Are two doses of human papillomavirus vaccine sufficient for girls aged 15-18 years? Results from a cohort study in India

Neerja Bhatla, Bhagwan M Nene, Smita Joshi, Pulikottil O Esmy, Usha Rani Reddy Poli, Geeta Joshi, Yogesh Verma, Eric Zomawia, Sharmila Pimple, Priya R Prabhu, Partha Basu, Richard Muwonge, Sanjay Hingmire, Catherine Sauvaget, Eric Lucas, Michael Pawlita, Tarik Gheit, Kasturi Jayant, Sylla G Malvi, Maqsood Siddiqi, Angelika Michel, Julia Butt, Subha Sankaran, Thiraviam Pillai Rameshwari Ammal Kannan, Rintu Varghese, Uma Divate, Martina Willhauck-Fleckenstein, Tim Waterboer, Martin Müller, Peter Sehr, Alka Kriplani, Gauravi Mishra, Radhika Jadhav, Ranjit Thorat, Massimo Tommasino, M Radhakrishna Pillai, Rengaswamy Sankaranarayanan, Indian HPV vaccine study group, Neerja Bhatla, Bhagwan M Nene, Smita Joshi, Pulikottil O Esmy, Usha Rani Reddy Poli, Geeta Joshi, Yogesh Verma, Eric Zomawia, Sharmila Pimple, Priya R Prabhu, Partha Basu, Richard Muwonge, Sanjay Hingmire, Catherine Sauvaget, Eric Lucas, Michael Pawlita, Tarik Gheit, Kasturi Jayant, Sylla G Malvi, Maqsood Siddiqi, Angelika Michel, Julia Butt, Subha Sankaran, Thiraviam Pillai Rameshwari Ammal Kannan, Rintu Varghese, Uma Divate, Martina Willhauck-Fleckenstein, Tim Waterboer, Martin Müller, Peter Sehr, Alka Kriplani, Gauravi Mishra, Radhika Jadhav, Ranjit Thorat, Massimo Tommasino, M Radhakrishna Pillai, Rengaswamy Sankaranarayanan, Indian HPV vaccine study group

Abstract

Extending two-dose recommendations of HPV vaccine to girls between 15 and 18 years will reduce program cost and improve compliance. Immunogenicity and vaccine targeted HPV infection outcomes were compared between 1795 girls aged 15-18 years receiving two (1-180 days) and 1515 girls of same age receiving three (1-60-180 days) doses. Immunogenicity outcomes in 15-18 year old two-dose recipients were also compared with the 10-14 year old three-dose (N = 2833) and two-dose (N = 3184) recipients. The 15-18 year old two-dose recipients had non-inferior L1-binding antibody titres at seven months against vaccine-targeted HPV types compared to three-dose recipients at 15-18 years and three-dose recipients at 10-14 years of age. Neutralizing antibody titres at 18 months in 15-18 year old two-dose recipients were non-inferior to same age three-dose recipients for all except HPV 18. The titres were inferior to those in the 10-14 year old three-dose recipients for all targeted types. Frequency of incident infections from vaccine-targeted HPV types in the 15-18 year old two-dose recipients was similar to the three dose recipients. None of the girls receiving two or three doses had persistent infection from vaccine-targeted types. These findings support that two doses of HPV vaccine can be extended to girls aged 15-18 years.

Keywords: Human papillomavirus; Immunogenicity; Incident infections; Persistent infections; Quadrivalent vaccine; Two doses; age 15–18 years.

Copyright © 2018. Published by Elsevier B.V.

Figures

Fig. 1
Fig. 1
Mean MFI values for HPV 16, 18, 6 and 11 L1 antibodies stratified by age.
Fig. 2
Fig. 2
Box plots of the avidity index of MFI for HPV types 16, 18, 6 and 11 L1 antibodies at month 18 after the first dose by age group.
Fig. 3
Fig. 3
Box plots of neutralisation titres of HPV types 16, 18 and 6 L1 antibodies at month 18 after the first dose by age group.

References

    1. International Agency for Research on Cancer . IARC; Lyon: 2007. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 90. Human Papillomaviruses).
    1. zur Hausen H. Papillomaviruses in the causation of human cancers – a brief historical account. Virology. 2009;384:260–265.
    1. Li N., Franceschi S., Howell-Jones R., Snijders P.J., Clifford G.M. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: variation by geographical region, histological type and year of publication. Int. J. Cancer. 2011;128:927–935.
    1. Smith J.S., Lindsay L., Hoots B., Keys J., Franceschi S., Winer R. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int. J. Cancer. 2007;121:621–632.
    1. World Health Organization . Vaccine in National Immunization Programme Update. 2017. (Available from: 〈 〉, Accessed June 12, 2017)
    1. Schiller J.T., Castellsague X., Garland S.M. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine. 2012;30(Suppl. 5):SF123–SF138.
    1. Bosch F.X., Broker T.R., Forman D., Moscicki A.B., Gillison M.L., Doorbar J. Comprehensive control of human papillomavirus infections and related diseases. Vaccine. 2013;31(Suppl. 5):SF1–SF31.
    1. Erickson B.K., Landers E.E., Huh W.K. Update on vaccination clinical trials for HPV-related disease. Clin. Ther. 2014;36:8–16.
    1. World Health Organization, Immunization, Vaccines and Biologicals: Summary of the SAGE April 2014 Meeting. Available from: , (Accessed 12 June 2017).
    1. World Health Organization, Evidence based recommendations on Human Papilloma Virus (HPV) Vaccines Schedules. Background paper for SAGE discussions. Available from: , (Accessed 12 June 2017).
    1. Block S.L., Nolan T., Sattler C., Barr E., Giacoletti K.E., Marchant C.D. Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics. 2006;118:2135–2145.
    1. Pedersen C., Petaja T., Strauss G., Rumke H.C., Poder A., Richardus J.H. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant. J. Adolesc. Health. 2007;40:564–571.
    1. Sankaranarayanan R., Prabhu P.R., Pawlita M., Gheit T., Bhatla N., Muwonge R. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study. Lancet Oncol. 2016;17:67–77.
    1. Waterboer T., Sehr P., Michael K.M., Franceschi S., Nieland J.D., Joos T.O. Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin. Chem. 2005;51:1845–1853.
    1. Michael K.M., Waterboer T., Sehr P., Rother A., Reidel U., Boeing H. Seroprevalence of 34 human papillomavirus types in the German general population. PLoS Pathog. 2008;4:e1000091.
    1. Sehr P., Rubio I., Seitz H., Putzker K., Ribeiro-Muller L., Pawlita M. High-throughput pseudovirion-based neutralization assay for analysis of natural and vaccine-induced antibodies against human papillomaviruses. PLoS One. 2013;8:e75677.
    1. Dillner J., Kjaer S.K., Wheeler C.M., Sigurdsson K., Iversen O.E., Hernandez-Avila M. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. BMJ. 2010;341:c3493.
    1. Lehtinen M., Paavonen J., Wheeler C.M., Jaisamrarn U., Garland S.M., Castellsague X. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012;13:89–99.
    1. Romanowski B., Schwarz T.F., Ferguson L.M., Peters K., Dionne M., Schulze K. Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study. Hum. Vaccin. 2011;7:1374–1386.
    1. World Health Organization Human papillomavirus vaccine: WHO position paper, may 2017. Wkly. Epidemiol. Rec. 2017;92:241–298.
    1. Bhatla N., Suri V., Basu P., Shastri S., Datta S.K., Bi D. Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Indian women. J. Obstet. Gynaecol. Res. 2010;36:123–132.
    1. Lowy D.R. HPV vaccination to prevent cervical cancer and other HPV-associated disease: from basic science to effective interventions. J. Clin. Invest. 2016;126:5–11.
    1. Schiller J.T., Lowy D.R. Understanding and learning from the success of prophylactic human papillomavirus vaccines. Nat. Rev. Microbiol. 2012;10:681–692.
    1. Day P.M., Kines R.C., Thompson C.D., Jagu S., Roden R.B., Lowy D.R. In vivo mechanisms of vaccine-induced protection against HPV infection. Cell Host Microbe. 2010;8:260–270.
    1. Kines R.C., Thompson C.D., Lowy D.R., Schiller J.T., Day P.M. The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding. Proc. Natl. Acad. Sci. USA. 2009;106:20458–20463.
    1. Brady A.M., Panicker G., Meites E., Bulkow L., Hurlburt D., Markowitz L. Maintenance of antibody avidity in Alaska native adolescents receiving quadrivalent human papillomavirus (HPV) vaccine. FASEB J. 2017;31(lb):191.
    1. World Health Organization . Primary End-Points for Prophylactic HPV Vaccine Trials. IARC Working Group Report. Vol. 7. IARC; Lyon: 2014.

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