HPV Vaccine and Anogenital Diseases
HPV Vaccine and Anogenital Diseases
Garland SM, Hernandez-Avila M, Wheeler CM, et al for the Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators.
N Engl J Med. 2007;356:1928-1943
These data come from an ongoing follow-up of a cohort of women studied as part of the US Food and Drug Administration approval process for the human papillomavirus (HPV) vaccine. The vaccine tested in this study was active against the 4 strains of HPV that cause the majority of lesions, from warts to respiratory papillomas to cervical and other genital lesions.
This was a double-blind, placebo-controlled, multicenter trial. More than 5000 women, ages 16-24 years, were enrolled at 62 sites internationally. The subjects were seen at enrollment, 7 months, and roughly every 6 months thereafter up to 48 months.
At each visit, the women underwent examinations and laboratory testing, including swabs for HPV DNA testing and Papanicolaou testing. All specimens were tested and graded centrally. The outcomes of interest were rates of a composite of any anogenital warts, vulvar or vaginal intraepithelial neoplasia (grades 1-3), or cancer associated with vaccine-strain HPV.
The authors also evaluated outcomes in relation to all cervical neoplasia, including vaccine strains and adenocarcinoma in situ. The analyses included looking at outcomes among women who were negative for vaccine strains of HPV as well as a 'general population' effect on women regardless of vaccine-strain HPV status at enrollment.
This report represents an average of 3 years follow-up per subject. The vaccine was very effective across multiple outcomes in the HPV-naive analyses, including 100% efficacy against any external anogenital or vaginal lesion (0 in vaccine group vs 60 in placebo group), and cervical lesions (0 in vaccine vs 65 in placebo group). It was also very efficacious in the 'intention-to-treat' population (regardless of HPV status at enrollment), but the rates were < 100%. For example, the vaccine was 73% efficacious against external anogenital or vaginal lesions and 55% efficacious against all cervical lesions in this population.
The authors conclude that the HPV vaccine was highly efficacious in reducing HPV-associated anogenital diseases in young women not previously exposed to vaccine-strain HPV.
The evidence regarding the efficacy of HPV vaccine is compelling, and just about every practitioner is likely struggling with questions of school mandates, how to answer parental questions, when to target girls in a particular practice for administration, and how to pay for the cost of the vaccine. However, at least the evidence of the vaccine efficacy is strong enough to reduce concerns in that area. This article was part of an HPV-themed issue of The New England Journal of Medicine, and an editorial by Baden and co-authors lays out other concerns such as duration of effect and whether males should receive the vaccine. The entire HPV-themed issue bears perusal, because it includes several other editorials, and a case-control study that demonstrated that HPV strain 16 DNA was present in 72% of oropharyngeal tumors. HPV and prevention of its disease manifestations are likely to remain a topic of discussion for years to come as we get longer-term follow-up on these large cohorts.
Abstract
Quadrivalent Vaccine against Human Papillomavirus to Prevent Anogenital Diseases
Garland SM, Hernandez-Avila M, Wheeler CM, et al for the Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators.
N Engl J Med. 2007;356:1928-1943
Summary
These data come from an ongoing follow-up of a cohort of women studied as part of the US Food and Drug Administration approval process for the human papillomavirus (HPV) vaccine. The vaccine tested in this study was active against the 4 strains of HPV that cause the majority of lesions, from warts to respiratory papillomas to cervical and other genital lesions.
This was a double-blind, placebo-controlled, multicenter trial. More than 5000 women, ages 16-24 years, were enrolled at 62 sites internationally. The subjects were seen at enrollment, 7 months, and roughly every 6 months thereafter up to 48 months.
At each visit, the women underwent examinations and laboratory testing, including swabs for HPV DNA testing and Papanicolaou testing. All specimens were tested and graded centrally. The outcomes of interest were rates of a composite of any anogenital warts, vulvar or vaginal intraepithelial neoplasia (grades 1-3), or cancer associated with vaccine-strain HPV.
The authors also evaluated outcomes in relation to all cervical neoplasia, including vaccine strains and adenocarcinoma in situ. The analyses included looking at outcomes among women who were negative for vaccine strains of HPV as well as a 'general population' effect on women regardless of vaccine-strain HPV status at enrollment.
This report represents an average of 3 years follow-up per subject. The vaccine was very effective across multiple outcomes in the HPV-naive analyses, including 100% efficacy against any external anogenital or vaginal lesion (0 in vaccine group vs 60 in placebo group), and cervical lesions (0 in vaccine vs 65 in placebo group). It was also very efficacious in the 'intention-to-treat' population (regardless of HPV status at enrollment), but the rates were < 100%. For example, the vaccine was 73% efficacious against external anogenital or vaginal lesions and 55% efficacious against all cervical lesions in this population.
The authors conclude that the HPV vaccine was highly efficacious in reducing HPV-associated anogenital diseases in young women not previously exposed to vaccine-strain HPV.
Viewpoint
The evidence regarding the efficacy of HPV vaccine is compelling, and just about every practitioner is likely struggling with questions of school mandates, how to answer parental questions, when to target girls in a particular practice for administration, and how to pay for the cost of the vaccine. However, at least the evidence of the vaccine efficacy is strong enough to reduce concerns in that area. This article was part of an HPV-themed issue of The New England Journal of Medicine, and an editorial by Baden and co-authors lays out other concerns such as duration of effect and whether males should receive the vaccine. The entire HPV-themed issue bears perusal, because it includes several other editorials, and a case-control study that demonstrated that HPV strain 16 DNA was present in 72% of oropharyngeal tumors. HPV and prevention of its disease manifestations are likely to remain a topic of discussion for years to come as we get longer-term follow-up on these large cohorts.
Abstract