Not long ago (in medical years), we were still trying to discover the cause of cervical cancer. Today, not only do we know that cause to be persistent human papillomavirus (HPV) infection, but we have two vaccines at our disposal to prevent the primary oncogenic strains of the virus.
We’ve come a long way.
The availability of two vaccines raises questions, however. What kind of data do we have on the bivalent (Cervarix, GlaxoSmithKline) and quadrivalent (Gardasil, Merck) vaccines so far? Is one of them clearly superior to the other? If not, what population is each vaccine best suited for—and how do we counsel patients about their options?
To address these and other questions, OBG Management Contributing Editor Neal M. Lonky, MD, MPH, assembled a panel of physicians who have expertise in cervical disease detection and prevention and asked them to sift the data that have accumulated thus far. In the discussion that follows, they touch on long-term efficacy, the likely impact of the vaccines on cervical cancer screening, and other aspects of disease prevention in the era of HPV vaccination.
Juan C. Felix, MD
Professor of Clinical Pathology and Obstetrics and Gynecology; Director of Cytopathology fellowship; and Chief of Gynecologic Pathology at the Keck School of Medicine, University of Southern California; and Chief of Cytopathology at Los Angeles County and University of Southern California Medical Center in Los Angeles.
Dr. Felix reports that he is a speaker for Merck and GlaxoSmithKline.
Diane M. Harper, MD, MS, MPH
Director of the Gynecologic Cancer Prevention Research Group and Professor of Obstetrics and Gynecology, Community and family Medicine, and Informatics and Personalized Medicine at the University of Missouri–Kansas City School of Medicine.
Dr. Harper reports that she has served as a speaker and advisor for Merck and GlaxoSmithKline, and that the institutions at which she conducted HPV vaccination trials have received funding from Merck and GlaxoSmithKline.
Warner K. Huh, MD
Associate Professor in the Department of Obstetrics and Gynecology, and Associate Scientist at the Comprehensive Cancer Center at the University of Alabama– Birmingham.
Dr. Huh reports that he receives grant or research support from and is a speaker and consultant to Merck and GlaxoSmithKline.
Karen K. Smith-McCune, MD, PhD
John Kerner Endowed Chair of Gynecologic Oncology, Director of the Dysplasia Clinic, and Professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California–San francisco.
Dr. Smith-McCune reports she has performed unpaid consulting for OncoHealth Inc. and is planning to join its Scientific Advisory Board.
1. How were the vaccines developed?
Neal M. Lonky, MD, MPH: What should clinicians know about the development, function, and mechanism of action of the two HPV vaccines?
Warner K. Huh, MD: The bivalent and quadrivalent vaccines are both excellent products, and their respective Phase-3 trials demonstrate that they provide impressive protection against HPV, particularly among women who test negative (by polymerase chain reaction) for the specific HPV types contained within the vaccines.1-3
Cervarix protects against HPV types 16 and 18, whereas Gardasil is effective against HPV types 6, 11, 16, and 18.
Dr. Lonky: Do the vaccines function similarly?
Diane M. Harper, MD, MS, MPH: Yes. Both stimulate an immediate antibody response in the woman who is not infected with the relevant virus and are effective in preventing cervical intraepithelial neoplasia grade 2 and higher (CIN 2+), as well as persistent infection, caused by vaccine-related and cross-protected HPV types. The quality of the antibody response is best for HPV 16 for both vaccines. The quality of the antibody response for HPV 6, 11, and 18 for Gardasil is much poorer than its response for HPV 16. Cervarix induces an equally high and sustained antibody response for HPV 18 as for HPV 16.
Juan C. Felix, MD: Both vaccines are based on the same virus-like particles (VLP). The functionality of the vaccines is, therefore, mainly dependent on the dosage of VLP and the adjuvant used. Gardasil uses a proprietary aluminum sulfate adjuvant, whereas Cervarix uses aluminum hydroxide and monophosphoryl lipid A.
Karen K. Smith-McCune, MD, PhD: Both adjuvants have an extensive track record of safety and efficacy in other vaccines. Because they have different structures, however, they may have varying effects on many components of the immune response elicited by the L1 antigens.
Dr. Harper: Both adjuvants contain aluminum, which has so far proved to be safe despite the newly established association between high aluminum intake and Alzheimer’s disease.
Dr. Lonky: Were there any notable challenges in developing the vaccines?
Dr. Harper: It was difficult to formulate the appropriate dosages of VLP in Gardasil. Higher dosages of HPV 11 and 16 were needed to prevent cross-inhibition by HPV 6 and 18. As a result, the antigenic protein component of Gardasil that is necessary to effect an immunologic antibody response is high, at 120 μg. In Cervarix, the antigenic VLP load is 20 μg each for HPV 16 and 18.