George F. Sawaya, M.D., and Karen Smith-McCune, M.D., Ph.D.
N Engl J Med 2007; 356:1991-1993May 10, 2007
The availability of a “cancer vaccine” has elicited enormous enthusiasm from the medical community and the public, culminating in advocacy for mandatory vaccination against human papillomavirus (HPV) and a recommendation from the Centers for Disease Control and Prevention (CDC) that 30 million girls and women between the ages of 11 and 26 years in the United States be vaccinated.1 Previous reports2,3 showed a remarkable 100% efficacy of a quadrivalent vaccine targeting HPV types 6, 11, 16, and 18 on outcomes related to vaccine HPV types in women with no evidence of previous exposure to those types. Since HPV types 16 and 18 are implicated in 70% of cervical cancers,4 these types are ideal targets for a new vaccine.
In this issue of the Journal, reports on two large, ongoing, randomized, placebo-controlled trials show the effect of this vaccine on important clinical outcomes, including rates of adenocarcinoma in situ and cervical intraepithelial neoplasia after an average of 3 years of follow-up.5,6 Investigators in these trials have hit their mark soundly: the vaccine showed significant efficacy against anogenital and cervical lesions related to vaccine type in women with no evidence of previous exposure to vaccine-specific types; the vaccine also appeared to be safe. In addition, the studies report outcomes in all subjects regardless of HPV status at baseline and regardless of whether outcomes were related to HPV types targeted by the vaccine. Policymakers now have more evidence to assess the benefits and risks of widespread vaccination.
Given the rarity of incident cervical cancer, preinvasive cervical lesions with high invasive potential are used in contemporary studies as surrogate outcomes for cervical cancer. Adenocarcinoma in situ is a rare lesion widely considered to be a precursor of cancer. Cervical intraepithelial neoplasia is graded from 1 to 3 on the basis of histopathological criteria. Grade 1 cervical intraepithelial neoplasia indicates the presence of active HPV infection and is not considered to be precancerous; current guidelines discourage treatment of this condition.7,8 Grade 2 cervical intraepithelial neoplasia is treated in most women but is not an irrefutable cancer surrogate, since up to 40% of such lesions regress spontaneously9; current guidelines suggest that some young women with such lesions do not need to be treated.7,8 Grade 3 cervical intraepithelial neoplasia, on the other hand, has the lowest likelihood of regression and the strongest potential to be invasive. The Food and Drug Administration (FDA) considers grade 2 and 3 cervical intraepithelial neoplasia and adenocarcinoma in situ to be acceptable surrogate outcomes for cervical cancer; other observers consider grade 3 cervical intraepithelial neoplasia and adenocarcinoma in situ to be more appropriate surrogates.9
[Note from SaneVax: This article was originally published in 2007, yet the CDC still insists HPV vaccines combat cervical cancer. There was no proof in 2007; there is no proof now. This is a case of a ‘rose by any other name’ not smelling so sweet. HPV vaccines are just that – vaccines that combat specific genotypes of human papillomavirus. They do not yet qualify to be called cancer vaccines – they maynever qualify to be called cancer vaccines. Why do health officials and medical professionals continue to claim thay are?]