Quadrivalent Vaccine against Human Papillomavirus to Prevent Anogenital Diseases

Garland, Suzanne M.; Hernández-Ávila, Mauricio; Wheeler, Cosette M.; Pérez, Gonzalo; Harper, Diane M.; Leodolter, Sepp; Tang, Grace; Ferris, Daron G.; Steben, Marc; Bryan, Janine T.; Taddeo, Frank J.; Railkar, Radha; Esser, Mark T.; Sings, Heather L.; Nelson, Micki; Boslego, John W.; Sattler, Carlos A.; Barr, Eliav; Koutsky, Laura A.

doi:10.1056/nejmoa061760

Cited by 1,674 publications

(1,209 citation statements)

References 28 publications

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“…12,13 Colposcopists were trained to locate and biopsy all discrete abnormal areas on the cervix. Women with CIN2, CIN3, or AIS (abbreviated as CIN2-3/AIS) or persistent CIN1 were referred for definitive therapy.…”

Section: Clinical Follow-up and Endpointsmentioning

confidence: 99%

“…Nonetheless, some women in the population for whom the vaccines are approved will have been exposed to vaccine HPV types through sexual activity before vaccination. 5,6 Though there have been extensive data published on the efficacy of both vaccines, [7][8][9][10][11][12][13][14][15] less is known about the impact of HPV vaccination in women with ongoing HPV16 or 18 infections. Adequate knowledge of the HPV vaccines' impact on such women has important clinical implications, particularly with respect to HPV16 and HPV18, as several studies have shown that women who are persistently or chronically infected with cervical HPV16 or HPV18 are at considerably higher risk for developing high grade cervical lesions and cancer, compared with women positive for non-HPV16/18 oncogenic types, oncogenic HPV-negative women, or those transiently infected with HPV16/18.…”

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confidence: 99%

“…21 In contrast, the HPV6/11/16/18 vaccine does not impact progression of HPV16 or HPV18 infections to disease (i.e., there was no impact in women who were seronegative and DNA positive to HPV16 or HPV18). 12,13 We have previously reported interim data ($3 years of follow-up) on the impact of the HPV6/11/18/18 vaccine in women who were both seropositive and DNA positive to HPV16 or HPV18 at the time of the initial vaccination with the first dose (Fig. 1).…”

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confidence: 99%

“…1). 12,13 Here we provide updated end of study data for these women who were enrolled in two phase 3 trials of the HPV6/11/16/18 vaccine. The objective of this post-hoc analysis was to determine if vaccine-induced immunity affects the progression of HPV infections to cervical intraepithelial neoplasia.…”

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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%

mentioning

confidence: 99%

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confidence: 99%

mentioning

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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“…While recognising the limitations of the still moderate (5 -6 years) follow-up in a few tens of thousand young women, two vaccines to date have shown high efficacy, safety, immunogenicity, long-term duration of protection and a strong suggestions of induction of immune memory (Harper et al, 2006;Garland et al, 2007;Paavonen et al, 2007; The Future II Study Group, 2007).…”

Section: Phase III Hpv Vaccination Trialsmentioning

confidence: 99%

HPV and cervical cancer: screening or vaccination?

2008

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Following the demonstration of the superior validity of human papillomavirus (HPV) tests in screening for cervical cancer and the arrival of highly efficacious HPV 16 and 18 vaccines, cervical cancer prevention enters a time of sustainable introduction in developing countries. Multidisciplinary efforts and novel protocols are being developed, and challenging situations are being faced to make cervical cancer, still the number two cancer in women worldwide, an eradicable condition. The provocative title proposed by the editors of the British Journal of Cancer could have at first sight, a quick and intuitive answer: we will need both. We need human papillomavirus (HPV) vaccines to significantly reduce the health care burden currently required for cervical cancer prevention, and we need screening because of the limitations of current HPV vaccines both in their lack of therapeutic effect (thus not protecting women with an ongoing neoplastic processes) and in their limited number of HPV types (thus leaving to evolve some 25 -30% of cervical cancer cases related to HPV types other than 16 or 18). However, the answer only applies in scenarios in which screening is already developed and reasonably efficient. In populations without adequate screening, one could equally argue that HPV vaccines at affordable prices are the only realistic option. While these arrive, more efficient screening schemes, for example with low-cost HPV tests, requiring fewer visits or strategies involving rapid intervention like 'screen and treat' protocols, remain the only option for currently living adult women. Moreover, should polyvalent vaccines (including some five -eight HPV types) result in extending protection against more than 90% þ of the oncogenic HPV types, vaccination alone would be the answer for both scenarios. Thus, a complex answer to an apparent straightforward question. PHASE III HPV VACCINATION TRIALSWith the publication of the key short-term results of the two major Phase III trials of HPV vaccines, the perspective of tackling cervical cancer prevention with vaccination has been unambiguously open. While recognising the limitations of the still moderate (5 -6 years) follow-up in a few tens of thousand young women, two vaccines to date have shown high efficacy, safety, immunogenicity, long-term duration of protection and a strong suggestions of induction of immune memory (Harper et al, 2006;Garland et al, 2007;Paavonen et al, 2007; The Future II Study Group, 2007).A number of clinically relevant issues remain to be fully described, including the magnitude and the HPV spectrum included in the cross protection effect, and the long-term effects of each of the HPV vaccines on cancer protection and safety. However, to solve these questions, it is unavoidable to continue the studies for additional follow-up time and the organisation of large Phase IV studies, some of which are already in place.The currently available vaccines offer full protection to HPV 16-and 18-naïve women for these two HPV types that cause an estimated 70% of ce...

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Postlicensure Safety Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine

Slade

Leidel²,

Vellozzi³

et al. 2009

JAMA

401

178

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N JUNE 8, 2006, THE FOOD and Drug Administration (FDA) licensed the quadrivalent human papillomavirus recombinant vaccine (qHPV) (Gardasil; Merck & Co, Inc, Whitehouse Station, New Jersey) for females aged 9 to 26 years to prevent infection with genital human papillomavirus (HPV) types 6, 11, 16, and 18. 1 Later that month, the Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination of females aged 11 to 12 years with 3 doses of qHPV and catch-up vaccination for females aged 13 to 26 years. Doses are administered intramuscularly on a schedule of 0, 2, and 6 months. 2 The viruses HPV-16 and HPV-18 can cause cervical cancer, other anogenital cancers, and precancerous or dysplastic lesions and are responsible for about 70% of cervical cancers worldwide. 3 The viruses HPV-6 and HPV-11 are the most common causes of genital warts. Prior to licensure, clinical trials were conducted in more than 21 000 women. Vaccination with qHPV was 90% to 100% effective in preventing precancerous cervical, vaginal, and vulvar lesions and genital warts caused by infection with the relevant HPV types (6, 11, 16, or 18) in women aged 15 to 26 years who were uninfected prior to vaccination. 4,5 Additional immunogenicity and safety studies in 9-to 15-year-See also pp 781 and 795.

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Quadrivalent Vaccine against Human Papillomavirus to Prevent Anogenital Diseases

Abstract: The quadrivalent vaccine significantly reduced the incidence of HPV-associated anogenital diseases in young women. (ClinicalTrials.gov number, NCT00092521 [ClinicalTrials.gov].).

Cited by 1,674 publications

References 28 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

HPV and cervical cancer: screening or vaccination?

Postlicensure Safety Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine

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