Safety and Immunogenicity of Quadrivalent HPV Vaccine: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 LUOWen ^1,2,3 , ZHANGShan-hu ^1,3 , ZHOUYan-zhi ² , WANGChen ² , YANGLan ^1,2 ,  QIUJie ^1,2

1. Maternal, Child and Adolescent Health Institute, School of Public Health, Lanzhou University, Lanzhou 730000, China;
2. Maternal and Child Care Service Hospital of Gansu Province, Lanzhou 730000, China;
3. Evidence-based Medicine Center of Lanzhou University, Lanzhou 730000, China;

Corresponding author：

QIUJie, Email: qioujie@21cn.com

Keywords：

Human papillomavirus; Quadrivalent HPV vaccine; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20150010

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Objective To systematically review the safety and immunogenicity of quadrivalent HPV vaccine among healthy population. Methods Databases including PubMed, EMbase, CBM, The Cochrane Library (Issue 9, 2013), CNKI, Web of Science and WanFang Data were searched for randomized controlled trials (RCTs) about safety and immunogenicity of quadrivalent HPV vaccine from inception to October 2013. Meanwhile handwork retrieval was also conducted and references of included literature were retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Meta-analysis was then conducted using RevMan 5.2 software. Results A total of 9 studies were finally included consisting of 8 RCTs and involving 39 688 patients. The result of meta-analysis showed that:a) for safety, the incidence of injection adverse reaction (swelling and red spots) in vaccine group was higher than that in placebo group (RR=1.22, 95%CI 1.13 to 1.32, P<0.000 01); while the incidences of systemic adverse reaction (RR=1.03, 95%CI 0.99 to 1.07, P=0.1) and serious adverse reaction (RR=1.06, 95%CI 0.75 to 1.50, P=0.74) were alike between the two groups; and b) for immunogenicity, the serum antibody seroconversion rates in the vaccine group (including subtypes of HPV6, HPV11 HPV16 and HPV18) were all higher than those in the placebo group, with significant differences. Conclusion Compared with placebo, quadrivalent HPV vaccine has relatively high incidences of adverse reaction and high-degree immunogenicity, which can be widely used in the prevention of relevant diseases of human papillomavirus infection among adolescents. The main adverse reaction is local dysfunction, which is well tolerated, so the vaccine can be safely used. Due to limited quantity and quality of the included studies, the above conclusion should be verified by further conducting more large-scale, multicentre, high quality RCTs.

Citation： LUOWen, ZHANGShan-hu, ZHOUYan-zhi, WANGChen, YANGLan, QIUJie. Safety and Immunogenicity of Quadrivalent HPV Vaccine: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(1): 47-53. doi: 10.7507/1672-2531.20150010 Copy

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2.	岑尧, 张翠英, 张雅丽, 等. 中国女性人乳头瘤病毒感染状况及高危型别分布的Meta分析. 癌症进展, 2013, (1):75-81.
3.	X CastellsaguéS, D Sanjosé, T Aguado, et al. HPV and cervical cancer in the world:2007 report. Elsevier, 2007.
4.	Block SL, Brown DR, Chatterjee A, et al. Clinical trial and post-licensure safety profile of a prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine. Pediatr Infect Dis J, 2010, 29(2):95-101.
5.	赵文华. HPV疫苗预防宫颈癌及HPV相关感染的有效性与安全性. 中国医药科学, 2012, 2(20):233-234.
6.	孙阳春, 吴令英. 人乳头状瘤病毒疫苗新进展. 癌症进展, 2009, 7(2):127-128.
7.	Castellsagué X, Muñoz N, Pitisuttithum P, et al. End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age. Br J Cancer, 2011, 105(1):28-37.
8.	宋云焕, 李莉. 四价HPV疫苗预防宫颈癌,HPV感染相关疾病Meta分析. 国际妇产科学杂志, 2009, 36(6):479-482.
9.	Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0).[cited 2012 Jan 5]. Available at:http://www.cochrane-handbook.org.
10.	Villa LL, Costa RLR, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women:a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol, 2005, 6(5):271-278.
11.	Villa LL, Ault KA, Giuliano AR, et al. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine, 2006, 24(27):5571-5583.
12.	Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med, 2007, 356(19):1928-1943.
13.	Reisinger KS, Block SL, Lazcano-Ponce E, et al. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents:a randomized controlled trial. Pediatr Infect Dis J, 2007, 26(3):201-209.
14.	Kang S, Kim KH, Kim YT, et al. Safety and immunogenicity of a vaccine targeting human papillomavirus types 6, 11, 16 and 18:a randomized, placebo-controlled trial in 176 Korean subjects. Int J Gynecol Cancer, 2008, 18(5):1013-1019.
15.	Munoz N, Manalastas JR, Pitisuttithum P, et al. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years:a randomised, double-blind trial. Lancet, 2009, 373(9679):1949-1957.
16.	Moreira ED, Palefsky JM, Giuliano AR, et al. Safety and reactogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 viral-like-particle vaccine in older adolescents and young adults. Hum Vaccin, 2011, 7(7):768-775.
17.	Li R, Li Y, Radley D, et al. Safety and immunogenicity of a vaccine targeting human papillomavirus types 6, 11, 16 and 18:a randomized, double-blind, placebo-controlled trial in Chinese males and females. Vaccine, 2012, 30(28):4284-4291.
18.	Villa LL, Costa RLR, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer, 2006, 95(11):1459-1466.
19.	沈克飞, 曹兰, 尹继刚, 等. 免疫佐剂研究进展. 动物医学进展, 2007, 28(8):34-36.
20.	Prevention. Summary of HPV Adverse Event Reports Published in JAMA. 2009. Available at:http://www.cdc.gov/vaccinesafety/Vaccines/.
21.	Whittle H, Jaffar S, Wansbrough M, et al. Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. BMJ, 2002, 325(7364):569.
22.	万磊, 万建平, 张燕玲, 等. 子宫颈癌年轻化趋势的临床分析. 中国肿瘤临床, 2004,31(10):547-549.
23.	Weinstock H, Berman S, Cates W. Sexually transmitted diseases among American youth:incidence and prevalence estimates, 2000. Perspect Sex Reprod Health, 2004, 36(1):6-10.

1. P Fuste R, Carreras MT, Lopez Yarto. Preventive vaccines against human papilloma virus and cervical cancer. Med Clin (Barc), 2007, 128(1):735-740.
2. 岑尧, 张翠英, 张雅丽, 等. 中国女性人乳头瘤病毒感染状况及高危型别分布的Meta分析. 癌症进展, 2013, (1):75-81.
3. X CastellsaguéS, D Sanjosé, T Aguado, et al. HPV and cervical cancer in the world:2007 report. Elsevier, 2007.
4. Block SL, Brown DR, Chatterjee A, et al. Clinical trial and post-licensure safety profile of a prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine. Pediatr Infect Dis J, 2010, 29(2):95-101.
5. 赵文华. HPV疫苗预防宫颈癌及HPV相关感染的有效性与安全性. 中国医药科学, 2012, 2(20):233-234.
6. 孙阳春, 吴令英. 人乳头状瘤病毒疫苗新进展. 癌症进展, 2009, 7(2):127-128.
7. Castellsagué X, Muñoz N, Pitisuttithum P, et al. End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age. Br J Cancer, 2011, 105(1):28-37.
8. 宋云焕, 李莉. 四价HPV疫苗预防宫颈癌,HPV感染相关疾病Meta分析. 国际妇产科学杂志, 2009, 36(6):479-482.
9. Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0).[cited 2012 Jan 5]. Available at:http://www.cochrane-handbook.org.
10. Villa LL, Costa RLR, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women:a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol, 2005, 6(5):271-278.
11. Villa LL, Ault KA, Giuliano AR, et al. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine, 2006, 24(27):5571-5583.
12. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med, 2007, 356(19):1928-1943.
13. Reisinger KS, Block SL, Lazcano-Ponce E, et al. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents:a randomized controlled trial. Pediatr Infect Dis J, 2007, 26(3):201-209.
14. Kang S, Kim KH, Kim YT, et al. Safety and immunogenicity of a vaccine targeting human papillomavirus types 6, 11, 16 and 18:a randomized, placebo-controlled trial in 176 Korean subjects. Int J Gynecol Cancer, 2008, 18(5):1013-1019.
15. Munoz N, Manalastas JR, Pitisuttithum P, et al. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years:a randomised, double-blind trial. Lancet, 2009, 373(9679):1949-1957.
16. Moreira ED, Palefsky JM, Giuliano AR, et al. Safety and reactogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 viral-like-particle vaccine in older adolescents and young adults. Hum Vaccin, 2011, 7(7):768-775.
17. Li R, Li Y, Radley D, et al. Safety and immunogenicity of a vaccine targeting human papillomavirus types 6, 11, 16 and 18:a randomized, double-blind, placebo-controlled trial in Chinese males and females. Vaccine, 2012, 30(28):4284-4291.
18. Villa LL, Costa RLR, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer, 2006, 95(11):1459-1466.
19. 沈克飞, 曹兰, 尹继刚, 等. 免疫佐剂研究进展. 动物医学进展, 2007, 28(8):34-36.
20. Prevention. Summary of HPV Adverse Event Reports Published in JAMA. 2009. Available at:http://www.cdc.gov/vaccinesafety/Vaccines/.
21. Whittle H, Jaffar S, Wansbrough M, et al. Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. BMJ, 2002, 325(7364):569.
22. 万磊, 万建平, 张燕玲, 等. 子宫颈癌年轻化趋势的临床分析. 中国肿瘤临床, 2004,31(10):547-549.
23. Weinstock H, Berman S, Cates W. Sexually transmitted diseases among American youth:incidence and prevalence estimates, 2000. Perspect Sex Reprod Health, 2004, 36(1):6-10.

Chinese Journal of Evidence-Based Medicine

Safety and Immunogenicity of Quadrivalent HPV Vaccine: A Meta-analysis

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