ArticlesCross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis
Introduction
Infection with the human papillomavirus (HPV) is a key cause of cervical cancer,1 and has been associated with other anogenital (vulvar, vaginal, penile, and anal) cancers2, 3 and head and neck cancers.4 HPV types of high oncogenic risk, 16 and 18, are detected in about 70% of invasive cervical cancers5 worldwide and in most anogenital and head and neck cancers that are positive for HPV.2, 4 The most common oncogenic HPV types worldwide—16, 18, 31, 33, 45, 52, and 58—contribute to about 90% of invasive cervical cancers.5
Two prophylactic vaccines have been licensed for use in many countries: the bivalent vaccine Cervarix (against HPV 16 and 18; GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent vaccine Gardasil (against HPV 6, 11, 16, and 18; Merck, Whitehouse Station, NJ, USA). Large clinical trials have shown almost 100% vaccine efficacy against precancerous lesions associated with these vaccine HPV types.6, 7, 8 Recent trials have also reported vaccine efficacy against non-vaccine type HPVs.8, 9, 10, 11
Public health officials worldwide continue to assess which HPV vaccine should be used in their vaccination programmes. Cross-protection afforded by the HPV vaccines is a key factor of interest.12, 13 However, differences between characteristics of trial participants such as baseline prevalence and distribution of HPV infection complicate the comparison of cross-protection between bivalent and quadrivalent vaccines. Through a systematic review of published work, we aimed to summarise and compare evidence from clinical trials about the cross-protective efficacy of the bivalent and quadrivalent vaccines in HPV-naive populations (ie, individuals who are DNA negative for all tested oncogenic HPV types). We focused on vaccine efficacy in this population because such efficacy is least diluted by the presence of women who are infected or immune at baseline, which can vary between trials. Thus, trials in HPV-naive populations provide improved estimates of the true prophylactic effect of vaccination.
Section snippets
Search strategy and selection criteria
We systematically reviewed published work and report it in accordance with the PRISMA guidelines.14 We searched for randomised controlled trials assessing the efficacy of the bivalent or quadrivalent vaccines that included populations who were HPV negative for all tested oncogenic types. We included trials reporting efficacy against either cervical or genital infection or disease (cervical intraepithelial neoplasia [CIN] or cervical cancer) endpoints associated with non-vaccine type oncogenic
Results
Figure 1 shows the search strategy. We identified 12 reports, including results from five different trials (two for the quadrivalent vaccine and three for the bivalent vaccine; appendix).9, 11, 21, 22, 23, 24, 25, 26, 27, 28, 29 The table summarises participant information and study characteristics and the appendix shows potential sources of bias. Populations from two trials of the quadrivalent vaccine (Females United to Unilaterally Reduce Endo/Ectocervical Disease [FUTURE] I and FUTURE II)
Discussion
Quadrivalent and bivalent HPV vaccines offer cross-protection against some non-vaccine HPV types for individuals without previous infection. In our analysis, quadrivalent vaccine was efficacious against outcomes associated with HPV 31, and bivalent vaccine was efficacious against outcomes associated with HPV 31, 33, and 45. We noted differences in estimates between the vaccines, with the bivalent vaccine showing greater efficacy than the quadrivalent vaccine against HPV 31, 33, and 45 for
References (43)
- et al.
Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study
Lancet Oncol
(2010) - et al.
The potential cost-effectiveness of prophylactic human papillomavirus vaccines in Canada
Vaccine
(2007) - et al.
Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women
Lancet
(2009) - et al.
Sustained efficacy up to 4·5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial
Lancet
(2006) - et al.
Cost-consequences evaluation between bivalent and quadrivalent HPV vaccines in Italy: the potential impact of different cross protection profiles
Gynecol Oncol
(2011) - et al.
Classification of papillomaviruses
Virology
(2004) - et al.
Meta-analysis in clinical trials
Control Clin Trials
(1986) - et al.
Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial
Lancet Oncol
(2012) - et al.
Sustained efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine up to 7·3 years in young adult women
Vaccine
(2010) - et al.
Neutralization of non-vaccine human papillomavirus pseudoviruses from the A7 and A9 species groups by bivalent HPV vaccine sera
Vaccine
(2011)
HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection
Vaccine
A review of cross-protection against oncogenic HPV by an HPV-16/18 AS04-adjuvanted cervical cancer vaccine: importance of virological and clinical endpoints and implications for mass vaccination in cervical cancer prevention
Gynecol Oncol
Epidemiologic classification of human papillomavirus types associated with cervical cancer
N Engl J Med
Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis
Int J Cancer
Systematic review of human papillomavirus prevalence in invasive penile cancer
Cancer Causes Control
Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review
Cancer Epidemiol Biomarkers Prev
Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases
N Engl J Med
The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in sexually active women aged 16–26 years
J Infect Dis
The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16–26 years
J Infect Dis
Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation based on transmission model
BMJ
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration
BMJ
Cited by (334)
Health and economic impact of delaying large-scale HPV vaccination and screening implementation on cervical cancer in China: a modelling study
2023, The Lancet Regional Health - Western PacificHPV vaccination and HPV-related malignancies: impact, strategies and optimizations toward global immunization coverage
2022, Cancer Treatment Reviews