45 results on '"Haupt RM"'
Search Results
2. Proximity of first sexual intercourse to menarche and risk of high-grade cervical disease.
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Ruiz AM, Ruiz JE, Gavilanes AV, Eriksson T, Lehtinen M, Pérez G, Sings HL, James MK, Haupt RM, and FUTURE I and II Study Group
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BACKGROUND: We assessed if risk of developing cervical intraepithelial neoplasia grade 2/3 (CIN2/3) or adenocarcinoma in situ (AIS) is associated with a short interval between menarche and first sexual intercourse (FSI). METHODS: A total of 1009 Colombian and 1012 Finnish females, aged 16-23, who were enrolled in the phase 3 trials of a quadrivalent human papillomavirus (HPV) 6/11/16/18 vaccine had nonmissing data for age of menarche and FSI. The impact of menarche interval on the odds of developing CIN2-3/AIS was evaluated in placebo recipients who were DNA negative to HPV 6/11/16/18/31/33/35/39/45/51/52/56/58/59 and seronegative to HPV 6/11/16/18 at day 1, and had a normal Pap result at day 1 and month 7, thus approximating sexually naive adolescents (n = 504). RESULTS: The mean age of menarche and FSI was 12.4 and 16.0 years, respectively. Among the women approximating sexually naive adolescents, 18 developed CIN2-3/AIS. Compared with women who postponed FSI beyond 3 years of menarche, those with FSI within 3 years of menarche had a greater risk of cytologic abnormalities (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.02-2.68; P = .04) and CIN2-3/AIS (OR, 3.56; 95% CI, 1.02-12.47; P = .05). CONCLUSIONS: A short interval between menarche and FSI was a risk factor for cytologic abnormalities and high-grade cervical disease. These data emphasize the importance of primary prevention through education and vaccination. CLINICAL TRIALS REGISTRATION: NCT00092521 and NCT00092534. [ABSTRACT FROM AUTHOR]
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- 2012
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3. Prevalence of and risk factors for human papillomavirus (HPV) infection among HIV-seronegative men who have sex with men.
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Goldstone S, Palefsky JM, Giuliano AR, Moreira ED Jr, Aranda C, Jessen H, Hillman RJ, Ferris DG, Coutlee F, Liaw KL, Marshall JB, Zhang X, Vuocolo S, Barr E, Haupt RM, Guris D, Garner EI, Goldstone, Stephen, Palefsky, Joel M, and Giuliano, Anna R
- Abstract
Background: We examined the baseline prevalence of penile, scrotal, perineal/perianal, and intra-anal human papillomavirus (HPV) infection in human immunodeficiency virus (HIV)-seronegative men who have sex with men (MSM).Methods: Data were analyzed from 602 MSM aged 16-27 years with ≤ 5 lifetime sexual partners. Serum samples were tested for antibodies to HPV6/11/16/18. Swab samples were collected separately from several anogenital areas for detection of HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59 DNA.Results: The prevalence of any tested HPV type was 18.5% at the penis, 17.1% at the scrotum, 33.0% at the perineal/perianal region, 42.4% in the anal canal, and 48.0% at any site. Overall, 415 MSM (69.7%) were negative to HPV 6, 11, 16, and 18 at enrollment by both serology and DNA detection. Men residing in Europe and Latin America had significantly increased risk of HPV infection at external genital sites and the anal canal compared to men from Australia. Tobacco use and greater number of lifetime sexual partners was associated with higher HPV infection prevalence.Conclusions: The prevalence of HPV infection is high among young sexually active MSM, with the anal canal being the most common site of infection. Lifetime number of sexual partners was the most important modifiable risk factor for anogenital HPV infection. [ABSTRACT FROM AUTHOR]- Published
- 2011
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4. External genital human papillomavirus prevalence and associated factors among heterosexual men on 5 continents.
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Vardas E, Giuliano AR, Goldstone S, Palefsky JM, Moreira ED Jr, Penny ME, Aranda C, Jessen H, Moi H, Ferris DG, Liaw KL, Marshall JB, Vuocolo S, Barr E, Haupt RM, Garner EI, Guris D, Vardas, Eftyhia, Giuliano, Anna R, and Goldstone, Stephen
- Abstract
Background: We examined the baseline prevalence of penile, scrotal, and perineal/perianal human papillomavirus (HPV) in heterosexual men (HM). We also evaluated baseline characteristics of HM to assess factors associated with prevalent HPV detection.Methods: We tested serum samples from 3463 HM aged 16-24 years with 1-5 lifetime female sexual partners for antibodies to HPV 6, 11, 16, and 18. We collected baseline swab specimens for the detection of DNA of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 from 3 areas: penile, scrotal, and perineal/perianal. Risk factors for prevalent HPV DNA detection were evaluated.Results: The prevalence of any tested HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. Having >3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% confidence interval (CI) 2.1-4.9) for HPV 6, 11, 16, and 18; and OR 4.5 (95% CI 3.3-6.1) for all HPV types tested. HPV DNA detection was highest in Africa. Neither condom usage nor circumcision was associated with HPV DNA prevalence.Conclusion: Genital-HPV DNA detection is common in young, sexually active HM. We found HPV to be most prevalent in African men and least prevalent in men from the Asia-Pacific region. Increased numbers of sexual partners was an important risk factor for HPV DNA prevalence. [ABSTRACT FROM AUTHOR]- Published
- 2011
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5. Pregnancy and infant outcomes in the clinical trials of a human papillomavirus type 6/11/16/18 vaccine: a combined analysis of five randomized controlled trials.
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Garland SM, Ault KA, Gall SA, Paavonen J, Sings HL, Ciprero KL, Saah A, Marino D, Ryan D, Radley D, Zhou H, Haupt RM, Garner EI, Quadrivalent Human Papillomavirus Vaccine Phase III Investigators, Garland, Suzanne M, Ault, Kevin A, Gall, Stanley A, Paavonen, Jorma, Sings, Heather L, and Ciprero, Karen L
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- 2009
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6. Pregnancy outcomes from the pregnancy registry of a human papillomavirus type 6/11/16/18 vaccine.
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Dana A, Buchanan KM, Goss MA, Seminack MM, Shields KE, Korn S, Cunningham ML, Haupt RM, Dana, Adrian, Buchanan, Karyn M, Goss, Mary Ann, Seminack, Margaret M, Shields, Kristine E, Korn, Scott, Cunningham, Michael L, and Haupt, Richard M
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- 2009
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7. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia.
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Palefsky JM, Giuliano AR, Goldstone S, Moreira ED Jr, Aranda C, Jessen H, Hillman R, Ferris D, Coutlee F, Stoler MH, Marshall JB, Radley D, Vuocolo S, Haupt RM, Guris D, and Garner EI
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- 2011
8. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial.
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Muñoz N, Manalastas R Jr, Pitisuttithum P, Tresukosol D, Monsonego J, Ault K, Clavel C, Luna J, Myers E, Hood S, Bautista O, Bryan J, Taddeo FJ, Esser MT, Vuocolo S, Haupt RM, Barr E, Saah A, Muñoz, Nubia, and Manalastas, Ricardo Jr
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Background: Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5-10 years of first sexual experience, all women remain at risk for acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24-45 years.Methods: Women aged 24-45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months' or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. This study is registered with ClinicalTrials.gov, number NCT00090220.Findings: 1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90.5% (95% CI 73.7-97.5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83.1% (50.6-95.8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30.9% (95% CI 11.1-46.5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22.6% (-2.9 to 41.9, 90/1886 cases vs 115/1883 cases), since infection and disease were present at baseline. We recorded no vaccine-related serious adverse events.Interpretation: The quadrivalent HPV vaccine is efficacious in women aged 24-45 years not infected with the relevant HPV types at enrolment.Funding: Merck (USA). [ABSTRACT FROM AUTHOR]- Published
- 2009
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9. Behavioral and sociodemographic risk factors for serological and DNA evidence of HPV6, 11, 16, 18 infections.
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Wiley DJ, Masongsong EV, Lu S, Heather L S, Salem B, Giuliano AR, Ault KA, Haupt RM, and Brown DR
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- 2012
10. 2022 Systematic Review of Evidence-Based Guidelines for Prehospital Care.
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Martin-Gill C, Brown KM, Cash RE, Haupt RM, Potts BT, Richards CT, and Patterson PD
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- Humans, Evidence-Based Medicine, Workforce, Emergency Medical Services
- Abstract
Introduction: Multiple national organizations and federal agencies have promoted the development, implementation, and evaluation of evidence-based guidelines (EBGs) for prehospital care. Previous efforts have identified opportunities to improve the quality of prehospital guidelines and highlighted the value of high-quality EBGs to inform initial certification and continued competency activities for EMS personnel., Objectives: We aimed to perform a systematic review of prehospital guidelines published from January 2018 to April 2021, evaluate guideline quality, and identify top-scoring guidelines to facilitate dissemination and educational activities for EMS personnel., Methods: We searched the literature in Ovid Medline and EMBASE from January 2018 to April 2021, excluding guidelines identified in a prior systematic review. Publications were retained if they were relevant to prehospital care, based on organized reviews of the literature, and focused on providing recommendations for clinical care or operations. Included guidelines were appraised to identify if they met the National Academy of Medicine (NAM) criteria for high-quality guidelines and scored across the six domains of the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool., Results: We identified 75 guidelines addressing a variety of clinical and operational aspects of EMS medicine. About half (n = 39, 52%) addressed time/life-critical conditions and 33 (44%) contained recommendations relevant to non-clinical/operational topics. Fewer than half (n = 35, 47%) were based on systematic reviews of the literature. Nearly one-third (n = 24, 32%) met all NAM criteria for clinical practice guidelines. Only 27 (38%) guidelines scored an average of >75% across AGREE II domains, with content relevant to guideline implementation most commonly missing., Conclusions: This interval systematic review of prehospital EBGs identified many new guidelines relevant to prehospital care; more than all guidelines reported in a prior systematic review. Our review reveals important gaps in the quality of guideline development and the content in their publications, evidenced by the low proportion of guidelines meeting NAM criteria and the scores across AGREE II domains. Efforts to increase guideline dissemination, implementation, and related education may be best focused around the highest quality guidelines identified in this review.
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- 2023
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11. The development of a staphylococcus aureus four antigen vaccine for use prior to elective orthopedic surgery.
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Gurtman A, Begier E, Mohamed N, Baber J, Sabharwal C, Haupt RM, Edwards H, Cooper D, Jansen KU, and Anderson AS
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- Antigens, Bacterial administration & dosage, Bacteremia prevention & control, Clinical Trials as Topic, Elective Surgical Procedures, Humans, Orthopedic Procedures, Staphylococcus aureus, Surgical Wound Infection microbiology, Antibodies, Bacterial blood, Antigens, Bacterial immunology, Staphylococcal Infections prevention & control, Staphylococcal Vaccines therapeutic use, Surgical Wound Infection prevention & control
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Staphylococcus aureus (S. aureus) is a challenging bacterial pathogen which can cause a range of diseases, from mild skin infections, to more serious and invasive disease including deep or organ space surgical site infections, life-threatening bacteremia, and sepsis. S. aureus rapidly develops resistance to antibiotic treatments. Despite current infection control measures, the burden of disease remains high. The most advanced vaccine in clinical development is a 4 antigen S. aureus vaccine (SA4Ag) candidate that is being evaluated in a phase 2b/3 efficacy study in patients undergoing elective spinal fusion surgery (STaphylococcus aureus suRgical Inpatient Vaccine Efficacy [STRIVE]). SA4Ag has been shown in early phase clinical trials to be generally safe and well tolerated, and to induce high levels of bactericidal antibodies in healthy adults. In this review we discuss the design of SA4Ag, as well as the proposed clinical development plan supporting licensure of SA4Ag for the prevention of invasive disease caused by S. aureus in elective orthopedic surgical populations. We also explore the rationale for the generalizability of the results of the STRIVE efficacy study (patients undergoing elective open posterior multilevel instrumented spinal fusion surgery) to a broad elective orthopedic surgery population due to the common pathophysiology of invasive S. aureus disease and commonalties of patient and procedural risk factors for developing postoperative S. aureus surgical site infections.
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- 2019
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12. An Overview of Quadrivalent Human Papillomavirus Vaccine Safety: 2006 to 2015.
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Vichnin M, Bonanni P, Klein NP, Garland SM, Block SL, Kjaer SK, Sings HL, Perez G, Haupt RM, Saah AJ, Lievano F, Velicer C, Drury R, and Kuter BJ
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- Adolescent, Adult, Child, Female, Humans, Male, Middle Aged, Pregnancy, Young Adult, Drug-Related Side Effects and Adverse Reactions epidemiology, Drug-Related Side Effects and Adverse Reactions pathology, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 administration & dosage, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 adverse effects, Papillomavirus Infections prevention & control, Product Surveillance, Postmarketing
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Background: A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal cancers and precancers, as well as external genital warts causally related to HPV types 6/11/16/18. Across 7 phase 3 clinical trials involving more than 29,000 males and females ages 9-45 years, vaccination was generally well tolerated. Because of its expected public health benefit in reducing cervical cancer and other HPV-related diseases, the vaccine has been implemented in the national vaccination programs of several countries, with over 178 million doses distributed worldwide., Methods: Extensive efforts to assess the safety of the vaccine in routine practice have been conducted over the past 9 years since licensure, including more than 15 studies in more than 1 million preadolescents, adolescents and adults from various countries. Most have been performed in the general population although there have been some in special populations (pregnant women, HIV-infected individuals and those with systemic lupus erythematosus)., Results: We present a summary of the published, postlicensure safety data from active and passive surveillance. Only syncope, and possibly skin infections were associated with vaccination in the postlicensure setting. Serious adverse events, such as adverse pregnancy outcomes, autoimmune diseases (including Guillain-Barre Syndrome and multiple sclerosis), anaphylaxis, venous thromboembolism and stroke, were extensively studied, and no increase in the incidence of these events was found compared with background rates., Conclusions: These results, along with the safety data from the prelicensure clinical trials, confirm that the HPV4 vaccine has a favorable safety profile. Key policy, medical and regulatory organizations around the world have independently reviewed these data and continue to recommend routine HPV vaccination.
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- 2015
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13. Incidence, clearance, and disease progression of genital human papillomavirus infection in heterosexual men.
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Moreira ED Jr, Giuliano AR, Palefsky J, Flores CA, Goldstone S, Ferris D, Hillman RJ, Moi H, Stoler MH, Marshall B, Vuocolo S, Guris D, and Haupt RM
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- Adolescent, Condylomata Acuminata complications, DNA, Viral genetics, DNA, Viral isolation & purification, Disease Progression, Female, Genotype, Global Health, Humans, Incidence, Male, Papillomaviridae classification, Papillomaviridae genetics, Penis pathology, Penis virology, Perineum pathology, Perineum virology, Scrotum pathology, Scrotum virology, Young Adult, Condylomata Acuminata epidemiology, Genital Neoplasms, Male epidemiology, Heterosexuality, Papillomaviridae isolation & purification, Papillomavirus Infections epidemiology
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Background: In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years., Methods: A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions., Results: The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively., Conclusion: The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2014
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14. Development of a human papillomavirus competitive luminex immunoassay for 9 HPV types.
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Roberts C, Green T, Hess E, Matys K, Brown MJ, Haupt RM, Luxembourg A, Vuocolo S, Saah A, and Antonello J
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- Animals, Antibodies, Monoclonal, Antigens, Viral, Cross Reactions, Humans, Immunoassay methods, Immunoglobulin G blood, Macaca mulatta, Sensitivity and Specificity, Virosomes, Antibodies, Neutralizing blood, Antibodies, Viral blood, Clinical Laboratory Techniques methods, Papillomaviridae immunology, Papillomavirus Infections immunology, Papillomavirus Infections virology
- Abstract
In the clinical trials of the quadrivalent human papillomavirus (qHPV) vaccine, antibodies were measured by a competitive Luminex immunoassay (HPV-4 cLIA). A nine-valent HPV (9vHPV) vaccine targeting the types in the qHPV vaccine (HPV6/11/16/18), as well as 5 of the next most frequent HPV types found in cervical cancers worldwide (HPV31/33/45/52/58) is under development. To support the 9vHPV vaccine program, a nine-multiplexed cLIA (HPV-9 cLIA) was developed. Antibody titers were determined in a competitive format, where type-specific phycoerythrin (PE)-labeled, neutralizing mAbs (mAbs-PE) compete with an individual's serum antibodies for binding to conformationally sensitive, neutralizing epitopes on the VLPs. Neutralizing antibody levels were quantitated against a reference standard - a pool of sera from 6 Rhesus macaques that were immunized with the 9vHPV vaccine. Specificity of the mAbs was assessed by measuring their individual binding capacities to the type-specific and non-type-specific VLPs at alternative concentrations of the mAbs. Antibody assignments to the HPV-9 cLIA reference standard for HPV6/11/16/18 were determined to provide for a measure of consistency in serostatus assignment between the HPV-4 and HPV-9 cLIAs. Antibody assignments to the HPV-9 reference standard for HPV31/33/45/52/58 were obtained by calibration to HPV11 using a direct binding IgG assay. For each HPV VLP type, the cross-reactivity of the mAb-PEs in the HPV-9 cLIA was <1% (i.e., the mAb-PEs result in <1% non-specific binding). The antibody concentrations assigned to the HPV-9 cLIA reference standard for types 6/11/16/18/31/33/45/52/58 were 3,817, 2,889, 23,061, 5,271, 3,942, 2,672, 1,489, 1274, and 2263 mMU/mL, respectively.
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- 2014
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15. Long-term follow-up observation of the safety, immunogenicity, and effectiveness of Gardasil™ in adult women.
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Luna J, Plata M, Gonzalez M, Correa A, Maldonado I, Nossa C, Radley D, Vuocolo S, Haupt RM, and Saah A
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- Adult, Colombia, Condylomata Acuminata prevention & control, Double-Blind Method, Female, Follow-Up Studies, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Human papillomavirus 11 immunology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Human papillomavirus 6 immunology, Humans, Middle Aged, Papillomavirus Infections prevention & control, Papillomavirus Vaccines adverse effects, Papillomavirus Vaccines immunology, Pregnancy, Safety, Treatment Outcome, Uterine Cervical Neoplasms prevention & control, Young Adult, Uterine Cervical Dysplasia prevention & control, Papillomavirus Vaccines therapeutic use
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Background: Previous analyses from a randomized trial in women aged 24-45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN) and external genital lesions (EGL) related to HPV 6/11/16/18 through 4 years. In this report we present long term follow-up data on the efficacy, safety and immunogenicity of the quadrivalent HPV vaccine in adult women., Methods: Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity, effectiveness, and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age (in the original vaccine group during the base study [n = 684]) or 29 to 50 years of age (in the original placebo group during the base study [n = 651]). This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study (median follow-up of 6.26 years) from both the original base study and the Colombian follow-up., Results: There were no cases of HPV 6/11/16/18-related CIN or EGL during the extended follow-up phase in the per-protocol population. Immunogenicity persists against vaccine-related HPV types, and no evidence of HPV type replacement has been observed. No new serious adverse experiences have been reported., Conclusions: Vaccination with qHPV vaccine provides generally safe and effective protection from HPV 6-, 11-, 16-, and 18-related genital warts and cervical dysplasia through 6 years following administration to 24-45 year-old women., Trial Registration: Clinicaltrials.govNCT00090220.
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- 2013
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16. Quadrivalent HPV vaccine efficacy against disease related to vaccine and non-vaccine HPV types in males.
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Goldstone SE, Jessen H, Palefsky JM, Giuliano AR, Moreira ED Jr, Vardas E, Aranda C, Hillman RJ, Ferris DG, Coutlee F, Marshall JB, Vuocolo S, Haupt RM, Guris D, and Garner E
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- Adolescent, Adult, Anal Canal pathology, Anal Canal virology, Anus Neoplasms epidemiology, Genital Neoplasms, Male pathology, Genital Neoplasms, Male prevention & control, Genital Neoplasms, Male virology, Human papillomavirus 11 pathogenicity, Human papillomavirus 16 pathogenicity, Human papillomavirus 18 pathogenicity, Human papillomavirus 6 pathogenicity, Humans, Male, Papillomavirus Infections epidemiology, Treatment Outcome, Young Adult, Anus Neoplasms virology, Papillomavirus Infections prevention & control, Papillomavirus Infections virology, Papillomavirus Vaccines therapeutic use
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A small number of HPV types are related to a majority of HPV-related neoplastic lesions in humans. High-risk types such as HPV 16 and 18 are most often implicated, although other oncogenic and non-oncogenic HPV types can cause disease in men. The efficacy of the quadrivalent HPV vaccine (qHPV) against external genital lesions and intra-anal disease related to HPV in men has been demonstrated. This report examines the vaccine's efficacy against disease due to 10 additional non-vaccine HPV types, as well as efficacy regardless of HPV detection. The data presented suggest that vaccinating males against HPV 6, 11, 16 and 18 protects them against most vaccine HPV-type related anogenital disease. However, significant efficacy against disease due to non-vaccine HPV types was not seen. In addition, the data do not provide any evidence that vaccination with qHPV vaccine will increase the likelihood of disease caused by non-vaccine types in the short term., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
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- 2013
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17. Clinical trial experience with prophylactic human papillomavirus 6/11/16/18 vaccine in young black women.
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Clark LR, Myers ER, Huh W, Joura EA, Paavonen J, Perez G, James MK, Sings HL, Haupt RM, Saah AJ, and Garner EI
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- Adolescent, Black or African American, Chlamydia Infections epidemiology, Chlamydia trachomatis isolation & purification, Female, Humans, Papillomavirus Infections epidemiology, United States epidemiology, Young Adult, Alphapapillomavirus, Black People, Human papillomavirus 11, Papilloma prevention & control, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use
- Abstract
Purpose: Human papillomavirus (HPV) is the causative agent of cervical cancer. Black women are disproportionally diagnosed and have higher mortality from cervical cancer in the United States. Here we describe the prophylactic efficacy and safety of a quadrivalent HPV-6/11/16/18 vaccine in black women., Methods: A total of 700 black women from Latin America, Europe, and North America (aged 16-24 years) received the vaccine or placebo in one of two studies. Analyses focused on the efficacy and safety of the vaccine., Results: Baseline rates of Chlamydia trachomatis infection and history of past pregnancy were more than twice as high in black women compared with the non-black women who were enrolled in these trials. HPV-6/11/16 or 18 DNA was detected in 18% of black women versus 14.6% in non-black women at day 1. For black women, vaccine efficacy against disease caused by HPV-6/11/16/18 was 100% for cervical intraepithelial neoplasia (0 vs. 15 cases; 95% confidence interval, 64.5%-100%) and 100% for vulvar and vaginal intraepithelial neoplasia and condylomata acuminata (0 vs. 17 cases; 95% confidence interval, 69.3%-100%). There were no serious vaccine-related adverse experiences. A similar proportion of pregnancies resulted in live births (75.8% vaccine; 72.7% placebo) and fetal loss (24.2% vaccine; 27.3% placebo)., Conclusions: Prophylactic quadrivalent HPV-6/11/16/18 vaccination of young black women demonstrated high efficacy, safety, and tolerability. HPV vaccination has the potential to reduce cervical cancer-related health disparities both in the United States and around the world., (Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)
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- 2013
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18. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data.
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Joura EA, Garland SM, Paavonen J, Ferris DG, Perez G, Ault KA, Huh WK, Sings HL, James MK, and Haupt RM
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- Adolescent, Double-Blind Method, Female, Humans, Incidence, Papillomavirus Infections epidemiology, Retrospective Studies, United States epidemiology, Uterine Cervical Neoplasms epidemiology, Victoria epidemiology, Vulvar Neoplasms epidemiology, Young Adult, Papillomaviridae immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use, Uterine Cervical Neoplasms prevention & control, Vaccination methods, Vulvar Neoplasms prevention & control
- Abstract
Objectives: To determine the effect of human papillomavirus (HPV) quadrivalent vaccine on the risk of developing subsequent disease after an excisional procedure for cervical intraepithelial neoplasia or diagnosis of genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia., Design: Retrospective analysis of data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II))., Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world., Participants: Among 17,622 women aged 15-26 years who underwent 1:1 randomisation to vaccine or placebo, 2054 received cervical surgery or were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia., Intervention: Three doses of quadrivalent HPV vaccine or placebo at day 1, month 2, and month 6., Main Outcome Measures: Incidence of HPV related disease from 60 days after treatment or diagnosis, expressed as the number of women with an end point per 100 person years at risk., Results: A total of 587 vaccine and 763 placebo recipients underwent cervical surgery. The incidence of any subsequent HPV related disease was 6.6 and 12.2 in vaccine and placebo recipients respectively (46.2% reduction (95% confidence interval 22.5% to 63.2%) with vaccination). Vaccination was associated with a significant reduction in risk of any subsequent high grade disease of the cervix by 64.9% (20.1% to 86.3%). A total of 229 vaccine recipients and 475 placebo recipients were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia, and the incidence of any subsequent HPV related disease was 20.1 and 31.0 in vaccine and placebo recipients respectively (35.2% reduction (13.8% to 51.8%))., Conclusions: Previous vaccination with quadrivalent HPV vaccine among women who had surgical treatment for HPV related disease significantly reduced the incidence of subsequent HPV related disease, including high grade disease., Trial Registrations: NCT00092521 and NCT00092534.
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- 2012
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19. Immunogenicity of the quadrivalent human papillomavirus (type 6/11/16/18) vaccine in males 16 to 26 years old.
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Hillman RJ, Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Vardas E, Aranda C, Jessen H, Ferris DG, Coutlee F, Marshall JB, Vuocolo S, Haupt RM, Guris D, and Garner EI
- Subjects
- Adolescent, Adult, Antibodies, Viral blood, Carcinoma in Situ virology, Condylomata Acuminata immunology, Condylomata Acuminata virology, Double-Blind Method, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Human papillomavirus 11 immunology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Human papillomavirus 6 immunology, Humans, Male, Papillomavirus Infections immunology, Young Adult, Carcinoma in Situ prevention & control, Condylomata Acuminata prevention & control, Papillomavirus Infections prevention & control, Papillomavirus Vaccines immunology
- Abstract
Human papillomavirus (HPV) infection can lead to significant disease in males, including anogenital warts, intraepithelial neoplasias, and several types of oral and anogenital cancers. The quadrivalent HPV (type 6/11/16/18) L1 virus-like particle (VLP) vaccine (qHPV vaccine; Gardasil) has recently been demonstrated to prevent persistent infection and associated disease related to vaccine HPV types in males. We report the overall immunogenicity results from a trial of the quadrivalent HPV vaccine in males. Overall, 3,463 heterosexual men and 602 men who had sex with men were enrolled into a randomized, placebo-controlled, double-blind safety, immunogenicity, and efficacy study. Serum samples were collected prior to vaccination at day 1 and at months 7, 24, and 36 postvaccination. Immunogenicity was evaluated with a multiplex, competitive Luminex immunoassay. Almost all subjects (97.4 to 99.2%) seroconverted for vaccine HPV types by month 7. At month 36, 88.9%, 94.0%, 97.9%, and 57.0% of subjects were still seropositive for HPV-6, -11, -16, and -18, respectively. For all vaccine HPV types, black subjects had significantly higher antibody titers at month 7 than did both Caucasian and Asian subjects. An anamnestic antibody response was seen in men seropositive before vaccination. The vaccine was highly immunogenic in males 16 to 23 years of age; responses were comparable to those observed in women. Furthermore, the immune responses were consistent with the established efficacy of the vaccine in the prevention of incident and persistent HPV infection, anogenital warts, and anal intraepithelial neoplasia.
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- 2012
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20. Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection.
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Haupt RM, Wheeler CM, Brown DR, Garland SM, Ferris DG, Paavonen JA, Lehtinen MO, Steben M, Joura EA, Giacoletti KE, Radley DR, James MK, Saah AJ, and Sings HL
- Subjects
- Adolescent, Adult, DNA, Viral genetics, Double-Blind Method, Female, Follow-Up Studies, Human papillomavirus 16 isolation & purification, Human papillomavirus 18 isolation & purification, Humans, Papillomavirus Infections immunology, Papillomavirus Infections virology, Polymerase Chain Reaction, Uterine Cervical Neoplasms immunology, Uterine Cervical Neoplasms virology, Young Adult, Uterine Cervical Dysplasia immunology, Uterine Cervical Dysplasia virology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Papillomavirus Infections therapy, Papillomavirus Vaccines therapeutic use, Uterine Cervical Neoplasms therapy, Vaccines, Virus-Like Particle immunology, Uterine Cervical Dysplasia therapy
- Abstract
The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2-3 or adenocarcinoma in situ (CIN2-3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six-hundred and twenty-two women aged 16-26 were enrolled in 1 of 2 randomized, placebo-controlled, efficacy trials (Protocols 013 and 015). Vaccine or placebo was given at day 1, month 2 and 6. Women were tested for HPV6/11/16/18 DNA and antibodies at day 1. We focus on the subset of women who were seropositive and DNA positive to HPV16 or HPV18 prevaccination. Incidence is expressed as the number of women with an endpoint per 100 person-years-at-risk. In total, 419 vaccine and 446 placebo recipients were both seropositive and DNA positive to HPV16 or HPV18 prevaccination and had at least one follow-up visit. In Protocol 013, the incidence of HPV16/18-related CIN2-3/AIS among these women was 10.9 in the vaccine arm and 7.0 in the placebo arm (vaccine efficacy = -54.9; 95% CI: -181.7, 13.0). In Protocol 015, the incidence of HPV16/18-related CIN2-3/AIS was 5.5 in the vaccine arm and 6.2 in the placebo arm (vaccine efficacy = 12.2%; 95% CI: -29.8, 40.9). These data suggest HPV vaccination neither reduces nor enhances progression to HPV16/18-related high grade cervical lesions, and cervical cytology screening and corresponding management should continue as per local recommendations. Ultimately, population-based surveillance of vaccinated individuals beyond these clinical trials will be required to further address questions regarding the impact of vaccination in women exposed to vaccine HPV types before vaccination., (Copyright © 2011 UICC.)
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- 2011
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21. The efficacy and safety of the quadrivalent human papillomavirus 6/11/16/18 vaccine gardasil.
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Haupt RM and Sings HL
- Subjects
- Adolescent, Adolescent Behavior, Female, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Male, Papillomavirus Infections epidemiology, Papillomavirus Vaccines adverse effects, Risk Factors, Sex Education statistics & numerical data, Sexual Behavior statistics & numerical data, Sexually Transmitted Diseases, Viral epidemiology, Uterine Cervical Neoplasms epidemiology, Vaccination adverse effects, Young Adult, Papillomavirus Infections prevention & control, Papillomavirus Vaccines administration & dosage, Sexually Transmitted Diseases, Viral prevention & control, Uterine Cervical Neoplasms prevention & control, Vaccination statistics & numerical data
- Abstract
Human papillomavirus (HPV) infection causes cervical cancer, a significant portion of anal, genital, and oropharyngeal cancers, genital warts, and recurrent respiratory papillomatosis. In June 2006, a quadrivalent HPV-6/11/16/18 vaccine (Gardasil/Silgard) was licensed in the United States, and subsequently in the European Union (September 2006). It has since been approved in 121 countries, with >74 million doses distributed globally as of March 2011. As the incidence of HPV infection peaks 5-10 years after the onset of sexual activity, preadolescents and adolescents represent an appropriate target group to implement HPV vaccination programs so as to achieve the maximal public health benefit. In this article, we provide an overview of the prophylactic efficacy of the vaccine in young women who were found to be negative to at least one of the four vaccine HPV types, thus approximating sexually naive adolescents. Because adolescents are also at high risk for other infections which are preventable by currently available vaccines, the development of concurrent immunization strategies may lead to better compliance, thereby contributing to the overall goal of protection against preventable diseases. We also summarize concomitant administration studies with meningococcal, diphtheria, tetanus, and pertussis vaccines, which were conducted in adolescents aged 9-15 years. Prophylactic efficacy in other populations (males aged 16-26 years) is also summarized along with long-term safety and efficacy studies., (Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)
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- 2011
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22. Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia.
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Lehtinen M, Ault KA, Lyytikainen E, Dillner J, Garland SM, Ferris DG, Koutsky LA, Sings HL, Lu S, Haupt RM, and Paavonen J
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- Adolescent, Adult, Chlamydia Infections diagnosis, Coitus, DNA, Viral, Disease Progression, Early Detection of Cancer, Female, Humans, Papillomaviridae isolation & purification, Papillomavirus Infections diagnosis, Risk Factors, Sexual Partners, Young Adult, Chlamydia Infections complications, Papillomavirus Infections complications, Uterine Cervical Dysplasia virology, Uterine Cervical Neoplasms virology
- Abstract
Objectives: High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined., Methods: The placebo arms of two large, multinational, clinical trials of an HPV6/11/16/18 vaccine were combined. A total of 8441 healthy women aged 15-26 years underwent cervicovaginal cytology (Papanicolaou (Pap) testing) sampling and C trachomatis testing at day 1 and every 12 months thereafter for up to 4 years. Protocol-specified guidelines were used to triage participants with Pap abnormalities to colposcopy and definitive therapy. The main outcome measured was CIN., Results: At baseline, 2629 (31.1%) tested positive for hrHPV DNA and 354 (4.2%) tested positive for C trachomatis. Among those with HPV16/18 infection (n = 965; 11.4%) or without HPV16/18 infection (n = 7382, 87.5%), the hazard ratios (HRs) associated with development of any CIN grade 2 according to baseline C trachomatis status were 1.82 (95% CI: 1.06 to 3.14) and 1.74 (95% CI 1.05 to 2.90), respectively. The results were comparable when only the 12 most common hrHPV infections were considered, but the excess risk disappeared when the outcome was expanded to include CIN grade 3 or worse., Conclusion: Further studies based on larger cohorts with longitudinal follow-up in relation to the C trachomatis acquisition and a thorough evaluation of temporal relationships of infections with hrHPV types, C trachomatis and cervical neoplasia are needed to demonstrate whether and how in some situations C trachomatis sets the stage for cervical carcinogenesis. Trial registration NCT00092521 and NCT00092534.
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- 2011
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23. Safety and reactogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 viral-like-particle vaccine in older adolescents and young adults.
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Moreira ED Jr, Palefsky JM, Giuliano AR, Goldstone S, Aranda C, Jessen H, Hillman RJ, Ferris D, Coutlee F, Vardas E, Marshall JB, Vuocolo S, Haupt RM, Guris D, and Garner EI
- Subjects
- Adolescent, Adult, Double-Blind Method, Female, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Human papillomavirus 11 immunology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Human papillomavirus 6 immunology, Humans, Male, Papillomavirus Infections immunology, Papillomavirus Infections prevention & control, Safety, Young Adult, Papillomavirus Vaccines administration & dosage, Papillomavirus Vaccines adverse effects, Papillomavirus Vaccines immunology, Vaccination adverse effects
- Abstract
Background: Prophylactic vaccination with a quadrivalent HPV (types 6, 11, 16, 18) vaccine (qHPV) has been shown to prevent infection with HPV 6/11/16/18 and associated disease in women and more recently, in men. Here we report on the safety and reactogenicity of the qHPV vaccine in males. A total of 4,065 healthy males aged 16-26 years were enrolled into a randomized, placebo-controlled, double-blind trial. Subjects were randomized 1:1 to receive qHPV vaccine or placebo at day 1, month 2, and month 6. Safety and tolerability were assessed via the collection of reported adverse experiences (AEs). All serious AEs (vaccine- or procedure-related or not) and all deaths occurring during the study were recorded. Safety analyses were conducted in all subjects who received at least one dose of vaccine or placebo. The proportion of subjects who reported at least one injection-site AE was higher in the qHPV vaccine group versus the placebo group (60.1% vs 53.7%, respectively), however most of these AEs were mild/moderate in intensity. The incidence of at least one systemic AE was comparable between the vaccine and placebo groups (31.7% vs 31.4%, respectively). There were no vaccine-related serious AEs or deaths. The occurrence of AEs did not increase with each successive injection, and among trial participants who were seropositive for at least one vaccine HPV type at enrollment, the profile of adverse events was similar to that of the entire study cohort. The qHPV vaccine was generally well tolerated in males aged 16-26 years and had a favorable safety profile.
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- 2011
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24. End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age.
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Castellsagué X, Muñoz N, Pitisuttithum P, Ferris D, Monsonego J, Ault K, Luna J, Myers E, Mallary S, Bautista OM, Bryan J, Vuocolo S, Haupt RM, and Saah A
- Subjects
- Adult, Clinical Trials as Topic, Double-Blind Method, Female, Follow-Up Studies, Humans, International Agencies, Middle Aged, Multicenter Studies as Topic, Ovarian Neoplasms virology, Papillomavirus Infections immunology, Papillomavirus Infections prevention & control, Papillomavirus Infections virology, Papillomavirus Vaccines immunology, Randomized Controlled Trials as Topic, Treatment Outcome, Vaccination, Vaccines, Synthetic immunology, Young Adult, Uterine Cervical Dysplasia immunology, Uterine Cervical Dysplasia prevention & control, Uterine Cervical Dysplasia virology, Ovarian Neoplasms immunology, Ovarian Neoplasms prevention & control, Papillomaviridae immunology, Papillomavirus Vaccines therapeutic use, Vaccines, Synthetic therapeutic use
- Abstract
Background: Previous analyses from a randomised trial in women aged 24-45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years., Methods: We enrolled 3819 24-45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations., Results: Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported., Conclusions: The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24-45 years, regardless of previous exposure to HPV vaccine type.
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- 2011
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25. The accuracy of colposcopic biopsy: analyses from the placebo arm of the Gardasil clinical trials.
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Stoler MH, Vichnin MD, Ferenczy A, Ferris DG, Perez G, Paavonen J, Joura EA, Djursing H, Sigurdsson K, Jefferson L, Alvarez F, Sings HL, Lu S, James MK, Saah A, and Haupt RM
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma virology, Adolescent, Adult, Cervix Uteri pathology, Cervix Uteri surgery, DNA, Viral genetics, Double-Blind Method, Female, Follow-Up Studies, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Middle Aged, Papillomaviridae isolation & purification, Papillomavirus Infections pathology, Papillomavirus Infections virology, Papillomavirus Vaccines therapeutic use, Placebos, Prognosis, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms virology, Vaginal Smears, Young Adult, Uterine Cervical Dysplasia pathology, Uterine Cervical Dysplasia virology, Adenocarcinoma prevention & control, Colposcopy, Papillomavirus Infections prevention & control, Papillomavirus Vaccines administration & dosage, Uterine Cervical Neoplasms prevention & control, Uterine Cervical Dysplasia prevention & control
- Abstract
We evaluated the overall agreement between colposcopically directed biopsies and the definitive excisional specimens within the context of three clinical trials. A total of 737 women aged 16-45 who had a cervical biopsy taken within 6 months before their definitive therapy were included. Per-protocol, colposcopists were to also obtain a representative cervical biopsy immediately before definitive therapy. Using adjudicated histological diagnoses, the initial biopsies and the same day biopsies were correlated with the surgically excised specimens. The overall agreement between the biopsies taken within 6 months of definitive therapy, and the definitive therapy diagnoses was 42% (weighted kappa = 0.34) (95% CI: 0.29-0.39). The overall underestimation of cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ (CIN2-3/AIS) and CIN3/AIS was 26 and 42%, respectively. When allowing for one degree of variance in the correlation, the overall agreement was 92% for CIN2-3/AIS. The overall agreement between the same day biopsy and definitive therapy specimen was 56% (weighted kappa = 0.41) (95% CI: 0.36-0.47), and the underestimation of CIN2-3/AIS was 57%. There were significant associations in the agreement between biopsies and excisional specimen diagnoses when patients were stratified by age, number of biopsies, lesion size, presence of human papillomavirus (HPV)16/18 and region. Of 178 diagnostic endocervical curettages performed, 14 (7.9%) found any HPV disease. Colposcopic accuracy improved when CIN2 and CIN3/AIS were grouped as a single predictive measure of high-grade disease. Colposcopy functioned well when allowed a one-degree difference between the biopsy and the surgical histologic interpretations, as done in clinical practice. Taking more than one biopsy improved colposcopic accuracy and could improve patient management., (Copyright © 2010 UICC.)
- Published
- 2011
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26. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine.
- Author
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Ault KA, Joura EA, Kjaer SK, Iversen OE, Wheeler CM, Perez G, Brown DR, Koutsky LA, Garland SM, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Majewski S, Muñoz N, Sings HL, Harkins K, Rutkowski MA, Haupt RM, and Garner EI
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma prevention & control, Adolescent, Adult, Colposcopy, DNA, Viral genetics, Double-Blind Method, Female, Follow-Up Studies, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Papanicolaou Test, Papillomavirus Infections pathology, Papillomavirus Infections prevention & control, Prognosis, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms prevention & control, Vaginal Smears, Young Adult, Uterine Cervical Dysplasia pathology, Uterine Cervical Dysplasia prevention & control, Adenocarcinoma virology, Papillomaviridae isolation & purification, Papillomavirus Infections virology, Papillomavirus Vaccines administration & dosage, Uterine Cervical Neoplasms virology, Uterine Cervical Dysplasia virology
- Abstract
The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis, we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total, with HPV16/18 present in 96% (24 of 25 with 15 of 25 as single infections). Only two of 22 women had concomitant cytology results suggesting glandular abnormality. Colposcopic impressions (25 total) were either negative or indicated squamous lesions only. Of women with AIS, all six in the vaccine cohort and seven of 16 in the placebo cohort were infected at baseline with the same HPV type that was detected in the AIS lesion. Concurrent squamous lesions were detected in 20 of these 22 women. In summary, our findings show that AIS evades colposcopic and cervical cytologic detection. As most AIS lesions were HPV16/18-related, prophylactic HPV vaccination should reduce the incidence of invasive adenocarcinoma., (Copyright © 2011 UICC.)
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- 2011
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27. Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males.
- Author
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Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Penny ME, Aranda C, Vardas E, Moi H, Jessen H, Hillman R, Chang YH, Ferris D, Rouleau D, Bryan J, Marshall JB, Vuocolo S, Barr E, Radley D, Haupt RM, and Guris D
- Subjects
- Adolescent, Adult, Alphapapillomavirus, Double-Blind Method, Genital Diseases, Male epidemiology, Genital Diseases, Male virology, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Incidence, Injections adverse effects, Intention to Treat Analysis, Male, Papillomavirus Infections epidemiology, Papillomavirus Infections virology, Treatment Outcome, Young Adult, Genital Diseases, Male prevention & control, Papillomavirus Infections prevention & control, Papillomavirus Vaccines adverse effects
- Abstract
Background: Infection with human papillomavirus (HPV) and diseases caused by HPV are common in boys and men. We report on the safety of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men., Methods: We enrolled 4065 healthy boys and men 16 to 26 years of age, from 18 countries in a randomized, placebo-controlled, double-blind trial. The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6, 11, 16, or 18. Efficacy analyses were conducted in a per-protocol population, in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment, and in an intention-to-treat population, in which subjects received vaccine or placebo, regardless of baseline HPV status., Results: In the intention-to-treat population, 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group, for an observed efficacy of 60.2% (95% confidence interval [CI], 40.8 to 73.8); the efficacy was 65.5% (95% CI, 45.8 to 78.6) for lesions related to HPV-6, 11, 16, or 18. In the per-protocol population, efficacy against lesions related to HPV-6, 11, 16, or 18 was 90.4% (95% CI, 69.2 to 98.1). Efficacy with respect to persistent infection with HPV-6, 11, 16, or 18 and detection of related DNA at any time was 47.8% (95% CI, 36.0 to 57.6) and 27.1% (95% CI, 16.6 to 36.3), respectively, in the intention-to-treat population and 85.6% (97.5% CI, 73.4 to 92.9) and 44.7% (95% CI, 31.5 to 55.6) in the per-protocol population. Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo (57% vs. 51%, P<0.001)., Conclusions: Quadrivalent HPV vaccine prevents infection with HPV-6, 11, 16, and 18 and the development of related external genital lesions in males 16 to 26 years of age. (Funded by Merck and others; ClinicalTrials.gov number, NCT00090285.).
- Published
- 2011
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28. The humoral response to Gardasil over four years as defined by total IgG and competitive Luminex immunoassay.
- Author
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Brown DR, Garland SM, Ferris DG, Joura E, Steben M, James M, Radley D, Vuocolo S, Garner EI, Haupt RM, and Bryan JT
- Subjects
- Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Time Factors, Virion immunology, Antibodies, Viral blood, Immunoassay methods, Immunoglobulin G blood, Papillomavirus Vaccines immunology
- Abstract
Safe and effective vaccines against anogenital human papillomaviruses (HPV) are now available. These vaccines, composed of virus-like particles (VLPs) made from the L1 major capsid protein of specific HPV types, induce a polyclonal antibody response directed against specific conformational and linear epitopes displayed on the VLP. Numerous studies indicated the importance of neutralizing antibodies in protection from infection. However, our understanding of the antibody responses to these vaccines is not complete, and there is no established immune correlate of protection nor antibody threshold that correlates with protection against HPV infection or disease. In the current study, antibody responses of young women to Gardasil®, the quadrivalent HPV 6, 11, 16 and 18 L1 VLP vaccine (qHPV), were assessed through 48 months (M) in total IgG and competitive Luminex immunoassays (total IgG LIA and cLIA). The total IgG LIA was developed as a research assay to evaluate preclinical multivalent HPV VLP vaccine formulations. The cLIA simultaneously evaluates the antibody response to a unique conformational, neutralizing epitope on each of the four HPV types present in the quadrivalent vaccine; HPV 6, 11, 16 and 18. The same sera from women vaccinated with the qHPV vaccine were tested in both the total IgG LIA and the cLIA assays. The proportion of vaccinated women achieving seropositivity and the anti-HPV VLP total IgG and cLIA geometric mean titers (GMTs) were summarized at M7, M24, M48 based on the serostatus cut-points defined for each immunoassay. Overall, greater than 99% of subjects seroconverted to all four vaccine types in both assays; GMTs peaked at M7. For all four HPV types, regardless of the immunoassay used, the most significant decline in GMTs was observed between M7 and M24. By M24, the antibody titers had reached a plateau and minimal declines in antibody titers were observed between M24 and M48 for all four HPV types in both immunoassays. Testing the same sera, seropositivity for M48 HPV18 remained high (96.7%) in the total IgG LIA, but was 64.8% in the cLIA. The current study illustrates potential important differences in serologic assays utilized in the clinical trials of the two currently available HPV VLP vaccines (quadrivalent and bivalent). Differences in seropositivity status are attributed to the measurement parameters and sensitivity of the individual immunoassays and do not indicate reduced anti-HPV18 protective antibodies.
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- 2011
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29. Incident cervical HPV infections in young women: transition probabilities for CIN and infection clearance.
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Insinga RP, Perez G, Wheeler CM, Koutsky LA, Garland SM, Leodolter S, Joura EA, Ferris DG, Steben M, Hernandez-Avila M, Brown DR, Elbasha E, Muñoz N, Paavonen J, and Haupt RM
- Subjects
- Adolescent, Adult, Double-Blind Method, Female, Follow-Up Studies, Humans, Incidence, International Agencies, Papillomavirus Infections virology, Papillomavirus Vaccines therapeutic use, Placebos, Prevalence, Prognosis, Risk Factors, Survival Rate, Uterine Cervical Neoplasms virology, Young Adult, Uterine Cervical Dysplasia virology, Cervix Uteri virology, Papillomaviridae pathogenicity, Papillomavirus Infections epidemiology, Uterine Cervical Neoplasms epidemiology, Uterine Cervical Dysplasia epidemiology
- Abstract
Background: We describe transition probabilities for incident human papillomavirus (HPV) 16/18/31/33/35/45/52/58/59 infections and cervical intraepithelial neoplasia (CIN) 1 lesions., Methods: Women ages 16 to 23 years underwent cytology and cervical swab PCR testing for HPV at approximately 6-month intervals for up to 4 years in the placebo arm of an HPV vaccine trial. The cumulative proportion of incident HPV infections with diagnosed CIN, clearing (infection undetectable), or persisting without CIN, were estimated., Results: Most incident infections cleared, without detection of CIN, ranging at 36 months from 66.9% for HPV31 to 91.1% for HPV59. There was little variation in the 36-month proportion of incident HPV16, 18, and 31 infections followed by a CIN1 lesion positive for the relevant HPV type (range 16.7%-18.6%), with lower risks for HPV59 (6.4%) and HPV33 (2.9%). Thirty-six-month transition probabilities for CIN2 ranged across types from 2.2% to 9.1%; however, the number of events was generally too small for statistically significant differences to be seen across types for this endpoint, or CIN3., Conclusions: Some incident HPV types appear more likely to result in diagnosed CIN1 than others. The relative predominance of HPV16, vis-à-vis some other high-risk HPV types (e.g., HPV33) in prevalent CIN2/3, appears more directly associated with relatively greater frequency of incident HPV16 infections within the population, than a higher risk of infection progression to CIN2/3., Impact: Nearly all incident HPV infections either manifest as detectable CIN or become undetectable within 36 months. Some HPV types (e.g., 16 and 33) appear to have similar risk of CIN2/3 despite widely varied incidence., (©2011 AACR.)
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- 2011
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30. A summary of the post-licensure surveillance initiatives for GARDASIL/SILGARD.
- Author
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Bonanni P, Cohet C, Kjaer SK, Latham NB, Lambert PH, Reisinger K, and Haupt RM
- Subjects
- Adolescent, Adult, Attitude of Health Personnel, Child, Clinical Trials as Topic, Condylomata Acuminata epidemiology, Condylomata Acuminata prevention & control, Drug Industry, Europe, Female, France, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Licensure, Managed Care Programs, Papillomavirus Infections epidemiology, Papillomavirus Vaccines adverse effects, Patient Acceptance of Health Care, Product Surveillance, Postmarketing, Registries, Uterine Cervical Neoplasms immunology, Uterine Cervical Neoplasms prevention & control, Young Adult, Papillomavirus Infections immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines immunology
- Abstract
GARDASIL has been shown to reduce the incidence of pre-cancerous cervical, vulvar, and vaginal lesions, and external genital warts causally related to HPV6/11/16/18. Because of its expected public health benefit on reduction of cervical cancer and other HPV-related diseases, this vaccine has been rapidly implemented in the routine vaccination programs of several countries. It is therefore essential to assess its impact and safety through post-licensure surveillance programs. Here, we present a summary of 16 post-licensure safety and impact studies across 20 countries. These studies address general safety, including autoimmune disorders, long-term effectiveness, and type replacement. A summary of the surveillance efforts of the Unites States Centers for Disease Control and Prevention can be found in the accompanying article by Markowitz et al., (Copyright 2010 Elsevier Ltd. All rights reserved.)
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- 2010
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31. HPV vaccine continues to be safe and effective, and its benefits continue to outweigh its risks.
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Haupt RM and Sattler C
- Subjects
- Female, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Risk, Vaccination methods, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines adverse effects, Papillomavirus Vaccines immunology
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- 2010
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32. Safety, tolerability, and immunogenicity of gardasil given concomitantly with Menactra and Adacel.
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Reisinger KS, Block SL, Collins-Ogle M, Marchant C, Catlett M, Radley D, Sings HL, Haupt RM, and Garner EI
- Subjects
- Adolescent, Alphapapillomavirus, Child, Diphtheria-Tetanus-acellular Pertussis Vaccines administration & dosage, Drug Interactions, Female, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Male, Meningococcal Vaccines administration & dosage, Papillomavirus Vaccines administration & dosage, Vaccines, Conjugate administration & dosage, Vaccines, Conjugate pharmacology, Diphtheria-Tetanus-acellular Pertussis Vaccines pharmacology, Meningococcal Vaccines pharmacology, Papillomavirus Vaccines pharmacology
- Abstract
Objectives: Multinational phase III trials of a human papillomavirus vaccine, Gardasil, have shown the vaccine to be generally well-tolerated, efficacious, and immunogenic. We evaluated the immunogenicity and safety of Gardasil administered concomitantly with Menactra and Adacel., Methods: In this open-label study, boys (n = 394) and girls (n = 648) aged 10 to 17 were randomly assigned in a 1:1 ratio as follows: group A (concomitant administration) received a 0.5-mL dose of Gardasil at day 1, month 2, and month 6 and a 0.5-mL dose of Menactra and Adacel on day 1; group B (nonconcomitant administration) received Gardasil at day 1, month 2, and month 6 and Menactra and Adacel at month 1. Antibody levels for all vaccine components were measured. Systemic, injection-site, and serious adverse experiences (AEs) were monitored., Results: Immune responses after concomitant administration of the 3 vaccines were noninferior to nonconcomitant administration. Seroconversion for Gardasil was > or = 99% in both groups A and B. For Menactra and Adacel, concomitant administration of the vaccines was demonstrated to be noninferior to nonconcomitant administration. Concomitant administration was generally well-tolerated. No participants withdrew because of an AE. One serious AE of transient muscular weakness of <24 hours' duration after the third Gardasil injection was reported in group B and was deemed possibly vaccine-related by the investigator., Conclusions: Overall, concomitant administration was generally well-tolerated and did not interfere with the immune response to the respective vaccines. Concomitant administration should minimize the number of visits required to deliver each vaccine individually, leading to increased compliance and more effective disease prevention.
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- 2010
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33. Incidence, duration, and reappearance of type-specific cervical human papillomavirus infections in young women.
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Insinga RP, Perez G, Wheeler CM, Koutsky LA, Garland SM, Leodolter S, Joura EA, Ferris DG, Steben M, Brown DR, Elbasha EH, Paavonen J, and Haupt RM
- Subjects
- Adolescent, Clinical Trials, Phase III as Topic, DNA, Viral analysis, Double-Blind Method, Female, Humans, Incidence, Papillomaviridae genetics, Papillomaviridae isolation & purification, Papillomavirus Infections prevention & control, Papillomavirus Infections virology, Polymerase Chain Reaction, Prevalence, Randomized Controlled Trials as Topic, Young Adult, Papillomavirus Infections epidemiology, Uterine Cervical Diseases epidemiology, Uterine Cervical Diseases virology
- Abstract
Background: We describe the incidence and duration of cervical human papillomavirus (HPV) infection episodes along with the risk of infection reappearance following a period of nondetection., Methods: Women (1,788) ages 16 to 23 years underwent cytologic testing and PCR-based testing of cervical swab samples for HPV DNA (HPV-16/18/31/33/35/45/52/58/59) at approximately 6-month intervals for up to 4 years in the context of a phase 3 clinical trial (placebo arm). HPV type-specific incidence rates were estimated per 100 person-years. Duration of type-specific cervical infection episodes and risk of reappearance following a period of nondetection were estimated using Kaplan-Meier methods., Results: HPV-16 exhibited the highest (5.9), and HPV-35 and HPV-33 exhibited the lowest (1.0) incidence rates per 100 person-years. Mean cervical infection durations ranged from 13 months for HPV-59 to 20 months for HPV-16 and 58 (with ongoing infections censored at the time of treatment, if done). The risk of cervical infection reappearance within approximately 3 years following a period of nondetection ranged from 0% to 16% across HPV types, with a mean of 8%. Limited evidence was found for a role of false-positive HPV tests, missed infections that were above the threshold for detection, or new acquisition of infection in accounting for patterns of infection reappearance., Conclusions: Incidence of high-risk cervical infection was observed to vary considerably more across HPV types than infection duration. A nontrivial proportion of women exhibited infection reappearance following a period of nondetection, with a potential explanation for many such events observed within this analysis being a return to detectable levels of a previously acquired infection., Impact: The risk of HPV infection reappearance following a period of nondetection has not been previously reported for individual HPV types, and this study finds that a nontrivial proportion of infected women exhibit reappearances. Future studies could ascertain subject-level factors that potentially modify the risk of infection reappearance., (Copyright 2010 AACR.)
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- 2010
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34. An open-label, randomized, multicenter study of the safety, tolerability, and immunogenicity of quadrivalent human papillomavirus (types 6/11/16/18) vaccine given concomitantly with diphtheria, tetanus, pertussis, and poliomyelitis vaccine in healthy adolescents 11 to 17 years of age.
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Vesikari T, Van Damme P, Lindblad N, Pfletschinger U, Radley D, Ryan D, Vuocolo S, Haupt RM, and Guris D
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- Adolescent, Alphapapillomavirus immunology, Bordetella pertussis immunology, Child, Diphtheria immunology, Diphtheria prevention & control, Diphtheria Toxoid administration & dosage, Diphtheria Toxoid immunology, Female, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Male, Papillomavirus Infections immunology, Papillomavirus Infections prevention & control, Poliomyelitis immunology, Poliomyelitis prevention & control, Tetanus immunology, Tetanus prevention & control, Tetanus Toxoid administration & dosage, Tetanus Toxoid immunology, Treatment Outcome, Whooping Cough immunology, Whooping Cough prevention & control, Antibodies, Bacterial blood, Antibodies, Viral blood, Diphtheria-Tetanus-acellular Pertussis Vaccines administration & dosage, Diphtheria-Tetanus-acellular Pertussis Vaccines adverse effects, Diphtheria-Tetanus-acellular Pertussis Vaccines immunology, Papillomavirus Vaccines administration & dosage, Papillomavirus Vaccines adverse effects, Papillomavirus Vaccines immunology, Poliovirus Vaccines administration & dosage, Poliovirus Vaccines immunology
- Abstract
Background: GARDASIL/SILGARD is a quadrivalent human papillomavirus (HPV) vaccine with activity against HPV 6/11/16/18. In many countries, GARDASIL is recommended for routine use among adolescents at the same age as other vaccines. In this study, we evaluated the immunogenicity and safety of GARDASIL administered concomitantly with REPEVAX (diphtheria, tetanus, acellular pertussis, and poliomyelitis vaccine)., Methods: This was an open-label, randomized, multicenter study. We enrolled males (n = 260) and females (n = 583) aged 11 to 17 years. All subjects received a 0.5 mL dose of GARDASIL at day 1, month 2, and month 6, and a 0.5 mL dose of REPEVAX either on day 1 (opposite limb from GARDASIL) or at month 1. Antibody levels for all vaccine components were measured. We monitored systemic and injection-site adverse experiences (AEs) and serious adverse experiences., Results: Immune response for all GARDASIL antigens following concomitant administration of the vaccines was demonstrated noninferior to nonconcomitant administration. Seroconversion for HPV 6, 11, 16, and 18 was >99.7% in both concomitant and nonconcomitant vaccination groups. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, and all polio and pertussis antigens. Concomitant administration of the 2 vaccines was generally well-tolerated, although there was a small increase in headache and injection-site swelling in the concomitant group., Conclusion: Overall, concomitant administration of GARDASIL and REPEVAX was generally well-tolerated and did not interfere with the immune response to either vaccine. Concomitant administration of vaccines would minimize the number of visits required to deliver each vaccine individually.
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- 2010
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35. Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women.
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Muñoz N, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia PJ, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Huh WK, Joura EA, Kurman RJ, Majewski S, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan JT, Lupinacci LC, Giacoletti KE, Sings HL, James MK, Hesley TM, Barr E, and Haupt RM
- Subjects
- Adolescent, Adult, Female, Genital Diseases, Female prevention & control, Genital Diseases, Female virology, Global Health, Human papillomavirus 11 immunology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Human papillomavirus 6 immunology, Humans, Kaplan-Meier Estimate, Papanicolaou Test, Papillomavirus Infections complications, Papillomavirus Infections epidemiology, Papillomavirus Infections virology, Sexual Partners, Sexually Transmitted Diseases epidemiology, Sexually Transmitted Diseases virology, Tumor Virus Infections complications, Tumor Virus Infections epidemiology, Tumor Virus Infections virology, Uterine Cervical Neoplasms epidemiology, Uterine Cervical Neoplasms virology, Vaginal Smears, Young Adult, Uterine Cervical Dysplasia epidemiology, Uterine Cervical Dysplasia virology, Alphapapillomavirus immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines administration & dosage, Papillomavirus Vaccines pharmacology, Sexually Transmitted Diseases prevention & control, Tumor Virus Infections prevention & control, Uterine Cervical Neoplasms prevention & control, Uterine Cervical Dysplasia prevention & control
- Abstract
Background: The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group)., Methods: This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk., Results: The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type., Conclusions: High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.
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- 2010
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36. Clinical trial and post-licensure safety profile of a prophylactic human papillomavirus (types 6, 11, 16, and 18) l1 virus-like particle vaccine.
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Block SL, Brown DR, Chatterjee A, Gold MA, Sings HL, Meibohm A, Dana A, Haupt RM, Barr E, Tamms GM, Zhou H, and Reisinger KS
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- Adolescent, Adult, Child, Drug-Related Side Effects and Adverse Reactions, Female, Fever, Headache, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Incidence, Male, Pain, Placebos administration & dosage, Product Surveillance, Postmarketing, United States, Vaccines, Virosome adverse effects, Vaccines, Virosome immunology, Young Adult, Papillomavirus Infections prevention & control, Papillomavirus Vaccines adverse effects, Papillomavirus Vaccines immunology
- Abstract
Background: We describe the safety of the human papillomavirus (HPV)-6/11/16/18 vaccine using updated clinical trial data (median follow-up time of 3.6 years) and summarize up to 3 years of post-licensure surveillance., Methods: In 5 clinical trials, 21,480 girls/women aged 9 to 26 years and boys aged 9 to 16 years received >or=1 dose of HPV-6/11/16/18 vaccine or placebo. All serious and non-serious adverse experiences (AEs) and new medical conditions were recorded for the entire study period(s). As of June 2009, >25 million doses of HPV-6/11/16/18 vaccine had been distributed in the United States with >50 million doses globally. Post-licensure safety as summarized by the Centers for Disease Control and Prevention using the United States Vaccine Adverse Event Reporting System database is also reported., Results: Eight subjects experienced a treatment-related serious AE (0.05% vaccine; 0.02% placebo). Of 18 deaths (0.1% vaccine; 0.1% placebo), all were considered unrelated to study treatment. New medical conditions which were potentially consistent with autoimmune phenomena were reported in 2.4% of both vaccine and placebo recipients. Pain, the most common injection-site AE, occurred more frequently with vaccine (81% vaccine; 75% placeboaluminum; 45% placebo-saline). No differences were seen in the incidence of the most common non-serious AEs-headache and pyrexia. The Vaccine Adverse Event Reporting System has received 14,072 reports for the HPV-6/11/16/18 vaccine since licensure, with only 7% being serious AEs, about half the average reported for licensed vaccines in general., Conclusions: HPV-6/11/16/18 vaccination was associated with more injection-site pain than placebo but similar incidences of systemic and serious AEs and new medical conditions potentially consistent with autoimmune phenomena. Based on review of post-licensure safety information, the benefits of vaccination to prevent the majority of genital tract precancers and cancers continue to far outweigh its risks.
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- 2010
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37. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection.
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Olsson SE, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Brown DR, Koutsky LA, Tay EH, García P, Ault KA, Garland SM, Leodolter S, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch FX, Dillner J, Joura EA, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Maansson R, Vuocolo S, Hesley TM, Saah A, Barr E, and Haupt RM
- Subjects
- Adolescent, Adult, Antibodies, Viral blood, Cervix Uteri cytology, Cervix Uteri pathology, Female, Follow-Up Studies, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Papillomavirus Infections pathology, Papillomavirus Infections virology, Papillomavirus Vaccines adverse effects, Placebos administration & dosage, Vulva pathology, Young Adult, Cervix Uteri virology, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines immunology, Vulva virology
- Abstract
Objective: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL/SILGARD) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed., Methods: 18,174 women were enrolled into 3 clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for >or=1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing, and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment., Results: Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrolment., Conclusions: These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.
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- 2009
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38. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervical and external genital lesions.
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Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Brown DR, Koutsky LA, Tay EH, García P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch FX, Dillner J, Joura EA, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Maansson R, Lu S, Vuocolo S, Hesley TM, Saah A, Barr E, and Haupt RM
- Subjects
- Adolescent, Adult, Clinical Trials, Phase III as Topic, Female, Genital Diseases, Female prevention & control, Genital Diseases, Female virology, Human papillomavirus 11, Human papillomavirus 16, Human papillomavirus 18, Human papillomavirus 6, Humans, Multicenter Studies as Topic, Papillomavirus Infections complications, Papillomavirus Infections prevention & control, Papillomavirus Infections virology, Randomized Controlled Trials as Topic, Young Adult, Uterine Cervical Dysplasia virology, Cancer Vaccines therapeutic use, Papillomavirus Vaccines therapeutic use, Uterine Cervical Neoplasms prevention & control, Uterine Cervical Neoplasms virology, Uterine Cervical Dysplasia prevention & control
- Abstract
Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18-related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18-related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination.
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- 2009
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39. Impact of a quadrivalent HPV6/11/16/18 vaccine in Mexican women: public health implications for the region.
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Lazcano-Ponce E, Pérez G, Cruz-Valdez A, Zamilpa L, Aranda-Flores C, Hernández-Nevarez P, Viramontes JL, Salgado-Hernández J, James M, Lu S, Sattler C, Haupt RM, and Hernández-Avila M
- Subjects
- Adenocarcinoma prevention & control, Adolescent, Double-Blind Method, Female, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Mexico, Papillomavirus Vaccines administration & dosage, Papillomavirus Vaccines immunology, Public Health, Randomized Controlled Trials as Topic, Safety, Young Adult, Uterine Cervical Dysplasia prevention & control, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use
- Abstract
Background and Aims: Recognition of human papillomavirus (HPV) as a necessary cause of cervical cancer (CC) led to new perspectives for its control and the demonstration of an effective primary prevention strategy through vaccination. We undertook this study to evaluate the safety, efficacy and immunogenicity of a quadrivalent HPV6/11/16/18 vaccine in Mexican women., Methods: A total of 679 Mexican women between 18 and 23 years old participated in two Phase III double-blind, randomized, placebo-controlled clinical trials of a quadrivalent HPV 6/11/16/18 vaccine. Women were enrolled who tested negative for pregnancy and reported having four or less sexual partners during their lifetime. Vaccine or placebo was administered at day 1, month 2 and month 6., Results: Among Mexican women who were naïve to the respective vaccine type at enrollment, the quadrivalent vaccine was highly efficacious, preventing 100% of HPV6/11/16/18-related cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ, condyloma and vaginal intraepithelial neoplasia. Statistical significance was not reached for every endpoint due to the limited sample size. Vaccination was generally well tolerated and immunogenic., Discussion: To widely administer the vaccine, collaborative efforts should be coordinated among public, private and local community sectors. In light of the scarce knowledge of many health professionals with respect to the primary prevention of CC, it will be necessary to educate health providers on the advantages and specific recommendations of HPV vaccines and secondary prevention. Decision making should be based on scientific evidence, allowing health professionals to provide an organized social response that supports the universal right to health.
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- 2009
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40. Age-based programs for vaccination against HPV.
- Author
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Elbasha EH, Dasbach EJ, Insinga RP, Haupt RM, and Barr E
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Condylomata Acuminata economics, Condylomata Acuminata prevention & control, Cost-Benefit Analysis, Costs and Cost Analysis, Female, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Middle Aged, Models, Econometric, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use, Quality-Adjusted Life Years, United States, Uterine Cervical Neoplasms economics, Uterine Cervical Neoplasms prevention & control, Young Adult, Mass Vaccination economics, Papillomavirus Infections economics, Papillomavirus Vaccines economics
- Abstract
Background: The risk of infection with human papillomavirus (HPV) increases with age. Answering the question of which age groups are appropriate to target for catch-up vaccination with the newly licensed quadrivalent HPV vaccine (types 6/11/16/18) will be important for developing vaccine policy recommendations., Objectives: To assess the value of varying female HPV vaccination strategies by specific age groups of a catch-up program in the United States., Methods: The authors used previously published mathematical population dynamic model and cost-utility analysis to evaluate the public health impact and cost-effectiveness of alternative quadrivalent HPV (6/11/16/18) vaccination strategies. The model simulates heterosexual transmission of HPV infection and occurrence of cervical intraepithelial neoplasia (CIN), cervical cancer, and external genital warts in an age-structured population stratified by sex and sexual activity groups. The cost-utility analysis estimates the cost of vaccination, screening, diagnosis, and treatment of HPV diseases, and quality-adjusted survival., Results: Compared with the current screening practices, vaccinating girls and women ages 12 to 24 years was the most effective strategy, reducing the number of HPV6/11/16/18-related genital warts, CIN grades 2 and 3, and cervical cancer cases among women in the next 25 years by 3,049,285, 1,399,935, and 30,021; respectively. The incremental cost-effectiveness ratio of this strategy when compared with vaccinating girls and women ages 12 to 19 years was $10,986 per quality-adjusted life-year gained. CONCLUSION;: Relative to other commonly accepted health-care programs, vaccinating girls and women ages 12 to 24 years appears cost-effective.
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- 2009
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41. Human papillomavirus infections and vulvar disease development.
- Author
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Garland SM, Insinga RP, Sings HL, Haupt RM, and Joura EA
- Subjects
- Adolescent, Adult, Cancer Vaccines therapeutic use, DNA, Viral analysis, DNA, Viral isolation & purification, Double-Blind Method, Female, Humans, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines therapeutic use, Polymerase Chain Reaction, Precancerous Conditions virology, Vulvar Neoplasms prevention & control, Carcinoma in Situ virology, Human papillomavirus 11, Human papillomavirus 16, Papillomavirus Infections complications, Vulvar Neoplasms virology
- Abstract
Background: We describe the prevalence of 14 common types [human papillomavirus (HPV)-6/11/16/18/31/33/35/39/45/51/52/56/58/59] in vulvar intraepithelial neoplasia grades 1 to 3 (VIN 1-3) and HPV genotype-specific infection in relation to the development of VIN 1-3., Methods: Data were analyzed from women enrolled in the placebo arms of three randomized double-blind trials. Anogenital examinations, including collection of labial/vulvar/perineal/perianal swabs, occurred at day 1 and every 6 to 12 months through 48 months. Lesions that were possibly, probably, or definitely HPV related or of unknown etiology were biopsied. Biopsies and swabs were HPV typed. Biopsies were read for endpoint determination (VIN 1-3) by up to four pathologists., Results: Incident infection with HPV-16 was the most common (6.0/100 person-years). The mean time from incident infection to the development of VIN 1-3 was 18.5 months (95% confidence interval, 13.4-23.6). HPV-6 or -11 was observed in 64.5% of VIN 1 and 29.0% of VIN 2/3, whereas HPV-16 was observed in 6.5% of VIN 1 and 64.5% of VIN 2/3., Conclusion: A vaccine that includes both low- and high-risk types could prevent more than half of VIN 1-3 lesions, including the precursor lesions to HPV-related vulvar carcinoma. Understanding the incidence and duration of vulvar HPV infection and risk for progression to VIN 1-3 may inform therapeutic decisions for vulvar disease and mathematical models that assess the cost-effectiveness of vaccination.
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- 2009
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42. Natural history of genital warts: analysis of the placebo arm of 2 randomized phase III trials of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine.
- Author
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Garland SM, Steben M, Sings HL, James M, Lu S, Railkar R, Barr E, Haupt RM, and Joura EA
- Subjects
- Adolescent, Adult, Clinical Trials, Phase III as Topic, Condylomata Acuminata epidemiology, Female, Follow-Up Studies, Genotype, Human papillomavirus 16 genetics, Human papillomavirus 18 genetics, Human papillomavirus 6 genetics, Humans, Papillomavirus Infections epidemiology, Papillomavirus Infections prevention & control, Randomized Controlled Trials as Topic, Risk Factors, Time Factors, Young Adult, Condylomata Acuminata immunology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Human papillomavirus 6 immunology, Papillomavirus Infections immunology, Viral Vaccines administration & dosage
- Abstract
Background: The placebo arm of human papillomavirus (HPV) vaccine trials helps define the natural history of genital warts (GW)., Methods: Women enrolled in the placebo arm (n = 8800) of 2 randomized trials of a quadrivalent vaccine were examined for the presence of GW for up to 9 visits over approximately 4 years. A comprehensive examination of the perianal area, vulva, and vagina prompted biopsy. Biopsy samples were analyzed by a blinded panel of up to 4 histopathologists and tested for 14 HPV genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) by use of a polymerase chain reaction-based assay. Risk factors for the development of GW were assessed., Results: Women were followed up for an average of 3.6 years (range, 0-4.9 years). Overall, 298 (3.4%) of 8800 participants developed GW related to HPV-6 or HPV-11 (incidence rate, 0.87 cases per 100 person-years-at-risk). In total, 520 distinct lesions were diagnosed as GW. HPV DNA was detected in 472 (90.8%) lesions, with HPV-6 and HPV-11 detected in 447 (86.0%) of these lesions (94.7% of 472 HPV DNA-positive lesions). We found high-risk HPV types in 161 (31.0%) of 520 lesions. Risk factors for HPV-6- and HPV-11-related GW included infection at baseline, acquisition of new sex partners, a higher number of sex partners, and DNA positivity at baseline for a high-risk HPV type., Conclusions: We confirm the major role played by HPV-6 and HPV-11 in GW, as well as associated risk factors. A vaccine that includes these types of HPV could substantially reduce the overall burden of HPV disease.
- Published
- 2009
- Full Text
- View/download PDF
43. HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine.
- Author
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Joura EA, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, Hernandez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH, García P, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Lehtinen M, Steben M, Bosch X, Dillner J, Kurman RJ, Majewski S, Muñoz N, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC, Giacoletti KE, Lu S, Vuocolo S, Hesley TM, Haupt RM, and Barr E
- Subjects
- Adolescent, Antibodies, Viral analysis, Condylomata Acuminata epidemiology, Condylomata Acuminata immunology, Condylomata Acuminata prevention & control, Female, Follow-Up Studies, Human papillomavirus 11 immunology, Human papillomavirus 16 immunology, Human papillomavirus 18 immunology, Human papillomavirus 6 immunology, Humans, Immunization Schedule, Papanicolaou Test, Papillomavirus Infections pathology, Reverse Transcriptase Polymerase Chain Reaction, Vagina pathology, Vaginal Smears, Vulva pathology, Young Adult, Antibodies, Viral biosynthesis, Antibodies, Viral immunology, Papillomavirus Infections immunology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines immunology
- Abstract
The efficacy of the quadrivalent Human Papillomavirus (HPV) vaccine is thought to be mediated by humoral immunity. We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy. 17,622 women were vaccinated at day 1, and months 2 and 6. At day 1 and at 6-12 months intervals for up to 48 months, subjects underwent Papanicolaou and genital HPV testing. No immune correlate of protection could be found due to low number of cases. Although 40% of vaccine subjects were anti-HPV 18 seronegative at end-of-study, efficacy against HPV 18-related disease remained high (98.4%; 95% CI: 90.5-100.0) despite high attack rates in the placebo group. These results suggest vaccine-induced protection via immune memory, or lower than detectable HPV 18 antibody titers.
- Published
- 2008
- Full Text
- View/download PDF
44. Impact of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine in a sexually active population of North American women.
- Author
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Barr E, Gause CK, Bautista OM, Railkar RA, Lupinacci LC, Insinga RP, Sings HL, and Haupt RM
- Subjects
- Adolescent, Adult, Canada, Female, Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Humans, Puerto Rico, Sexual Behavior, United States, Alphapapillomavirus, Genital Diseases, Female prevention & control, Genital Diseases, Female virology, Papillomavirus Infections prevention & control, Papillomavirus Vaccines, Warts prevention & control, Warts virology
- Abstract
Objective: The purpose of this study was to inform policy regarding human papillomavirus (HPV) vaccination in North America. We measured the clinical impact of HPV-6/-11/-16/-18 vaccination in North American women., Study Design: The study enrolled 21,954 women, the majority aged 16-25, across 5 studies of a quadrivalent HPV vaccine or its HPV-16 vaccine prototype. The North American subjects (n = 5996) were pooled from these trials, and the prevalence of HPV-6/-11/-16/-18 exposure was measured. The impact of vaccination on the burden of anogenital HPV lesions in an intention-to-treat population (regardless of enrollment HPV status) was calculated., Results: At enrollment, the median age was 20 years; 13% of the women had had a Papanicolaou test abnormality, and 76% of the women had negative tests results for all 4 vaccine HPV types. With approximately 3 years of follow-up evaluations in the intention-to-treat population (regardless of enrollment HPV status), vaccination reduced the rate of HPV-16- and -18-related precancers and HPV-6/-11/-16/-18-related genital lesions by 66.4% (95% CI, 42.7%-81.1%) and 57.7% (95% CI, 27.3%-76.3%), respectively., Conclusion: The administration of HPV vaccine to sexually active North American women reduced the burden of HPV-6/-11/-16/-18-related disease. Catch-up vaccination programs in this population are warranted.
- Published
- 2008
- Full Text
- View/download PDF
45. Physicians' knowledge and attitudes about rotavirus gastroenteritis and rotavirus vaccine.
- Author
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Haupt RM, Isikci O, Kimble WL, Sotos GL, and Fu J
- Subjects
- Child, Drug Evaluation, Education, Medical, Continuing, Health Care Surveys, Humans, Infant, Product Surveillance, Postmarketing, United States, Attitude of Health Personnel, Clinical Competence, Family Practice education, Gastroenteritis prevention & control, Intussusception chemically induced, Pediatrics education, Rotavirus Infections prevention & control, Rotavirus Vaccines adverse effects
- Abstract
The morbidity and mortality associated with rotavirus gastroenteritis are significant. Despite the past safety concerns with RotaShield, many physicians believed the need for rotavirus vaccination remains. Although most physicians were not aware of specific rotavirus gastroenteritis disease burden statistics, they perceive rotavirus gastroenteritis to pose a serious risk for children for which a vaccine would be beneficial. Proof of safety and efficacy, an ACIP/AAP/AAFP recommendation, and private insurance coverage/reimbursement were critical features that would allow physicians to overcome barriers to the adoption of a new rotavirus vaccine.
- Published
- 2006
- Full Text
- View/download PDF
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