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

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.

Cancers That U.S. Physicians Believe the HPV Vaccine Prevents: Findings from a Physician Survey, 2009

“…We found that the majority of physicians in all specialties, except OB-GYNs, reported that the HPV vaccine was effective in preventing cervical cancer alone (60%-68%). Despite increasing evidence demonstrating that the HPV vaccine confers protection against vaginal, vulvar, and anal cancers, [3][4][5][6] most physicians in this survey were unaware of this additional protection. OB-GYNs were the best informed, with identification of noncervical cancer protection at least twice as often as other specialties, which is consistent with prior research.…”

The humoral response to Gardasil over four years as defined by Total IgG and competitive Luminex immunoassay

“…[30][31][32][33] Correspondingly, a high level of vaccine efficacy, for the quadrivalent vaccine, has been demonstrated against infection and disease caused by HPV types 6, 11, 16 and 18. [1][2][3][4][5]34 Although an immune correlate of protection against HPV infection has not yet been established, understanding the limitations and benefits of various immunoassays will help inform and refine immunogenicity studies and shed light on the current tools, the ability of the current immunoassays, to distinguish an immune correlate of protection if breakthrough cases should be observed in the future.…”

“…[1][2][3][4][5][6][7] These vaccines are composed of viruslike particles (VLPs), which are made by expressing the L1 major capsid protein of specific HPV types in eukaryotic cells. These types are: HPV types 6, 11, 16 and 18 in the quadrivalent vaccine (Gardasil ® ), and HPV types 16 and 18 in the bivalent vaccine (Cervarix TM ).…”

Reduction in cervical intraepithelial neoplasia in young women inBritishColumbia after introduction of theHPVvaccine: An ecological analysis

“…Randomized trials have shown that both the quadrivalent and bivalent HPV vaccines are highly efficacious in preventing HPV infection, cervical dysplasia, anal dysplasia and in the case of the quadrivalent vaccine, genital warts. [1][2][3][4][5] As part of the introduction of HPV vaccine globally, jurisdictions that started public programs were encouraged to embark on comprehensive monitoring programs to determine HPV vaccine safety, uptake, acceptability and impact of the program on HPV prevalence, cervical dysplasia and ultimately, cervical cancer. 6 Data from Australia, the United States and the United Kingdom have shown that the vaccine is effective, with population level reductions in rates of genital warts, HPV and cervical cancer lesions.…”