Efficacy of the AS04-adjuvanted HPV-16/18 vaccine in young Chinese women with oncogenic HPV infection at baseline: post-hoc analysis of a randomized controlled trial

Shangying Hu, Xiaoqian Xu, Fengcai Zhu, Ying Hong, Yuemei Hu, Xun Zhang, Qinjing Pan, Wenhua Zhang, Chengfu Zhang, Xiaoping Yang, Jiaxi Yu, Jiahong Zhu, Yejiang Zhu, Feng Chen, Shuang Zhao, Naveen Karkada, Haiwen Tang, Dan Bi, Frank Struyf, Fanghui Zhao, Shangying Hu, Xiaoqian Xu, Fengcai Zhu, Ying Hong, Yuemei Hu, Xun Zhang, Qinjing Pan, Wenhua Zhang, Chengfu Zhang, Xiaoping Yang, Jiaxi Yu, Jiahong Zhu, Yejiang Zhu, Feng Chen, Shuang Zhao, Naveen Karkada, Haiwen Tang, Dan Bi, Frank Struyf, Fanghui Zhao

Abstract

Human papillomavirus (HPV) vaccines are efficacious against HPV infections and associated lesions in women HPV-naïve at vaccination. However, vaccine efficacy (VE) against oncogenic, high-risk HPV (HR-HPV) types in women infected with any other HR-HPV type at first vaccination (baseline) remains unclear. This post-hoc analysis of a phase II/III study (NCT00779766) evaluated AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) VE against HR-HPV type infection in 871 Chinese women aged 18-25 years over a 72-month follow-up period. Study participants were DNA-negative at baseline to HR-HPV type(s) considered for VE and DNA-positive to any other HR-HPV type. Initial serostatus was not considered. Baseline DNA prevalence was 14.6% for any HR-HPV type and 10.6% excluding HPV-16/18. In the total vaccinated cohort for efficacy, VE against 6-month and 12-month HPV-16/18 persistent infections (PIs) in women DNA-negative to HPV-16/18 but DNA-positive to any other HR-HPV type at baseline was 100.0% (95% Confidence Interval [CI]: 79.8-100.0) and 100.0% (95%CI: 47.2-100.0), respectively. VE against HPV-16/18 incident infections in women DNA-positive to one vaccine type but DNA-negative to the other one at baseline was 66.8% (95%CI: -18.9-92.5). VE against HPV-31/33/45 incident infections, in women DNA-positive to HPV-16/18 and DNA-negative to the considered HPV type at baseline was 71.0% (95%CI: 27.3-89.8). No HPV-16/18 PIs were observed in vaccinated women with non-vaccine HPV A7/A9 species cervical infection at baseline. These findings indicated that women with existing HR-HPV infection at vaccination might still benefit from the AS04-HPV-16/18 vaccine. However, this potential benefit needs further demonstration in the future.

Keywords: China; Human papillomavirus; cervical cancer; clinical trial; efficacy; infection; prevention; vaccines.

Conflict of interest statement

All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf and declare the following potential conflicts of interest: The institutions of Fang-Hui Zhao, Shangying Hu, Ying Hong, Yue-Mei Hu, Xun Zhang, Qin-Jing Pan, Wen-Hua Zhang, Cheng-Fu Zhang, Xiaoping Yang, Jia-Xi Yu, Jiahong Zhu, Yejiang Zhu, Feng Chen, Xiaoqian Xu, Shuang Zhao and Feng-Cai Zhu received grants/investigator fees from the GSK group of companies for the conduct and follow-up of this study. Fang-Hui Zhao, Feng-Cai Zhu and Yue-Mei Hu received support for travel to meetings related to the study from the GSK group of companies. Naveen Karkada, Haiwen Tang, Dan Bi are employees of the GSK group of companies. Frank Struyf was an employee of the GSK group of companies at the time the study was performed and is currently an employee of Janssen, Pharmaceutical companies of Johnson & Johnson. Haiwen Tang, Dan Bi, and Frank Struyf hold shares in the GSK group of companies.

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Plain language summary
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Analysis flowchart

References

    1. Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR, 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;374:301–14. doi:10.1016/S0140-6736(09)61248-4.
    1. Huh WK, Joura EA, Giuliano AR, Iversen OE, de Andrade RP, Ault KA, Bartholomew D, Cestero RM, Fedrizzi EN, Hirschberg AL, et al. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16–26 years: a randomised, double-blind trial. Lancet. 2017;390:2143–59. doi:10.1016/S0140-6736(17)31821-4.
    1. FUTURE II Study Group . Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356:1915–27. doi:10.1056/NEJMoa061741.
    1. Beachler DC, Kreimer AR, Schiffman M, Herrero R, Wacholder S, Rodriguez AC, Lowy DR, Porras C, Schiller JT, Quint W, et al. Multisite HPV16/18 vaccine efficacy against cervical, anal, and oral HPV infection. J Natl Cancer Inst. 2016;108:pii: djv302. doi:10.1093/jnci/djv302.
    1. World Health Organization . Human papillomavirus vaccines: WHO position paper, May 2017-recommendations. Vaccine. 2017;35:5753–55. doi:10.1016/j.vaccine.2017.05.069.
    1. Arbyn M, Xu L, Simoens C, Martin-Hirsch PP.. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;5:Cd009069.
    1. Black LL, Zimet GD, Short MB, Sturm L, Rosenthal SL. Literature review of human papillomavirus vaccine acceptability among women over 26 years. Vaccine. 2009;27:1668–73. doi:10.1016/j.vaccine.2009.01.035.
    1. National Medical Products Administration . The first domestic recombinant human papillomavirus vaccine was approved into market. 2019, December 31. [Accessed 2020 April17]. . [In Chinese].
    1. World Health Organization . Vaccines in National Immunization Programme Update. 2020, June. [Accessed 2020 June19]. .
    1. Zhang Y, Wang Y, Liu L, Fan Y, Liu Z, Wang Y, Nie S. Awareness and knowledge about human papillomavirus vaccination and its acceptance in China: a meta-analysis of 58 observational studies. BMC Public Health. 2016;16:216. doi:10.1186/s12889-016-2873-8.
    1. Zhao FH, Tiggelaar SM, Hu SY, Zhao N, Hong Y, Niyazi M, Gao XH, Ju LR, Zhang LQ, Feng XX, et al. A multi-center survey of HPV knowledge and attitudes toward HPV vaccination among women, government officials, and medical personnel in China. Asian Pac J Cancer Prev. 2012;13:2369–23678.
    1. World Health Organization . Global health observatory data repository. Cervical cancer screening: Response by country. [Accessed 2020 April17]. .
    1. World Health Organization . Guide to introducing HPV vaccine into national immunization programmes. [Accessed 2020 April17]. .
    1. Chrysostomou AC, Stylianou DC, Constantinidou A, Kostrikis LG. Cervical cancer screening programs in Europe: the transition towards HPV vaccination and population-based HPV testing. Viruses. 2018;10:pii: E729. doi:10.3390/v10120729.
    1. Olsson SE, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Brown DR, Koutsky LA, Tay EH, et al. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection. Hum Vaccin. 2009;5:696–704. doi:10.4161/hv.5.10.9515.
    1. Szarewski A, Poppe WA, Skinner SR, Wheeler CM, Paavonen J, Naud P, Salmeron J, Chow SN, Apter D, Kitchener H, et al. Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15–25 years with and without serological evidence of previous exposure to HPV-16/18. Int J Cancer. 2012;131:106–16. doi:10.1002/ijc.26362.
    1. Zhu FC, Chen W, Hu YM, Hong Y, Li J, Zhang X, Zhang YJ, Pan QJ, Zhao FH, Yu JX, et al. Efficacy, immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese women aged 18–25 years: results from a randomized controlled trial. Int J Cancer. 2014;135:2612–22. doi:10.1002/ijc.28897.
    1. Zhu FC, Hu SY, Hong Y, et al. Efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine in Chinese women aged 18–25 years: event-triggered analysis of a randomized controlled trial. Cancer Med. 2017;6:12–25. doi:10.1002/cam4.869.
    1. Future II Study Group . Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection. J Infect Dis. 2007;196:1438–46. doi:10.1086/522864.
    1. Wheeler CM, Skinner SR, Del Rosario-Raymundo MR, Garland SM, Chatterjee A, Lazcano-Ponce E, Salmerón J, McNeil S, Stapleton JT, Bouchard C, et al. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 7-year follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet Infect Dis. 2016;16:1154–68. doi:10.1016/S1473-3099(16)30120-7.
    1. Struyf F, Colau B, Wheeler CM, Naud P, Garland S, Quint W, Chow SN, Salmerón J, Lehtinen M, Del Rosario-Raymundo MR, et al. Post hoc analysis of the PATRICIA randomized trial of the efficacy of human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against incident and persistent infection with nonvaccine oncogenic HPV types using an alternative multiplex type-specific PCR assay for HPV DNA. Clin Vaccine Immunol. 2015;22:235–44.
    1. Brown DR, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Tay EH, Garcia P, et al. 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. 2009;199:926–35. doi:10.1086/597307.
    1. Wheeler CM, Castellsague X, Garland SM, Szarewski A, Paavonen J, Naud P, Salmerón J, Chow SN, Apter D, Kitchener H, 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;13:100–10. doi:10.1016/S1470-2045(11)70287-X.
    1. Zhao FH, Lewkowitz AK, Hu SY, Chen F, Li LY, Zhang QM, Wu RF, Li CQ, Wei LH, Xu AD, et al. Prevalence of human papillomavirus and cervical intraepithelial neoplasia in China: a pooled analysis of 17 population-based studies. Int J Cancer. 2012;131:2929–38.
    1. Gu XY, Zheng RS, Sun KX, Zhang SW, Zeng HM, Zou XN, Chen WQ, He J. Incidence and mortality of cervical cancer in China, 2014. Zhonghua Zhong Liu Za Zhi. 2018;40:241–46.
    1. Ryser M, Berlaimont V, Karkada N, Mihalyi A, Rappuoli R, van der Most R. Post-hoc analysis from phase III trials of human papillomavirus vaccines: considerations on impact on non-vaccine types. Expert Rev Vaccines. 2019;18:309–22. doi:10.1080/14760584.2019.1579647.
    1. Castellsague X, Munoz N, Pitisuttithum P, Ferris D, Monsonego J, Ault K, Luna J, Myers E, Mallary S, Bautista OM, 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;105:28–37. doi:10.1038/bjc.2011.185.
    1. Skinner SR, Szarewski A, Romanowski B, Garland SM, Lazcano-Ponce E, Salmerón J, Del Rosario-Raymundo MR, Verheijen RH, Quek SC, da Silva DP, et al. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet. 2014;384:2213–27. doi:10.1016/S0140-6736(14)60920-X.
    1. Bosch FX, Robles C, Diaz M, Arbyn M, Baussano I, Clavel C, Ronco G, Dillner J, Lehtinen M, Petry KU, et al. HPV-FASTER: broadening the scope for prevention of HPV-related cancer. Nat Rev Clin Oncol. 2016;13:119–32. doi:10.1038/nrclinonc.2015.146.
    1. IARC HPV Working Group . Primary end-points for prophylactic HPV vaccine trials. IARC Working Group Reports. 2014;7.

Source: PubMed

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