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Human papillomaviruses (HPVs) account for more than 30% of cancer cases, with definite identification of the oncogenic role of viral E6 and E7 genes. However, the identification of high-risk HPV genotypes has largely relied on lagged biological exploration and clinical observation, with types unclassified and oncogenicity unknown for many HPVs. In the present study, we retrieved and cleaned HPV sequence records with high quality and analyzed their genomic compositional traits of dinucleotide (DNT) and DNT representation (DCR) to overview the distribution difference among various types of HPVs. Then, a deep learning model was built to predict the oncogenic potential of all HPVs based on E6 and E7 genes. Our results showed that the main three groups of Alpha, Beta, and Gamma HPVs were clearly separated between/among types in the DCR trait for either E6 or E7 coding sequence (CDS) and were clustered within the same group. Moreover, the DCR data of either E6 or E7 were learnable with a convolutional neural network (CNN) model. Either CNN classifier predicted accurately the oncogenicity label of high and low oncogenic HPVs. In summary, the compositional traits of HPV oncogenicity-related genes E6 and E7 were much different between the high and low oncogenic HPVs, and the compositional trait of the DCR-based deep learning classifier predicted the oncogenic phenotype accurately of HPVs. The trained predictor in this study will facilitate the identification of HPV oncogenicity, particularly for those HPVs without clear genotype or phenotype.
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Aprendizaje Profundo , Genoma Viral , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Infecciones por Papillomavirus/virología , Papillomaviridae/genética , Genoma Viral/genética , Genotipo , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Carcinogénesis/genéticaRESUMEN
Cervical cancer (CC) is a common gynecologic malignancy, accounting for a significant proportion of women death worldwide. Human papillomavirus (HPV) infection is one of the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible for disease expansion. Circular RNAs (circRNAs), which are known as a particular subset of non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported to be involved in the progression of diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs are in strong correlation with CC pathogenesis through regulating substantial signaling pathways. Also, these RNA molecules can be considered as promising biomarkers and therapeutic targets for CC diagnosis/prognosis and treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/ß-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, as well as angiogenesis and metastasis, by which circRNAs interfere with CC development. Then, diagnostic, prognostic, and therapeutic potentials of these ncRNA molecules will be highlighted in depth.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/genética , ARN Circular/genética , Infecciones por Papillomavirus/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/genéticaRESUMEN
The cervicovaginal microbiota is influenced by host physiology, immunology, lifestyle, and ethnicity. We hypothesized that there would be differences in the cervicovaginal microbiota among pregnant, nonpregnant, and menopausal women living in Puerto Rico (PR) with and without human papillomavirus (HPV) infection and cervical cancer. We specifically wanted to determine if the microbiota is associated with variations in cervical cytology. A total of 294 women, including reproductive-age nonpregnant (N = 196), pregnant (N = 37), and menopausal (N = 61) women, were enrolled. The cervicovaginal bacteria were characterized by 16S rRNA amplicon sequencing, the HPV was genotyped with SPF10-LiPA, and cervical cytology was quantified. High-risk HPV (HR-HPV, 67.3%) was prevalent, including genotypes not covered by the 9vt HPV vaccine. Cervical lesions (34%) were also common. The cervical microbiota was dominated by Lactobacillus iners. Pregnant women in the second and third trimesters exhibited a decrease in diversity and abundance of microbes associated with bacterial vaginosis. Women in menopause had greater alpha diversity, a greater proportion of facultative and strictly anaerobic bacteria, and higher cervicovaginal pH than premenopausal women. Cervical lesions were associated with greater alpha diversity. However, no significant associations between the microbiota and HPV infection (HR or LR-HPV types) were found. The cervicovaginal microbiota of women living in Puerto Rican were either dominated by L. iners or diverse microbial communities regardless of a woman's physiological stage. We postulate that the microbiota and the high prevalence of HR-HPV increase the risk of cervical lesions among women living in PR. IMPORTANCE In the enclosed manuscript, we provide the first in-depth characterization of the cervicovaginal microbiota of Hispanic women living in Puerto Rico (PR), using a 16S rRNA approach, and include women of different physiological stages. Surprisingly we found that high-risk HPV was ubiquitous with a prevalence of 67.3%, including types not covered by the 9vt HPV vaccine. We also found highly diverse microbial communities across women groups-with a reduction in pregnant women, but dominated by nonoptimal Lactobacillus iners. Additionally, we found vaginosis-associated bacteria as Dialister spp., Gardnerella spp., Clostridium, or Prevotella among most women. We believe this is a relevant and timely article expanding knowledge on the cervicovaginal microbiome of PR women, where we postulate that these highly diverse communities are conducive to cervical disease.
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Cuello del Útero , Microbiota , Infecciones por Papillomavirus , Femenino , Humanos , Embarazo , Bacterias/genética , Hispánicos o Latinos , Microbiota/genética , Infecciones por Papillomavirus/epidemiología , Puerto Rico/epidemiología , ARN Ribosómico 16S/genética , Cuello del Útero/microbiologíaRESUMEN
This study aims to describe the natural history of and identify the risk factors associated with oral human papillomavirus (HPV) infections in an Australian Indigenous cohort. A longitudinal cohort study design, with baseline (2018), 12-month, and 24-month data obtained from Indigenous Australians aged 18+ years in South Australia, was performed. Face-to-face interviews were conducted, and saliva samples for HPV testing were collected at each time point. Basic descriptive analyses were conducted to calculate prevalence, incidence, persistence, clearance, and incidence proportions of any HPV infection. Multivariable logistic regression analyses with adjusted prevalence ratios (PRs) were conducted to identify risk factors associated with oral HPV infection. Among 993 participants with valid saliva samples, 44 HPV types were identified. The prevalence of infection with any oral HPV infection was 51.3%, high-risk HPV was 11%, and types implicated in Heck's disease (HPV 13 or 32) was 37.4%. The incidence, persistence, and clearance of any and high-risk HPV infections were 30.7%, 11.8% and 33.3% vs. 9.3%, 2.8%, and 9%, respectively. Our findings indicate that the prevalence, incidence, and persistence of oral HPV infection in a large sample of Indigenous Australians were high, and clearance was low. Oral sex behaviours and recreational drug use were risk factors associated with incident high-risk HPV infection.
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Enfermedades de la Boca , Infecciones por Papillomavirus , Humanos , Australia del Sur/epidemiología , Estudios Longitudinales , Enfermedades de la Boca/epidemiología , Australia/epidemiología , Factores de Riesgo , Papillomaviridae/genética , PrevalenciaRESUMEN
BACKGROUND: Plantar warts, or verrucae plantaris, are common lesions causing considerable pain during weightbearing activity. Although current treatment modalities have low success rates, microwave therapy has been introduced as a promising intervention. This study aimed to determine the effectiveness of microwave therapy for the treatment of plantar warts and to determine the clinical factors associated with plantar wart resolution. METHODS: A retrospective analysis of 150 plantar warts from 45 patients treated with microwave therapy was undertaken. Binomial regression was conducted to explore clinical characteristics (age, gender, immunosuppression, impaired healing, multiple vs single wart, location of lesion, lesion diameter) associated with lesion resolution. RESULTS: Of the total 150 plantar warts treated with microwave therapy, 125 (83.3%) warts resolved and 25 (17%) warts did not resolve. The mean (SD) total treatment sessions for resolved lesions was 2.8 (1.0). Decreasing age (P = 0.046) was the only clinical characteristic associated with resolution. CONCLUSIONS: This retrospective study has shown that plantar warts may be resolved with two to three sessions of microwave therapy, which may be more successful in younger populations.
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Enfermedades del Pie , Verrugas , Humanos , Estudios Retrospectivos , Microondas/uso terapéutico , Verrugas/tratamiento farmacológico , Enfermedades del Pie/terapia , Manejo del Dolor , Resultado del TratamientoRESUMEN
AIMS: The aim of the study was to assess the effect of blocking TLR9 signaling on the proliferation of cervical cancer cells and its angiogenic property. BACKGROUND: Toll-Like Receptors (TLRs) have been implicated for their crucial role in not only cervical cancer but also in other malignancies. TLR9 is expressed on an array of cells such as macrophages, dendritic cells, melanocytes, and keratinocytes and is reported to modulate oncogenesis along with tumorigenesis by augmenting NF-κB mediated inflammation within the tumor environment. TLR9 has also been reported to positively regulate oncogenesis within the cervix and as a marker to evaluate malignant remodeling of cervical squamous cells. Therefore, this study was designed to explore the functional relevance of blocking the TLR9signaling pathway in cervical cancer cells. OBJECTIVE: The objective of the current study was to investigate the effect of human TLR9 antagonist, ODN INH-18, on apoptosis and cell cycle regulation, and angiogenic property of human cervical cancer Caski cells. METHODS: MTT assay was performed to measure cell viability and flow cytometry analysis was performed to assess cell cycle arrest. Quantitative Real-Time PCR (qRT-PCR) analysis was performed to measure fold change in the gene expression of various markers of apoptosis, cell cycle regulation, and angiogenesis. RESULTS: The qRT-PCR results showed a higher expression level of TLR9 mRNA in Caski cervical cancer cells as compared to normal cervical keratinocytes. The apoptotic, angiogenic, and cell cycle regulatory factors were also deregulated in Caski cells in comparison to normal keratinocytes. The MTT assay demonstrated that treatment of TLR9 antagonist, ODN INH18, significantly reduced the proliferation of Caski cells in a dose-dependent manner. Treatment of ODN INH18 led to substantial cell cycle arrest in Caski cells at G0/G1 phase. Moreover, the qRT-PCR results demonstrated that ODN INH18 treatment led to suppressed mRNA expression of Bcl-2 and enhanced expression of Bax, signifying the induction of apoptosis in Caski cells. Moreover, the expression of cyclin D1, Cdk4, and Cdc25A was found to be reduced whereas expression of p27 was increased in ODN INH18-treated Caski cells; indicating G0/G1 phase arrest. Interestingly, expression of VEGF and VCAM-1 was found to be significantly inhibited in ODN INH18-treated Caski cells, substantiating alleviation of angiogenic property of cervical cancer cells. CONCLUSION: The results of our study suggest that inhibiting TLR9 signaling might be an interesting therapeutic intervention for the treatment of cervical cancer.
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Transducción de Señal , Neoplasias del Cuello Uterino , Apoptosis , Carcinogénesis , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Femenino , Humanos , ARN Mensajero , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 9/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genéticaRESUMEN
OBJECTIVE: The objective of this study was to review evidence on the effectiveness of vaccination in the prevention of human papilloma virus (HPV) infection at the cervix, anal, and oral. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The key search limitations are as follows: "Human Papilloma Virus", "Papilloma Virus, Human" "Human Papillomavirus Virus", "HPV" and "oral", "anus", "anal", "penis", "cervical," and "vaccine". Randomized controlled studies were searched and analyzed the risk ratio by Review Manager 5.3; funnel plot was adopted for publication bias analysis. RESULTS: Five randomized controlled studies enrolling 13,686 participants were retrieved, analyzed, and showed that HPV vaccination can effectively block HPV infection at cervical, anal, and oral. Subgroup analysis, moreover, proved that HPV 16/18 is more effective than HPV 6/11/16/18 in preventing anal and oral infections. CONCLUSION: HPV vaccine is efficacious in preventing HPV infection not only at cervical but also at anal and oral, as evidence supported by relevant studies.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Femenino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Papillomaviridae , Infecciones por Papillomavirus/prevención & control , VacunaciónRESUMEN
Human papillomavirus (HPV) is a sexually transmitted infection common among men and women of reproductive age worldwide. HPV viruses are associated with epithelial lesions and cancers. HPV infections have been shown to be significantly associated with many adverse effects in reproductive function. Infection with HPVs, specifically of high-oncogenic risk types (HR HPVs), affects different stages of human reproduction, resulting in a series of adverse outcomes: 1) reduction of male fertility (male infertility), characterized by qualitative and quantitative semen alterations; 2) impairment of couple fertility with increase of blastocyst apoptosis and reduction of endometrial implantation of trophoblastic cells; 3) defects of embryos and fetal development, with increase of spontaneous abortion and spontaneous preterm birth. The actual molecular mechanism(s) by which HPV infection is involved remain unclear. HPV-associated infertility as Janus, has two faces: one reflecting anti-HPV immunity, and the other, direct pathogenic effects of HPVs, specifically, of HR HPVs on the infected/HPV-replicating cells. Adverse effects observed for HR HPVs differ depending on the genotype of infecting virus, reflecting differential response of the host immune system as well as functional differences between HPVs and their individual proteins/antigens, including their ability to induce genetic instability/DNA damage. Review summarizes HPV involvement in all reproductive stages, evaluate the adverse role(s) played by HPVs, and identifies mechanisms of viral pathogenicity, common as well as specific for each stage of the reproduction process.
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BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.
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Virus BK/aislamiento & purificación , Cistitis/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Polyomavirus/etiología , Infecciones Tumorales por Virus/etiología , Adolescente , Niño , Preescolar , Cistitis/terapia , Femenino , Humanos , Incidencia , Lactante , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Masculino , Infecciones por Polyomavirus/terapia , Estudios Prospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Infecciones Tumorales por Virus/terapiaRESUMEN
OBJECTIVES/HYPOTHESIS: To investigate the growth pattern of recurrent respiratory papilloma (RRP) implants on chicken embryo chorioallantoic membranes (CAMs) and to evaluate possible associations between the clinical course of the disease and the behavior of experimentally implanted RRP tumors. STUDY DESIGN: Experimental study. METHODS: Fresh 172 RRP tissue samples from 12 patients were implanted onto chick embryo CAMs. Morphological and morphometric analysis of the experimental CAM and chorionic epithelium was performed. The microvascular network of the CAM with the RRP implant was investigated under the effect of fluoresceinated anionic dextran. The peculiarities of the clinical course of the disease were evaluated. RESULTS: The implanted RRP tissue samples survived on CAMs in 86% of cases, retaining their essential morphologic characteristics and proliferative capacity of the original tumor. Implants induced thickening of both the CAM and the chorionic epithelium, but none of the RRP implants crossed the basement membrane of the hosting CAM. A "crawling film" of acellular material with newly formed papilloma sprouts located on the outer chorionic epithelium of the CAM was detected. Direct association between a recurrence rate of RRP and the number of newly formed papilloma sprouts around the implanted tumor on CAMs was revealed. CONCLUSION: The chicken embryo CAM-based model is appropriate for investigations of RRP and facilitates the understanding of tumor biology and the clinical course of the disease, thus providing the basis for further research and acceleration of the identification and development of new specific therapeutic compounds that limit the spread and recurrence of RRP. LEVEL OF EVIDENCE: N/A Laryngoscope, 131:E914-E920, 2021.
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Membrana Corioalantoides , Modelos Animales de Enfermedad , Infecciones por Papillomavirus/etiología , Infecciones del Sistema Respiratorio/etiología , Adolescente , Adulto , Animales , Embrión de Pollo , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/patología , Infecciones del Sistema Respiratorio/patología , Adulto JovenRESUMEN
OBJECTIVES: This study aimed to compare the effectiveness of the bacillus Calmette-Guérin (BCG) vaccine with topical salicylic acid (SA) in the treatment of viral warts. METHODS: This non-randomised controlled trial was conducted at the Al-Sader Teaching Hospital, Basrah, Iraq, from January 2016 to April 2017. A total of 201 patients with viral warts were injected with an intradermal purified protein derivative. Subsequently, those with negative tuberculin test results received an intradermal BCG vaccination, while those with positive results underwent conventional treatment with topical SA. Patients were assessed for any signs of improvement at one, two and three months. RESULTS: Overall, 190 patients completed the trial; of these, 133 (70%) received the BCG vaccine and 57 (30%) were treated with topical SA. Complete response to treatment was observed in 9.8% and 5.3% of patients in the BCG and SA groups, respectively (P <0.001). Cure rates were significantly higher for patients with genital (22.2% versus 7.7%; P = 0.002) and common warts (8.5% versus 0%; P = 0.001) treated with the BCG vaccine; however, the reverse was true for flat warts (12.9% versus 25%; P = 0.041). A binary logistic regression analysis indicated that BCG therapy was the only significant independent predictor of positive treatment response (odds ratio: 7.56, 95% confidence interval: 3.72-15.36; P <0.001). CONCLUSION: The BCG vaccine was more effective than topical SA for treating viral warts, with the best response noted in the treatment of genital warts, followed by flat warts. However, plantar warts demonstrated least response to this treatment.
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Vacuna BCG/farmacología , Verrugas/tratamiento farmacológico , Adulto , Vacuna BCG/uso terapéutico , Femenino , Humanos , Irak , Masculino , Persona de Mediana Edad , Mycobacterium bovis/efectos de los fármacos , Mycobacterium bovis/patogenicidad , Verrugas/diagnóstico por imagenRESUMEN
A 68-year-old woman developed an asymptomatic left caruncular multilobular lesion over one year. Excision of the lesion displayed a benign sebaceous neoplasm taking origin from the surface squamous epithelium which invaginated into the stroma to create crypts resembling the conjunctival pseudoglands of Henle or the glands of Lieberkuhn of the small intestine. Scattered sebaceous cells were also discovered in the surface squamous epithelium. The cryptal walls spawned lateral sebaceous gland lobules that were adipophilin positive. p16 was positive in the surface epithelium, the cryptal walls, and in the basal cells of the sebaceous lobules. No defects in nuclear mismatch repair protein expression were identified, which together with the absence of a familial cancer history, rendered unlikely an association with the Muir-Torre syndrome.
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BACKGROUND: In the field of immunotherapy of head and neck squamous cell carcinoma (HNSCC), a high level of study activity can still be observed. The results of the Keynote-048 study on first-line therapy with pembrolizumab were a highlight at this year's meeting of the American Society of Clinical Oncology (ASCO). MATERIALS AND METHODS: All abstracts and presentations on immunotherapy of head and neck tumors presented at ASCO 2019 were evaluated for relevance and the most interesting studies were summarized. RESULTS: The Keynote-048 study showed an improvement in overall survival with pembrolizumab monotherapy for patients with measurable programmed cell death ligand 1 (PD-L1) expression according to the combined positive score (CPS), and for the whole cohort with the combination of pembrolizumab and platin/5-fluorouracil (FU). The EAGLE study on durvalumab⯱ tremelimumab in second-line therapy did not demonstrate any improvement in response rates or overall survival compared to standard therapy. In addition, several new immunotherapeutic approaches and combinations were presented. CONCLUSION: The results of the Keynote-048 study have already led to the approval of pembrolizumab in the first line for platin-sensitive HNSCC in the USA and the expected approval in Europe will presumably change the therapeutic landscape in the long term. In the future, effective therapies for patients without a response to programmed cell death 1 (PD-1)/PD-L1 inhibition will be needed.
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Neoplasias de Cabeza y Cuello , Inmunoterapia/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello , Congresos como Asunto , Europa (Continente) , Humanos , Factores InmunológicosRESUMEN
Introduction: Genital warts in young adults aged 18-28 years are very common. Several approaches are routinely used in the treatment of warts, viz., medical treatment (podophyllin and trichloroacetic acid), conventional surgery (excision or electrocautery), cryotherapy, and laser treatment. Because of high recurrence rates after treatment, complications and long duration of treatment, newer modalities have been developed. One of these newer methods is laser, which has been used in several urologic diseases. However, there are only a few studies about use of Holmium laser for treatment of genital warts. This retrospective study compared the success rate of Holmium laser with other available treatments for genital warts. Methods: Between October 2011 and May 2016, 142 patients with genital warts attended the urology clinics at Shohada-e-Tajrish hospital in Tehran, Iran. Out of these, a total of 101 patients were included in this study consisting of 42, 39, 11 and 9 patients treated with cryotherapy, laser, conventional surgery and podophyllin respectively. Results: The most successfully cleared lesions were seen in the holmium laser treatment group (P=0.001). The lowest recurrence rate was observed in the holmium laser treatment group (P=0.001). 17 patients had one of these following problems: dysuria, initial hematuria or a change in the force and caliber of their urinary stream that after physical examination showed them to have a meatal wart. These patients then underwent cystoscopy up to urinary sphincter. All of them in addition to the meatus wart had a penile shaft lesion(s). Thirteen patients had meatal lesions, 9 of whom received holmium laser therapy and 4 patients were treated with electrocautery. Based on routine follow up after treatment, none of the patients treated with holmium laser had urinary stricture, but one case treated with electrocautery returned with a penile urethral stricture. Conclusion: This study showed that treatment with Holmium laser has the highest clearance rate (92.2%) and lowest recurrence rate (14.3%) compared to other available treatments in this study. It may be concluded that holmium laser is a safe and effective treatment for genital warts with a low rate of recurrence.
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Objective: To identify high risk HPV associations by evaluating linked p16 overexpression and also the expression of p53 and RARß together with histopathology for risk categorization of cervical pre-neoplastic lesions. Materials and Methods: Immunohistochemical staining was performed on 100 cases of cervical pre- neoplastic lesions for expression of biomarkers like p16, p53 and RARß for comparison with haematoxylin/eosin (HE) findings. All the experimentally generated data were statistically analyzed. Results: In this study 70% cases showed overexpression of p16INK4A increasing progressively from CIN I to CIN II but reduced in CIN III (p <0.01). p53 oncoprotein expression was seen in 51% cases, again with increments from CIN I to CIN II with slight reduction in CIN III (p<0.01). Some 24% cases showed negative immunoreactivity for the putative tumor suppressor gene RARß (p>0.05). Conclusion: Our study provides support for the idea that p16 can be used to identify associations with HPV , as well as having potential along with p53 and RARß for categorizing cervical pre-neoplastic cases having a higher risk of neoplastic conversion. Thus it may be concluded that accurate risk categorization can be achieved with the help of genetic markers as well as histopathology.
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Biomarcadores de Tumor/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Infecciones por Papillomavirus/complicaciones , Lesiones Precancerosas/patología , Receptores de Ácido Retinoico/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias del Cuello Uterino/patología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/virología , Medición de Riesgo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
The human papilloma virus (HPV) vaccine is the recommended prevention strategy for viruses-related cancers, but its acceptability remains controversial, primarily because of the relationship between sexual activity and HPV infection. Countries in the Middle East and North Africa are conservative vis-à-vis sexual behaviors, where Islam shapes people's practices including sexual health, and imposes that sex be carried out within lawful context. Many sexually transmitted infections can be prevented if the rules of Islam are unfailingly applied by Muslims in that region. However, this is not guaranteed and a noticeable shift in the sexual behavior of the youth has been detected, including a drastic increase in unofficial sexual practices, which in the long-term increase HPV incidence and its related diseases. This study examines the available epidemiological data as well as the teachings in Islam's sacred texts and scholars' perspectives to describe the tensions that exist in Muslim cultures around sexuality. Understanding their influence and the function of these tensions can help illuminate the factors that contribute to barriers to accepting the vaccine.
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Islamismo , Vacunas contra Papillomavirus/administración & dosificación , Aceptación de la Atención de Salud/estadística & datos numéricos , Educación Sexual , África del Norte , Humanos , Medio OrienteRESUMEN
A reduced incidence and decreased clinical progression of uterine cervical intraepithelial neoplasia (CIN) has been observed in women infected with human immunodeficiency virus (HIV) treated with HIV-protease inhibitors (PIs). The HIV-PIs saquinavir (SQV) and ritonavir (RTV) have been demonstrated to efficiently inhibit invasion of human primary CIN cells by downregulating the expression of matrix metalloproteinase (MMP)-9. The present study further investigated the molecular mechanisms underlying the activity of SQV and RTV in CIN. The results of the present study indicate that the treatment of human primary CIN cells with SQV or RTV directly impairs events leading to MMP-9 expression, including the phosphorylation of AKT and the nuclear localisation of the Fos-related antigen transcription factor. In addition, neither SQV nor RTV affected the expression of human papilloma virus proteins, such as E6 or E7. In view of the important role that the AKT/Fra-1/MMP-9 signalling pathway serves in CIN progression to invasive cervical carcinoma, these data further support the use of HIV-PIs in the treatment of CIN in women infected with HIV and women who are not infected with HIV. Furthermore, the present study identified a molecular mechanism underlying the anti-invasive effects of SQV/RTV, providing useful information for the development of SQV/RTV derivatives, which may be employed as novel anticancer drugs.
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Keratoacanthomas (KA) and Spitz naevus (SN) are both lesions with unknown aetiology; therefore, the possibility of a viral involvement, more specifically the involvement of human polyomaviruses (HPyV), was investigated. In total, 22 cases of KA and 25 cases of SN were tested for the presence of HPyVs. DNA was extracted and amplified by multiplex PCR and thereafter tested with a multiplex bead-based assay for HPyVs (BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, TSPyV, HPyV6, 7 and 9) and two primate viruses (SV40 and LPyV). HPyV DNA was found in 20 of the 47 lesions. There was no significant difference in HPyV DNA detection frequency between patients diagnosed with KA and patients diagnosed with SN, nor any over-representation of a specific HPyV type in any of the two patient categories. In conclusion, evidence for a specific aetiological role of any of the above tested HPyVs in either KA or SN was not disclosed.