[asa] NEJM Editorial on HPV Vaccine

From: Rich Blinne <rich.blinne@gmail.com>
Date: Fri May 11 2007 - 20:43:33 EDT

*Human Papillomavirus Vaccine Opportunity and
Challenge*<http://content.nejm.org/cgi/content/full/356/19/1990>
* 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<http://content.nejm.org/cgi/content/full/356/19/1990#R1>
,2 <http://content.nejm.org/cgi/content/full/356/19/1990#R2>,3<http://content.nejm.org/cgi/content/full/356/19/1990#R3>
two
Perspective articles,4<http://content.nejm.org/cgi/content/full/356/19/1990#R4>
,5 <http://content.nejm.org/cgi/content/full/356/19/1990#R5> two editorials,
6 <http://content.nejm.org/cgi/content/full/356/19/1990#R6>,7<http://content.nejm.org/cgi/content/full/356/19/1990#R7>a
letter to the
editor,8 <http://content.nejm.org/cgi/content/full/356/19/1990#R8> and an
audio interview9
<http://content.nejm.org/cgi/content/full/356/19/1990#R9>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<http://content.nejm.org/cgi/content/full/356/19/1990#R5>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
article4<http://content.nejm.org/cgi/content/full/356/19/1990#R4>and
related audio interview (podcast
available at www.nejm.org).9<http://content.nejm.org/cgi/content/full/356/19/1990#R9>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<http://content.nejm.org/cgi/content/full/356/19/1990#R3>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 *Journal*1<http://content.nejm.org/cgi/content/full/356/19/1990#R1>
,2 <http://content.nejm.org/cgi/content/full/356/19/1990#R2> 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<http://content.nejm.org/cgi/content/full/356/19/1990#R6>

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
cancer3 <http://content.nejm.org/cgi/content/full/356/19/1990#R3>)?

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]<http://content.nejm.org/cgi/ijlink?linkType=ABST&journalCode=nejm&resid=356/19/1915>
   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]<http://content.nejm.org/cgi/ijlink?linkType=ABST&journalCode=nejm&resid=356/19/1928>
   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]<http://content.nejm.org/cgi/ijlink?linkType=ABST&journalCode=nejm&resid=356/19/1944>
   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]<http://content.nejm.org/cgi/ijlink?linkType=FULL&journalCode=nejm&resid=356/19/1905>
   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]<http://content.nejm.org/cgi/ijlink?linkType=FULL&journalCode=nejm&resid=356/19/1908>
   6. Sawaya GF, Smith-McCune K. HPV vaccination -- more answers, more
   questions. N Engl J Med 2007;356:1991-1993. [Free Full
Text]<http://content.nejm.org/cgi/ijlink?linkType=FULL&journalCode=nejm&resid=356/19/1991>
   7. Syrjanen S. Human papillovmaviruses in head and neck carcinomas. N
   Engl J Med 2007;356:1993-1995. [Free Full
Text]<http://content.nejm.org/cgi/ijlink?linkType=FULL&journalCode=nejm&resid=356/19/1993>
   8. Stewart S. Mandating HPV vaccination -- private rights, public
   good. N Engl J Med 2007;356:1998-1999. [Free Full
Text]<http://content.nejm.org/cgi/ijlink?linkType=FULL&journalCode=nejm&resid=356/19/1998>
   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 Fri May 11 20:44:01 2007

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