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1.
BMC Infect Dis ; 20(1): 259, 2020 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-32245369

RESUMEN

BACKGROUND: In Bolivia the incidence and mortality rates of uterine cervix cancer are the highest in America. The main factor contributing to this situation is the difficulty of establishing and maintaining quality prevention programs based on cytology. We aimed to evaluate the effectiveness of HR-HPV testing on self-collected samples to detect cervical intra-epithelial neoplasia and identify the best combination of screening tests. METHODS: A total of 469 women, divided in two groups, were included in this study. The first group included 362 women that underwent three consecutively primary screening tests: self-collected sampling for HR-HPV detection, conventional cervical cytology and visual inspection under acetic acid (VIA). The second group included 107 women referred with a positive HR-HPV test that underwent conventional cervical cytology and VIA. The presence of high grade intraepithelial lesion (CIN 2+) or invasive cancer was verified by colposcopy and biopsy. RESULT: In the screening group the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer were 100, 76, 44% for the VIA, HR-HPV test and cytology, respectively. In the referred group, the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer by VIA and cytology were 100 and 81%, respectively. CONCLUSIONS: VIA and HR-HPV self-sampling were the best combination to detect CIN2+ lesions. Cytology analysis gave the poorest performance.


Asunto(s)
Tamizaje Masivo/métodos , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Adulto , Bolivia/epidemiología , Colposcopía , Estudios Transversales , Detección Precoz del Cáncer , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Prueba de Papanicolaou/métodos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa/métodos , Pronóstico , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/virología , Frotis Vaginal
2.
BMC Infect Dis ; 20(1): 274, 2020 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-32264841

RESUMEN

BACKGROUND: Human papillomaviruses (HPVs) have been divided into mucosal and cutaneous types according to their primary epithelial tissue tropism. However, recent studies showed the presence of several cutaneous types in mucosal lesions and healthy mucosa from different anatomical sites. METHODS: Here, the HPV prevalence and type-specific distribution were assessed in a variety of mucosal samples from 435 individuals using a combination of two established broad-spectrum primer systems: Gamma-PV PCR and CUT PCR. RESULTS: Overall HPV prevalence in anal canal swabs, cervical cancer biopsies, genital warts and oral swabs was 85, 47, 62 and 4%, respectively. In anal canal swabs, Alpha-PVs were most frequently found (59%), followed by Gamma- (37%) and Beta-PVs (4%). The prevalence and persistence of HPV infection in the anal canal of 226 individuals were further explored. Overall HPV, Gamma-PVs and multiple HPV infections were significantly higher in men vs. women (p = 0.034, p = 0.027 and p = 0.003, respectively); multiple HPV infections were more common in individuals ≤40 years (p = 0.05), and significantly higher prevalence of Gamma-PVs and multiple HPV infections was observed in HIV-1-positive vs. HIV-1-negative individuals (p = 0.003 and p = 0.04, respectively). Out of 21 patients with follow-up anal swabs, only one persistent infection with the same type (HPV58) was detected. CONCLUSIONS: Our findings suggest that Gamma-PVs (except species Gamma-6) are ubiquitous viruses with dual muco-cutaneous tissue tropism. Anal canal Gamma-PV infections may be associated with sexual behavior and the host immune status. This study expands the knowledge on Gamma-PVs' tissue tropism, providing valuable data on the characteristics of HPV infection in the anal canal.


Asunto(s)
Enfermedades del Ano/complicaciones , Gammapapillomavirus/genética , Seropositividad para VIH/complicaciones , VIH-1/inmunología , Mucosa Bucal/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Enfermedades del Ano/virología , Secuencia de Bases/genética , Condiloma Acuminado/virología , Epitelio/virología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Prevalencia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Adulto Joven
3.
Zhonghua Zhong Liu Za Zhi ; 42(3): 252-256, 2020 Mar 23.
Artículo en Chino | MEDLINE | ID: mdl-32252206

RESUMEN

Objective: To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions. Methods: A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval (CI) of high-risk HPV and HPV16/18 tests were calculated. Results: The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95%CI: 75.8%-96.8%) and 78.0% (95%CI: 74.5%-81.2%) as well as 56.3% (95%CI: 39.3%-71.8%) and 95.7% (95%CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95%CI: 88.1%-98.1%) and 87.6% (95%CI: 86.9%-88.2%) as well as 65.9% (95%CI: 55.1%-75.2%) and 97.8% (95%CI: 97.5%-98.1%), respectively. Conclusions: The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.


Asunto(s)
Neoplasia Intraepitelial Cervical/diagnóstico , Detección Precoz del Cáncer , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Prueba de Papanicolaou , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Biopsia , Neoplasia Intraepitelial Cervical/patología , Neoplasia Intraepitelial Cervical/virología , Cuello del Útero/patología , Cuello del Útero/virología , Colposcopía , ADN Viral/análisis , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Valor Predictivo de las Pruebas , Embarazo , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología
4.
Anticancer Res ; 40(4): 2219-2223, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32234917

RESUMEN

AIM: To investigate the prevalence of cervico-vaginal co-infection with high-risk (HR) HPV types and other sexually transmitted pathogens (STPs) in women with anogenital warts (AGWs). PATIENTS AND METHODS: In this cross-sectional study, cervico-vaginal smears of women with AGWs were examined with real-time polymerase chain reaction for the presence of HR-HPV types and common STPs. Women with recent cervical HPV infection and general population were used for comparisons. RESULTS: A total of 689 women participated in the study. Among the examined groups, higher rates of cervico-vaginal co-infection with HR-HPV types and other STPs collectively were recorded in women with AGWs (p=0.0049 and p<0.004, respectively). Within the AGWs group, cervical co-infection with HR-HPV types was detected more often in women with recurrent disease (p<0.001). CONCLUSION: The higher rates of cervico-vaginal co-infection with HR-HPV types and common STPs in women with AGWs may affect their risk for cervical carcinogenesis and the natural course of their disease.


Asunto(s)
Enfermedades del Ano/epidemiología , Condiloma Acuminado/epidemiología , Enfermedades de los Genitales Femeninos/epidemiología , Infecciones por Papillomavirus/epidemiología , Verrugas/epidemiología , Adolescente , Adulto , Enfermedades del Ano/virología , Cuello del Útero/virología , Condiloma Acuminado/virología , Estudios Transversales , Femenino , Enfermedades de los Genitales Femeninos/virología , Grecia/epidemiología , Humanos , Persona de Mediana Edad , Papillomaviridae/fisiología , Infecciones por Papillomavirus/virología , Prevalencia , Frotis Vaginal , Verrugas/virología , Adulto Joven
5.
Anticancer Res ; 40(4): 2117-2123, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32234904

RESUMEN

BACKGROUND/AIM: The incidence of human papilloma virus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has been increasing in the last decades. Analysis of oral brushing or rinsing samples for screening or stratification could potentially improve screening and prevention. PATIENTS AND METHODS: Oral brushes and mouthwashes were taken from 20 patients with HPV-associated HNSCC before definite therapy. HPV genotyping was performed for the detection of 14 high-risk HPV subtypes and correlated to DNA isolated from tumor tissue. RESULTS: Ten of 20 patients were tested HPV positive by using either method. There was a significant correlation between macroscopic visibility of tumor and positive HPV detection (p<0.001) and HPV detection and tumor size (p<0.001). HPV was detected in all macroscopically visible tumors. Half of the HPV cases who had macroscopically invisible tumors were missed by both methods. CONCLUSION: Both techniques are limited in the detection of macroscopically non-visible and small tumors. Therefore, the application of these techniques for screening or diagnosis of HNSCC is not recommended.


Asunto(s)
Neoplasias Orofaríngeas/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Anciano , ADN Viral/genética , ADN Viral/aislamiento & purificación , Femenino , Genotipo , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Antisépticos Bucales/análisis , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Papillomaviridae/aislamiento & purificación , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/virología
6.
Cancer Invest ; 38(4): 228-239, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32208057

RESUMEN

The aim of this study was to characterize both by flow cytometry analysis and immunohistochemistry cervix uteri cells of nulliparous women screened for cervical intraepithelial neoplasia (CIN) in comparison to a group without CIN by using mesenchymal stem cell-like and hematopoietic lineage markers. A significant expression for CD29, CD38, HLA-I, and HLA-II was correlated positively to the CIN degree and it was more relevant in patients positive for human papilloma virus (HPV). Thus, identification and detailed characterization of pluripotent resident in uteri cells could be a promising therapeutic target.


Asunto(s)
Neoplasia Intraepitelial Cervical/patología , Cuello del Útero/citología , Células Madre Neoplásicas/patología , Infecciones por Papillomavirus/patología , Neoplasias del Cuello Uterino/patología , ADP-Ribosil Ciclasa 1/análisis , ADP-Ribosil Ciclasa 1/inmunología , ADP-Ribosil Ciclasa 1/metabolismo , Adulto , Biopsia , Neoplasia Intraepitelial Cervical/inmunología , Neoplasia Intraepitelial Cervical/virología , Cuello del Útero/inmunología , Cuello del Útero/patología , Cuello del Útero/virología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/inmunología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Femenino , Citometría de Flujo , Antígenos de Histocompatibilidad Clase I/análisis , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos de Histocompatibilidad Clase II/análisis , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Inmunohistoquímica , Inmunofenotipificación , Integrina beta1/análisis , Integrina beta1/inmunología , Integrina beta1/metabolismo , Glicoproteínas de Membrana/análisis , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Clasificación del Tumor , Células Madre Neoplásicas/inmunología , Células Madre Neoplásicas/virología , Papillomaviridae/inmunología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/virología , Estudios Prospectivos , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología
7.
Medicine (Baltimore) ; 99(9): e19273, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32118737

RESUMEN

A subgroup of women who are co-infected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV), progress rapidly to cervical disease. We characterized HPV genotypes within cervical tumor biopsies, assessed the relationships of cervical disease stage with age, HIV-1 status, absolute CD4 count, and CD4 percentage, and identified the predictive power of these variables for cervical disease stage in a cohort of South African women.We recruited 181 women who were histologically diagnosed with cervical disease; 87 were HIV-1-positive and 94 were HIV-1-seronegative. Colposcopy-directed tumor biopsies were confirmed by histology and used for genomic DNA extraction. The Roche Linear Array HPV genotyping test was used for HPV genotyping. Peripheral whole blood was used for HIV-1 rapid testing. Fully automated FC500MPL/CellMek with PanLeucogate (PLG) was used to determine absolute CD4 count, CD4 percentage, and CD45 count. Chi-squared test, a logistic regression model, parametric Pearson correlation, and ROC curves were used for statistical analyses. We used the Benjamini-Horchberg test to control for false discovery rate (FDR, q-value). All tests were significant when both P and q were <.05.Age was a significant predictor for invasive cervical cancer (ICC) in both HIV-1-seronegative (P < .0001, q < 0.0001) and HIV-1-positive women (P = .0003, q = 0.0003). Sixty eight percent (59/87) of HIV-1-positive women with different stages of cervical disease presented with a CD4 percentage equal or less than 28%, and a median absolute CD4 count of 400 cells/µl (IQR 300-500 cells/µl). Of the HIV-1-positive women, 75% (30/40) with ICC, possessed ≤28% CD4 cells vs 25% (10/40) who possessed >28% CD4 cells (both P < .001, q < 0.001). Furthermore, 70% (28/40) of women with ICC possessed CD4 count >350 compared to 30% (12/40) who possessed CD4 count ≤ 350 (both P < .001, q < 0.001).Age is an independent predictor for ICC. In turn, development of ICC in HIV-1-positive women is independent of the host CD4 cells and associates with low CD4 percentage regardless of absolute CD4 count that falls within the normal range. Thus, using CD4 percentage may add a better prognostic indicator of cervical disease stage than absolute CD4 count alone.


Asunto(s)
Neoplasia Intraepitelial Cervical/epidemiología , Infecciones por VIH , VIH-1 , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adulto , Factores de Edad , Recuento de Linfocito CD4 , Neoplasia Intraepitelial Cervical/sangre , Neoplasia Intraepitelial Cervical/virología , Estudios de Cohortes , Femenino , Humanos , Estadificación de Neoplasias , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/virología , Factores de Riesgo , Sudáfrica/epidemiología , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/virología
8.
Anticancer Res ; 40(3): 1513-1517, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32132051

RESUMEN

BACKGROUND/AIM: Cervical cancer is the most common cancer among women in Ethiopia. The objective was to evaluate the participation rate of a free of charge vaginal self-sample (Aptima multitest swab, Hologic) for the detection of human papillomavirus (HPV) in an Ethiopian cohort. PATIENTS AND METHODS: Specimens were collected from women employed by Ethiopian Airlines in Addis Abeba (N=5950). Samples were analysed for the presence of high-risk (HR) HPV mRNA by the Aptima HPV assay (Hologic) and HPV positive women were referred for cytology. Identification of HPV types among HPV positive samples was performed by Modified general primer-PCR and Luminex assay. RESULTS: Participation rate was 3.1% and the prevalence of HPV mRNA was 20.6% (37/180). CONCLUSION: Primary HPV mRNA screening with vaginal self-sampling may be an acceptable approach in Ethiopia. One out of five women harbor HPV in their vaginal self-sample in agreement with other similar studies from the region.


Asunto(s)
Papillomaviridae/genética , ARN Mensajero/análisis , ARN Viral/análisis , Vagina/virología , Adolescente , Adulto , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricos , Etiopía/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Prevalencia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Vagina/patología , Frotis Vaginal , Adulto Joven
9.
Anticancer Res ; 40(3): 1597-1604, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32132062

RESUMEN

Background/Aim: The incidence of oropharyngeal tumours induced by human papillomaviruses (HPV) is ever increasing. Information about oral HPV prevalence and its risk factors are very important for future screening and early diagnosis of the disease. The present study aimed to assess oral HPV prevalence in healthy population and risk factors for HPV infection, since this data is scarce or even missing in Central Europe. Patients and Methods: HPV prevalence in oral rinse and HPV-specific antibodies in peripheral blood were investigated in two groups of healthy participants. Group I consisted of 294 students who reached sexual maturity after the HPV vaccine had been licensed with mean age 23.2 years, and Group II of 215 unvaccinated participants with the mean age 55.7 years. Additionally, the risk factors were evaluated. Results: In Group I, 2% of participants were positive for oral HPV DNA. A statistically significantly higher rate (8.8%) was found in Group II. The seropositivity rates for anamnestic HPV antibodies were comparable in both groups. None of the analysed risk factors was significantly associated with oral HPV positivity. Conclusion: The lower prevalence of oral HPV DNA in younger participants suggests the positive influence of vaccination against oral HPV.


Asunto(s)
Infecciones por Papillomavirus/epidemiología , Adulto , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Patología Bucal , Prevalencia , Factores de Riesgo , Adulto Joven
10.
PLoS One ; 15(2): e0228660, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32053648

RESUMEN

Until 2018, cervical cancer screening in France was an unorganized individual screening, with the exception of some pilot programs in some territories. We aimed to assess, before the implementation of organized cervical cancer screening and human papillomavirus (HPV) nonavalent vaccine introduction in the vaccination schedule in 2018, (i) the individual cervical cancer screening coverage, (ii) the management of squamous intraepithelial lesions (SIL) and (iii) the related costs. We used the Système National des Données de Santé (SNDS) (Echantillon Généraliste de Bénéficiaires [EGB] and Programme de Médicalisation des systèmes d'information [PMSI]) to assess the cervical screening coverage rate in France between January 1st, 2012 and December 31st, 2014, and to describe diagnostic investigations and therapeutic management of SIL in 2013. After extrapolation to the general population, a total of 10,847,814 women underwent at least one smear test over the 3-year study period, corresponding to a coverage rate of 52.4% of the women aged 25 to 64 included. In 2013, 126,095 women underwent HPV test, 327,444 women underwent colposcopy, and 9,653 underwent endocervical curettage; 31,863 had conization and 12,162 had laser ablation. Besides, 34,067 women experienced hospital stays related to management of SIL; 25,368 (74.5%) had high-grade lesions (HSIL) and 7,388 (21.7%) low-grade lesions (LSIL). Conization was the most frequent in-hospital therapeutic procedure: 89.5% (22,704) of women with an in-hospital procedure for HSIL and 64.7% (4,781) for LSIL. Mean cost of smear test, colposcopy and HPV tests were around 50€. Total cost for hospital stays in 2013 was estimated at M41€, or a mean cost of 1,211€ per woman; 76% were due to stays with HSIL. This study highlights the low coverage rate of individual cervical cancer screening and a high burden related to SIL management.


Asunto(s)
Detección Precoz del Cáncer/métodos , Tamizaje Masivo/métodos , Lesiones Intraepiteliales Escamosas/diagnóstico , Lesiones Intraepiteliales Escamosas/terapia , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Anciano , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/economía , Neoplasia Intraepitelial Cervical/epidemiología , Neoplasia Intraepitelial Cervical/virología , Cuello del Útero/patología , Cuello del Útero/virología , Colposcopía/economía , Conización , Estudios Transversales , Detección Precoz del Cáncer/economía , Femenino , Francia/epidemiología , Costos de la Atención en Salud , Humanos , Tamizaje Masivo/economía , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Lesiones Intraepiteliales Escamosas/economía , Lesiones Intraepiteliales Escamosas/epidemiología , Neoplasias del Cuello Uterino/economía , Neoplasias del Cuello Uterino/epidemiología , Frotis Vaginal/economía , Frotis Vaginal/métodos
11.
PLoS One ; 15(2): e0229311, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32084217

RESUMEN

Glial cell-derived neurotrophic factor (GDNF) is reported to promote the survival of neurons and salivary gland regeneration after radiation damage. This study investigated the effect of GDNF on cell migration, growth, and response to radiation in preclinical models of head and neck squamous cell carcinoma (HNSCC) and correlated GDNF expression to treatment outcomes in HNSCC patients. Our ultimate goal is to determine whether systemic administration of GDNF at high dose is safe for the management of hyposalivation or xerostomia in HNSCC patients. Three HPV-positive and three HPV-negative cell lines were examined for cell migration, growth, and clonogenic survival in vitro and tumor growth assay in vivo. Immunohistochemical staining of GDNF, its receptors GFRα1 and its co-receptor RET was performed on two independent HNSCC tissue microarrays (TMA) and correlated to treatment outcomes. Results showed that GDNF only enhanced cell migration in two HPV-positive cells at supra-physiologic doses, but not in HPV-negative cells. GDNF did not increase cell survival in the tested cell lines post-irradiation. Likewise, GDNF treatment affected neither tumor growth in vitro nor response to radiation in xenografts in two HPV-positive and two HPV-negative HNSCC models. High stromal expression of GDNF protein was associated with worse overall survival in HPV-negative HNSCC on multivariate analysis in a combined cohort of patients from Stanford University (n = 82) and Washington University (n = 189); however, the association between GDNF gene expression and worse survival was not confirmed in a separate group of HPV-negative HNSCC patients identified from the Cancer Genome Atlas (TCGA) database. Based on these data, we do not believe that GNDF is a safe systemic treatment to prevent or treat xerostomia in HNSCC and a local delivery approach such as intraglandular injection needs to be explored.


Asunto(s)
Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Neoplasias de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Animales , Apoptosis , Femenino , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/virología , Humanos , Masculino , Ratones , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Crit Rev Oncol Hematol ; 147: 102866, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32058913

RESUMEN

The precursor lesion of vulvar squamous cell carcinoma (VSCC), namely vulvar intraepithelial neoplasia (VIN), is classified as: human papillomavirus (HPV)-related high grade squamous intraepithelial lesion (HSIL), and HPV-independent differentiated VIN (dVIN). Traditionally, histology and immunohistochemistry (IHC) have been the basis of diagnosis and classification of VIN. HSIL shows conspicuous histological atypia, and positivity on p16-IHC, whereas dVIN shows less obvious histological atypia, and overexpression or null-pattern on p53-IHC. For both types of VIN, other diagnostic immunohistochemical markers have also been evaluated. Molecular characterization of VIN has been attempted in few recent studies, and novel genotypic subtypes of HPV-independent VSCC and VIN have been identified. This systematic review appraises the VSCC precursors identified so far, focusing on histology and biomarkers (immunohistochemical and molecular). To gain further insights into the carcinogenesis and to identify additional potential biomarkers, gene expression omnibus (GEO) datasets on VSCC were analyzed; the results are presented.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Neoplasia Intraepitelial Cervical/patología , Papillomaviridae/aislamiento & purificación , Neoplasias de la Vulva/patología , Carcinoma de Células Escamosas/virología , Femenino , Humanos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Neoplasias de la Vulva/virología
14.
Mol Genet Genomics ; 295(3): 675-684, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32002629

RESUMEN

Laryngeal papillomas (LP) is a difficult disease to manage due to its frequent recurrence, airway compromise, and risk of cancer. Recently, growing evidence indicates the aberrant expression of OGFPD1, a stress granule protein, links closely to the development of tumorigenesis; however, little is known about its role in LP progression. Here, we investigated the tumor promoting action of OGFOD1 in LP. The transcriptional and translational levels of OGFOD1 were significantly up-regulated in LP tissues and cells. Moreover, OGFOD1 promoted viability and proliferation, and inhibited LP cells apoptosis. We further revealed that OGFOD1 was directly targeted by miR-1224-5p, which was significantly down-regulated in LP. Overexpression of the miR-1224-5p suppressed OGFOD1-induced cell proliferation and viability, and promoted apoptosis of LP. In accordance, knockdown of miR-1224-5p inversed the inhibitory effects. In confederation of the central involvement of OGFOD1 in LP progression, targeting the miR-1224-5p/OGFOD1 pathway might provide a novel strategy for LP treatment.


Asunto(s)
Proteínas Portadoras/metabolismo , Proliferación Celular , Neoplasias Laríngeas/patología , MicroARNs/genética , Proteínas Nucleares/metabolismo , Papiloma/patología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Apoptosis , Proteínas Portadoras/genética , China/epidemiología , Regulación Neoplásica de la Expresión Génica , Humanos , Incidencia , Neoplasias Laríngeas/epidemiología , Neoplasias Laríngeas/virología , Proteínas Nucleares/genética , Papiloma/epidemiología , Papiloma/virología , Infecciones por Papillomavirus/virología , Células Tumorales Cultivadas
15.
Cancer Sci ; 111(4): 1407-1416, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32012407

RESUMEN

Irradiation, or chemoradiotherapy, is a curative treatment for oropharyngeal squamous cell carcinoma (OPSCC). Its invasiveness, however, can often negate its efficacy. Therefore, developing methods to predict which patients would benefit from irradiation is urgent. Promoter DNA hypermethylation was recently reported to correlate with favorable OPSCC prognosis. It is still unclear, however, whether there is an association between promoter DNA methylation and response to irradiation. In this study, we analyzed DNA methylation in the specimens from 40 OPSCC patients who had undergone irradiation, using the Infinium assay. Our results showed significant correlation between high levels of promoter DNA methylation and better response to treatment (P < 0.01). We used the 10 most differentially-methylated genes between responders and non-responders to develop a panel of predictive markers for efficacy. Our panel had high sensitivity, specificity and accuracy (92%, 93% and 93%, respectively). We conducted pyrosequencing to quantitatively validate the methylation levels of 8 of the 10 marker genes (ROBO1, ULK4P3, MYOD1, LBX1, CACNA1A, IRX4, DPYSL3 and ELAVL2) obtained by Infinium. The validation by pyrosequencing showed that these 8 genes had a high prediction performance for the training set of 40 specimens and for a validation set of 35 OPSCC specimens, showing 96% sensitivity, 89% specificity and 94% accuracy. Methylation of these markers correlated significantly with better progression-free and overall survival rates, regardless of human papillomavirus status. These results indicate that increased DNA methylation is associated with better responses to irradiation therapy and that DNA methylation can help establish efficacy prediction markers in OPSCC.


Asunto(s)
Biomarcadores de Tumor/genética , Metilación de ADN/efectos de la radiación , Neoplasias Orofaríngeas/radioterapia , Infecciones por Papillomavirus/radioterapia , Anciano , Metilación de ADN/genética , Epigenómica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Papillomaviridae/patogenicidad , Papillomaviridae/efectos de la radiación , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Regiones Promotoras Genéticas/efectos de la radiación
16.
DNA Cell Biol ; 39(4): 645-653, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32045269

RESUMEN

Cervical cancer (CC) is a malignant tumor that could seriously endanger women's life and health, of which cervical squamous cell carcinoma (CESC) accounts for more than 80%. High-risk human papillomavirus (HR-HPV) infection is the primary cause of CC. The 5-year survival rate is low due to poor prognosis. We need to explore the pathogenesis of CC and seek effective biomarkers to improve prognosis. The purpose of this research is to construct an HR-HPV-related long non-coding RNA (lncRNA) signature for predicting the survival and finding the biomarkers related to CC prognosis. First, we downloaded the CESC data from The Cancer Genome Atlas (TCGA) database to find HR-HPV-related lncRNAs in CC. Then, the differentially expressed lncRNAs were analyzed by univariate and multivariate Cox regression. Six lncRNAs were found to be associated with the prognosis and can be used as independent prognostic factors. Next, based on these prognostic genes, we established a risk score model, which showed that patients with higher score had poorer prognosis and higher mortality. Moreover, the Kaplan-Meier curve of the model indicated that the model was statistically significant (p < 0.05). The survival-receiver operating characteristic curve showed that the model could also predict the survival of CC patients (the area under the curve, AUC = 0.65). More importantly, nomogram was drawn with clinical features and risk score, which verified the above conclusion, and its calibration curve and c-index index fully demonstrated that the prediction model could predict the progress of CC. We also validated the risk score model in head and neck cancer, and the results indicated that the model had obvious prognostic ability. Finally, we analyzed the correlation between clinical features and survival, and found that neoplasm cancer (p < 0.000) and risk score (p < 0.000) were independent prognostic factors for CC. In conclusion, the study established HR-HPV-related lncRNA signature, which provided a reliable prognostic tool, and was of great significance for finding the biomarkers related to HR-HPV infection in CC.


Asunto(s)
Biomarcadores de Tumor/genética , Papillomaviridae/genética , ARN Largo no Codificante/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virología , Adulto , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Pronóstico , Tasa de Supervivencia
17.
Int J Gynaecol Obstet ; 149(2): 123-129, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32037532

RESUMEN

BACKGROUND: Human papillomavirus (HPV) testing may be feasible for primary cervical cancer screening in low-resource countries. OBJECTIVE: To compare self-sampling by women with clinician-performed sampling for HPV testing in Africa. SEARCH STRATEGY: MEDLINE, Google scholar, EMBASE, and several journals were searched from 2000 until 2015 using relevant terms. SELECTION CRITERIA: Selected studies compared self-sampled and clinician-sampled HPV tests. DATA COLLECTION AND ANALYSIS: Data extraction forms included description of the type of HPV screening, description of any additional intervention components, study design, sample size, follow-up periods, analytic approach, reported numerical outcomes, results, and limitations. RESULTS: Twenty-five studies were identified. Women of a wide age range were successful at self-sampling in many African countries. More than 95% of self-samples yielded HPV DNA results. The concordance in test results between self-collected samples and clinician-collected samples was reasonably high in most studies. In all studies, the quality of cytology from self-sampling matched that of clinician-sampling. Women were generally positive about self-collection, but noted some concerns. CONCLUSION: Self-sampling for HPV DNA testing seems to represent a feasible alternative to the Pap test. Further research is needed to provide a solid evidence base to inform using of self-sampling for HPV DNA testing for primary cervical cancer screening.


Asunto(s)
Tamizaje Masivo/métodos , Infecciones por Papillomavirus/diagnóstico , Manejo de Especímenes/métodos , Adulto , África , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Autocuidado/psicología , Neoplasias del Cuello Uterino/prevención & control
18.
Crit Rev Oncol Hematol ; 148: 102885, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32062315

RESUMEN

Patients with HPV associated (HPV+ve) head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal cancer, show better treatment response, higher survival rates, and lower risks of recurrence as compared to HPV-ve HNSCC patients. Despite increased sensitivity to treatment modality, HPV+ve HNSCC patients are subjected to the same intensive anti-cancer therapy as HPV-ve HNSCC patients and thus subjecting them to unwarranted long-term toxicity. To identify predictive biomarkers for risk-stratification, we have analyzed the mutational spectrum, and the evidence suggests that gain-of-function mutations in the NRF2 pathway are highly prevalent in HPV-ve HNSCC. At the same time, it is rare in HPV+ve HNSCC tumors. We have reviewed the importance of gain-of-NRF2 function and loss of p53 in the prognosis of HNSCC patients and discussed a predictive scoring system using a combination of HPV status (p16), NRF2 pathway and p53 to stratify HPV+ve HNSCC into good versus poor responders, which could immensely help in guiding future de-escalation treatment approaches in patients with HPV+ve HNSCC.


Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virología , Neoplasias de Cabeza y Cuello/genética , Factor 2 Relacionado con NF-E2/genética , Papillomaviridae/genética , Proteína p53 Supresora de Tumor/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Papillomavirus Humano 16/genética , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Recurrencia Local de Neoplasia , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/virología , Proteína p53 Supresora de Tumor/metabolismo
19.
Cancer Immunol Immunother ; 69(4): 549-558, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31970439

RESUMEN

In oropharyngeal squamous cell carcinoma (OPSCC), the relationships between immune responses, carcinogens, and prognoses are not clarified yet. Here, we retrospectively reviewed the pathology samples of 46 OPSCC patients, and used p16 to determine their human papillomavirus (HPV) status. The Cancer Genome Atlas (TCGA) database was also analyzed for further comparison. The immunofluorescence staining of proinflammatory cytokines showed that high interferon gamma (IFNγ; T helper 1; Th1), low interleukin 4 (IL4; T helper 2; Th2), low thymic stromal lymphopoietin (TSLP; Th2), and low transforming growth factor beta (TGFß; T regulatory; Treg) expressions were good prognostic factors for OPSCC. p16-positive OPSCC showed higher Th1, lower Th2/Treg proinflammatory cytokine expressions, and a better prognosis than p16-negative OPSCC. In smokers alone, although p16-positive OPSCC smokers showed weaker Th2/Treg predominant cytokine expressions than p16-negative OPSCC smokers, the prognoses of both groups were equally poor. As for p16-positive OPSCC patients alone, p16-positive nonsmokers showed a significantly better prognosis than p16-positive smokers, but the immune responses of both groups were all weakly Th2/Treg predominant. Overall, higher Th1 and lower Th2/Treg proinflammatory cytokine expressions are associated with a better prognosis for OPSCC. HPV may be related to increased Th1, decreased Th2/Treg responses, and a good prognosis, while smoking may be related to increased Th2/Treg, decreased Th1 responses, and a poor prognosis in OPSCC. The impact of smoking on immune deviation may be weaker than that of HPV, but the impact of smoking on prognosis may be stronger than that of HPV in OPSCC.


Asunto(s)
Carcinógenos/metabolismo , Carcinoma de Células Escamosas/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Citocinas/metabolismo , Neoplasias Orofaríngeas/metabolismo , Infecciones por Papillomavirus/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/complicaciones , Femenino , Papillomavirus Humano 16/fisiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/complicaciones , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Estudios Retrospectivos , Fumar
20.
Int J Oral Sci ; 12(1): 3, 2020 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-31911577

RESUMEN

High-risk human papillomaviruses (HPVs) are involved in the development of several human cancers, including oropharyngeal squamous cell carcinomas. However, many studies have demonstrated that HPV alone is not sufficient for the oncogenic transformation of normal human epithelial cells, indicating that additional cofactors are required for the oncogenic conversion of HPV-infected cells. Inasmuch as chronic inflammation is also closely associated with carcinogenesis, we investigated the effect of chronic exposure to tumor necrosis factor α (TNFα), the major proinflammatory cytokine, on oncogenesis in two immortalized oral keratinocyte cell lines, namely, HPV16-immortalized and human telomerase reverse transcriptase (hTERT)-immortalized cells. TNFα treatment led to the acquisition of malignant growth properties in HPV16-immortalized cells, such as (1) calcium resistance, (2) anchorage independence, and (3) increased cell proliferation in vivo. Moreover, TNFα increased the cancer stem cell-like population and stemness phenotype in HPV16-immortalized cells. However, such transforming effects were not observed in hTERT-immortalized cells, suggesting an HPV-specific role in TNFα-promoted oncogenesis. We also generated hTERT-immortalized cells that express HPV16 E6 and E7. Chronic TNFα exposure successfully induced the malignant growth and stemness phenotype in the E6-expressing cells but not in the control and E7-expressing cells. We further demonstrated that HPV16 E6 played a key role in TNFα-induced cancer stemness via suppression of the stemness-inhibiting microRNAs miR-203 and miR-200c. Overexpression of miR-203 and miR-200c suppressed cancer stemness in TNFα-treated HPV16-immortalized cells. Overall, our study suggests that chronic inflammation promotes cancer stemness in HPV-infected cells, thereby promoting HPV-associated oral carcinogenesis.


Asunto(s)
Carcinoma de Células Escamosas/genética , Papillomavirus Humano 16/metabolismo , MicroARNs/metabolismo , Neoplasias de la Boca/genética , Boca/metabolismo , Proteínas Oncogénicas Virales/metabolismo , Infecciones por Papillomavirus/virología , Telomerasa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Carcinogénesis/genética , Carcinogénesis/inmunología , Carcinoma de Células Escamosas/patología , Transformación Celular Viral/genética , Regulación de la Expresión Génica , Genes Virales , Papillomavirus Humano 16/genética , Humanos , MicroARNs/genética , Boca/virología , Neoplasias de la Boca/patología , Proteínas Oncogénicas Virales/genética , Papillomaviridae/genética , Telomerasa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
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