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Gingiva hyperpigmentation resulting from physiological melanosis causes aesthetic discomfort and is usually perceived as a disease by patients because healthy attached gingiva is typically characterized by coral pink coloring with stippling and scalloped contours. When physiological melanosis compromises the aesthetics of smiling, it may induce insecurity in patients, who usually seek out alternatives for reducing or eliminating hyperpigmentation. We present a case report of a surgical procedure combining gingivectomy with gingivoplasty for the management of physiological melanosis. The surgical procedure was performed on a 40-year-old female patient with bilateral pigmentation in both arches. The results of the histological analysis confirm the diagnoses of melanotic macula, with papillary hyperplasia and cytopathic changes being suggestive of HPV infection, which was verified using an immunohistochemistry analysis based on the detection of a major capsid protein of HPV. Acceptable functional and aesthetic results were obtained for the patient without major discomfort during the postoperative period. In cases when HPV infection is present, long-term follow-up becomes necessary.
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Objective: This study aimed to assess the association of body mass index (BMI) with anal high-risk human papillomavirus (HR-HPV) and biopsy-confirmed histologic anal high-grade squamous intraepithelial lesions (HSIL) among a clinic-based sample of Hispanics in Puerto Rico. Methods: This cross-sectional study evaluated medical records of adults who received services at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center between October 2014 and December 2022. The study included 543 records with complete clinical information regarding anal HR-HPV and anal HSIL status. Chi-square and logistic regression analyses were performed. Results: Mean age of participants was 44.10 ± 13.24 years, 65.2% were men, 71.7% were HIV-infected, 74.4% had anal HR-HPV infection, and 37.9% had biopsy-confirmed HSIL. Regarding BMI, 2.4% were underweight, 31.9% normal weight, and 39.0 % overweight; while 17.3 % had class I, 5.2% class II, and 4.2% class III obesity. No significant association was observed between BMI and anal HR-HPV infection in adjusted analyses. Lower odds of anal HSIL were observed among overweight individuals (OR: 0.63, 95% CI: 0.41 - 0.99) and those with class II/III obesity (OR: 0.48, 95% CI: 0.22 - 1.01) compared to adults with underweight/normal BMI, after adjusting for potential confounders. No significant association was observed for class I obesity. Conclusion: BMI was not associated with anal HR-HPV infection. Overweight and obese individuals had lower odds of having anal HSIL than adults with underweight/normal BMI. This finding could suggest underdiagnosis of HSIL among overweight/obese individuals, or reduced risk in this group.
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Gut microbiota plays a crucial role in modulating immune responses, including effector response to infection and surveillance of tumors. This article summarizes the current scientific evidence on the effects of supplementation with prebiotics, probiotics, and synbiotics on high-risk human papillomavirus (HPV) infections, precancerous lesions, and various stages of cervical cancer development and treatment while also examining the underlying molecular pathways involved. Our findings indicate that a higher dietary fiber intake is associated with a reduced risk of HPV infection, while certain probiotics have shown promising results in clearing HPV-related lesions. Additionally, certain strains of probiotics, prebiotics such as inulin and fructo-oligosaccharides, and synbiotics decrease the frequency of gastrointestinal adverse effects in cervical cancer patients. These agents attain their results by modulating crucial metabolic pathways, including the reduction of inflammation and oxidative stress, promoting apoptosis, inhibiting cell proliferation, and suppressing the activity of oncogenes, thus attenuating tumorigenesis. We conclude that although further human studies are necessary, robust evidence in preclinical models demonstrates that prebiotics, probiotics, and synbiotics play an essential role in cervical cancer, from infection to carcinogenesis and its medical treatment. Consequently, we strongly recommend conducting high-quality clinical trials using these agents as adjuvants since they have proven safe.
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Introducción: La prueba de Papanicolaou estudia las células exfoliadas de la unión escamo-columnar del cuello uterino para la detección de células anómalas y también es útil para el diagnóstico de infecciones cervicovaginales. Objetivo: Caracterizar a las pacientes con infecciones cervicovaginales asintomáticas, diagnosticadas por prueba de Papanicolaou. Métodos: Se realizó una investigación observacional, descriptiva y transversal, en 656 pacientes con infección cervicovaginal asintomática, diagnosticadas por prueba de Papanicolaou. Se estudiaron: gérmenes, edad, inicio de las relaciones sexuales, número de compañeros sexuales, anomalías de células epiteliales cervicales. La información se obtuvo mediante interrogatorio, examen clínico y prueba de Papanicolaou. Se utilizaron técnicas de estadística descriptiva para el cálculo de las frecuencias absolutas, porcentajes, media y desviación estándar. Resultado: Se halló un predominio de la vaginosis bacteriana (46 %), seguido de la infección por Candida spp (38,2 %). La edad media de las pacientes fue de 36,4 años. Se observó que en 244 mujeres la edad de inicio de las relaciones sexuales fue de 16 - 20 años (37,2 %). Tuvieron un compañero sexual activo 531 casos (80,9 %). El 86 % no presentó lesiones cervicales, pero el 72,7 % de las infecciones por VPH sí tuvieron. Conclusiones: La generalidad de las mujeres tiene vaginosis bacteriana, son adultas, con inicio precoz de las relaciones sexuales y un compañero sexual activo. Gran parte no presentan lesiones cervicales, la mayoría, con infección por VPH, poseen anomalías de las células epiteliales cervicales.
Introduction: The Papanicolaou test studies the exfoliated cells of the squamo-columnar junction of the cervix for the detection of abnormal cells and is also useful for the diagnosis of cervicovaginal infections. Objective: To characterize patients with asymptomatic cervicovaginal infections diagnosed by Papanicolaou test. Methods: An observational, descriptive and cross-sectional investigation was carried out in 656 patients with asymptomatic cervicovaginal infection, diagnosed by Papanicolaou test. The following were studied: germs, age, initiation of sexual relations, number of sexual partners, anomalies of cervical epithelial cells. The information was obtained through interrogation, clinical examination and Papanicolaou test. Descriptive statistical techniques were used to calculate absolute frequencies, percentages, mean and standard deviation. Result: A predominance of bacterial vaginosis was found (46%), followed by Candida spp infection (38.2%). The average age of the patients was 36.4 years. It was observed that in 244 women the age at which sexual relations began was 16 - 20 years (37.2%). 531 cases (80.9%) had an active sexual partner. 86% did not present cervical lesions, but 72.7% of HPV infections did. Conclusions: The majority of women have bacterial vaginosis, they are adults, with early onset of sexual relations and an active sexual partner. Most of them do not have cervical lesions, the majority, with HPV infection, have anomalies of the cervical epithelial cells.
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SUMMARY OBJECTIVE: This systematic review and meta-analysis aimed to investigate the effects of herbal treatments on cervicovaginal human papillomavirus infection. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Science Direct, and the Cochrane Library until December 2023, following Cochrane guidelines. Data were analyzed using the Review Manager computer program (Version 5.4.1). RESULTS: Five randomized controlled trials involving a total sample size of 662 women were included in the study. The pooled odds ratio for individuals testing negative for human papillomavirus after herbal intervention among human papillomavirus-positive patients was 1.86 (95% confidence interval (CI) 0.64-5.43), according to the fixed-effects model. Three out of the five studies indicated a significant relationship. The relationship between positive human papillomavirus infection and herbal treatments, measured by the fixed-effects model, resulted in a pooled odds ratio of 0.41 (95%CI 0.17-1.01), reporting a significant association (p=0.05). Subgroup analysis revealed a significant reduction in the relationship between herbal treatment and atypical squamous cells of undetermined significance (OR 0.16, 95%CI 0.03-0.88, p=0.04) but no significant impact on the relationship between herbal treatment and low-grade squamous intraepithelial lesion (OR 0.33, 95%CI 0.01-8.77, p=0.51). CONCLUSION: The meta-analysis suggests that herbal treatments reduce human papillomavirus infections. While herbal treatments show a significant reduction in atypical squamous cells of undetermined significance, they do not significantly impact the regression of low-grade squamous intraepithelial lesions.
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Human papillomavirus (HPV) is associated with infection of different tissues, such as the cervix, anus, vagina, penis, vulva, oropharynx, throat, tonsils, back of the tongue, skin, the lungs, among other tissues. HPV infection may or may not be associated with the development of cancer, where HPVs not related to cancer are defined as low-risk HPVs and are associated with papillomatosis disease. In contrast, high-risk HPVs (HR-HPVs) are associated with developing cancers in areas that HR-HPV infects, such as the cervix. In general, infection of HPV target cells is regulated by specific molecules and receptors that induce various conformational changes of HPV capsid proteins, allowing activation of HPV endocytosis mechanisms and the arrival of the HPV genome to the human cell nucleus. After the transcription of the HPV genome, the HPV genome duplicates exponentially to lodge in a new HPV capsid, inducing the process of exocytosis of HPV virions and thus releasing a new HPV viral particle with a high potential of infection. This infection process allows the HPV viral life cycle to conclude and enables the growth of HPV virions. Understanding the entire infection process has been a topic that researchers have studied and developed for decades; however, there are many things to still understand about HPV infection. A thorough understanding of these HPV infection processes will allow new potential treatments for HPV-associated cancer and papillomatosis. This chapter focuses on HPV infection, the process that will enable HPV to complete its HPV life cycle, emphasizing the critical role of different molecules in allowing this infection and its completion during the HPV viral life cycle.
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Papiloma , Infecciones por Papillomavirus , Masculino , Femenino , Humanos , Infecciones por Papillomavirus/complicaciones , Virus del Papiloma Humano , Proteínas de la Cápside/genética , Papiloma/complicaciones , PielRESUMEN
BACKGROUND: Given the disproportionately elevated anal cancer risk in high-risk populations, it is important to assess the performance of commonly used anal cancer screening tools to improve the effectiveness of detection and treatment methods. This study evaluates 1) the concordance between anal cytology and histology results and 2) the performance of cytology and high-risk human papillomavirus (HR-HPV) genotyping as screening tools for detecting histologically confirmed anal high-grade squamous intraepithelial lesions (HSIL). METHODS: Data from the Anal Neoplasia Clinic in Puerto Rico (2014-2021; n = 466) was used. The clinical performance of anal cytology and HR-HPV genotyping to detect HSIL was compared to the gold standard: high-resolution anoscopy-guided biopsy. Sensitivity, specificity, positive predictive value, negative predictive value, and κ coefficients were calculated. RESULTS: A total of 66.95% of the patients were men, 74.0% were people living with HIV, 76.2% had anal HR-HPV infection, and 40.34% had histologically confirmed anal HSIL. The weighted κ statistic between the tests (cytology and histology) was 0.25 (p < .001). The sensitivity and specificity of cytology alone to detect anal HSIL were 84.3% (95% confidence interval [CI], 78.3%-89.1%) and 36.0% (95% CI, 30.3%-42.0%), respectively. Anal HR-HPV genotyping had higher sensitivity (92.2%; 95% CI, 87.4%-95.6%) and similar specificity (34.8%; 95% CI, 29.2%-40.7%) compared to cytology. The two tests combined (positive results following cytology or HR-HPV test) improved sensitivity to detect anal HSIL (97.9%; 95% CI, 94.8%-99.4%), but specificity was compromised (19.2%; 95% CI, 14.7%-24.4%). CONCLUSION: Although HR-HPV genotyping improved the detection of anal HSIL, HR-HPV testing had lower specificity than anal cytology alone.
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Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Masculino , Humanos , Femenino , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Puerto Rico/epidemiología , Genotipo , Factores de Riesgo , Infecciones por VIH/complicaciones , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/epidemiología , Neoplasias del Ano/patología , Papillomaviridae/genéticaRESUMEN
It has been previously proposed that some types of cancer cells reprogram their metabolic pathways, favoring the metabolism of glucose by aerobic glycolysis (Warburg effect) instead of oxidative phosphorylation, mainly because the mitochondria of these cells are damaged, thus displaying mitochondrial dysfunction. However, in several cancers, the mitochondria do not exhibit any dysfunction and are also necessary for the tumor's growth and maintenance. Remarkably, if the mitochondria are dysfunctional, specific processes associated with the release of cytochrome c (cyt c), such as apoptosis, are significantly impaired. In these cases, cellular biotherapies such as mitochondrial transplantation could restore the intrinsic apoptotic processes necessary for the elimination of cancers. On the other hand, if the mitochondria are in good shape, drugs that target the mitochondria are a valid option for treating the related cancers. Famously, the mitochondria are targeted by the human papillomavirus (HPV), and HPV-related cancers depend on the host's mitochondria for their development and progression. On the other hand, the mitochondria are also important during treatment, such as chemotherapy, since they are key organelles for the increase in reactive oxygen species (ROS), which significantly increases cell death due to the presence of oxidative stress (OS). In this way, the mitochondria in HPV infection and in the development of HPV-related cancer could be targeted to reduce or eliminate HPV infections or HPV-related cancers. To our knowledge, there was no previous review specifically focusing on this topic, so this work aimed to summarize for the first time the potential use of mitochondria-targeting drugs, providing molecular insights on the main therapeutics developed so far in HPV infection and HPV-related cancer. Thus, we reviewed the mechanisms associated with HPV-related cancers, with their early proteins and mitochondrial apoptosis specifically induced by different compounds or drugs, in which these molecules induce the production of ROS, the activation of proapoptotic proteins, the deactivation of antiapoptotic proteins, the loss of mitochondrial membrane potential (Δψm), cyt c release, and the activation of caspases, which are all events which lead to the activation of mitochondrial apoptosis pathways. This makes these compounds and drugs potential anticancer therapeutics that target the mitochondria and could be exploited in future biomedical strategies.
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ABSTRACT BACKGROUND: Cervical cancer is a type of cancer caused by human papillomavirus (HPV). OBJECTIVE: To determine the relationship between awareness of cervical cancer and HPV infection and attitudes towards HPV vaccine among women aged 15-49 years. DESIGN AND SETTING: Cross-sectional study conducted at Karabük Training and Research Hospital, Turkey. METHODS: 500 women who visited the gynecology outpatient clinic of a public hospital between July 15 and December 31, 2019, were selected through random sampling. Data were collected using a sociodemographic questionnaire comprising nine questions (created by the researchers), the HPV and Cervical Cancer Awareness Questionnaire and the Carolina HPV Immunization Attitudes and Beliefs Scale. RESULTS: The relationship between the awareness questionnaire and the beliefs scale was explained through simple effect modeling of a structural equation. The women's knowledge score regarding cervical cancer and HPV infection was 4.69 ± 4.02 out of 15. Women were afraid of being diagnosed with cervical cancer and HPV infection, but they did not have sufficient information. They had poor information about the HPV vaccine, did not know how to obtain the vaccine and did not have enough information about its benefits and harmful effects. Women who were afraid of getting cervical cancer, and who thought that they were at risk, had more information about the HPV vaccine. CONCLUSION: Women need information about cervical cancer, HPV infection and the HPV vaccine. Midwives, nurses and physicians who provide healthcare services in gynecological follow-ups should provide information to women about the HPV vaccine and cervical cancer.
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Neoplasias del Cuello Uterino/prevención & control , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Conocimientos, Actitudes y Práctica en Salud , Estudios Transversales , Encuestas y CuestionariosRESUMEN
BACKGROUND: Cervical cancer (CC) is the fourth most common malignancy of the female genital tract. Human Papillomavirus (HPV) is the main cause of precancerous lesions and CC cases worldwide. OBJECTIVE: We assessed the prevalence and distribution of HPV types and their association with precancerous lesions and CC. METHODS: HPV genotypes were detected by 3 methods depending on the year of in which the sample was analyzed: MY09/11 RFLPs (1997 to 2010), GP5+/6+ primer systems (2005 to 2010) and INNO-LiPA HPV Genotyping Extra (2010 to 2019) in cervical samples (No-IL: 4445; LSIL: 2464; HSILs: 151 and CC: 253) from women from southern Mexico. RESULTS: The overall HPV prevalence was 54.17%, and hpv-16 was the most common genotype. In single infection, the high-risk HPV genotypes (group 1) were associated with squamous intraepitelial lesions (LSIL: HPV-39 (OR = 10.58, 95% CI 4.09-27.36, P < .001); HSIL: HPV-31 (OR = 14.76, 95% CI 6.56-33.20, P < .001); and CC: HPV-16 (OR = 25.01, 95% CI 18.83-33.21, P < .001). In multiple infections, the HPV genotypes (HPV-16 and HPV-18) were also associated with a high risk of lesions [LSIL: HPV-18 (OR = 3.45; 95% CI 1.36-8.91; P = .009); HSIL: HPV-18 (OR = 5.12; 95% CI 1.21-21.68; P = .026); and CC: HPV-16 (OR = 3.03; 95% CI 1.72-5.32; P < .001)] compared to single infection. In the analysis adjusted for age, giving birth, and cigarette smoking, a significant increase in the risk of LSIL, HSIL, and CC was maintained. CONCLUSIONS: This study provides current data on the prevalence and distribution of HPV genotypes in women from southern Mexico, which could serve as a valuable reference to guide nationwide CC screening programs and provide scientific evidence that could be useful for vaccine development efforts. Likewise, it was identified that infection with carcinogenic HPV genotypes is an independent risk factor for LSIL, HSIL, and CC.
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Alphapapillomavirus , Infecciones por Papillomavirus , Lesiones Precancerosas , Lesiones Intraepiteliales Escamosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Genotipo , Papillomavirus Humano 16/genética , Humanos , México/epidemiología , Papillomaviridae/genética , Lesiones Precancerosas/epidemiología , Embarazo , Prevalencia , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patologíaRESUMEN
INTRODUCTION: Current smoking is a risk factor for anal cancer. Yet, its association with anal human papillomavirus infection (HPV) and anal high-grade squamous intraepithelial lesions (HSIL) remains unclear. We assessed the association of smoking with 1) anal high-risk HPV (HR-HPV) infection and 2) anal HSIL. METHODS: Data from the baseline visit of patients from the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center (May 2015- June 2021) was analyzed. Patients were eligible if they had information on smoking status, complete high-resolution anoscopy (HRA) with biopsy, and HR-HPV testing (n = 427). Logistic regression models estimated the odds ratio (OR) with 95% confidence intervals (CIs) adjusting for covariates. RESULTS: Mean age was 44 ± 13 years, 69% were men, 74% were HIV-infected, and 25% reported being current smokers. 74% had anal HR-HPV infection. HSIL was diagnosed in 40% of patients. Current smokers had significantly higher odds (OR: 1.71, 95% CI: 1.04-2.82) of having HSIL compared to non-smokers after adjusting for age, sexual risk group, lifetime number of sexual partners, HIV status, and HR-HPV infection. Smoking was not associated with HR-HPV infection (OR: 1.56, 95% CI: 0.83-2.95) after adjusting for age, sexual risk group, lifetime number of sexual partners, and HIV status. CONCLUSIONS: Current smoking was associated with histologically confirmed HSIL but not with HR-HPV infection among this high-risk Hispanic population. Results highlight the need to explore targeted smoking cessation campaigns among populations at higher risk of developing HSIL, as an anal cancer prevention strategy.
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HPV vaccination of adolescent girls is the most effective measure to prevent cervical cancer. The World Health Organization recommends that adolescent girls receive two doses of vaccine but only a small proportion of girls from regions with the highest disease burden are vaccinated because of cost and logistical considerations. Our Costa Rica HPV Vaccine trial suggested that one dose of the bivalent HPV vaccine provides robust and lasting protection against persistent HPV infections for over a decade. Data from a post-licensure trial of the quadrivalent vaccine in India also suggested that a single dose may be effective in reducing cervical cancer risk. To formally compare one versus two doses of the bivalent and nonavalent HPV vaccines, we implemented a large, randomized, double-blind trial to investigate the non-inferiority of one compared to two vaccine doses in the prevention of new HPV16/18 infections that persist 6 or more months. Bivalent and nonavalent vaccines will be evaluated separately. The trial enrolled and randomized (1:1:1:1 to 1- and 2-dose arms of the bivalent and nonavalent vaccines) 20,330 girls 12 to 16 years old residing in Costa Rica. Trial participants are followed every 6 months for up to 5 years. We also aim to estimate vaccine efficacy by comparing the rates of 6 month persistent infection in unvaccinated women with the rates in the follow-up visits of trial participants. We included one survey of unvaccinated women at the start of the study (N = 4452) and will include another survey concomitant with follow up visits of trial participants at year 4.5 (planned N = 3000). Survey participants attend two visits 6 months appart. Herein, we present the rationale, design, and enrolled study population of the ESCUDDO trial. ClinicalTrials.gov Identifier: NCT03180034.
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Alphapapillomavirus , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Adolescente , Niño , Costa Rica/epidemiología , Femenino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Papillomaviridae , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Infección Persistente , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Eficacia de las VacunasRESUMEN
BACKGROUND: Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota. METHODS: We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3-V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants' sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI). RESULTS: Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517-.8527) for MB score and 0.7027 (95% CI, .6419-.7636) for SBC score (Pâ =â .0163). CONCLUSIONS: The proposed MB score is strongly correlated with hrHPV positivity-exceeding the predictive value of behavioral variables-suggesting its potential as an indicator of infection and possible value for clinical risk stratification.
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Alphapapillomavirus , Microbiota , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Alphapapillomavirus/genética , Estudios Transversales , Femenino , Humanos , Microbiota/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , ARN Ribosómico 16S/genética , Vagina/microbiologíaRESUMEN
The incidence of human papillomavirus (HPV)-associated cancers, especially those from the head and neck region, has increased. The relatively early age of presentation of HPV-positive head and neck cancer (HNC) indicates that viral infection might be acquired early in life. Persistent HPV infection has been recognized as the main risk factor for cancer development, but most studies have focused on evaluating HPV persistence in the genital region. Thus, in this work, we aimed to evaluate the prevalence of HPV in oral cavity and oropharynx in a young population, as well as the possible persistence of the infection after 12 months. Our results indicate that almost half (46.8%) of the analyzed population harbors an HPV infection either in the oral cavity or in the oropharynx. Furthermore, after 1 year of initial identification, half of them eliminated the infection, and only one person (5.26%) exhibited persistence. Interestingly, 50% of the individuals who successfully eliminated the infection acquired a new viral type, indicating that even when the primary infection is effectively eliminated by the immune system, there is a dynamic circulation of HR-HPV types that produce reinfection. This dynamic HPV infection among young individuals could influence the future establishment of cancer in some proportion of the cases.
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Alphapapillomavirus , Enfermedades de la Boca , Orofaringe , Infecciones por Papillomavirus , Adolescente , Adulto , Alphapapillomavirus/genética , Femenino , Neoplasias de Cabeza y Cuello/etiología , Humanos , Masculino , México/epidemiología , Boca/virología , Enfermedades de la Boca/epidemiología , Enfermedades de la Boca/virología , Orofaringe/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Prevalencia , Adulto JovenRESUMEN
The role and prognostic value of tetraspanins (TSPANs) in vulvar squamous cell carcinoma (VSCC) remain poorly understood. We sought to primarily determine, at both the molecular and tissue level, the expression profile of the TSPANs CD9, CD63, CD81, and CD82 in archived VSCC samples (n = 117) and further investigate their clinical relevance as prognostic markers. Our studies led us to identify CD63 as the most highly expressed TSPAN, at the gene and protein levels. Multicomparison studies also revealed that the expression of CD9 was associated with tumor size, whereas CD63 upregulation was associated with histological diagnosis and vascular invasion. Moreover, low expression of CD81 and CD82 was associated with worse prognosis. To determine the role of TSPANs in VSCC at the cellular level, we assessed the mRNA levels of CD63 and CD82 in established metastatic (SW962) and non-metastatic (SW954) VSCC human cell lines. CD82 was found to be downregulated in SW962 cells, thus supporting its metastasis suppressor role. However, CD63 was significantly upregulated in both cell lines. Silencing of CD63 by siRNA led to a significant decrease in proliferation of both SW954 and SW962. Furthermore, in SW962 particularly, CD63-siRNA also remarkably inhibited cell migration. Altogether, our data suggest that the differential expression of TSPANs represents an important feature for prognosis of VSCC patients and indicates that CD63 and CD82 are likely potential therapeutic targets in VSCC.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Regulación Neoplásica de la Expresión Génica , Tetraspaninas/genética , Transcriptoma , Neoplasias de la Vulva/genética , Neoplasias de la Vulva/mortalidad , Adulto , Anciano , Carcinoma de Células Escamosas/diagnóstico , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Modelos Biológicos , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Tetraspaninas/metabolismo , Neoplasias de la Vulva/patologíaRESUMEN
In 2011, Argentina launched a government-funded national Human papillomavirus (HPV) immunization program incorporating a bivalent HPV vaccine, with a 0-1-6-month schedule, for girls 11 years of age, born after January 2000. Monitoring the changes of HPV infection prevalence among young women has been proposed as an endpoint for early assessment of HPV vaccination programs. However, the data on HPV prevalence at young ages are very limited. The aim of this work was to determine the prevalence of HPV infection and type-specific distribution in sexually active 15-17-year-old non-vaccinated girls. Cervical samples from 1073 adolescents were collected for HPV detection and genotyping using the BSGP5+/GP6+PCR-reverse line blot (RLB) assay. Out of 957 specimens analyzed, 56.3% were positive for any HPV type; 42.2% harbored at least one high-risk HPV (HR-HPV) type and 30.8% low-risk HPV (LR-HPV) types. Multiple and single infections were identified in 36.3% and 20.0% of the samples respectively. The 6 most common HR-HPV types were HPV16 (11.1%), HPV52 (10.8%), HPV56 (8.3%), HPV51 (7.4%), HPV58 (7.3%) and HPV31 (7.1%). The prevalence of HR-HPV-16/18 was 15.2%. In conclusion, results confirm that HPV (particularly HR-types) are very common among sexually active adolescents, and prevalence rises quickly after their sexual debut. Our HPV type-specific prevalence baseline may be used to monitor post-vaccinal longitudinal changes in Argentina.
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Alphapapillomavirus , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Adolescente , Argentina/epidemiología , Femenino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Papillomaviridae , Infecciones por Papillomavirus/epidemiología , PrevalenciaRESUMEN
BACKGROUND: Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non-HPV-16/18 infections among HPV-vaccinated women. METHODS: We analyzed 2153 women aged 18-25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index. RESULTS: A total of 1777 incident oncogenic non-HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior-related variables were associated with oncogenic non-HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non-HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19-5.73] ever vs never), and increasing FTPs (P for trend = .034). CONCLUSIONS: In a cohort of HPV-16/18-vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non-HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adolescente , Adulto , Costa Rica/epidemiología , ADN , Femenino , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Humanos , Papillomaviridae , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Embarazo , Factores de Riesgo , Resultado del Tratamiento , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Adulto Joven , Displasia del Cuello del ÚteroRESUMEN
Multiple infections by HPV genotypes are frequently detected in HPV+ cervical lesions but the interaction between each viral genotype during carcinogenesis is poorly understood. Here we carried out a comprehensive study to characterize the multiple HPV expression and integration by RNA-seq analyses of 19 invasive cervical carcinomas coinfected by several HPV genotypes. Analysis of tumor DNA by a hybridization assay indicated multiple infections ranging from 2 to 6 different HPV genotypes. RNA-seq analysis showed that a single HPV genotype was preferentially expressed. Finally, the search for HPV/human chimeric transcripts indicated integration from preferentially expressed genotypes. In conclusion, the present study indicated that, in invasive cervical carcinomas infected by multiple HPV genotypes, one HPV was preferentially expressed, supporting the hypothesis that a single HPV genotype was associated with cancer development.
Asunto(s)
Carcinoma/virología , Coinfección/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Femenino , Genotipo , Humanos , Proteínas Oncogénicas Virales/genética , Papillomaviridae/metabolismo , Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/complicaciones , Empalme del ARN , Integración ViralRESUMEN
Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.
Asunto(s)
Coinfección/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Carga Viral , Adulto , Coinfección/epidemiología , Coinfección/patología , ADN Viral/genética , Femenino , Estudios de Seguimiento , Genotipo , Humanos , México/epidemiología , Prueba de Papanicolaou , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Prevalencia , Frotis VaginalRESUMEN
Cervical carcinoma and cervical intraepithelial neoplasia (CIN) are associated with persistent infection by oncogenic subtypes of HPV (Human Papillomavirus). Factors linked to immunity, genetics and others like oral contraceptive use, sexual behavior, coinfections with other microorganisms and smoking seem to influence the mechanisms that determine regression or progression to CIN and cervical cancer. We investigated the effect of the MHC class I chain-related gene A (MICA) and Killer Cell Lectin Like receptor K1 (KLRK1) genes on cervical cancer and CIN lesions susceptibility in a group of 195 patients from southern Brazil. There were found a significantly higher number of ex-smokers in the control group (p = 0.005). There were more oral contraceptives (OC) users in the patient group. MICA*008:01/04 allele showed a significant difference between patient and control groups (p = 0.03; OR = 0.63, 95% CI 0.41-0.96), as well as MICA*018:01(p = 0.004, OR = 0.15, 95% CI 0.03-0.64) and MICA*002:01/020 (p = 0.01; OR = 0.60, 95% CI 0.40-0.88). We also analyzed cases and controls according to the MICA-129 genotypes (Met/Val). There was found a difference (p = 0.02) with the Met/Val genotype in a higher frequency in controls and Val/Val and Val/MICA del at a higher frequency in the patient group. For the KLRK1 gene there was no significant difference between groups.