Human Papillomavirus Vaccine

Kyung Hyo Kim

doi:10.5124/jkma.2008.51.2.144

J Korean Med Assoc > Volume 51(2); 2008 > Article

Kim: Human Papillomavirus Vaccine

Focused Issue of This Month

Newly Developed Vaccines and New Vaccination

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2008; 51(2): 144-157.

Published online: February 28, 2008

DOI: http://dx.doi.org/10.5124/jkma.2008.51.2.144

Human Papillomavirus Vaccine

Kyung Hyo Kim, MD

Department of Pediatrics, Ewha Womans University College of Medicine, Korea. kaykim@ewha.ac.kr

Abstract

Vaccination has had a major effect on protection of humans against disease. The human papillomavirus (HPV) vaccine is the most recent breakthrough in the vaccine development, which provides an exceptional opportunity for cancer prevention through vaccination. The prophylactic quadrivalent vaccine using L1 virus-like particles (VLPs) of HPV 6, 11, 16, and 18 is now available in Korea, and the bivalent vaccine containing VLPs of HPV16 and HPV18 is available in other countries. Results from the phase IIb and III trials show that these two HPV vaccines are safe and well-tolerated. They offer HPV-naive women a very high level of efficacy against persistent infection and cervical intra-epithelial lesions associated with the HPV types included in the vaccine. The quadrivalent vaccine has also been shown to protect against vulvar and vaginal lesions and genital warts caused by types 6 and 11. Recent studies on both vaccines indicate there is a high level of cross-protection against infections associated with other related oncogenic HPV types, which are responsible for a further 10% of cervical cancers globally. The Korean Society of Pediatrics has developed guidelines for the use of the prophylactic HPV vaccine for the prevention of cervical intraepithelial neoplasia and cervical cancer. They address the use of prophylactic HPV vaccines, including who should be vaccinated and at what age, as well as a summary of policy and implementation issues. With the introduction of the vaccines, general issues have to be raised such as duration of protection after vaccination, data on different immunization schedules, data on infants and young children, cross-protection, impact on cervical cancer screening, vaccination of males, potential replacement infection and vaccine compatibility. This review provides an up-to-date summary of recent studies and available information concerning HPV vaccination.

Papillomavirus vaccines; Guideline

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Figure 1

Serum anti-HPV 6 antibody titers after quadrivalent HPV vaccination by age at enrollment. Immunogenicity bridge study was done in female 9~15 year of age and efficacy program was done in female 16~23 year of age.

Abbreviation: GMT; geometric mean titer, CI; confidence interval

Source: Merck, unpublished data, Presented at ACIP meeting, February 2006

Figure 2

Papillomavirus phylogenetic tree.

Table 1

Efficacy data from Phase III randomised controlled trials of human papillomavirus vaccines

^*97.9% CI reported for Paavonen, et al (33), 95% CI reported for Future 2 Study (34) and Garland, et al (35)

^†: Defined as "This analysis assesses prophylactic efficacy I women uninfected sith the indivdual HPV type at study entry (day O). The total vaccinated cohort included women who had prevalent infection with oncogenic HPV often with several types, as well as low-grade cytological abnormalities at study entry and who received at least one vaccine dose."

^‡: Defined as "all women who were serongative and PCR-negative to HPV 16, HPV 18 or both at day 1, including those who received incomplete vaccination regimens. were exposed to HPV 16/18 before receiving three doses or who had major protocol violations."

^§: Defined as "subjects who were seronegative and HPV DNA negative on PCR analysis for HPV6, HPV11, HPV16 or HPV18 at day 1: were included even if protocol violations were present: were included even if results on cervical cytologic examinations at day 1 were abnormal."

V: vaccine group. C: control group. CIN2+: cervical intraepithelial neoplasia grade 2 or more severe, AIS: adenocarcinoma in situ

Table 2

Summary of HPV cLIA geometric mean titers by age among subjects who received GARDASIL®

^†: The "all HPV-type specific naive subjects" immunogenicity population includes all subjects who received all 3 vaccinations and were seronegative at Day 1 for the relevant HPV type(s)

N: Number of subjects with the indicated age group; n: Number of subjects contributing to the analysis

CI: Confidence interval; cLIA: Competitive Luminex immunoassay; GMT: Geometric mean titer; mMU: Milli Merck units

Table 3

Data of cross protection against non-vaccine human papillomavirus types from randomised controlled trials

^*: 97.9% Confidence intervals reported for Paavonen, et al (33), 95% CI reported for Brown (47)

V: group. C: control group. PI: persistent infection. CIN1+: cervical intraepithelial neoplasia grade 1 or more severe.

CIN2+: cervical intraepithelial neoplasia grade 2 or more severe. AIS: adenocarcinoma in situ

Table 4

Global policy recommendations for human papillomavirus vaccine

Abbreviations: P; primary cohort