Germline rare variants in HER2-positive breast cancer predisposition: a systematic review and meta-analysis.

Introduction: Approximately 10% of breast cancer (BC) cases result from hereditary causes. Genetic testing has been widely implemented in BC care to determine hereditary cancer syndromes and personalized medicine. Thus, identification of individuals carrying germline pathogenic variants could be useful to provide appropriate prophylactic or screening measures for each BC subtype, however, there are few formal recommendations for genetic testing in this sense so far. In this study, we assessed rare germline variants in a specific group of genes in order to determine the association with human epidermal growth factor 2 enriched (HER2+) BC phenotype through a systematic review and meta-analysis comparing subtypes overexpressing HER2 with other clinically recognized subtypes of BC. This review was registered with PROSPERO (ID: CRD42023447571). Methods: We conducted an online literature search in PubMed (MEDLINE), Scopus, and EMBASE databases. We included original studies that investigated germline variants in HER2+ BC patients and selected the studies that reported only rare and/or pathogenic germline variants. We assessed the risk of bias and quality of the studies using the Joanna Briggs Institute Critical Appraisal checklists and the Modified Newcastle-Ottawa Scale for Genetic Studies, respectively. Considering hormone receptor and HER2 expression status, we compared gene-based risks initially in HR-HER2-, HR+HER2-, HR+HER2+, and HR-HER2+ groups, conducting separate meta-analyses using the random effects model for each comparison, and within them for each gene. Results: Of the total 36 studies describing germline variants, 11 studies provided information on the prevalence of variants in the different clinically relevant BC subtypes and allowed comparisons. Germline variants within eight genes showed significant differences when meta-analyzed between the BC groups: BRCA1, BRCA2, TP53, ATM, CHEK2, PALB2, RAD51C, and BARD1. Notably, TP53, ATM, and CHEK2 germline variants were identified as predisposing factors for HER2+ subtypes, whereas BRCA1, BRCA2, PALB2, RAD51C, and BARD1 germline variants were associated with a predisposition to low HER2 expression. Main concerns about bias and quality assessment were the lack of confounding factors control; and comparability or outcome assessment, respectively. Discussion: Our findings underscore the connection between germline variants and differential expression of the HER2 protein and BC subtypes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023447571.

Comparative evaluation of HPV genotyping: A study on the performance concordance between Anyplex II HPV28 detection and Linear Array genotyping tests in nationwide studies in Brazil.

BACKGROUND: Advances in laboratory techniques for HPV diagnosis necessitate a thorough assessment of the efficiency, replicability, sensitivity, and specificity of those methods. This study aims to validate and compare HPV detection/genotyping using the Anyplex™ II HPV28 Detection assay (Seegene) assay and the Linear Array HPV Genotyping test (Roche Diagnostics) on genital samples for use in epidemiological studies. METHODS: From 6,388 penile and cervical DNA samples collected in the POP-Brazil, 1,745 were randomly selected to be included in this study. The samples were submitted to HPV detection and genotyping following the manufacturers' protocols. DNA was genotyped using the Anyplex™ II HPV28 Detection kit (Seegene), and the results were compared to those obtained using the Linear Array HPV Genotyping test (Roche Diagnostics). Concordance of HPV genotyping results was assessed by the percentage agreement and Cohen's kappa score (κ). RESULTS: The agreement between the two methodologies was deemed good for HPV detection (κ = 0.78). Notably, Anyplex™ II HPV28 demonstrated enhanced capability in detecting a broader spectrum of genotypes compared to Linear Array. CONCLUSION: Anyplex™ II HPV28 exhibited comparable results to the Linear Array assay in clinical specimens, showcasing its potential suitability for a diverse array of research applications requiring the detection and genotyping of HPV. The study supports the utility of Anyplex™ II HPV28 as an effective tool for HPV screening in epidemiological studies, emphasizing its robust performance in comparison to established diagnostic tests.

Mapping breast and prostate cancer in the Brazilian public health system: study protocol of the Onco-Genomas Brasil.

Background: Breast and prostate cancers are the most common malignancies diagnosed in women and men respectively, and present with great clinical heterogeneity, even in tumors with the same histology and same site of origin. Somatic and germline molecular alterations in DNA may have prognostic and predictive impact, influencing response to therapies and overall survival. Our aim is to characterize the somatic and germline genomic landscape of women with locally advanced HER2-positive breast cancer and men with metastatic prostate cancer in Brazil. Secondarily, we aim to identify genetic variants associated with tumor prognosis and treatment response, identify patients carrying pathogenic alterations in cancer-predisposing genes, and characterize the genetic ancestry of the population included in the study. Methods: This observational multicenter cohort study will include 550 adult patients from the five macro-regions of Brazil, divided into two arms: 1) breast cancer and 2) prostate cancer. Clinical and pathological data will be collected, as well as DNA samples from peripheral blood and tumor samples. In arm 1, the inclusion criteria are a histological diagnosis of breast carcinoma with overexpression of HER-2, clinical stage II or III, and current neoadjuvant treatment with chemotherapy plus trastuzumab. In arm 2, the criterion is a histological diagnosis of prostate adenocarcinoma, clinical stage IV. Whole-exome sequencing (WES) will be performed to identify variants that may be drivers and/or actionable in a specific patient or tumor. These variants will be interpreted and classified according to their population frequencies, in silico predictors, functional studies, and literature data, following international guidelines proposed by expert societies. Discussion: This trial will contribute to the construction of a robust database that should provide a better understanding of the genomic profile of patients with breast and prostate cancer in Brazil. Considering the miscegenation of the Brazilian population, knowledge generated from these data will have implications for future studies of this specific population. Clinical trial registration: [clinicaltrial.gov], identifier [NCT05306600].

The Brazilian national prospective active surveillance (AS) cohort of patients with low-risk prostate cancer in the public health system: vigiaSUS study protocol.

BACKGROUND: Prostate cancer exhibits a very diverse behaviour, with some patients dying from the disease and others never needing treatment. Active surveillance (AS) consists of periodic PSA assessment (prostate-specific antigen), DRE (digital rectal examination) and periodic prostate biopsies. According to the main guidelines, AS is the preferred strategy for low-risk patients, to avoid or delay definitive treatment. However, concerns remain regarding its applicability in certain patient subgroups, such as African American men, who were underrepresented in the main cohorts. Brazil has a very racially diverse population, with 56.1% self-reporting as brown or black. The aim of this study is to evaluate and validate the AS strategy in low-risk prostate cancer patients following an AS protocol in the Brazilian public health system. METHODS: This is a multicentre AS prospective cohort study that will include 200 patients from all regions of Brazil in the public health system. Patients with prostate adenocarcinoma and low-risk criteria, defined as clinical staging T1-T2a, Gleason score ≤ 6, and PSA < 10 ng/ml, will be enrolled. Archival prostate cancer tissue will be centrally reviewed. Patients enrolled in the study will follow the AS strategy, which involves PSA and physical examination every 6 months as well as multiparametric MRI (mpMRI) every two years and prostate biopsy at month 12 and then every two years. The primary objective is to evaluate the reclassification rate at 12 months, and secondary objectives include determining the treatment-free survival rate, metastasis-free survival, and specific and overall survival. Exploratory objectives include the evaluation of quality of life and anxiety, the impact of PTEN loss and the economic impact of AS on the Brazilian public health system. DISCUSSION: This is the first Brazilian prospective study of patients with low-risk prostate cancer under AS. To our knowledge, this is one of the largest AS study cohort with a majority of nonwhite patients. We believe that this study is an opportunity to better understand the outcomes of AS in populations underrepresented in studies. Based on these data, an AS national clinical guideline will be developed, which may have a beneficial impact on the quality of life of patients and on public health. TRIAL REGISTRATION: Clinicaltrials registration is NCT05343936.

The impact of the distance traveled between residence and gestational trophoblastic neoplasia reference center and clinical outcomes in Brazilian women.

OBJECTIVE: To relate the distance traveled from the patient's residence to the gestational trophoblastic neoplasia (GTN) reference center (RC) and the occurrence of unfavorable clinical outcomes, as well as to estimate the possible association between this distance and the risk of metastatic disease at presentation, the need for multiagent chemotherapy to achieve remission and loss to follow-up before remission. STUDY DESIGN: Retrospective historical cohort study of patients with GTN followed at 8 Brazilian GTN-RC, from January 1st, 2000 - December 31st, 2017. RESULTS: Evaluating 1055 cases of GTN, and using a receiver operating characteristic curve, we found a distance of 56 km (km) from the residence to the GTN-RC (sensitivity = 0.57, specificity = 0.61) best predicted the occurrence of at least one of the following outcomes: occurrence of metastatic disease, need for multiagent chemotherapy to achieve remission, or loss to follow-up during chemotherapy. Multivariate logistic regression adjusted by age, ethnicity, marital status and the reference center location showed that when the distance between residence and GTN-RC was ≥56 km, there was an increase in the occurrence of metastatic disease (relative risk - RR:3.27; 95%CI:2.20-4.85), need for multiagent chemotherapy (RR:1.36; 95%CI:1.05-1.76), loss to follow-up during chemotherapy (RR:4.52; 95CI:1.93-10.63), occurrence of chemoresistance (RR:4.61; 95%CI:3.07-6.93), relapse (RR:10.27; 95%CI:3.08-34.28) and death due to GTN (RR:3.62; 95%CI:1.51-8.67). CONCLUSIONS: The distance between the patient's residence and the GTN-RC is a risk factor for unfavorable outcomes, including death from this disease. It is crucial to guarantee these patients get prompt access to the GTN-RC and receive follow-up support.

Presentation, medical complications and development of gestational trophoblastic neoplasia of hydatidiform mole after intracytoplasmic sperm injection as compared to hydatidiform mole after spontaneous conception - a retrospective cohort study and literature review.

OBJECTIVE: To describe the natural history of hydatidiform mole (HM) after intracytoplasmic sperm injection (ICSI), emphasizing the clinical and oncological outcomes, as compared to patients who had HM after spontaneous conception (SC). STUDY DESIGN: Retrospective historical cohort study of patients with HM followed at the Rio de Janeiro Federal University, from January 1st 2000-December 31st 2020. RESULTS: Comparing singleton HM after SC to those following ICSI there were differences in terms of maternal age (24 vs 34 years, p < 0.01), gestational age at diagnosis (10 vs 7 weeks, p < 0.01), preevacuation human chorionic gonadotropin levels (200,000 vs 99,000 IU/L, p < 0.01), occurrence of genital bleeding (60.5 vs 26.9%, p < 0.01) and hyperemesis (23 vs 3.9%, p = 0.02) at presentation, and time to remission (12 vs 5 weeks, p < 0.01), respectively. There were no differences observed in the cases of twin mole, regardless of the form of fertilization that gave rise to HM, except molar histology with greater occurrence of partial hydatidiform mole (10.7 vs 40.0%, p = 0.01) following ICSI. Univariate logistic regression for occurrence of postmolar GTN after ICSI identified no predictor variable for this outcome. However, after adjusting for maternal age and complete hydatidiform mole histology, multivariable logistic regression showed the risk of GTN with HM after ICSI had an adjusted odds ratio of 0.22 (95%CI:0.05-0.93, p = 0.04), suggesting a possible protective effect when compared to HM after SC. CONCLUSIONS: Singleton HM after ICSI are diagnosed earlier in gestation, present with fewer medical complications, and may be less likely to develop GTN when compared with HM after SC.

Neutrophil/lymphocyte ratio and other blood cell component counts are not associated with the development of postmolar gestational trophoblastic neoplasia.

OBJECTIVE: To relate preevacuation platelet count and leukogram findings, especially neutrophil/lymphocyte ratios (NLR) and platelet/lymphocyte ratios with the occurrence of gestational trophoblastic neoplasia (GTN) after complete hydatidiform mole (CHM) among Brazilian women. METHODS: Retrospective cohort study of patients with CHM followed at Rio de Janeiro Federal University, from January/2015-December/2020. Before molar evacuation, all patients underwent a medical evaluation, complete blood count and hCG measurement, in addition to other routine preoperative tests. The primary outcome was the occurrence of postmolar GTN. RESULTS: From 827 cases of CHM treated initially at the Reference Center, 696 (84.15%) had spontaneous remission and 131 (15.85%) developed postmolar GTN. Using optimal cut-offs from receiver operating characteristic curves and multivariable logistic regression adjusted for the possible confounding variables of age and preevacuation hCG level (already known to be associated with the development of GTN) we found that ≥2 medical complications at presentation (aOR: 1.96, CI 95%: 1.29-2.98, p<0.001) and preevacuation hCG ≥100,000 IU/L (aOR: 2.16, CI 95%: 1.32-3.52, p<0.001) were significantly associated with postmolar GTN after CHM. However, no blood count profile findings were able to predict progression from CHM to GTN. CONCLUSION: Although blood count is a widely available test, being a low-cost test and mandatory before molar evacuation, and prognostic for outcome in other neoplasms, its findings were not able to predict the occurrence of GTN after CHM. In contrast, the occurrence of medical complications at presentation and higher preevacuation hCG levels were significantly associated with postmolar GTN and may be useful to guide individualized clinical decisions in post-molar follow-up and treatment of these patients.

Sexual practices and HPV infection in unvaccinated young adults.

The present study aimed to evaluate the association of genital and oral HPV infection among different sexual practices in both sexes. In total, 6388 unvaccinated men and women aged 16-25 years from all state capitals of Brazil were enrolled in through primary care services between September 2016 and November 2017. Genital and oral HPV genotyping was performed using the Roche Linear Array. Poisson regression analysis with robust variance was conducted to examine factors associated with overall HPV infection. A higher prevalence of genital HPV was found in women who practiced oral sex (57.85%) and in men who practiced all types of sex (65.87%). However, having more sexual partners and being younger were more important than the type of sex practiced. HPV 6 (7.1%) and 16 (10.5%) were significantly more prevalent in women who practiced oral sex, while HPV 6 (23.96%) and 11 (21.49%) were more prevalent in men who practiced anal sex. The type of sex was not associated with oral HPV prevalence. Genital and oral HPV infection were not associated by different sexual practices in the studied population.

Success and failure after surgery of degenerative disease of the lumbar spine: an operational definition based on satisfaction, pain, and disability from a prospective cohort.

BACKGROUND: To describe success and failure (S&F) after lumbar spine surgery in terms equally understandable across the entire health ecosystem. METHODS: Back and leg pain and disability were prospectively recorded before and up to 12 months after the procedure. Satisfaction was recorded using a Likert scale. Initially, patients were classified as satisfied or unsatisfied. Optimal satisfaction/unsatisfaction cutoff values for disability and pain were estimated with ROC curves. Satisfied and unsatisfied groups underwent a second subdivision into four subcategories: success (satisfied AND pain and disability concordant with cutoff values), incomplete success (satisfied AND pain and disability nonconformant with cutoff values), incomplete failure (unsatisfied AND pain and disability nonconformant with cutoff values), and failure (unsatisfied AND pain and disability concordant with cutoff values). RESULTS: A total of 486 consecutive patients were recruited from 2019-2021. The mean values of preoperative PROMs were ODI 42.2 (+ 16.4), NPRS back 6.6 (+ 2.6) and NPRS leg 6.2 points (+ 2.9). Of the total, 80.7% were classified as satisfied, and 19.3% were classified as unsatisfactory. The optimal disability and pain cutoff values for satisfaction/unsatisfaction (NPRS = 6, AND ODI = 27) defined a subdivision: 59.6% were classified as success, 20.4% as incomplete success, 7.1% as incomplete failure and 12.4% as failure. The descriptions of each group were translated to the following: success-all patients were satisfied and presented no or only mild to tolerable pain and no or borderline disability; incomplete success - all patients were satisfied despite levels of pain and/or disability worse than ideal for success; incomplete failure - all patients were not satisfied despite levels of pain and/or disability better than expected for failure; failure - all patients were unsatisfied and presented moderate to severe pain and disability. CONCLUSION: It is possible to report S&F after surgery for DDL with precise and meaningful operational definitions focused on the experience of the patient.

A Nationwide Evaluation of the Prevalence of Human Papillomavirus in Brazil (POP-Brazil Study): Protocol for Data Quality Assurance and Control.

BACKGROUND: The credibility of a study and its internal and external validity depend crucially on the quality of the data produced. An in-depth knowledge of quality control processes is essential as large and integrative epidemiological studies are increasingly prioritized. OBJECTIVE: This study aimed to describe the stages of quality control in the POP-Brazil study and to present an analysis of the quality indicators. METHODS: Quality assurance and control were initiated with the planning of this nationwide, multicentric study and continued through the development of the project. All quality control protocol strategies, such as training, protocol implementation, audits, and inspection, were discussed one by one. We highlight the importance of conducting a pilot study that provides the researcher the opportunity to refine or modify the research methodology and validating the results through double data entry, test-retest, and analysis of nonresponse rates. RESULTS: This cross-sectional, nationwide, multicentric study recruited 8628 sexually active young adults (16-25 years old) in 119 public health units between September 2016 and November 2017. The Human Research Ethics Committee of the Moinhos de Vento Hospital approved this project. CONCLUSIONS: Quality control processes are a continuum, not restricted to a single event, and are fundamental to the success of data integrity and the minimization of bias in epidemiological studies. The quality control steps described can be used as a guide to implement evidence-based, valid, reliable, and useful procedures in most observational studies to ensure data integrity. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/31365.

Prevalence, Circumstances, and Risk Factors of Falls Among Community Dwelling Members of University of the Third Age.

Introduction: The transition from adolescence to adulthood involves a variety of physical, behavioral, and social transformations, often including tobacco use. Because understanding smoking at this stage is important for tobacco control, we aimed to analyze the prevalence of cigarette smoking in the Brazilian youth population. Methods: This study included participants aged 16-25 years from all Brazilian capitals. A standardized questionnaire was administered by trained healthcare professionals to collect information about sociodemographic status, sexual behavior, and tobacco use. The samples from each capital were weighted by age range and sex. Results: Of the 8,581 participants, 15.1% were current smokers, and 20.0% were former smokers; the average age at first tobacco use was 15.5 years. The prevalence of smoking in men was higher than that in women (20.1 vs. 10.3%, p < 0.01). Education level was associated with current smoking and former smoking. Participants with an elementary education level had a higher smoking prevalence (PR: 5.84, 95%, CI: 4.29-7.95) than those with a secondary education (PR: 2.19, 95% CI: 1.63-2.93) and those with higher education. Those without current partners (PR: 1.27, 95% CI: 1.03-1.56) also had a higher prevalence of smoking than those with partners, and participants who had a previous same-sex sexual experience smoked more (PR: 2.29, 95% CI: 1.78-2.96) than those who did not. In addition, regular use of alcohol was associated with higher prevalence of cigarette smoking (PR: 5.65, 95% CI: 4.03-7.90) than a lack of alcohol consumption. Skin color and socioeconomic class did not exhibit significant relationships with tobacco use patterns. Conclusions: Smoking was associated with education level regardless of social class, and some specific behaviors associated with a same-sex sexual experience were associated with a higher prevalence of smoking. These findings are important for formulating policies and directing actions to combat and prevent smoking among young populations.

Behavioral factors associated with multiple-type HPV genital infections: data from a cross-sectional study in young women in Brazil.

OBJECTIVES: To investigate the pattern of multiple human papillomavirus (HPV) infections and associated factors in young women who access the Brazilian public health care system to better understand the characteristics of multiple HPV infections, a critical issue in this era of multivalent vaccines. METHODS: This was a cross-sectional, multicenter study with sexually active unvaccinated women (16-25 years old) from 119 primary Brazilian healthcare centers between September 2016 and November 2017. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. RESULTS: Of the 5268 women, 33.00% (95% CI 31.07-34.92) had multiple infections. At least one type of high-risk HPV was present in 85.50% of all multiple infections. All HPV types were detected more frequently in association with other types than alone. Young individuals who were single or in a casual relationship and those who had more than one sexual partner in the past year were more likely to have multiple infections. CONCLUSIONS: In this work, a high rate of multiple HPV infections among unvaccinated young adults tended to increase due to certain risk factors. Such data can provide insight for decision makers in the development of public policies regarding HPV prevention.

Understanding the characteristics of multiple infections is critical in the era of HPV multivalent vaccines for the prevention of cervical carcinomas. Therefore, in this cross-sectional study, we aimed to investigate the pattern of multiple HPV infections and associated factors in 5,268 sexually active unvaccinated women (16­25 years old) who access the Brazilian public health care system. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. A total of 33.00% (95% CI 31.07­34.92) had multiple infections (60.43% of the HPV-positive sample). The number of HPV types in a multiple infection ranged from 2 to 14 different types. The viral types more frequently identified were HPV 16 and 52. All HPV types were detected more frequently in association with other types than alone. The incidence of multiple infections was 1.29 times higher in single than in married or cohabitating participants. Women who had two or more partners in the last year also had higher rates of multiple infections than those who had fewer than two sexual partners. In conclusion, a high prevalence of multiple infections prior to the national HPV immunization program was observed, especially with the increase in less safe behavior factors.

Prevalence of oral HPV infection in unvaccinated young adults in Brazil.

OBJECTIVES: This study aimed to report the national prevalence of oral HPV infection among unvaccinated women and men aged 16-25 years who utilized the public primary care services. METHODS: POP-Brazil is a cross-sectional, multicentric, nationwide survey conducted between September 2016 and November 2017. Recruitment was based in 119 public primary care practices in 26 state capitals and the Federal District of Brazil. Trained health professionals conducted face-to-face interviews. Oral samples were collected with mouthwash and gargle cycles. Genotyping was performed using the Roche PCR-based linear array genotyping test. Sampling weights by sex and age were applied. RESULTS: Valid oral HPV samples were collected from 5071 (96.88%) participants; 4005 women and 1066 men. Mean participant age was 21.63 years. Overall HPV prevalence was 1.69% (n = 73, 95% CI 1.05-2.32). Thirty individuals presented at least one high-risk HPV type [0.57% (95% CI, 0.29-0.85)]. There were no associations between age, sex, sociodemographic characteristics, drug use or sexual behavior and oral HPV prevalence. CONCLUSION: The prevalence of oral HPV infection in Brazilian teenagers and young adults is low, with no sociodemographic or behavioral correlates.

Effectiveness of a universal vaccination program with an HPV quadrivalent vaccine in young Brazilian women.

We examined human papillomavirus (HPV) vaccine effectiveness in a nationwide sample of women aged 16 to 25 years who utilized the public health system in Brazil. This was a cross-sectional, multicentric survey conducted between September 2016 and November 2017 (POP-Brazil Study). A total of 5,945 young adult women were recruited from 119 public primary care units from all 27 federative units of Brazil by trained health professionals. The participants participated in a face-to-face interview and provided biological samples for genital HPV analysis. HPV genotyping was performed using a Linear Array HPV genotyping test in a central laboratory. Sampling weights were applied to the data. Overall, 11.92% (95% CI 10.65, 13.20) of the participants reported having been vaccinated. The frequency of vaccination was highest in 16- to 17-year-old women, with a decreasing vaccination rate with increasing age, and vaccinated women were more likely to belong to the high socioeconomic status group. The use of a quadrivalent vaccine decreased the HPV types 6, 11, 16, and 18 by 56.78%, from 15.64% in unvaccinated women to 6.76% in vaccinated women (P < 0.01), even after adjustment for age. Those who received the vaccine had lower HPV 16 (2.34% in vaccinated vs 8.91% in unvaccinated, P < 0.01) and 6 rates (2.06% vs 5.77%, P < 0.01). Additionally, a higher rate of high-risk HPV types other than HPV 16 and 18 (40.47% in vaccinated vs 32.63% in unvaccinated, P < 0.01) was observed. In conclusion, the results of this study support the effectiveness of HPV vaccination in Brazil. Continuous surveillance must be assured to monitor the HPV infection rate in the vaccination era.

The impact of socioeconomic status on HPV infection among young Brazilians in a nationwide multicenter study.

The aim of this study is to evaluate genital human papillomavirus (HPV) infection according to socioeconomic categories in Brazil. This cross-sectional, nationwide study included 7,694 sexually active women and men aged 16-25 years. Individuals of all socioeconomic groups in all 26 Brazilian capitals and the Federal District were enrolled through public primary care units between September 2016 and November 2017. All participants answered a standardized interview administered by trained primary care health professionals. Socioeconomic class was analyzed using a pricing classification system for the Brazilian public that divides the market exclusively in terms of economic class based on the ownership of assets and the education level. Cervical samples were obtained using a Digene® HC2 DNA Collection, and penile/scrotum samples were obtained using a wet Dacron swab. HPV typing (overall and high-risk) was performed in a central lab. Of the 7,694 participants (47.85% women), 17.92% belonged to class A-B, 56.08% to class C, and 26.00% to class D-E. The prevalence of overall HPV was similar among the social classes: 51.16% for classes A-B, 53.39% for class C, and 55.47% for classes D-E (P = 0.479). Similar results were found for high-risk HPV. After adjustments, the presence of HPV in individuals with a brown skin color belonging to classes A-B was 57.00% higher [prevalence ratio 1.57 (95%: 1.23, 2.01)] than that in whites and had no impact on the other social classes. In conclusion, HPV infection affects all socioeconomic classes in Brazil, evidencing the importance of offering the HPV vaccine to the entire population.

Sexual behavior and its association with persistent oral lesions: analysis of the POP-Brazil study.

OBJECTIVES: To investigate whether the presence of persistent self-reported oral lesions (PSOLs) is associated with sexual behaviors and with the presence of sexually transmitted infections (STIs) in individuals aged 16-25 years in the state capitals of Brazil. MATERIALS AND METHODS: Data from the POP-Brazil study were analyzed. An association analysis was performed by Poisson regression with the presence of PSOLs as the outcome. The exposure variables were the age at first sexual intercourse, the number of partners, oral sex practice, and aspects of condom use for model 1, and the presence of a self-reported STI or a positive rapid test for HIV/syphilis and the presence of genital human papillomavirus (HPV) for model 2. The results were adjusted for socioeconomic variables. RESULTS: The prevalence of PSOLs was 76% higher among individuals who had two or more sexual partners in the past year (p = 0.046) and 68% higher in those who reported not using condoms for contraception (p = 0.032). The group with HIV/syphilis or self-reported STI had a 140% higher PSOL prevalence (p = 0.003). CONCLUSIONS: The self-report of oral lesions in adolescents and young adults may suggest risky sexual behavior and the presence of STI. CLINICAL RELEVANCE: It is necessary to contextualize the reality of the young person to optimize oral health care.

Open-source real-time quantitative RT-PCR-based on a RNA standard for the assessment of SARS-CoV-2 viral load

BACKGROUND Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target genes by molecular methods has been chosen as the main approach to identify individuals with Coronavirus disease 2019 (COVID-19) infection. OBJECTIVES In this study, we developed an open-source RNA standard-based real-time quantitative RT-PCR (RT-qPCR) assay for quantitative diagnostics of SARS-CoV-2 from nasopharynx, oropharynx, saliva and plasma samples. METHODS AND FINDINGS We evaluated three SARS-CoV-2 target genes and selected the RNA-dependent RNA polymerase (RdRp) gene, given its better performance. To improve the efficiency of the assay, a primer gradient containing 25 primers forward and reverse concentration combinations was performed. The forward and reverse primer pairs with 400 nM and 500 nM concentrations, respectively, showed the highest sensitivity. The LOD95% was ~60 copies per reaction. From the four biological matrices tested, none of them interfered with the viral load measurement. Comparison with the AllplexTM 2019-nCoV assay (Seegene) demonstrated that our test presents 90% sensitivity and 100% specificity. MAIN CONCLUSIONS We developed an efficient molecular method able to measure absolute SARS-CoV-2 viral load with high replicability, sensitivity and specificity in different clinical samples.

Características clínicas e preditores de ventilação mecânica em pacientes com COVID-19 hospitalizados no sul do país / Clinical characteristics and predictors of mechanical ventilation in patients with COVID-19 hospitalized in Southern Brazil

RESUMO Objetivo: Descrever as características clínicas e os preditores de ventilação mecânica em pacientes adultos internados com COVID-19. Métodos: Conduziu-se um estudo de coorte retrospectiva com inclusão de pacientes hospitalizados entre 17 de março e 3 de maio de 2020, que tiveram o diagnóstico de infecção pelo SARS-CoV-2. As características clínicas e demográficas foram extraídas de registros em prontuário eletrônico. Resultados: Incluíram-se no estudo 88 pacientes consecutivos. A mediana da idade dos pacientes foi de 63 anos (IQR: 49 - 71); 59 (67%) pacientes eram do sexo masculino, 65 (86%) tinham educação universitária e 67 (76%) tinham, no mínimo, uma comorbidade. Dentre eles, 29 (33%) pacientes foram admitidos à unidade de terapia intensiva, 18 (20%) necessitaram de ventilação mecânica e nove (10,2%) morreram durante a hospitalização. O tempo mediano de permanência na unidade de terapia intensiva e o tempo mediano de ventilação mecânica foram, respectivamente, de 23 e 29,5 dias. Idade acima ou igual a 65 anos foi fator de risco independente para ventilação mecânica (RC: 8,4; IC95% de 1,3 - 55,6; valor de p = 0,02). Conclusão: Nossos achados descrevem a primeira onda de pacientes brasileiros hospitalizados por COVID-19. Em nossa população, idade foi o maior preditor de insuficiência respiratória e necessidade de ventilação mecânica.

Abstract Objective: This study aims to describe the clinical characteristics and predictors of mechanical ventilation of adult inpatients with COVID-19 in a single center. Methods: A retrospective cohort study was performed and included adult inpatients hospitalized from March 17th to May 3rd, 2020, who were diagnosed with SARS-CoV-2 infection. Clinical and demographic characteristics were extracted from electronic medical records. Results: Overall, 88 consecutive patients were included in this study. The median age of the patients was 63 years (IQR 49 - 71); 59 (67%) were male, 65 (86%) had a college degree and 67 (76%) had at least one comorbidity. Twenty-nine (33%) patients were admitted to the intensive care unit, 18 (20%) patients needed mechanical ventilation, and 9 (10.2%) died during hospitalization. The median length of stay in the intensive care unit and the median duration of mechanical ventilation was 23 and 29.5 days, respectively. An age ≥ 65 years was an independent risk factor for mechanical ventilation (OR 8.4 95%CI 1.3 - 55.6 p = 0.02). Conclusion: Our findings describe the first wave of Brazilian patients hospitalized for COVID-19. Age was the strongest predictor of respiratory insufficiency and the need for mechanical ventilation in our population.

Sex differences in the prevalence and determinants of HPV-related external genital lesions in young adults: a national cross-sectional survey in Brazil.

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