções por Papillomavirus/complicações , Linfonodos/virologia , Estudos Retrospectivos , Neoplasias Orofaríngeas/patologia , Carcinoma/patologia , Infecções por Papillomavirus/patologia , Metástase Linfática , Linfonodos/patologia , Intervalo Livre de Doença , Estimativa de Kaplan-Meier , Papillomaviridae/isolamento & purificação , Fatores de Tempo
14.
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
15.
PLoS One ; 15(7): e0233986, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634143

RESUMO

BACKGROUND AND OBJECTIVE: China carries a heavy burden of cervical cancer and has an alarmingly low cervical cancer screening rate. In order to achieve the goal of cervical cancer elimination, there is an urgent need for suitable methods and strategies in China. MATERIALS AND METHODS: A total 9972 woman who received cervical cancer screening services of National Cervical Cancer Screening Program in Rural Areas (NCCSPRA) in 8 project counties participated in this study. TruScreen, HPV test and LBC test were performed in all participants. A total of 1945women had one or more than one positive or abnormal screening results of the above three screening tests subsequently received colposcopy. The detection rate of CIN2+ between the three tests were compared. RESULTS: No matter what kind of screening method is used, the CIN2+ detection rate in the eastern regions was much higher than that in the central and western regions. The total detection rate of CIN2+ in HPV group was highest (0.73%), following in LBC group (0.44%) and TS group (0.31%). There was statistically significant difference in the total detection rate of CIN2+ between TS and HPV groups, LBC and HPV groups, respectively. There was no statistical difference in the total detection rate of CIN2+ between TS and LBC screening groups. Moreover, except for the eastern regions, there was no statistical difference in the detection rate of CIN2+ between TS group and the other two groups in central and western regions. CONCLUSION: If it can meet the requirements of the laboratory and personnel, HPV test seems to be the preferred method for cervical cancer screening in rural areas of China. The characteristics of minimal training requirements, simple operation, real-time results obtained without the collection of cervical cell samples and the help of laboratory equipment and cytologists of TS make it ideal for cervical cancer screening in low-resource regions.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Alphapapillomavirus , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/patologia , China/epidemiologia , Colposcopia , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Geografia Médica , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Prevalência , Avaliação de Programas e Projetos de Saúde , População Rural , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/métodos
16.
Arch Virol ; 165(10): 2241-2247, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32681408

RESUMO

Cervical cancer is primarily caused by persistent infection with high-risk human papillomavirus (HPV), and 70% of cases are associated with HPV16 and 18 infections. The objective of this study was to establish rapid, simple, and sensitive internally controlled recombinase-aided amplification (IC-RAA) assays for the detection of HPV16 and 18. The assays were performed at 39 ℃ and were completed within 30 min. A total of 277 clinical samples of exfoliated cervical cells were tested by IC-RAA assays and commercial HPV real-time fluorescent PCR kits using extracted DNA and samples treated with nucleic acid releasing agent. The analytical sensitivity of the IC-RAA assay was found to be 10 copies/µL for the detection of HPV16 and 18 when using recombinant plasmids as targets. The optimal concentration of the internal control (IC) plasmid and 18 was 1000 copies/µL for HPV16 and 100 copies/µL for HPV18. The clinical sensitivity of the IC-RAA assays for HPV16 using extracted DNA and samples treated with nucleic acid releasing agent was 98.73% and 97.47%, respectively, with kappa values of 0.977 (P < 0.01) and 0.955 (P < 0.01), respectively, and 100% The specificity in both cases. For HPV18, the sensitivity and specificity were 100%, and the kappa value was 1 for both samples (P < 0.01). The IC-RAA assay is a promising tool for the detection of HPV16 and HPV18, especially in resource-constrained settings.


Assuntos
DNA Viral/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Técnicas de Amplificação de Ácido Nucleico , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Idoso , Colo do Útero/patologia , Colo do Útero/virologia , Primers do DNA/síntese química , Primers do DNA/genética , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Papillomavirus Humano 16/classificação , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/classificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
17.
PLoS One ; 15(6): e0235065, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584870

RESUMO

INTRODUCTION: Human papillomavirus (HPV) infection is associated with the development of anogenital and head and neck cancers. In recent years a potential role of HPV in colorectal cancer (CRC) has been suggested. OBJECTIVE: To investigate the presence of HPV in colorectal carcinomas and to study the role of p16INK4a as a marker of transcriptionally active HPV infection. In addition, to investigate the correlation between these findings and the CRC prognostic factors. METHODS: Case control study with 92 cases of colorectal cancers, 75 controls of normal tissue adjacent to the tumor, and 30 controls of precursor lesions, including polyps and colorectal adenomas. Paraffinized samples were used, HPV detection and genotyping were performed by PCR and reverse hybridization by using the INNO LIPA kit, with SPF10 plus primers. The expression of the p16INK4a protein was investigated using immunohistochemistry. Data analysis was performed using descriptive, univariate statistics and survival curves were calculated by using the Kaplan Meier and log-rank method. RESULTS: HPV was detected in 13% of the cases and the most prevalent genotype was HPV 16. HPV DNA was not detected in either control groups. The high expression of p16INK4a was observed in 30% of the cases, but it was not associated to the presence of HPV. The overall survival was 53.3% and was influenced by prognostic factors such as later stage, lymph node and distant metastasis. CONCLUSIONS: Based on these results, HPV is unlikely to be involved in colorectal carcinogenesis and p16INK4a expression is not a relevant marker of transcriptionally active HPV infection in CRC.


Assuntos
Neoplasias Colorretais , Inibidor p16 de Quinase Dependente de Ciclina , Regulação Neoplásica da Expressão Gênica , Papillomavirus Humano 16 , Infecções por Papillomavirus , Adulto , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/virologia , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/patologia
19.
Int J Clin Oncol ; 25(10): 1854-1860, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32583223

RESUMO

BACKGROUND: To adopt HPV self-sampling in Japan, we assessed the concordance between self- and physician-collected human papillomavirus (HPV) samples from Japanese patients and examined the performance of HPV self-sampling for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: Patients who had previously tested negative for intraepithelial lesions or malignancy/HPV-positive, and patients with atypical squamous cells of undetermined significance or worse (ASCUS+) cytology were eligible for this cross-sectional study. Participants performed HPV self-sampling using an Evalyn brush, which was submitted at the Fukui Prefectural Health Care Association. The Evalyn brush heads were stored in ThinPrep vials. The physician, however, performed HPV and cell sampling using an endocervical brush and immediately stored the brush heads in ThinPrep vials. All participants underwent colposcopy and biopsy. Histopathological diagnoses were made by pathologists at Fukui University Hospital. HPV infection was confirmed using a PCR-based Cobas 4800 HPV DNA test. Cytological analysis was performed at Fukui Prefectural Health Care Association. RESULTS: HPV-positive rates for physician-collected samples and self-collected samples were 51 and 50%, respectively. The perfect match rate of HPV type between the groups was 88% (κ = 0.76). HPV16/18 showed higher agreement rates than other HPVs (99%, kappa 0.96 and 89% kappa 0.77, respectively). Both groups showed 100% sensitivity to CIN2+, but specificity was 57.0 and 58.1%, respectively. CONCLUSION: For HPV typing, a good concordance rate was seen between self- and physician-collected samples. Self-sampling showed high sensitivity for CIN2+. Self-sampling using the Evalyn brush and Cobas 4800 may be feasible for screening Japanese individuals.


Assuntos
Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Autocuidado/instrumentação , Manejo de Espécimes/instrumentação , Manejo de Espécimes/métodos , Adulto , Grupo com Ancestrais do Continente Asiático , Células Escamosas Atípicas do Colo do Útero/patologia , Células Escamosas Atípicas do Colo do Útero/virologia , Colposcopia , Estudos Transversais , Feminino , Testes de DNA para Papilomavírus Humano , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Médicos , Reação em Cadeia da Polimerase , Autocuidado/métodos , Sensibilidade e Especificidade
20.
PLoS Pathog ; 16(6): e1008624, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32555725

RESUMO

Human papillomaviruses (HPV) are a major cause of malignancy worldwide. They are the aetiological agents of almost all cervical cancers as well as a sub-set of other anogenital and head and neck cancers. Hijacking of host cellular pathways is essential for virus pathogenesis; however, a major challenge remains to identify key host targets and to define their contribution to HPV-driven malignancy. The Hippo pathway regulates epithelial homeostasis by down-regulating the function of the transcription factor YAP. Increased YAP expression has been observed in cervical cancer but the mechanisms driving this increase remain unclear. We found significant down-regulation of the master Hippo regulatory kinase STK4 (also termed MST1) in cervical disease samples and cervical cancer cell lines compared with healthy controls. Re-introduction of STK4 inhibited the proliferation of HPV positive cervical cells and this corresponded with decreased YAP nuclear localization and decreased YAP-dependent gene expression. The HPV E6 and E7 oncoproteins maintained low STK4 expression in cervical cancer cells by upregulating the oncomiR miR-18a, which directly targeted the STK4 mRNA 3'UTR. Interestingly, miR-18a knockdown increased STK4 expression and activated the Hippo pathway, significantly reducing cervical cancer cell proliferation. Our results identify STK4 as a key cervical cancer tumour suppressor, which is targeted via miR-18a in HPV positive tumours. Our study indicates that activation of the Hippo pathway may offer a therapeutically beneficial option for cervical cancer treatment.


Assuntos
Transformação Celular Viral , MicroRNAs/metabolismo , Papillomaviridae/metabolismo , Infecções por Papillomavirus/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA Neoplásico/metabolismo , Transdução de Sinais , Proteínas Supressoras de Tumor/metabolismo , Neoplasias do Colo do Útero/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Proteínas Serina-Treonina Quinases/genética , RNA Neoplásico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
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