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BACKGROUND: Human Papillomavirus-associated oropharyngeal cancer (HPV-OPC) incidence is increasing among men in the United States. Poor dental health has previously been associated with risk of head and neck cancers, oral HPV infection, and persistence but it is not understood whether dental health is associated with outcomes. We sought to determine the association of dental health with progression free survival and overall mortality among men with an HPV-OPC. METHODS: A cross sectional study of men diagnosed with HPV-OPC between 2014-2020 at Moffitt Cancer Center in Tampa, FL was conducted. Dental records were abstracted for assessment of dental fitness prior to cancer treatment. Five dental factors including number of teeth lost, pocket depth, gingival score, loss of attachment, and bone loss were individually examined. Risk factor and outcome data were collected from a patient risk questionnaire and medical record. Using item response theory, an overall dental fitness score from five dental factors was developed in which missing data were multiply imputed. Cox proportional hazards model was used to assess whether dental factors were associated with progression-free survival or overall mortality. RESULTS: Among 206 HPV-OPC cases, median follow-up was 3.4 years (IQR: 2.4-4.4) during which 40 cases involved progression or mortality and 25 deaths occurred. Overall dentition was significantly associated with progression free survival (p = 0.04) and with overall survival (p = 0.03) though findings were not significant after adjustment for age at diagnosis, stage, and smoking history (p = 0.146 and p = 0.120, respectively). A pocket depth of 7 mm or more was associated with overall survival (HR: 5.21; 95% CI: 1.43-19.11) and this remained significant after adjustment for confounding (aHR: 4.14; 95% CI: 1.72-16.26). CONCLUSIONS: Among men diagnosed with an HPV-associated OPC in the US, worse dental health was associated with reduced progression free survival and overall survival, but not after adjustment for confounders. Further studies are needed to examine whether dental health is associated with other prognostic factors and subsequent treatment-related outcomes.
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Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Estados Unidos , Estudos Transversais , Infecções por Papillomavirus/complicações , Papillomavirus HumanoRESUMO
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).
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COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Florida/epidemiologia , Humanos , Pandemias , Estudos SoroepidemiológicosRESUMO
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.
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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 EspecificidadeRESUMO
BACKGROUND: Human papillomavirus virus type 16 (HPV-16) and HPV-18 cause a large proportion of oropharyngeal cancers, which are increasing in incidence among males, and vaccine efficacy against oral HPV infections in men has not been previously evaluated. METHODS: Sera and saliva collected in mouthwash and Merocel sponges at day 1 and month 7 were obtained from 150 men aged 27-45 years from Tampa, Florida, and Cuernavaca, Mexico, who received Gardasil at day 1 and months 2 and 6. Specimens were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G (IgG) levels by an L1 virus-like particle-based enzyme-linked immunosorbent assay. RESULTS: All participants developed detectable serum anti-HPV-16 and anti-HPV-18 antibodies, and most had detectable antibodies in both oral specimen types at month 7 (HPV-16 was detected in 93.2% of mouthwash specimens and 95.7% of sponge specimens; HPV-18 was detected in 72.1% and 65.5%, respectively). Antibody concentrations in saliva were approximately 3 logs lower than in serum. HPV-16- and HPV-18-specific antibody levels, normalized to total IgG levels, in both oral specimen types at month 7 were significantly correlated with serum levels (for HPV-16, ρ was 0.90 for mouthwash specimens and 0.92 for sponge specimens; for HPV-18, ρ was 0.89 and 0.86, respectively). CONCLUSIONS: This is the first study demonstrating that vaccination of males with Gardasil induces HPV antibody levels at the oral cavity that correlate with circulating levels.
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Anticorpos Antivirais/imunologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Boca/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Florida , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , México , Pessoa de Meia-Idade , Saliva/imunologia , Vacinação/métodosRESUMO
BACKGROUND: Compared to the general population, cancer patients are at higher risk of morbidity and mortality following SARS-CoV-2 infection. The immune response to a two-dose regimen of mRNA vaccines in cancer patients is generally lower than in immunocompetent individuals. Booster doses may meaningfully augment immune response in this population. We conducted an observational study with the primary objective of determining the immunogenicity of vaccine dose three (100 µg) of mRNA-1273 among cancer patients and a secondary objective of evaluating safety at 14 and 28 days. METHODS: The mRNA-1273 vaccine was administered â¼7 to 9 months after administering two vaccine doses (i.e., the primary series). Immune responses (enzyme-linked immunosorbent assay [ELISA]) were assessed 28 days post-dose three. Adverse events were collected at days 14 (± 5) and 28 (+5) post-dose three. Fisher exact or X2 tests were used to compare SARS-CoV-2 antibody positivity rates, and paired t-tests were used to compare SARS-CoV-2 antibody geometric mean titers (GMTs) across different time intervals. RESULTS: Among 284 adults diagnosed with solid tumors or hematologic malignancies, dose three of mRNA-1273 increased the percentage of patients seropositive for SARS-CoV-2 antibody from 81.7% pre-dose three to 94.4% 28 days post-dose three. GMTs increased 19.0-fold (15.8-22.8). Patients with lymphoid cancers or solid tumors had the lowest and highest antibody titers post-dose three, respectively. Antibody responses after dose three were reduced among those who received anti-CD20 antibody treatment, had lower total lymphocyte counts and received anticancer therapy within 3 months. Among patients seronegative for SARS-CoV-2 antibody pre-dose three, 69.2% seroconverted after dose three. A majority (70.4%) experienced mostly mild, transient adverse reactions within 14 days of dose three, whereas severe treatment-emergent events within 28 days were very rare (<2%). CONCLUSION: Dose three of the mRNA-1273 vaccine was well-tolerated and augmented SARS-CoV-2 seropositivity in cancer patients, especially those who did not seroconvert post-dose two or whose GMTs significantly waned post-dose two. Lymphoid cancer patients experienced lower humoral responses to dose three of the mRNA-1273 vaccine, suggesting that timely access to boosters is important for this population.
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COVID-19 , Neoplasias , Adulto , Humanos , Vacina de mRNA-1273 contra 2019-nCoV , COVID-19/prevenção & controle , SARS-CoV-2 , Neoplasias/tratamento farmacológicoRESUMO
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.
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Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal-Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.
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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.
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Neoplasias Orofaríngeas , Infecções por Papillomavirus , Masculino , Humanos , Papillomavirus Humano 16/genética , Metilação , Papillomaviridae , Biomarcadores , Proteínas dos Microfilamentos/genéticaRESUMO
OBJECTIVES: Chronic hepatitis C virus (HCV) infection is one of the main causes of hepatocellular carcinoma. Before initiating a multilevel HCV screening intervention, we sought to (1) describe concordance between the electronic health record (EHR) data warehouse and manual medical record review in recording aspects of HCV testing and treatment and (2) estimate the percentage of patients with chronic HCV infection who initiated and completed HCV treatment using manual medical record review. METHODS: We examined the medical records for 177 patients (100 randomly selected patients born during 1945-1965 without evidence of HCV testing and 77 adult patients of any birth cohort who had completed HCV testing) with a primary care or relevant specialist visit at an academic health care system in Tampa, Florida, from 2015 through 2018. We used the Cohen κ coefficient to examine the degree of concordance between the searchable data warehouse and the medical record review abstractions. Descriptive statistics characterized referral to and receipt of treatment among patients with chronic HCV infection from medical record review. RESULTS: We found generally good concordance between the data warehouse abstraction and medical record review for HCV testing data (κ ranged from 0.66 to 0.87). However, the data warehouse failed to capture data on HCV treatment variables. According to medical record review, 28 patients had chronic HCV infection; 16 patients were prescribed treatment, 14 initiated treatment, and 9 achieved and had a reported posttreatment undetected HCV viral load. CONCLUSIONS: Using data warehouse data provides generally reliable HCV testing information. However, without the use of natural language processing and purposeful EHR design, manual medical record reviews will likely be required to characterize treatment initiation and completion.
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Hepatite C Crônica , Hepatite C , Adulto , Registros Eletrônicos de Saúde , Hepacivirus , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Programas de RastreamentoRESUMO
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.
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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 TratamentoRESUMO
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.
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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 & controleRESUMO
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.
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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 JovemRESUMO
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 27-45â¯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, 12â¯months, and 24â¯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, R2â¯=â¯0.93; HPV-18, R2â¯=â¯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.
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Anticorpos Antivirais/imunologia , Vacinas contra Papillomavirus/imunologia , Vacinação , Ensaio de Imunoadsorção Enzimática , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Masculino , Saliva/virologiaRESUMO
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 (1â¯month post-dose 3), and Month 18 (12â¯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 2119.8â¯EU/mL, and HPV-18: 285.8 versus 611.6â¯EU/mL, pâ¯<â¯0.001) but not significantly different at Month 18 (HPV-16: 281.8 versus 359.7â¯EU/mL, pâ¯=â¯0.145, and HPV-18: 120.2 versus 93.4â¯EU/mL, pâ¯=â¯0.372). Post-vaccination, only oral HPV-16 antibody levels at Month 7 were significantly different between HIV+ and HIV- men (127.7 versus 177.1â¯EU/mg of IgG, pâ¯=â¯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: 1.95â¯M versus 2.12â¯M, pâ¯=â¯0.027; HPV-18: 1.50â¯M versus 1.72â¯M, pâ¯<â¯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.
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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 JovemRESUMO
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 <3â¯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%, pâ¯=â¯0.01). Oral gargle-tumor oncogenic HPV and HPV 16 agreement was independently associated with age ≥50â¯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 RiscoRESUMO
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 ProspectivosRESUMO
BACKGROUND: The quadrivalent (types 6/11/16/18) human papillomavirus (HPV) vaccine, Gardasil, has demonstrated efficacy against persistent HPV infection and associated anogenital disease in males. The goal of this Phase II trial was to establish the immunogenicity and safety of Gardasil among mid-adult men ages 27-45 years. METHODS: One hundred and fifty men from Tampa, FL, US, and Cuernavaca, Mexico who met eligibility criteria (male, 27-45 years old, completed four years of follow-up in the HPV Infection in Men (HIM) natural history study) were enrolled. Subjects completed four visits over seven months, with Gardasil administered at Day 1 and Months 2 and 6. Sera were collected at Day 1 (pre-vaccination) and Month 7 (one month post-dose three). Anti-HPV6, 11, 16, and 18 IgG levels were determined by competitive Luminex immunoassay. FINDINGS: 100% of men seroconverted to each of the four HPV vaccine components, and the vaccine was generally well-tolerated. Antibody responses to vaccine did not differ by age group or sexual orientation, regardless of HPV type, and were significantly higher at Month 7 among men who entered the trial seropositive for HPV 6 or 11. INTERPRETATION: The immune response to HPV vaccination in men ages 27-45 was comparable to that observed in younger men, in whom clinical efficacy was demonstrated. Further trials to assess the efficacy of HPV vaccines to prevent persistent HPV infections in mid-adult men are needed. FUNDING: Merck & Co. Inc. was the main sponsor of this trial (IISP39256) and provided the study product.