Re: [asa] NEJM Editorial on HPV Vaccine

From: Jack <drsyme@cablespeed.com>
Date: Sat May 12 2007 - 12:58:50 EDT

There are few good arguments against mandating the vaccine, since hepatitis B is already a mandated vaccine, and it is only transmitted through sexual or other intimate contact (i.e. sharing needles), so that camel is already inside the tent. As far as I am concerned that is a slam dunk on this issue, it is going to be mandated eventually, and we will all have to live with it. And frankly, there is probably nothing wrong with it. It does prevent cancer, and there is no evidence for significant harm, and only those who abstain from sex throughout their lives are going to have close to zero risk, and that number is very small.

However there are not some concerns about this. First was the lobbying effort for the virus. It is very expensive, three injections at about $150 dollars each as I recall, and is only offered by one manufacturer. This manufacturer heavily lobbied state legislatures to make this mandated. But after the controversy when the Texas governor overoad the legislation to mandate it, the manufacturer has decided to stop lobbying efforts. Second, it appears that this vaccine will only work for 15 years, so it raises a question of how young should we start the vaccination. The vaccine will work anytime before exposure, so even if a child becomes sexually active as a teen, there is no reason to believe that if she is not exposed that getting the vaccine later will not be effective.

  ----- Original Message -----
  From: David Opderbeck
  To: Rich Blinne
  Cc: AmericanScientificAffiliation
  Sent: Friday, May 11, 2007 10:02 PM
  Subject: Re: [asa] NEJM Editorial on HPV Vaccine

  Stewart's letter concerning the jurisprudential issues is lame. The Supreme Court has held that states may mandate vaccines for schoolchildren -- well, duh. That says nothing about whether any particular vaccine ought to be required as a general policy matter. And note the conclusions in Sawaya and McLune's editorial, which isn't quite so sanguine, given the variety of HPV types. Personally, I don't think it's wise to consider this a simple question of whether folks are willing to accept established science or not.

  Sawaya and McLune:

    Another factor explaining the modest efficacy of the vaccine is the role of oncogenic HPV types not included in the vaccine. At least 15 oncogenic HPV types have been identified, 4 so targeting only 2 types may not have had a great effect on overall rates of preinvasive lesions. Findings from the FUTURE II trial showed that the contribution of nonvaccine HPV types to overall grade 2 or 3 cervical intraepithelial neoplasia or adenocarcinoma in situ was sizable. In contrast to a plateau in the incidence of disease related to HPV types 16 and 18 among vaccinated women, the overall disease incidence regardless of HPV type continued to increase, raising the possibility that other oncogenic HPV types eventually filled the biologic niche left behind after the elimination of HPV types 16 and 18. An interim analysis of vaccine trial data submitted to the FDA 11 showed a disproportionate, but not statistically significant, number of cases of grade 2 or 3 cervical intraepithelial neoplasia related to nonvaccine HPV types among vaccinated women. Updated analyses of data from these ongoing trials will be important to determine the effect of vaccination on rates of preinvasive lesions caused by nonvaccine HPV types.
    What can be inferred from these data about the potential effect of vaccination among girls 11 and 12 years of age? The FUTURE trials did not enroll subjects in this age group. Within both trials, subgroups of subjects with no evidence of previous exposure to relevant vaccine HPV types were evaluated separately for vaccine efficacy. In these subgroups, efficacy of nearly 100% against all grades of cervical intraepithelial neoplasia and adenocarcinoma in situ related to vaccine HPV types was reported in both trials. However, it would be important to know the overall rates of grade 2 or 3 cervical intraepithelial neoplasia or adenocarcinoma in situ regardless of HPV types. Without these data, it is difficult to infer both the effectiveness of vaccination and the role of nonvaccine HPV types in overall rates of preinvasive lesions.

   
  On 5/11/07, Rich Blinne <rich.blinne@gmail.com> wrote:
    Human Papillomavirus Vaccine Opportunity and Challenge
     
    Lindsey R. Baden, M.D., Gregory D. Curfman, M.D., Stephen Morrissey, Ph.D., and Jeffrey M. Drazen, M.D.
    In this issue of the Journal, we publish three Original Articles,1 , 2, 3 two Perspective articles,4 , 5 two editorials,6, 7 a letter to the editor,8 and an audio interview 9 on the subject of human papillomavirus (HPV). We bring together this unique body of information in response to the enormity of the health problems that stem from HPV and the broad interest that has been kindled by the possibility of preventing HPV-related cervical cancer and other anogenital conditions through vaccination.

    The HPV vaccine is the first vaccine explicitly designed to prevent cancer induced by a virus. (The hepatitis B vaccine was not primarily designed to prevent cancer.) As noted in the Perspective article by Agosti and Goldie, 5 the consequences of HPV infection are a global health concern that disproportionately affects those in developing countries. The potential ability to reduce the burden of HPV-related disease by vaccination against certain disease-inducing strains of the virus has created a volatile intersection between the community's interest in limiting the transmission of infectious diseases and promoting health on the one hand and social mores on the other, as discussed by Charo in her Perspective article 4 and related audio interview (podcast available at www.nejm.org). 9 However, this volatility should not keep us from recognizing the enormous potential for medical progress and from addressing the numerous unanswered questions that remain.

    The finding that infection with HPV is a critical factor in the majority of cases of cervical cancer allowed the development of strategies to prevent this form of oncogenesis. It is important to note that several other cancers are also associated with HPV infection, including head and neck cancers, as demonstrated by D'Souza and colleagues. 3 Although there are many HPV serotypes, two of them 16 and 18 account for the lion's share of the oncogenesis. The data that are presented in reports on the vaccine efficacy trials in this issue of the Journal1, 2 confirm the success in reducing the incidence of precancerous cervical lesions with vaccine directed against the HPV-16 and HPV-18 serotypes.

    Although this is a remarkable achievement, the efficacy of the vaccine is limited by at least these two factors. First, not all cervical cancer is caused by HPV-16 or HPV-18, and second, it appears necessary to vaccinate young women before they are infected with these two serotypes. Also, whether this approach will extend the paradigm of vaccination to the prevention of death and disability from cervical cancer is an unanswered question. [emphasis mine]

    It is difficult to show that an intervention prevents cancer, given the relatively long induction phase between exposure to an inducing agent and development of disease. Thus, key surrogate markers, in this case cervical intraepithelial neoplasia grades 2 and 3, were used so that data could be gathered in a timely fashion. However, correlation with the ultimate outcome cancer prevention will require the long-term observation of a large number of treated women. We must also carefully monitor for unintended adverse consequences of vaccination. For example, when selective immunologic pressure is applied with vaccination, the potential exists for nonvaccine-related strains to emerge as important oncogenic serotypes. These critical points are clarified in the editorial by Sawaya and Smith-McCune. 6

    Many other questions are raised by these remarkable data. Should young men be vaccinated? What is the durability of immune protection? Could fewer than three vaccinations provide adequate protection? Will future HPV vaccines extend protection to cover additional pathogenic serotypes? Will the economics allow this therapy to reach all who may benefit, such as those in the developing world? Might HPV vaccination be beneficial in preventing other, noncervical HPV-induced cancers (such as HPV-related oropharyngeal cancer 3)?

    There is no doubt that the findings reported in this issue of the Journal open a new field at the interface of basic science, clinical medicine, public health, and public policy. It is important to keep in mind that these new treatments raise many scientific, medical, economic, and sociological questions. We have begun an exciting journey; we need to continue in the right direction.

    References

      1.. The FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007;356:1915-1927. [Free Full Text]
      2.. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against the human papillovmavirus to prevent anogenital diseases. N Engl J Med 2007;356:1928-1943. [Free Full Text]
      3.. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 2007;356:1944-1956. [Free Full Text]
      4.. Charo RA. Politics, parents, and prophylaxis -- mandating HPV vaccination in the United States. N Engl J Med 2007;356:1905-1908. [Free Full Text]
      5.. Agosti JM, Goldie SJ. Introducing HPV vaccine in developing countries -- key challenges and issues. N Engl J Med 2007;356:1908-1910. [Free Full Text]
      6.. Sawaya GF, Smith-McCune K. HPV vaccination -- more answers, more questions. N Engl J Med 2007;356:1991-1993. [Free Full Text]
      7.. Syrjanen S. Human papillovmaviruses in head and neck carcinomas. N Engl J Med 2007;356:1993-1995. [Free Full Text]
      8.. Stewart S. Mandating HPV vaccination -- private rights, public good. N Engl J Med 2007;356:1998-1999. [Free Full Text]
      9.. Interview with R. Alta Charo. (Available at http://content.nejm.org/cgi/content/full/356/19/1905/DC1 .)

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Received on Sat May 12 12:59:24 2007

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