Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial

Villa, Luisa L.; Costa, Ronaldo; Petta, Carlos Alberto; Andrade, Rosíres Pereira de; Ault, Kevin A.; Giuliano, Anna R.; Wheeler, Cosette M.; Koutsky, Laura A.; Malm, Christian; Lehtinen, Matti; Skjeldestad, Finn Egil; Olsson, Sven Eric; Steinwall, Margareta; Brown, Darron R.; Kurman, Robert J.; Ronnett, Brigitte M.; Stoler, Mark H.; Ferenczy, Alex; Harper, Diane M.; Tamms, Gretchen; Yu, Jimmy; Lupinacci, Lisa; Railkar, Radha; Taddeo, Frank J.; Jansen, Kathrin U.; Esser, Mark T.; Sings, Heather L.; Saah, Alfred J.; Barr, Eliav

doi:10.1016/s1470-2045(05)70101-7

Cited by 1,394 publications

(896 citation statements)

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“…Cervical biopsies, endocervical curettage specimens, specimens from loop electrosurgical excision procedures and conization procedures, obtained at any time during the studies were tested for the four types in the vaccine (6/11/16/18) and 10 other oncogenic HPV types (31/33/ 35/39/45/51/52/56/58/59) using a PCR-based assay. 22,24,25 For each participant, blood samples were obtained at enrollment and at defined intervals throughout the study for anti-HPV serology testing. Serum concentrations of antibodies to HPV 6, 11, 16 and 18 were measured by competitive immunoassay (Luminex Corporation, Austin, TX, USA).…”

Section: Clinical Follow-up and Endpointsmentioning

confidence: 99%

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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

Haupt¹,

Wheeler²,

Brown

et al. 2011

Intl Journal of Cancer

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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.

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Section: Clinical Follow-up and Endpointsmentioning

confidence: 99%

“…Seventeen thousand six-hundred and twenty-two women aged [16][17][18][19][20][21][22][23][24][25][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.…”

mentioning

confidence: 99%

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

Haupt¹,

Wheeler²,

Brown

et al. 2011

Intl Journal of Cancer

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“…Due to the high prevalence of HPV16 and 18 in cervical cancer, HPV vaccine research has led to the development of prophylactic vaccines against HPV16 and 18. HPV L1 virus-like particle (VLP) vaccines have demonstrated excellent safety, immunogenicity, and protection against infection by homologous HPV types [6][7][8][9][10][11][12][13]. Based on several preclinical models, neutralizing antibodies are expected to be the primary immune mechanism for protection against persistent HPV16/18 infection in women vaccinated with HPV L1 VLP-based vaccine [14,15].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of systemic and mucosal anti-HPV16 and anti-HPV18 antibody responses from vaccinated women

Kemp¹,

Garcı́a-Piñeres²,

Falk³

et al. 2008

Vaccine

106

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Ideal methods to monitor HPV neutralizing antibodies induced by vaccination have not been established yet. Here, we evaluated systemic and cervical antibody levels induced by HPV16/18 AS04-adjuvanted vaccine (GlaxoSmithKline Biologicals) using a secreted alkaline phosphatase neutralization assay (SEAP) and ELISA. Serum and cervical secretions from 50 vaccinated women were used to assess 1) overall assay reproducibility, 2) inter-assay and inter-specimen correlation; 3) correlations between month 1 and month 12 titers. Strong correlations between SEAP-NA and ELISA were observed (serum anti-HPV16/18, ρ=0.91/0.85; cervix anti-HPV16/18, ρ=0.84/0.89). Systemic and cervical antibody measures also correlated well (ρ range: 0.64 -0.75); except at mid-cycle (ρ range: 0.28 -0.65). Correlations between antibody levels at one and twelve months following the start of vaccination were poor (ρ range: 0.16 -0.38). In conclusion, HPV16/18 VLP-based ELISA is a reliable and valid method to monitor anti-HPV16/18 neutralizing potential for the first year following vaccination; however, additional studies will be Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Conflict of Interest: Troy J. Kemp, no conflict; Alfonso García-Piñeres, no conflict; Roni T. Falk, no conflict; Sylviane Poncelet is employed by GSK Biologicals, the manufacturer of the vaccine used in this trial; Francis Dessy is employed by GSK Biologicals, the manufacturer of the vaccine used in this trial; Sandra L. Giannini is employed by GSK Biologicals, the manufacturer of the vaccine used in this trial; Ana Cecilia Rodriguez, no conflict; Carolina Porras, no conflict; Rolando Herrero, no conflict; Allan Hildesheim, no conflict; Ligia A. Pinto, no conflict. Merocel is a trademark of Medtronic Ophthalmics, a division of Medtronic Xomed, Inc., Jacksonville, FL, and Hemastix is a trademark of Bayer Corporation, Elkhart, IN. NIH Public Access Author ManuscriptVaccine. Author manuscript; available in PMC 2014 August 13.

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“…However, cervical cancer incidence in Finnish women aged 30 -39 years is now four times higher than 15 years ago (2.9/100 000 in 1986 -1990; 9.8/ 100 000 in 2000: Finnish Cancer Registry, 2006. This is probably due to an increase in incidence and prevalence of hr HPV types in young (23 -28 year old) Finnish women (Laukkanen et al, 2003;Lehtinen et al, 2006).In phase III trials, two HPV virus-like particle vaccines have been shown effective in preventing incident and persistent HPV16 and 18 infection and associated precancerous lesions, with reported efficacies in the region of 90 -100% (Koutsky et al, 2002;Harper et al, 2004Harper et al, , 2006Villa et al, 2005;Mao et al, 2006). The vaccines could prevent around 70% of all cervical cancer (Munoz et al, 2003).…”

mentioning

confidence: 99%

“…In phase III trials, two HPV virus-like particle vaccines have been shown effective in preventing incident and persistent HPV16 and 18 infection and associated precancerous lesions, with reported efficacies in the region of 90 -100% (Koutsky et al, 2002;Harper et al, 2004Harper et al, , 2006Villa et al, 2005;Mao et al, 2006). The vaccines could prevent around 70% of all cervical cancer (Munoz et al, 2003).…”

mentioning

confidence: 99%

Strategies for the introduction of human papillomavirus vaccination: modelling the optimum age- and sex-specific pattern of vaccination in Finland

et al. 2007

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Phase III trials have demonstrated the efficacy of human papillomavirus (HPV) vaccines in preventing transient and persistent high-risk (hr) HPV infection and precancerous lesions. A mathematical model of HPV type 16 infection and progression to cervical cancer, parameterised to represent the infection in Finland, was used to explore the optimal age at vaccination and pattern of vaccine introduction. In the long term, the annual proportion of cervical cancer cases prevented is much higher when early adolescents are targeted. Vaccinating against hr HPV generates greater long-term benefits if vaccine is delivered before the age at first sexual intercourse. However, vaccinating 12 year olds delays the predicted decrease in cervical cancer, compared to vaccinating older adolescents or young adults. Vaccinating males as well as females has more impact on the proportion of cases prevented when vaccinating at younger ages. Implementing catch-up vaccination at the start of a vaccination programme would increase the speed with which a decrease in HPV and cervical cancer incidence is observed. Human papillomavirus (HPV) is a common sexually transmitted agent (Trottier and Franco, 2006) and persistent infection with high risk (hr) types of HPV, most notably types 16 and 18, is the most important risk factor for cervical cancer (Ho et al, 1998). Rates of invasive cervical cancer (ICC) in fertile aged women in Finland declined significantly from 1960 to 1990 (Figure 1), mostly as a result of the national screening programme. However, cervical cancer incidence in Finnish women aged 30 -39 years is now four times higher than 15 years ago (2.9/100 000 in 1986 -1990; 9.8/ 100 000 in 2000: Finnish Cancer Registry, 2006. This is probably due to an increase in incidence and prevalence of hr HPV types in young (23 -28 year old) Finnish women (Laukkanen et al, 2003;Lehtinen et al, 2006).In phase III trials, two HPV virus-like particle vaccines have been shown effective in preventing incident and persistent HPV16 and 18 infection and associated precancerous lesions, with reported efficacies in the region of 90 -100% (Koutsky et al, 2002;Harper et al, 2004Harper et al, , 2006Villa et al, 2005;Mao et al, 2006). The vaccines could prevent around 70% of all cervical cancer (Munoz et al, 2003). One vaccine has recently been licensed for use in the US and in Europe. However, there remain important questions about how a HPV vaccine should be used at a population level (Lowndes and Gill, 2005). These include: the age chosen for vaccination, whether the vaccine is given to female subjects only or to female and male subjects and whether a catch-up vaccination campaign should accompany the introduction of routine vaccination. As mathematical models provide a framework for exploring these questions (Garnett, 2002), we have examined these questions with a model of single-type HPV using the observed epidemiology of HPV in Finland (Barnabas et al, 2006). MATERIALS AND METHODSIn earlier work, we used sexual behaviour data along with HPV seroprevalenc...

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Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial

Cited by 1,394 publications

References 25 publications

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

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

Evaluation of systemic and mucosal anti-HPV16 and anti-HPV18 antibody responses from vaccinated women

Strategies for the introduction of human papillomavirus vaccination: modelling the optimum age- and sex-specific pattern of vaccination in Finland

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