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1.
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
2.
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
3.
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
4.
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
5.
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
6.
Int J Gynaecol Obstet ; 149(2): 219-224, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32037539

RESUMEN

OBJECTIVES: To assess the efficacy of self-collected vaginal samples compared with physician-collected cervical samples for the detection of HPVDNA. METHODS: A hospital-based cross-sectional study was carried out among patients with newly diagnosed cervical cancer attending the Gynecologic Oncology Division, Department of Obstetrics and Gynecology and Radiation Oncology Department at Government Medical College, Kozhikode, Kerala between March 2017 and April 2019. Consenting patients collected their vaginal samples, followed by cervical sample collection by the clinician. The paired samples were transported at 4-8 °C to the laboratory. Amplification of LCR/E6/E7 regions of the HPV genome was done by polymerase chain reaction (PCR). The agreement level between paired samples was assessed by the Kappa index. RESULTS: Among the 114 cervical cancer patients enrolled in the present cross-sectional study, the prevalence of HPV DNA was 78.1% (95% confidence interval [CI] 69.2%-85%) in cervical samples and 77.2% in vaginal samples (95% CI 68.7%-83.9%). The overall agreement between the two sampling methods was 93.9% and the kappa value was 0.82 (P<0.001). The sensitivity of HPV detection using vaginal samples was 98.9% (95% CI 93.9%-99.8%) and the specificity was 100% (95% CI 86.7%-100%) with cervical sampling as the gold standard. By Kappa index, an almost perfect agreement for HPV DNA detection between self-collected and physician-collected samples was observed. CONCLUSION: Self-collection of vaginal samples ensures equity of cervical cancer screening in low-income countries such as India.


Asunto(s)
Pruebas de ADN del Papillomavirus Humano/métodos , Infecciones por Papillomavirus/genética , Manejo de Especímenes/métodos , Neoplasias del Cuello Uterino/virología , Adulto , Estudios Transversales , Detección Precoz del Cáncer/métodos , Femenino , Humanos , India , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Prevalencia
7.
Int J Gynaecol Obstet ; 149(2): 237-246, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32086940

RESUMEN

OBJECTIVE: To characterize human papillomavirus (HPV) prevalence and distribution among female university students in Maputo, Mozambique, and evaluate the determinants of HPV infection. METHODS: A cross-sectional study among 504 female university students between February and April 2017. Cervicovaginal self-collected samples were analyzed for HPV genotypes by polymerase chain reaction-restriction fragment length polymorphism and AnyplexTM II HPV28 Detection kit (Seegene® ). RESULTS: The prevalence of any HPV genotype was 28.6% (144/504). Single and multiple HPV infections were detected in 76 (15.1%) and 68 (13.5%) participants, respectively. Prevalence of high-risk HPV was significantly higher than that of low-risk HPV (P<0.001). HPV16 was the most frequent genotype, followed by HPV58, HPV66, HPV52, HPV18, HPV56, HPV61, and HPV70. The prevalence of genotypes covered by the bivalent, quadrivalent, and nonavalent vaccine was 14.3%, 15.9%, and 23.4%, respectively. Number of sexual partners over lifetime and in the past 12 months was associated with HPV infection (P<0.001 and P=0.039, respectively). CONCLUSIONS: Knowledge of HPV genotype-specific prevalence among young women is important to set up strategies for HPV vaccination. The findings suggest that introduction of the nonavalent HPV vaccine might be the way forward in the present low-resource setting. In addition, self-sampling was useful for HPV detection and genotyping.


Asunto(s)
Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Adolescente , Adulto , Estudios Transversales , Femenino , Genotipo , Pruebas de ADN del Papillomavirus Humano/métodos , Pruebas de ADN del Papillomavirus Humano/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Mozambique/epidemiología , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Vacunas contra Papillomavirus/genética , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de Riesgo , Manejo de Especímenes/métodos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/prevención & control , Adulto Joven
8.
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
9.
PLoS Pathog ; 16(1): e1008295, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31971989

RESUMEN

The HECT domain E3 ubiquitin ligase E6AP (UBE3A) is critical for the development of human papillomavirus (HPV) associated cancers, the neurodevelopment disorder Angelman Syndrome, and some cases of autism spectrum disorders. How E6AP recognizes its cellular targets and how its ubiquitin ligase activity is triggered remain poorly understood, and HPV E6 proteins are models for these processes. We examined diverse E6 proteins from human and non-human papillomaviruses and identified two different modes of interaction between E6 and E6AP. In Type I interactions, E6 can interact directly with the LXXLL peptide motif alone of E6AP (isolated from the rest of E6AP), and then recruit cellular substrates such as p53. In Type II interactions, E6 proteins require additional auxiliary regions of E6AP in either the amino terminus or in the carboxy-terminal HECT domain to interact with the LXXLL peptide motif of E6AP. A region of E6AP amino-terminal to the LXXLL peptide motif both augments association with E6 proteins and is required for E6 proteins to trigger ubiquitin ligase activity in the carboxy-terminal HECT ubiquitin ligase domain of E6AP. In Type I interactions, E6 can associate with E6AP and recruit p53, but a Type II interaction is required for the degradation of p53 or NHERF1. Interestingly, different E6 proteins varied in E6AP auxiliary regions that contributed to enhanced association, indicating evolutionary drift in the formation of Type II interactions. This classification of E6-E6AP interaction types and identification of a region in the E6AP amino terminus that is important for both E6 association and stimulation of ubiquitin ligase activity will inform future structural data of the E6-E6AP complex and future studies aiming to interfere with the activity of the E6-E6AP complex.


Asunto(s)
Proteínas Oncogénicas Virales/metabolismo , Papillomaviridae/metabolismo , Infecciones por Papillomavirus/enzimología , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/metabolismo , Secuencias de Aminoácidos , Humanos , Proteínas Oncogénicas Virales/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Unión Proteica , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Intercambiadores de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/genética
10.
APMIS ; 128(2): 72-79, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31990119

RESUMEN

This review aims to present data on the association between human papillomavirus (HPV) and urinary bladder cancer (BC), especially of the subtype squamous cell carcinoma (SCC). Furthermore, the current data on the relation between p16, HPV, and BC are reviewed. PubMed was searched for 'Humans' [MESH] AND 'Papillomaviridae' [MESH] AND 'Urinary Bladder Neoplasms' [MESH], resulting in 157 potential articles. After profound reviewing, 18 articles were included in this review. Only original articles in English were included. A variable number of HPV genotypes in a small number of cases have been investigated in several studies with various methodology. HPV was present in 0-100% of cases depending on inclusion and exclusion criteria. SCC studies are mostly hampered by low number of cases whereas the few studies with a high number show a slightly higher prevalence of different HPV genotypes compared to pure urothelial carcinoma. Studies on p16 status in HPV positive cases are even more scarcely reported and show conflicting results. Most studies fail to prove clear-cut relevance of HPV in BC irrespectively of histological subtype. Negative p16 staining cannot rule out positive HPV status.


Asunto(s)
Infecciones por Papillomavirus/complicaciones , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias de la Vejiga Urinaria/virología , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/virología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , ADN Viral/genética , Genotipo , Humanos , Papillomaviridae/genética
12.
Bull Cancer ; 107(1): 10-20, 2020 Jan.
Artículo en Francés | MEDLINE | ID: mdl-31982092

RESUMEN

Papillomavirus (HPV), the first sexually transmitted disease in the world, is the main infectious agent responsible for cancer (6300 per year, in France). The cycle of HPV infection - >precancerous lesions - >cancer is well documented with regard to the cervix (cf. Nobel Prize in 2008). While this area is the most frequent (3000), it is far from being the only one. Other cancers include the anus, oropharyngeal sphere, glans and vulva. The sum of these other induced HPV cancers is greater than the total number of cervical cancers and also concerns boys. Screening is essential but insufficient and only concerns the cervix. Only vaccination can provide primary and general prevention. Since 2007, there have been many studies demonstrating its excellent efficacy and tolerance. However, France lags behind other countries with a vaccination coverage (<30 %) that does not allow for an epidemiological impact.


Asunto(s)
Neoplasias del Ano/prevención & control , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Enfermedades Virales de Transmisión Sexual/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Neoplasias del Ano/epidemiología , Neoplasias del Ano/virología , Niño , Condiloma Acuminado/epidemiología , Condiloma Acuminado/prevención & control , Condiloma Acuminado/virología , Femenino , Francia/epidemiología , Genotipo , Vacuna Tetravalente Recombinante contra el Virus del Papiloma Humano Tipos 6, 11 , 16, 18/administración & dosificación , Humanos , Masculino , Números Necesarios a Tratar , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Vacunas contra Papillomavirus/inmunología , Lesiones Precancerosas/complicaciones , Enfermedades Virales de Transmisión Sexual/complicaciones , Enfermedades Virales de Transmisión Sexual/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Adulto Joven
13.
Acta Cytol ; 64(1-2): 63-70, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30889579

RESUMEN

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


Asunto(s)
Citodiagnóstico/métodos , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Detección Precoz del Cáncer/métodos , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Papillomaviridae/fisiología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Triaje , Neoplasias del Cuello Uterino/complicaciones
14.
Int J Cancer ; 146(6): 1514-1522, 2020 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-31173641

RESUMEN

The study aim was to describe human papillomavirus (HPV)-attributable cancer burden in Rwanda, according to anogenital cancer site, HPV type, age and HIV status. Tissue specimens of cervical, vulvar, vaginal, penile and anal cancer diagnosed in 2012-2018 were retrieved from three cancer referral hospitals and tested for high-risk (HR) HPV DNA. Cervical cancer represented the majority of cases (598 of 738), of which 96.0% were HR-HPV positive. HPV-attributable fractions in other cancer sites varied from 53.1% in 81 penile, through 76.7% in 30 vulvar, 83.3% in 24 vaginal, up to 100% in 5 anal cases. HPV16 was the predominant HR-HPV type in cervical cancer (55.0%), followed by HPV18 (16.6%) and HPV45 (13.4%). HPV16 also predominated in other cancer sites (60-80% of HR-HPV-attributable fraction). For cervical cancer, type-specific prevalence varied significantly by histology (higher alpha-9 type prevalence in 509 squamous cell carcinoma vs. higher alpha-7 type prevalence in 80 adenocarcinoma), but not between 501 HIV-negative and 97 HIV-positive cases. With respect to types targeted, and/or cross-protected, by HPV vaccines, HPV16/18 accounted for 73%, HPV31/33/45/52/58 for an additional 22% and other HR-HPV types for 5%, of HPV-attributable cancer burden, with no significant difference by HIV status nor age. These data highlight the preventive potential of the ongoing national HPV vaccination program in Rwanda, and in sub-Saharan Africa as a whole. Importantly for this region, the impact of HIV on the distribution of causal HPV types was relatively minor, confirming type-specific relevance of HPV vaccines, irrespective of HIV status.


Asunto(s)
Neoplasias del Ano/virología , Neoplasias de los Genitales Femeninos/virología , Infecciones por VIH/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Neoplasias del Pene/virología , Adulto , Neoplasias del Ano/epidemiología , Neoplasias del Ano/patología , Estudios Transversales , Femenino , Neoplasias de los Genitales Femeninos/epidemiología , Neoplasias de los Genitales Femeninos/patología , Genotipo , Infecciones por VIH/patología , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Neoplasias del Pene/epidemiología , Neoplasias del Pene/patología , Prevalencia , Rwanda/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Neoplasias Vaginales/epidemiología , Neoplasias Vaginales/patología , Neoplasias Vaginales/virología , Neoplasias de la Vulva/epidemiología , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/virología
15.
Gynecol Oncol ; 156(1): 203-210, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31757465

RESUMEN

OBJECTIVE: Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and their prognostic significance. METHODS: During 2008-2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeq™ Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STK11 were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay. RESULTS: The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild-type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029). CONCLUSIONS: More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations.


Asunto(s)
Proteínas Serina-Treonina Quinasas/genética , Neoplasias del Cuello Uterino/genética , Grupo de Ascendencia Continental Asiática/genética , Análisis Mutacional de ADN , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Femenino , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/enzimología , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Valor Predictivo de las Pruebas , Proteínas Serina-Treonina Quinasas/metabolismo , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología
16.
Acta Cytol ; 64(1-2): 30-39, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30783052

RESUMEN

Human papilloma virus (HPV)-related squamous cell carcinoma (SCC) is biologically unique and has a better prognosis than conventional SCC of the head and neck. p16 immunohistochemistry emerged as a valuable surrogate marker for HPV in oropharyngeal SCC. The criteria for a positive p16 result in tissue specimens are well established. However, there is no consensus regarding interpreting p16 staining in cell blocks and other cytology specimens. This review discusses the current evidence on p16 testing in cytology specimens and also highlights other methods for HPV testing, including DNA and RNA in situ hybridization, as well as other molecular HPV tests.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Inmunohistoquímica/métodos , Infecciones por Papillomavirus/metabolismo , Biopsia con Aguja Fina/métodos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Humanos , Hibridación in Situ/métodos , Papillomaviridae/genética , Papillomaviridae/fisiología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Sensibilidad y Especificidad
17.
Int J Cancer ; 146(7): 2047-2058, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31732968

RESUMEN

More than one-third of patients with locally advanced cervical cancer do not respond to chemoradiation therapy (CRT). We aimed to characterize the transcriptional landscape of paired human cervical tumors before and during CRT in order to gain insight into the evolution of treatment response and to elucidate mechanisms of treatment resistance. We prospectively collected cervical tumor biopsies from 115 patients both before and 3 weeks into CRT. RNA-sequencing, Gene Set Enrichment Analysis and HPV gene expression were performed on 20 paired samples that had adequate neoplastic tissue mid-treatment. Tumors from patients with no evidence of disease (NED) at last follow-up had enrichment in pathways related to the immune response both pretreatment and mid-treatment, while tumors from patients dead of disease (DOD) demonstrated enrichment in biosynthetic and mitotic pathways but not in immune-related pathways. Patients DOD had decreased expression of T-cell and cytolytic genes and increased expression of PD-L2 mid-treatment compared to patients NED. Histological and immunohistochemical analysis revealed a decrease in tumor-associated lymphocytes (TAL) during CRT in all patients but tumors from patients DOD had a significantly more pronounced decrease in TALs and CD8+ cells mid-treatment, which was validated in a larger mid-treatment cohort. Finally, patients DOD retained more HPV E6/E7 gene expression during CRT and this was associated with increased expression of genes driving mitosis, which was corroborated in vitro. Our results suggest that decreased local immune response and retained HPV gene expression may be acting together to promote treatment resistance during CRT in patients with cervical cancer.


Asunto(s)
Resistencia a Antineoplásicos , Regulación Viral de la Expresión Génica , Inmunomodulación/efectos de los fármacos , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Terapia Combinada , Resistencia a Antineoplásicos/inmunología , Femenino , Perfilación de la Expresión Génica , Humanos , Metástasis Linfática , Estadificación de Neoplasias , Papillomaviridae/clasificación , Papillomaviridae/inmunología , Infecciones por Papillomavirus/inmunología , Pronóstico , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/mortalidad
18.
J Clin Pathol ; 73(1): 30-34, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31315894

RESUMEN

AIMS: The purpose of the present study was to elucidate the presence of human herpesvirus 6A (HHV-6A), HHV-6B and HHV-7 in samples of the uterine cervix through detection of viral DNA. We analysed normal tissues, samples with low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). We correlated the presence of HHV-6 and HHV-7 with the finding of human papillomavirus (HPV) in mucosal samples. METHODS: Cervical samples were examined and grouped as follows: group 1 (n=29), normal cytology; group 2 (n=61), samples with LSIL; group 3 (n=35), samples with HSIL. Molecular biology examinations were performed in all samples to detect HHV-6, HHV-7 and HPV DNA and to typify HHV-6 species. RESULTS: Group 1: normal cytology and HPV (-): HHV-6: 6.8% (2/29), HHV-7: 79.3% (23/29); group 2: LSIL and HPV (-): HHV-6: 93.1% (27/29), HHV-7: 96.5% (28/29); LSIL and HPV (+): HHV-6: 0% (0/32), HHV-7: 90.6% (29/32); group 3: HSIL and HPV (-): HHV-6: 20% (2/10), HHV-7: 70% (7/10); HSIL HPV (+): HHV-6: 12% (3/25), HHV-7: 68% (17/25). HHV-6A DNA was not detected in any samples. CONCLUSIONS: (1) Both HHV-6 and HHV-7 infect the mucosal cells of the cervix with higher prevalence of HHV-7. (2) The higher prevalence of HHV-6 in LSIL HPV (-) samples compared with those with normal cytology indicates that it constitutes a possible risk factor for atypia production. (3) The presence of HHV-7 in all samples questions its role in the production of atypia. (4) The finding of HHV-6 and HHV-7 suggests that the cervical mucosa is a possible transmission pathway for these viruses.


Asunto(s)
Neoplasia Intraepitelial Cervical/diagnóstico , ADN Viral/genética , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Técnicas de Diagnóstico Molecular , Infecciones por Roseolovirus/diagnóstico , Lesiones Intraepiteliales Escamosas de Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adolescente , Adulto , Argentina , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/virología , Femenino , Pruebas de ADN del Papillomavirus Humano , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Infecciones por Roseolovirus/genética , Infecciones por Roseolovirus/transmisión , Infecciones por Roseolovirus/virología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/genética , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virología , Adulto Joven
19.
Genes Chromosomes Cancer ; 59(2): 84-95, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31407403

RESUMEN

Cervical carcinogenesis, the second leading cause of cancer death in women worldwide, is caused by multiple types of human papillomaviruses (HPVs). To investigate a possible role for HPV in a cervical carcinoma that was HPV-negative by PCR testing, we performed HPV DNA hybridization capture plus massively parallel sequencing. This detected a subgenomic, URR-E6-E7-E1 segment of HPV70 DNA, a type not generally associated with cervical cancer, inserted in an intron of the B-cell lymphoma/leukemia 11B (BCL11B) gene in the human genome. Long range DNA sequencing confirmed the virus and flanking BCL11B DNA structures including both insertion junctions. Global transcriptomic analysis detected multiple, alternatively spliced, HPV70-BCL11B, fusion transcripts with fused open reading frames. The insertion and fusion transcripts were present in an intraepithelial precursor phase of tumorigenesis. These results suggest oncogenicity of HPV70, identify novel BCL11B variants with potential oncogenic implications, and underscore the advantages of thorough genomic analyses to elucidate insights into HPV-associated tumorigenesis.


Asunto(s)
Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/genética , Secuencia de Bases , Carcinogénesis/genética , Carcinogénesis/metabolismo , ADN Viral/análisis , Femenino , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Persona de Mediana Edad , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , Proteínas Represoras/genética , Proteínas Supresoras de Tumor/genética , Neoplasias del Cuello Uterino/metabolismo
20.
Int J Cancer ; 146(3): 731-738, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30963559

RESUMEN

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


Asunto(s)
Infecciones por Papillomavirus/complicaciones , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/virología , Adulto , Anciano , Brasil , Estudios Transversales , ADN de Neoplasias/genética , Femenino , Humanos , Persona de Mediana Edad , Proteínas Oncogénicas Virales/genética , Papillomaviridae/genética , Reacción en Cadena de la Polimerasa/métodos , ARN Viral/genética , Integración Viral/genética
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