Editorial
Human Papillomavirus Vaccine — Opportunity and Challenge
N Engl J Med 2007; 356:1990-1991May 10, 2007
- Article
In this issue of the Journal, we publish three Original Articles,1-3 two Perspective articles,4,5 two editorials,6,7 a letter to the editor,8 and an audio interview9 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 article4 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 Journal 1,2 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.
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 cancer3)?
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
References
1
The FUTURE II Study Group
Full Text | Web of Science | Medline2
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
Full Text | Web of Science | Medline3
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
Full Text | Web of Science | Medline4
Charo RA . Politics, parents, and prophylaxis -- mandating HPV vaccination in the United States. N Engl J Med 2007;356:1905-1908
Full Text | Web of Science | Medline5
Agosti JM ,Goldie SJ . Introducing HPV vaccine in developing countries -- key challenges and issues. N Engl J Med 2007;356:1908-1910
Full Text | Web of Science | Medline6
Sawaya GF ,Smith-McCune K . HPV vaccination -- more answers, more questions. N Engl J Med 2007;356:1991-1993
Full Text | Web of Science | Medline7
Syrjanen S . Human papillovmaviruses in head and neck carcinomas. N Engl J Med 2007;356:1993-1995
Full Text | Web of Science | Medline8
Stewart S . Mandating HPV vaccination -- private rights, public good. N Engl J Med 2007;356:1998-1999
Full Text | Web of Science | Medline9
Interview with R. Alta Charo. (Available at www.nejm.org.)
- Citing Articles (15)
Citing Articles
1
Timon P.H. Buys, Scott B. Cantor, Martial Guillaud, Karen Adler-Storthz, Dennis D. Cox, Clement Okolo, Oyedunni Arulogon, Oladimeji Oladepo, Karen Basen-Engquist, Eileen Shinn, José-Miguel Yamal, J. Robert Beck, Michael E. Scheurer, Dirk van Niekerk, Anais Malpica, Jasenka Matisic, Gregg Staerkel, Edward Neely Atkinson, Luc Bidaut, Pierre Lane, J. Lou Benedet, Dianne Miller, Tom Ehlen, Roderick Price, Isaac F. Adelwole, Calum MacAulay, Michele Follen. (2011) Optical Technologies and Molecular Imaging for Cervical Neoplasia: A Program Project Update. Gender Medicine
CrossRef2
M. Amparo Torrecilla Rojas, Miguel Pedregal González, Fermín García Rodríguez, Josefa Ruiz Fernández. (2011) Efectos adversos de la vacunación contra el virus del papiloma humano. Atención Primaria 43:1, 5-9
CrossRef3
Ingrid T. Katz, Norma C. Ware, Glenda Gray, Jessica E. Haberer, Claude A. Mellins, David R. Bangsberg. (2010) Scaling up human papillomavirus vaccination: a conceptual framework of vaccine adherence. Sexual Health 7:3, 279
CrossRef4
EJ Crosbie, L Brabin. (2010) Cervical cancer: problem solved? Vaccinating girls against human papillomavirus. BJOG: An International Journal of Obstetrics & Gynaecology 117:2, 137-142
CrossRef5
Joslyn W. Fisher, Susan I. Brundage. (2009) The Challenge of Eliminating Cervical Cancer in the United States: A Story of Politics, Prudishness, and Prevention. Women & Health 49:2-3, 246-261
CrossRef6
Bernard Duval, Vladimir Gilca, Nicole Boulianne, Karen Pielak, Beth Halperin, Mary Anne Simpson, Chantal Sauvageau, Manale Ouakki, Eve Dube, France Lavoie. (2009) Cervical cancer prevention by vaccination: nurses’ knowledge, attitudes and intentions. Journal of Advanced Nursing 65:3, 499-508
CrossRef7
Miguel Ángel Martínez-González, Silvia Carlos, Jokin de Irala. (2008) Vacuna contra el virus del papiloma humano: razones para el optimismo y razones para la prudencia. Medicina Clínica 131:7, 256-263
CrossRef8
Haug, Charlotte J., . (2008) Human Papillomavirus Vaccination — Reasons for Caution. New England Journal of Medicine 359:8, 861-862
Full Text9
Warren R. Heymann. (2008) The human papillomavirus vaccine. Journal of the American Academy of Dermatology 58:6, 1047-1048
CrossRef10
B.H. Thiers. (2008) Quadrivalent Vaccine against Human Papillomavirus to Prevent Anogenital Diseases. Yearbook of Dermatology and Dermatologic Surgery 2008, 148-149
CrossRef11
B.H. Thiers. (2008) Quadrivalent Vaccine against Human Papillomavirus to Prevent High-Grade Cervical Lesions. Yearbook of Dermatology and Dermatologic Surgery 2008, 147-148
CrossRef12
Syrjänen, Stina, . (2007) Human Papillomaviruses in Head and Neck Carcinomas. New England Journal of Medicine 356:19, 1993-1995
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Charo, R. Alta, . (2007) Politics, Parents, and Prophylaxis — Mandating HPV Vaccination in the United States. New England Journal of Medicine 356:19, 1905-1908
Full Text14
Agosti, Jan M., Goldie, Sue J., . (2007) Introducing HPV Vaccine in Developing Countries — Key Challenges and Issues. New England Journal of Medicine 356:19, 1908-1910
Full Text15
Sawaya, George F., Smith-McCune, Karen, . (2007) HPV Vaccination — More Answers, More Questions. New England Journal of Medicine 356:19, 1991-1993
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