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1.
J Clin Virol Plus ; 3(3)2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37654784

RESUMO

Background: The role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody response from natural infection and vaccination, and the potential determinants of this response are poorly understood. Characterizing this antibody response and the factors associated with neutralization can help inform future prevention efforts and improve clinical outcomes in those infected. Objectives: The goals of this study were to prospectively evaluate SARS-CoV-2 antibody levels and the neutralizing antibody responses among naturally infected adults and to determine demographic and behavioral factors independently associated with these responses. Methods: Serum was collected from seropositive individuals at baseline, four-weeks, and three-months following their first study visit to be evaluated for antibody levels. Detection of neutralizing antibodies was performed at baseline. Participant demographic and behavioral information was collected via web questionnaire prior to their first visit. Results: At baseline, higher antibody levels were associated with better neutralization capacity, with 83% of participants having detectable neutralizing antibodies. We found an age-dependent effect on antibody level and neutralization capacity with participants over 65 years having significantly higher levels. Ethnicity, heart disease, autoimmune disease, and COVID symptoms were associated with higher antibody levels, but not with increased neutralization capacity. Work environment during the pandemic correlated with increased neutralization capacity, while kidney or liver disease and traveling out of state after February 2020 correlated with decreased neutralization capacity, however neither correlated with antibody levels. Conclusions: Our data show that natural infection by SARS-CoV-2 can induce a humoral response reflected by high antibody levels and neutralization capacity.

2.
J Infect Dis ; 227(2): 256-260, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35679351

RESUMO

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal cancer (OPC) incidence is increasing among men. Biomarkers that can identify oral HPV16/18 infections likely to persist, the obligate precursor for HPV-OPC, are needed. METHODS: We assessed the association between oral Epstein-Barr virus (EBV) and oral HPV16/18 persistence among 63 men in the HPV Infection in Men Study who tested positive for HPV16/18 at the baseline visit. Control of oral coinfections, including EBV, could serve as a biomarker of immune competence and the ability to control oral HPV. RESULTS: Detection of oral EBV was significantly associated with oral HPV16/18 ≥12-month persistence. CONCLUSIONS: Detection of oral EBV deserves evaluation as a biomarker for oral HPV persistence and HPV-related OPC.


Assuntos
Infecções por Vírus Epstein-Barr , Doenças da Boca , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Herpesvirus Humano 4 , Papillomavirus Humano , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Neoplasias Orofaríngeas/epidemiologia , Doenças da Boca/epidemiologia , Papillomaviridae
3.
Cancer Med ; 11(20): 3735-3742, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35619332

RESUMO

As oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) increases in men, the need for a screening test to diagnose OPC early is crucial. While HPV-associated OPC has a favorable prognosis, recurrence is likely, and metastatic OPC is often incurable regardless of HPV status. Our previous study of pretreatment, male OPC cases (n = 101) and age- and smoking-matched controls (n = 101) found methylation of the host EPB41L3 tumor suppressor gene and HPV16 in the oral gargle was correlated with these biomarkers in the tumor. Methylation of these genes in the oral gargle was significantly (p < 0.0001) higher among cases compared to controls. To further study the utility of HPV16/EPB41L3 methylation, we expanded the sample size and specifically increased the number of early OPC cases (T1-T2, N0-N1; small tumors with a single ipsilateral node <3 cm) to evaluate these biomarkers in early and late OPC. This study included 228 OPC cases, 92 of which were early cases and frequency matched to 142 healthy controls. In logistic regression, the AUC for HPV16/EPB41L3 methylation for all OPC cases was 0.82. Among early and late OPC cases, the AUC was 0.78 and 0.85, respectively. For early cases, 76% sensitivity was achieved, replicating results from our prior study, with a specificity of 65%, indicating room for improvement. The ability of HPV16/EPB41L3 methylation to distinguish OPC from healthy controls highlights its utility as a potential biomarker for OPC. However, the inability to predict early OPC better than late stage OPC indicates the need for additional biomarkers to improve screening performance.


Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Papillomavirus Humano 16/genética , Metilação , Papillomaviridae , Biomarcadores , Proteínas dos Microfilamentos/genética
4.
Emerg Infect Dis ; 28(3): 556-563, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35081021

RESUMO

Estimating the actual extent of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging because virus test positivity data undercount the actual number and proportion of persons infected. SARS-CoV-2 seroprevalence is a marker of past SARS-CoV-2 infection regardless of presence or severity of symptoms and therefore is a robust biomarker of infection period prevalence. We estimated SARS-CoV-2 seroprevalence among residents of Hillsborough County, Florida, USA, to determine factors independently associated with SARS-CoV-2 antibody status overall and among asymptomatic antibody-positive persons. Among 867 participants, SARS-CoV-2 period prevalence (October 2020-March 2021) was 19.5% (asymptomatic seroprevalence was 8%). Seroprevalence was 2-fold higher than reported SARS-CoV-2 virus test positivity. Factors related to social distancing (e.g., essential worker status, not practicing social distancing, contact with a virus-positive person, and length of contact exposure time) were consistently associated with seroprevalence but did not differ by time since suspected or known infection (<6 months vs. >6 months).


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Florida/epidemiologia , Humanos , Pandemias , Estudos Soroepidemiológicos
5.
Sex Transm Dis ; 49(1): 55-58, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34282740

RESUMO

BACKGROUND: Studies in women have shown an increased risk of human immunodeficiency virus (HIV) acquisition with prior human papilloma virus (HPV) infection; however, few studies have been conducted among men. Our objective was to assess whether HPV-related external genital lesions (EGLs) increase risk of HIV seroconversion among men. METHODS: A total of 1379 HIV-negative men aged 18 to 70 years from the United States, Mexico, and Brazil were followed for up to 7 years and underwent clinical examination for EGLs and blood draws every 6 months. Human immunodeficiency virus seroconversion was assessed in archived serum. Cox proportional hazards and marginal structural models assessed the association between EGL status and time to HIV seroconversion. RESULTS: Twenty-nine participants HIV seroconverted during follow-up. Older age was associated with a lower hazard of HIV seroconversion. We found no significant difference in the risk of HIV seroconversion between men with and without EGLs (adjusted hazard ratio, 0.94; 95% confidence interval, 0.32-2.74). Stratified analyses focusing on men that have sex with men found no association between EGLs and HIV seroconversion risk (hazards ratio, 0.63; 95% confidence interval, 0.00-1.86). CONCLUSIONS: External genital lesions were not associated with higher risk for HIV seroconversion in this multinational population, although statistical power was limited as there were few HIV seroconversions. Results may differ in populations at higher risk for HIV.


Assuntos
Infecções por HIV , Soropositividade para HIV , Adolescente , Adulto , Idoso , Feminino , Genitália , HIV , Infecções por HIV/epidemiologia , Soropositividade para HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Soroconversão , Estados Unidos/epidemiologia , Adulto Jovem
6.
Vaccine ; 39(37): 5295-5301, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34373120

RESUMO

Strong quantitative and functional antibody responses to the quadrivalent human papillomavirus (HPV) vaccine were reported in mid-adult aged men, but there are limited data on the avidity of the antibody response and the memory B-cell response following vaccination. Although circulating antibodies induced by vaccination are believed to be the main mediators of protection against infection, evaluation of avidity of antibodies and memory B cell responses are critical for a better understanding of the vaccine immunogenicity mechanisms. Both the modified enzyme-linked immunosorbent assay (ELISA) and the enzyme-linked immunosorbent spot (ELISpot) assay are tools to measure the humoral and cellular immune responses post vaccination to characterize vaccine immunogenicity. The avidity of HPV-16 and HPV-18 specific IgG in the serum of mid-adult aged men (N = 126) who received three quadrivalent HPV vaccine doses was examined using a modified ELISA. HPV-16 memory B-cell responses were assessed via ELISpot at month 0 (prior to vaccination) and 1-month post-dose three of the vaccine (month 7). The quadrivalent vaccine induced an increase in HPV-16 and HPV-18 antibody avidity at month 7. HPV-18 avidity levels moderately correlated with anti-HPV-18 antibody titers, but no association was observed for HPV-16 antibody titers and avidity levels. The HPV-16-specific memory B-cell response was induced following three vaccine doses, however, no association with anti-HPV-16 antibody avidity was observed. Three doses of quadrivalent HPV vaccine increased antibody affinity maturation for HPV-16/18 and increased the frequency of anti-HPV-16 memory B-cells in mid-adult aged men.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adulto , Idoso , Anticorpos Antivirais , Afinidade de Anticorpos , Linfócitos B , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Masculino , Infecções por Papillomavirus/prevenção & controle
7.
Int J Cancer ; 149(7): 1483-1494, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34224588

RESUMO

Oral human papillomavirus (HPV) is associated with increasing rates of HPV-associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection after a genital infection of the same type in the HPV infection in men study was investigated. Samples from 3140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58); and then also sequential, same-type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7-3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7-3.1) and 3.5 (95% CI: 1.9-6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.


Assuntos
Doenças dos Genitais Masculinos/epidemiologia , Genitália/patologia , Doenças da Boca/epidemiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Estudos de Coortes , Seguimentos , Doenças dos Genitais Masculinos/virologia , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Doenças da Boca/virologia , Infecções por Papillomavirus/virologia , Prognóstico , Comportamento Sexual , Estados Unidos/epidemiologia , Adulto Jovem
8.
PLoS One ; 16(7): e0254161, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214131

RESUMO

BACKGROUND: Rates of oropharyngeal cancer (OPC) associated with alcohol & tobacco use have decreased, while human papillomavirus (HPV) associated OPC has increased among men in the US. Secretory leukocyte protease inhibitor (SLPI), detectable in a variety of secretions, has been implicated in cancers of the head and neck, associated with tumor progression and anti-viral activity. Using the recently verified oral gargle specimen, this study aimed to assess the association of salivary SLPI expression with risk of OPC and response to treatment. METHODS: A case-control study design compared levels of salivary SLPI among OPC cases to age and tobacco smoking matched healthy controls. Oral HPV DNA and SLPI was quantified from oral gargle specimens. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations of oral SLPI and risk of OPC and treatment outcomes. RESULTS: In crude and adjusted analyses of 96 OPC cases and 97 age- and smoking-matched controls, OPC was not significantly associated with oral gargle SLPI levels. Among cases, oral SLPI was associated with tonsillectomy (p = 0.018) and among controls oral SLPI was associated with HPV in the oral gargle (p = 0.008). Higher concentrations of SLPI was significantly associated with increased odds of incomplete treatment response (T2: OR: 12.39; 95% CI: 1.44-106.72; T3: OR: 9.86; 95% CI: 1.13-85.90) among all cases, but not among P16+ cases. CONCLUSIONS: Salivary SLPI was not associated with OPC risk but was associated with higher odds of an incomplete treatment response.


Assuntos
Neoplasias Orofaríngeas/metabolismo , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Antissépticos Bucais , Razão de Chances , Neoplasias Orofaríngeas/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/metabolismo , Saliva/metabolismo , Fumar/efeitos adversos , Fumar/metabolismo , Resultado do Tratamento
9.
PLoS One ; 16(5): e0250871, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33939747

RESUMO

OBJECTIVE: Young women in South Africa are highly affected by sexually transmitted infections (STI), like C. trachomatis (CT) and N. gonorrhoeae (NG). We aimed to estimate the incidence of CT and NG, and its determinants, among young women from the Western Cape, South Africa, participating in an HPV vaccine trial (the EVRI study). METHODS: HIV-negative women aged 16-24 years were enrolled between October 2012 and July 2013. At enrolment and month 6 participants were screened for CT and NG (Anyplex CT/NG real-time detection method). A questionnaire on demographic and sexual history characteristics was completed at enrolment and month 7. Treatment for CT and/or NG was offered to infected participants. Incidence rates (IR) of CT and NG were estimated. Determinants of incident CT and NG infections were assessed using Poisson regression. RESULTS: 365 women were tested for CT and/or NG at least twice. Prevalence of CT and NG at baseline was 33.7% and 10.4%, respectively. Prevalence of co-infection with CT and NG was 7.1%. During 113.3 person-years (py), 48 incident CT infections were diagnosed (IR = 42.4 per 100 py, 95% confidence interval (CI) 31.9-56.2). Twenty-nine incident NG were diagnosed during 139.3 py (IR = 20.8 per 100 py, 95%CI 14.5-29.9). Prevalent CT infection at baseline was associated with incident CT (adjusted incidence rate ratio (aIRR) 5.8, 95%CI 3.0-11.23. More than three lifetime sex partners increased the risk for incident NG (3-4 partners aIRR = 7.3, 95%CI 2.1-26.0; ≥5 partners aIRR = 4.3, 95%CI 1.1-17.5). CONCLUSIONS: The IR of bacterial STIs among young women in the Western Cape is very high. Besides being previously infected and a higher lifetime number of sex partners, no other risk factors were found for CT and NG, suggesting that the majority of these women were at risk. This indicates the need for intensified prevention of STIs as well as screening and treatment programs to increase sexual health in this region.


Assuntos
Infecções por Chlamydia/epidemiologia , Gonorreia/epidemiologia , Adolescente , Adulto , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/virologia , Chlamydia trachomatis/patogenicidade , Coinfecção/epidemiologia , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Gonorreia/microbiologia , Gonorreia/virologia , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Incidência , Programas de Rastreamento/métodos , Neisseria gonorrhoeae/patogenicidade , Prevalência , Fatores de Risco , Comportamento Sexual/fisiologia , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/microbiologia , África do Sul/epidemiologia , Adulto Jovem
10.
Clin Infect Dis ; 73(9): e3227-e3234, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33173937

RESUMO

BACKGROUND: Human papillomavirus (HPV)-attributable oropharyngeal cancer (HPV-OPC) incidence is increasing in many high-income countries among men. Factors associated with oral HPV persistence, the precursor of HPV-OPC, are unknown. Data from the HPV Infection in Men (HIM) Study, which followed participants >7 years, were utilized to examine rates of persistence and associated factors. METHODS: Oral gargle samples from 3095 HIM study participants were HPV genotyped using the SPF10 PCR-DEIA-LiPA25 assay (DDL Diagnostic Laboratory). Oral HPV persistence for individual and grouped high-risk HPV types among 184 men positive for any high-risk HPV at their oral baseline visit was assessed at 6-month intervals. Factors associated with grouped high-risk HPV/HPV16 persistence were examined using logistic regression. Kaplan-Meier curves were constructed to examine median time to HPV clearance overall, and by selected risk factors. RESULTS: Among the 7 HPV vaccine types, HPV33 had the longest median duration (7.6 months) followed by HPV16 and HPV45 (6.4 months). 10-30% of oral high-risk HPV infections persisted ≥24 months. Six months' persistence of oral high-risk HPV infections was positively associated with age and gingivitis and negatively with lifetime number of sexual partners, while 12 months' persistence was only inversely associated with lifetime number of sexual partners. Oral HPV16 persistence was positively associated with baseline HPV16 L1 antibody status. CONCLUSIONS: Eighteen percent of HPV16 infections persisted beyond 24 months, potentially conferring higher risk of HPV-OPC among these men. Older age appears to be an important factor associated with oral high-risk HPV persistence. More studies among healthy men are required to understand the progression of oral HPV infection to HPV-OPC.


Assuntos
Alphapapillomavirus , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Idoso , Papillomavirus Humano 16/genética , Humanos , Masculino , Neoplasias Orofaríngeas/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia
11.
J Infect Dis ; 223(12): 2099-2107, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33151300

RESUMO

BACKGROUND: Human papillomavirus (HPV) causes oral warts and oropharyngeal cancer (OPC). Human papillomavirus-attributable OPC incidence among men is significantly increasing worldwide, yet few studies have reported oral HPV across multiple countries or examined factors associated with low- and high-risk HPV separately. METHODS: Oral gargles from 3095 men in the multinational HPV Infection in Men (HIM) Study were HPV genotyped. Multivariable models assessed factors independently associated with high-risk and low-risk HPV prevalence. RESULTS: The prevalence of high-risk and low-risk HPV was 6.0% and 2.8%, respectively. Greater number of sexual partners was only associated with high-risk HPV (1.88; 95% confidence interval [CI], 1.22-2.90) prevalence. In multivariable models, residing in Mexico (1.66; 95% CI, 1.15-2.40) and smoking (1.66; 95% CI, 1.13-2.44) were significantly associated with high-risk HPV, and history of consistent gum bleeding (2.16; 95% CI, 1.35-3.45) was significantly associated with low-risk HPV. Gender of the sexual partner did not alter the results for either high- or low-risk HPV endpoints. CONCLUSIONS: Different factors were independently associated with high- and low-risk oral HPV. Oral sexual behaviors were associated with high-risk HPV, and oral health was associated with low-risk HPV. High-risk HPV prevalence differed by country of residence, highlighting the need for additional studies in multiple countries.


Assuntos
Alphapapillomavirus , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Alphapapillomavirus/genética , Genótipo , Humanos , Masculino , México/epidemiologia , Saúde Bucal , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/epidemiologia , Prevalência , Fatores de Risco , Comportamento Sexual
12.
Papillomavirus Res ; 9: 100199, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32464335

RESUMO

INTRODUCTION: Oral human papillomavirus (HPV) attributable oropharyngeal cancers are on the rise in many countries. Oral HPV infections among healthy individuals are commonly detected using oral gargle samples. However, the optimal method for HPV genotyping oral gargle specimens in research studies has not been previously evaluated. MATERIALS AND METHODS: Oral gargle samples from 1455 HPV Infection in Men (HIM) study participants were HPV genotyped using two different methods: Linear Array and the SPF10 PCR-DEIA-LiPA25. The sensitivity of the two tests for detecting individual HPV types and grouped HPV types, high-risk HPV, low-risk HPV, grouped 4-HPV-vaccine types, and grouped 9-HPV-vaccine-types, and the degree of concordance between the two tests was assessed. We also examined whether socio-demographic-behavioral factors were associated with concordance between the two assays. RESULTS: The sensitivity of SPF10 PCR-DEIA-LiPA25 was higher than Linear Array, with the exception of HPV 70, for the detection of oral HPV. The prevalence ratio of SPF10 PCR-DEIA-LiPA25 to Linear Array varied between 1.0 and 9.0 for individual HPV genotypes, excluding HPV 70, and between 3.8 and 4.4 for grouped 4-valent and 9-valent HPV vaccine types, respectively. There was no association between socio-demographic-behavioral factors and discordance in results between the two tests for oral HPV 16 detection. DISCUSSION: SPF10 PCR-DEIA-LiPA25 was more sensitive than Linear Array for detecting HPV in oral gargle samples. Given the growing importance of detecting oral HPV infection for research studies of oral HPV natural history and vaccine effectiveness evaluation, we recommend using methods with higher sensitivity such as SPF10 PCR-DEIA-LiPA25 for detecting HPV in oral gargle samples.


Assuntos
Alphapapillomavirus/isolamento & purificação , Boca/virologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Idoso , Alphapapillomavirus/classificação , Brasil/epidemiologia , DNA Viral/genética , Genótipo , Técnicas de Genotipagem , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Prevalência , Estudos Prospectivos , Sensibilidade e Especificidade , Estados Unidos/epidemiologia , Adulto Jovem
13.
Int J Cancer ; 146(4): 1018-1030, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31304592

RESUMO

Oropharyngeal cancer (OPC) incidence is increasing significantly among men and often requires intensive therapy causing significant morbidity. Early detection of OPC is needed, when monotherapy can be safely delivered with less treatment-associated morbidity, while maintaining high cure rates. We conducted a study of 101 pretreatment male OPC cases matched 1:1 to 101 disease-free controls for age and smoking history. Oral gargles were collected from cases and controls with additional biopsies or aspirates from cases. The HPV SPF10 -LiPA25 PCR assay was utilized for HPV genotyping. Methylation of three CpG sites (438, 427 and 425) in the EPB41L3 gene and methylation status of the L1 (6,367, 6,389), L2 (4,257, 4,262, 4,266, 4,269, 4,275, 4,282) and E2 (3,412, 3,415, 3,417, 3,433, 3,436) CpG sites of HPV 16 positive specimens was assessed by pyrosequencing. Significant correlations were observed between tumor and oral specimens for all methylation biomarkers (p < 0.01). EPB41L3 and HPV 16 L1, L2 and E2 methylation were significantly (p < 0.0001) higher among cases than controls, regardless of early vs. late disease. When HPV 16 genes and EPB41L3 methylation status were combined in a logistic regression analysis, a sensitivity of 70.3% and a specificity of 90.9% were observed for the detection of OPC from an oral gargle. Our data suggest that methylation biomarkers measured in oral gargles may have utility in identifying OPC early. Future studies are needed to replicate these findings and to inform additional biomarkers that can maximize specificity and sensitivity for early OPC detection.


Assuntos
Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , Proteínas dos Microfilamentos/genética , Proteínas Oncogênicas Virais/genética , Neoplasias Orofaríngeas/diagnóstico , Infecções por Papillomavirus/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , Ilhas de CpG/genética , Metilação de DNA , DNA Viral/genética , DNA Viral/isolamento & purificação , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mucosa Bucal/virologia , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Estudo de Prova de Conceito , Sensibilidade e Especificidade
14.
Int J Cancer ; 146(11): 3026-3033, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31583681

RESUMO

Incidence of human papillomavirus (HPV) attributable oropharyngeal cancers (OPCs) has been increasing globally, especially among men in high-income countries. There is a lack of studies comparing oral HPV prevalence by age and country among healthy men. The purpose of our study was to assess oral HPV prevalence by country and age. Participants of the HPV Infection in Men Study (HIM), a cohort of 3,098 healthy men from São Paulo, Brazil, Cuernavaca, Mexico and Tampa, USA, were studied. Oral HPV prevalence and type distribution were assessed using the SPF10 PCR-DEIA-LiPA25 system. The prevalence of any HPV in Brazil, Mexico and the US was 8.7% (95% CI: 7.1%, 10.4%), 10.0% (95% CI: 8.3%, 12.1%) and 7.6% (95% CI: 5.9%, 9.5%), respectively, while the prevalence of high-risk HPV was 5.3% (95% CI: 4.1%, 6.7%), 7.3% (95% CI: 5.7%, 9.0%) and 5.4% (95% CI: 4.0%, 7.0%), respectively. No significant differences in prevalence of grouped HPV types were observed by country despite significant differences in sexual behaviors. However, the age-specific prevalence of oral HPV differed by country. Brazilian (6.0% [95% CI: 3.4%, 9.7%]) and Mexican (9.2% [95% CI: 5.6%, 14.0%]) participants had peak high-risk HPV prevalence among men aged 41-50 years whereas the US participants had peak prevalence at ages 31-40 years (11.0% [95% CI: 6.4%, 17.3%]). In conclusion, oral HPV prevalence was low with no difference in overall prevalence observed by country. Factors associated with the differences in oral HPV age-patterning by country and sexual orientation require further study.


Assuntos
Doenças da Boca/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Brasil/epidemiologia , Feminino , Papillomavirus Humano 16/isolamento & purificação , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Doenças da Boca/virologia , Neoplasias Orofaríngeas/virologia , Estados Unidos/epidemiologia , Adulto Jovem
15.
Vaccine ; 37(18): 2502-2510, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30940485

RESUMO

Duration and functional aspects of the oral and systemic antibody responses following HPV vaccination in HIV-negative (HIV-) and HIV-positive (HIV+) men are not well characterized. Oral and systemic HPV-16 and HPV-18-specific antibody levels were evaluated over 18-months of follow-up, in HIV+ and HIV- men. Sera and oral gargles from 147 HIV- men, ages 27-45 and 75 HIV+ men, ages 22-61, who received 3-doses of quadrivalent HPV vaccine were tested for HPV-16 and HPV-18 antibodies at Day 1, Month 7 (1 month post-dose 3), and Month 18 (12 months post-dose 3) and HPV avidity (Day 1, and Month 7) using L1-VLP ELISA. All individuals seroconverted, regardless of HIV-status, following 3-doses of vaccine for HPV-16 and HPV-18. Serum HPV-16 and HPV-18 antibody geometric mean levels were >2-fold lower in HIV+ compared to HIV- men at Month 7 (HPV-16: 808.5 versus 2119.8 EU/mL, and HPV-18: 285.8 versus 611.6 EU/mL, p < 0.001) but not significantly different at Month 18 (HPV-16: 281.8 versus 359.7 EU/mL, p = 0.145, and HPV-18: 120.2 versus 93.4 EU/mL, p = 0.372). Post-vaccination, only oral HPV-16 antibody levels at Month 7 were significantly different between HIV+ and HIV- men (127.7 versus 177.1 EU/mg of IgG, p = 0.008). Among baseline HPV-seronegative men, circulating levels of HPV-16 and HPV-18 antibodies were up to >3 fold lower in HIV+ men, at Months 7 and 18. In contrast, levels of HPV-16 and HPV-18 antibodies after vaccination were not inferior in baseline HPV-seropositive, HIV+ men. HPV-16 and HPV-18 avidity was lower among HIV+ compared to HIV- men at Month 7 (HPV-16: 1.95 M versus 2.12 M, p = 0.027; HPV-18: 1.50 M versus 1.72 M, p < 0.001). Although differences in peak antibody levels were observed between HIV+ and HIV- men following 3 doses of vaccine, plateau antibody levels were overall comparable, and avidity was relatively high for both groups. These data indicate that the vaccine induced antibody affinity maturation in both HIV+ and HIV- men and will likely result in long-term protective immune responses.


Assuntos
Alphapapillomavirus/imunologia , Anticorpos Antivirais/sangue , Infecções por HIV/complicações , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Boca/imunologia , Infecções por Papillomavirus/prevenção & controle , Adulto , Anticorpos Neutralizantes/sangue , Afinidade de Anticorpos , Infecções por HIV/epidemiologia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/imunologia , Vacinação , Adulto Jovem
16.
Oral Oncol ; 92: 85-91, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31010629

RESUMO

OBJECTIVE: Assess oral gargle-tumor human papillomavirus (HPV) agreement among oropharyngeal squamous cell carcinoma (OPSCC) cases by several disease characteristics. MATERIALS AND METHODS: 171 treatment naïve OPSCC were enrolled 2014-2017. Tumors were categorized as early or late disease with early disease defined as T1-2 with no nodal involvement or at most a single ipsilateral positive node <3 cm. Oral gargle samples were obtained via a 30-second rinse and gargle. The RHA Kit HPV SP10-LiPA25 was utilized for HPV genotyping of tumor (FFPE) and oral gargle specimens. Sensitivity, specificity, positive and negative predictive value, percent agreement, and 95% exact binomial confidence intervals were estimated. Multivariable logistic regression models were fit to predict agreement. RESULTS: 83.0% and 93.0% of oral gargle and tumor specimens were HPV positive. Oral gargle-tumor agreement for any oncogenic HPV type and HPV 16 was 73.7%. High oncogenic HPV oral gargle-tumor agreement was observed for late disease presentation, p16 positive cases, and tumors at the tonsils (74.5-80.8%). Similar trends were observed for HPV 16. Agreement for any oncogenic HPV and HPV 16 was significantly higher for late vs. early disease (77.9% vs 57.1%, p = 0.01). Oral gargle-tumor oncogenic HPV and HPV 16 agreement was independently associated with age ≥50 years and late disease presentation. CONCLUSION: Overall, oral-tumor HPV agreement among OPSCC was relatively high. However, oral-tumor HPV agreement was significantly lower among younger cases and those diagnosed with earlier disease. Additional biomarkers are needed to improve oral HPV test characteristics to identify OPSCC early.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/etiologia , Infecções por Papillomavirus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Reprodutibilidade dos Testes , Fatores de Risco
17.
Vaccine ; 37(21): 2864-2869, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31005426

RESUMO

BACKGROUND: HPV-16 and HPV-18 cause most oropharyngeal cancers, which are increasing in incidence among males. Although HPV vaccines are highly effective against a number of HPV-associated cancers, efficacy for oropharyngeal cancers has not yet been demonstrated. In addition, the level of antibodies required for protection against oral HPV infection is unknown. METHODS: 150 men ages 27-45 years from Tampa, FL, USA, and Cuernavaca, Mexico, received Gardasil at Day 1, Months 2, and 6. Then, sera and oral gargles were collected one month, 12 months, and 24 months after completion of the three doses (Month 7, 18 and 30 of the study) and tested for anti-HPV-16 and HPV-18 IgG antibody levels by a L1 VLP ELISA. RESULTS: All participants developed detectable serum anti-HPV-16 and anti-HPV-18 antibodies and most had detectable antibodies in oral gargles at Month 7 (HPV-16: 93.2%; HPV-18: 72.1%). By months 18 and 30, oral antibodies were detectable in a lower number of participants (HPV-16, 39.8% and 29.6%; HPV-18, 10.7% and 4.6% of individuals, respectively). Overall, oral HPV-16- and 18-specific antibody levels, normalized to total IgG at months 7, 18, and 30, correlated with serum levels (HPV-16, R2 = 0.93; HPV-18, R2 = 0.91). CONCLUSIONS: Reduced detectability of oral and serum HPV-16 and HPV-18 antibodies was observed at months 18 and 30 after initiation of the quadrivalent vaccination. However, when detectable, serum and oral HPV-16 and HPV-18 antibody levels were strongly correlated.


Assuntos
Anticorpos Antivirais/imunologia , Vacinas contra Papillomavirus/imunologia , Vacinação , Ensaio de Imunoadsorção Enzimática , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Masculino , Saliva/virologia
18.
JAMA Otolaryngol Head Neck Surg ; 145(5): 460-466, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30920604

RESUMO

Importance: The most common cause of oropharyngeal squamous cell carcinoma is human papillomavirus (HPV) infection, and currently the standard of care to determine the HPV infection status in this type of carcinoma is to use p16 immunohistochemistry as a surrogate marker of high-risk HPV infection. Although p16 immunohistochemistry is limited by the inability to determine the specific HPV genotypes, oral gargle samples may be a readily available source of HPV DNA for genotyping. Objective: To determine the specific HPV genotypes present in both oral gargle samples and tumor specimens. Design, Setting, and Participants: This prospective, biomarker cohort study conducted at a single specialized cancer hospital in Florida screened approximately 800 potentially eligible participants from May 2014 through October 2017. To be eligible for participation, patients had to meet all of the following criteria: 18 years of age or older, male sex, newly diagnosed as having stage I to IV cancer of the oropharynx, a squamous cell carcinoma diagnosis, treatment naive or at least 4 weeks after chemoradiation or surgical treatment of other diseases, fully understand the study procedures and risks involved, and voluntarily agree to participate by signing an informed consent statement. Main Outcomes and Measures: Detection rate of HPV infection and HPV genotypes in oral gargle samples and tumor specimens. Results: A cohort of 204 male participants with newly diagnosed oropharyngeal squamous cell carcinoma was assessed in this prospective collection of comprehensive clinical data and oral gargle samples. Most study participants (190 [93.1%]) were white and ever smokers (114, 55.9%), with a median age of 61 years (range, 35-87 years). The HPV infection status could be assessed in 203 of 204 participants (99.5%) using oral gargle samples: 35 samples (17.2%) were negative for HPV infection, whereas 168 samples (82.8%) were positive for HPV infection. The detection rate of HPV genotypes was 93.0% in tumor specimens (160 specimens) and 82.8% (168 samples) in oral gargle samples. The oral gargle samples frequently had low-risk HPV genotypes that were not detected in tumors, but these low-risk genotypes were always a coinfection with high-risk genotypes. Conclusions and Relevance: Oral gargle samples can be used to detect the majority of clinically relevant HPV genotypes found in oropharyngeal squamous cell carcinoma, but the interpretation of HPV detected in these samples should be assessed with caution for general cancer risk assessment given that sensitive assays can concomitantly detect low-risk genotypes.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma de Células Escamosas/patologia , Florida , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Estudos Prospectivos
19.
Hum Vaccin Immunother ; 15(7-8): 1911-1919, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30897017

RESUMO

Background: While receptive anal sex is an established risk factor for anal human papillomavirus (HPV) infection and squamous cell carcinoma of the anus (SCCA), people with anal HPV infection and SCCA commonly report no lifetime receptive anal sex suggesting other factors may also increase risk for anal HPV infection and persistence. Given potential associations between obesity and conditions that may cause perianal or anal canal lesions, we hypothesized that body mass index (BMI) was associated with HPV infection. Methods: Genotyping for 36 HPV types was conducted on anal canal specimens from men, ages 18-70, from Brazil, Mexico, and the USA. Eligibility included no history of genital warts or HIV. Evaluable specimens were collected from 328 men having sex with men (MSM) and 1348 men having sex with women (MSW) who reported no lifetime receptive anal sex. Prevalence of anal HPV infection and six-month persistence by BMI were estimated in addition to adjusted prevalence ratios for the association between BMI and HPV infection. Results: Among MSW, obese men had a higher prevalence of HPV-16 in the anal canal (3.1%), compared to normal weight men (1.3%) although 95% CI overlapped. Among MSM, prevalence of HPV decreased with increasing BMI. A similar pattern was observed for persistence. After adjustment for confounders, obese MSW had 2.4 times higher odds of HPV-16 compared to normal weight men. Conclusions: BMI may be positively associated with anal HPV (especially HPV-16) among MSW and negatively associated with anal HPV among MSM which supports continued universal HPV vaccination programs.


Assuntos
Canal Anal/virologia , Doenças do Ânus/epidemiologia , Índice de Massa Corporal , Obesidade/complicações , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Idoso , Doenças do Ânus/virologia , Brasil/epidemiologia , DNA Viral/análise , Feminino , Genótipo , Heterossexualidade/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Obesidade/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/etiologia , Prevalência , Fatores de Risco , Comportamento Sexual , Adulto Jovem
20.
J Infect Dis ; 219(5): 703-710, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30388232

RESUMO

BACKGROUND: Genital wart (GW) incidence is high among men. The percentage and rate at which subsequent GW events occur are understudied. The purpose of this study was to describe the rate of subsequent GWs, associated human papillomavirus (HPV) types, and time to subsequent GW event among unvaccinated men. METHODS: The study was nested within a multinational prospective HPV natural history study of men aged 18-70 years in the United States, Mexico, and Brazil, examined every 6 months for a median follow-up of 50.4 months. Subsequent GW events were defined as GWs detected after ≥16 weeks of the prior event. RESULTS: Forty-four percent of men experienced ≥1 GW following the initial episode. Men with ≥2 subsequent events were at highest risk of continued GW experiences, with as high as 10 postinitial GW events. The incidence rate of each subsequent GW increased with increasing events (incidence of first subsequent event was 13.1 vs 36.6/1000 person-months for the fourth event). The proportion of GWs among HPV-6 and/or -11-positive patients remained constant across events. Approximately 63%-69% were positive for ≥1 of the 9-valent HPV vaccine types. CONCLUSIONS: These data highlight the high burden of GWs among men across the lifespan and the need for vaccination to prevent multiple GW episodes.


Assuntos
Condiloma Acuminado/epidemiologia , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Seguimentos , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Estados Unidos/epidemiologia , Adulto Jovem
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