JANUARY 2010 • WWW.SKINANDALLERGYNEWS.COM INFECTIOUS DISEASES 21 HPV Vaccine Exhibits Efficacy Beyond 6 Years

riod of time, compared of the follow-up study. lowing clearance of a natural infection in Major Finding: At 6.4 years, vaccine efficacy with the same antigens At 6.4 years, vaccine efficacy against in- a previous study (Lancet 2007;369:2161-70). against incident HPV infection was 95% in the ac- cording-to-protocol cohort. adjuvanted with alu- cident HPV-16 or HPV-18 infection in the Safety profiles of the HPV-16/18 vac- minum salts alone, ac- ATP analysis was 95.3%, and long-term cine and placebo were similar, with ap- Source of Data: A three-country, 27-site study of cording to the GSK efficacy against persistent infection was proximately one-third of each group re- 1,113 women aged 15-26 years. Vaccine HPV-007 Study 100% at both 6 and 12 months. In the to- porting any adverse event, 10% or fewer Disclosures: The study, led by Dr. Romanowski, was Group, led by Dr. Bar- tal vaccinated cohort analysis, protection reporting a serious adverse event, and VITALS funded by GlaxoSmithKline (GSK) Biologicals, bara Romanowski against cervical intraepithelial neoplasia less than 10% reporting new-onset chron- manufacturer of Cervarix. Dr. Clifford declared that he had no conflicts of interest. (Lancet 2009 Dec. 3 grade 1 or higher associated with either ic diseases. None of the serious adverse [doi:10.1016/S0140- vaccine HPV type was 100%. For the events was judged to be related to the vac- 6736(09)61567-1]). nonvaccine types HPV-31 and -45, vac- cine, and there were no deaths. BY MIRIAM E. TUCKER Of 1,113 women included in the initial cine efficacy against incident infection In an accompanying editorial, Dr. three-country, 27-site study, a total of was 59.8% and 77.7%, while overall effi- Gary M. Clifford wrote that the data he human papillomavirus 16/18 700 completed the follow-up study. The cacy against any cervical intraepithelial showing no evidence of further decline vaccine showed efficacy, sustained total vaccinated cohort included 560 neoplasia grade 2 or higher independent from 3 to 6 years are “perhaps the most Timmunogenicity, and continued women in the vaccine group and 553 in of HPV type was 71.9%, said Dr. Ro- interesting” because they suggest that safety for up to 6.4 years in a combination the placebo group, while the according- manowski of the University of Alberta, mean antibody concentrations should of initial and follow-up placebo-con- to-protocol (ATP) efficacy cohort in- Edmonton, and her associates. remain well above those associated with trolled studies involving more than 1,000 cluded 465 in the vaccine group and 454 Almost all vaccine recipients (99%) re- natural infection long into the future. women aged 15-26 years. in the placebo group. At baseline, all had mained seropositive for anti–HPV-16 and The target age of vaccination is a bal- The human papillomavirus (HPV) vac- normal cervical cytology and were neg- anti–HPV-18 total IgG antibodies. After a ance between “being early enough to cine, Cervarix, is now licensed in the ative for both HPV-16 and -18. peak response at 7 months, geometric catch girls before sexual debut, but late United States, Europe, and elsewhere The mean follow-up period from the mean titers for both antibodies reached a enough to provide an as yet unknown du- around the world. It contains the HPV start of the initial study was 5.9 years, plateau between 18 and 24 months post ration of immunity that protects during as types 16 and 18 adjuvanted with ASO4, with a maximum duration of 6.4 years. vaccination, and remained stable there- many subsequent years of sexual activity comprising aluminum salt and an im- The study population was racially di- after. During months 63-76, antibody con- as possible,” wrote Dr. Clifford of the In- munostimulatory molecule that has verse, with a mean age of 20 years centrations against HPV-16 and HPV-18 ternational Agency for Research on Can- been shown to produce higher antibody (range 15-26 years) at entry to the ini- were at least 13-fold and 12-fold higher cer, Lyon, France (Lancet 2009 Dec. 3 titers that are sustained over a longer pe- tial study and 23 years at the beginning than were concentrations recorded fol- [doi:10.1016/S0140-6736(09)61789-X]). ■ EXPERT OPINION Gardasil and Cervarix Are Not Interchangeable ith the licensure of Glaxo- Although both vaccines are manufac- prevention of vulvar and vaginal in- other vaccine that could have prevent- WSmithKline’s human papillo- tured with similar technology using traepithelial neoplasias. ed it? Conversely, a male or female pa- mavirus vaccine Cervarix in October, we viruslike particles, Cervarix contains a Although not specifically mentioned tient given Cervarix later develops gen- will soon have two vaccines that prevent novel adjuvant, ASO4, that is believed to in Gardasil’s label, there is evidence that ital warts, or a female develops cervical cervical cancer in women. But they’re be responsible for its ability to generate HPV strains 6 and 11, while not associat- atypia associated with HPV-6 or -11. not interchangeable, and this could lead a greater antibody response to HPV-16 ed with cervical cancer, are responsible for Might these patients similarly feel that to problems. and -18, compared with Gardasil. 8%-10% of cases of CIN 1 (mild atypia). they were denied the chance to have Cervarix is expected to join Merck’s According to a head-to-head compari- These lesions typically resolve, and prevented those outcomes? Gardasil on the U.S. market in February. son conducted by GSK, geometric mean guidelines from the American College of Who decides which vaccine is used? In For the first time ever in vaccine histo- titers of serum neutralizing antibodies Obstetricians and Gynecologists do not managed care settings, the decision is of- ry, we will have a situation in which two ranged from 2.3- to 4.8-fold higher for recommend intervention beyond moni- ten made based on cost when vaccines competing vaccines have very different HPV-16 and 6.8- to 9.1-fold higher for toring after CIN 1 is recognized, with the are equivalent, but what about the HPV components and adjuvants HPV-18 after vaccination with intent to intervene only if the lesion vaccines where the products are not that could complicate the de- Cervarix, compared with Gar- progresses to CIN 2. However, in prac- equivalent? The same goes for the man- cision for practicing physi- dasil, across all ages (Hum. tice women often request that the lesions ufacturer-run vaccine buying groups that cians—as well as insurers Vaccin. 2009;5:705-19). be removed, and their physicians often offer discounts to increasing numbers of and buying groups—regard- Although not proven, we do so, thereby incurring excess time, participating physicians who sign con- ing which one to use. I think might infer from those data money, and some risk. Gardasil could po- tracts that impose strict limits on the we need to view human pa- that Cervarix might provide tentially reduce a significant number of amount of vaccine that can be purchased pillomavirus (HPV) vaccines longer-lasting protection those procedures. outside of the specified brands. as exceptions to the usual against HPV serotypes 16 and Meanwhile, data included in the label This has never happened before with rules of “equivalent and in- 18 and, therefore, a longer for Cervarix show that it provides cross- vaccines: The two competing brands are terchangeable” and consider duration of time before a protection against the carcinogenic HPV not interchangeable. I believe that health stocking both. BY MICHAEL E. booster is needed. strain 31, which is responsible for a small plans and vaccine buying groups need to Patients should be in- PICHICHERO, M.D. Both companies are cur- yet significant proportion of cervical recognize these factors and grant an ex- formed of the features of rently studying duration of cancer cases. ception to HPV vaccines. each vaccine, and the decision to use protection with their respective vaccines, In one landmark study, serotype 31 I think we all should stock both in our one or the other should be made with and a just-published study showed sus- accounted for 3.4% of squamous cell practices, and explain the differences to informed consent. tained efficacy and immunogenicity of cancers in 1,739 patients (N. Engl. J. parents. I plan to distribute pamphlets to Most clinicians know that both vac- Cervarix up to 6.4 years (Lancet 2009 Med. 2003;348:518-27). Gardasil’s label, patients and families and let them cines protect against HPV serotypes 16 Dec. 3 [doi:10.1016/S0140-6736(09)61567- in contrast, states that it has not demon- choose, with signatures confirming in- and 18, the dominant causes of cervical 1]). For both vaccines, we should have an- strated cross-protection against diseases formed consent. cancer. But Gardasil also protects against swers before current vaccinees begin to caused by HPV strains not included in I serve as a consultant to both GSK and HPV-6 and -11, primarily associated with lose protection. the vaccine. Merck & Co. and have shared this infor- genital warts, and has recently received Both vaccines are indicated for the These differences may seem slight, mation with both companies. approval for use in males, which Cer- prevention of cervical cancer and cer- but consider a case in which a young This is going to be complicated. ■ varix has not. But other differences be- vical intraepithelial neoplasia (CIN) woman who received Gardasil later de- tween the two vaccines are less well rec- grades 1-3 due to HPV-16 and -18, and velops a case of cervical cancer due to DR. PICHICHERO, a specialist in pediatric ognized, and I believe will turn out to be cervical adenocarcinoma in situ. How- HPV-31. Might she be quite upset that infectious diseases, is director of the important. ever, Gardasil also has indications for the she wasn’t informed that there was an- Rochester (N.Y.) General Research Institute.