RESUMO
BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal cancer screening is being explored in research studies, but strategies to identify an appropriate population are not established. The authors evaluated whether a screening population could be enriched for participants with oncogenic HPV biomarkers using risk factors for oral HPV. METHODS: Participants were enrolled at Johns Hopkins Hospitals and Mount Sinai Icahn School of Medicine. Eligible participants were either men aged 30 years or older who had two or more lifetime oral sex partners and a personal history of anogenital dysplasia/cancer or partners of patients who had HPV-related cancer. Oral rinse and serum samples were tested for oncogenic HPV DNA, RNA, and E6 or E7 antibodies, respectively. Participants with any biomarker were considered at-risk. RESULTS: Of 1108 individuals, 7.3% had any oncogenic oral HPV DNA, and 22.9% had serum antibodies for oncogenic HPV E6 or E7. Seventeen participants (1.5%) had both oral and blood biomarkers. HPV type 16 (HPV16) biomarkers were rarer, detected in 3.7% of participants, including 20 with oral HPV16 DNA and 22 with HPV16 E6 serum antibodies (n = 1 had both). In adjusted analysis, living with HIV (adjusted odds ratio, 2.65; 95% CI, 1.60-4.40) and older age (66-86 vs. 24-45 years; adjusted odds ratio, 1.70; 95% CI, 1.07-2.70) were significant predictors of being at risk. Compared with the general population, the prevalence of oral HPV16 (1.8% vs. 0.9%), any oncogenic oral HPV DNA (7.3% vs. 3.5%), and HPV16 E6 antibodies (2.2% vs. 0.3%) was significantly elevated. CONCLUSIONS: Enrichment by the eligibility criteria successfully identified a population with higher biomarker prevalence, including HPV16 biomarkers, that may be considered for screening trials. Most in this group are still expected to have a low risk of oropharyngeal cancer.
Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Papillomavirus Humano , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Prevalência , Boca , Papillomavirus Humano 16/genética , Biomarcadores , Fatores de RiscoRESUMO
BACKGROUND: Cryptosporidium is a leading contributor to diarrheal morbidity and mortality in under-5 children worldwide. As there is no vaccine and no effective drug therapy in young children for this infection, preventing infection is critical. We undertook a pilot case-control study to define the extent of person-to-person transmission of cryptosporidiosis within an urban and a rural community in Bangladesh. METHODS: We enrolled 48 case families with a Cryptosporidium-infected child aged 6-18 months. Controls were age- and sex-matched Cryptosporidium-negative children in 12 households. Children and household members were followed for 8 weeks with weekly illness survey and stool testing with quantitative polymerase chain reaction for Cryptosporidium. RESULTS: In the 24 urban case families, the secondary attack rate was 35.8% (19/53) vs 0% (0/11) in controls (P = .018, χ2 test). In contrast, in the 24 rural case families, the secondary attack rate was 7.8% (5/64) vs 0% (0/21) in controls (P = .19, χ2 test). Genotyping by gp60 demonstrated infection with the same subspecies in 5 families, and evidence of transmission in 2. Serologic response to Cryptosporidium infection was associated with younger age, longer duration of infection, and Cryptosporidium hominis gp60_IbA9G3R2 infection. CONCLUSIONS: In the urban site, the high rate of secondary infection and infection with the same subspecies within families suggests that person-to-person transmission is a major source of Cryptosporidium infection for young children living in this region. Molecular genotyping can be applied to determine transmission of Cryptosporidium in endemic regions. Further work is needed to understand the differences in parasite transmissibility and immunity to different genotypes.
Assuntos
Criptosporidiose/transmissão , Cryptosporidium/isolamento & purificação , Transmissão de Doença Infecciosa , Características da Família , Adulto , Bangladesh/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Criptosporidiose/epidemiologia , Cryptosporidium/classificação , Cryptosporidium/genética , Feminino , Genótipo , Técnicas de Genotipagem , Humanos , Lactente , Recém-Nascido , Masculino , População Rural , População Urbana , Adulto JovemRESUMO
PURPOSE: African American/Black (AA/B) individuals are under-represented in genomic databases and thus less likely to receive definitive information from germline genetic testing (GGT) than non-Hispanic White (NHW) individuals. With nearly 500,000 AA/B and NHW individuals having undergone multigene panel testing (MGPT) for hereditary cancer risk at a single commercial laboratory, to our knowledge, we present the largest study to date investigating cancer GGT results in AA/B and NHW individuals. METHODS: MGPT results from a retrospective cohort of AA/B (n = 48,684) and NHW (n = 444,831) patients were evaluated. Frequencies of pathogenic germline variants (PGVs) and variants of uncertain significance (VUS) were compared between AA/B and NHW individuals. Changes in frequency of VUS over time were determined. Pearson's chi-squared test was used to compare categorical variables among groups. All significance tests were two-tailed, and P < .05 was considered statistically significant. RESULTS: Between 2015 and 2022, rates of VUS decreased 2.3-fold in AA/B and 1.8-fold in NHW individuals; however, frequencies of VUS and PGV remained significantly higher (46% v 32%; P < .0001) and lower (9% v 13%; P < .0001) in AA/B compared with NHW individuals. Rates of VUS in ATM, BRCA1, BRCA2, PALB2, and PMS2 were significantly higher in AA/B compared with NHW individuals, whereas rates of PGV in BRCA1, BRCA2, and PALB2 were higher in AA/B compared with NHW individuals (P < .001). CONCLUSION: Despite reductions in VUS frequencies over time, disparities in definitive GGT results persist. Increasing inclusion of AA/B populations in both testing and research will further increase knowledge of genetic variants across these racial groups.
Assuntos
Negro ou Afro-Americano , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Neoplasias , Brancos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Negro ou Afro-Americano/genética , Testes Genéticos/métodos , Neoplasias/genética , Neoplasias/etnologia , Estudos Retrospectivos , Brancos/genéticaRESUMO
Performance of commercially available human papillomavirus (HPV) assays (approved for cervical HPV detection) is unknown for detecting HPV-related oropharyngeal cancer (HPV-OPC). Assays for detection of HPV DNA [ELISA (DEIA) and Cobas], and RNA (Aptima) in oral rinse samples, and serum HPV oncogene antibodies were evaluated. Sensitivity and specificity of each test was explored among HPV-OPC cases and controls. Biomarker prevalence was evaluated among 294 "at-risk" people (screening) and 133 "high-risk" people [known to previously have oral oncogenic HPV (oncHPV) DNA and/or HPV16 E6/E7 antibodies detected]. HPV16 E6 antibodies had the best overall test performance with sensitivity of 88%, compared with oral HPV16 DNA sensitivity of 51% by DEIA and 43% by Cobas (each P < 0.001). Specificity was comparable in each of these tests (≥98%). When positivity for any oncHPV type was compared with HPV16 for the same test, sensitivity was comparable (60% vs. 51%, 40% vs. 43%, and 92% vs. 88% for DEIA, Cobas, and E6 antibodies, respectively), but specificity was reduced (93%-97%). Aptima had poor sensitivity (23%). Sensitivity decreased when cotesting HPV16 oral rinse DNA and E6 antibodies (37%-48%), or multiple E antibodies (69%-72%). HPV16 DNA were detected in â¼2% of the at-risk by either DEIA or Cobas and up to 15% of the high-risk population. HPV16 E6 seroprevalence was 2.3% and 2.4% in the at-risk and high-risk populations, respectively. Oral rinse HPV testing had moderate-to-poor sensitivity for HPV-OPC, suggesting many true positives would be missed in a potential screening scenario. HPV16 E6 serum antibody was the most promising biomarker evaluated.