Common vaccine protects against more HPV viruses than previously known
Human papillomavirus (HPV) is a common and highly infectious sexually transmitted disease. While in most cases, the HPV infection heals on its own, it can become chronic and cause various kinds of cancer.
The HPV group comprises over 200 types of virus, thirteen of which are classified as high-risk causes of cancer. For example, HPV types 16 and 18 cause around 70 per cent of all cases of cervical cancer; HPV types 6 and 11 cause benign genital warts.
Today, bivalent (comprising HPV types 16 and 18) and quadrivalent (comprising HPV types 6, 11, 16 and 18) vaccines are used against HPV around the world, with different reported efficacy.
As a measure of a vaccinated individual’s protection against tumours caused by HPV infection, use of serum antibodies to different types of HPV is desired. However, researchers have not yet defined which antibody levels provide full and lasting protection, or whether vaccines for certain HPV types also protect other types than those the vaccine is intended for (cross-protection).
In two studies, researchers at several institutions including German Cancer Research Centre (DKFZ) in Heidelberg, Karolinska Institutet, an Tampere University have made independent comparisons of directly and cross-protecting antibody responses, including antibodies that protect against both vaccine HPV types and HPV types not covered by different national vaccine programmes.
The researchers have assessed the sustainability of the antibody protection for bivalent and quadrivalent vaccines up to 12 years. The results are based on over 3,000 women in Finland who were 16-17 when they were vaccinated in 2002 and 2004.
Retrieval of serum samples collected and stored over 12 years was done from the Finnish Maternity Cohort Biobank. The serological analyses included antibodies to 16 different HPV types.
The results show that the women who received the quadrivalent vaccine had antibodies to HPV types 6/11/16/18 for up to 12 years. Those who had received the bivalent vaccine had antibodies to HPV types 16/18 for equally as long.
In the women who had received the bivalent vaccine, both the neutralising and binding ability of the vaccine-induced antibodies to HPV16/18/31 were significantly higher than in those women who had received the quadrivalent vaccine. Neutralising refers to the virus being prevented from entering host cells.
“Our results on the correlation between vaccine efficacy and antibody positivity by HPV type explain why the bivalent HPV vaccine seems to give broader protection against different cancer-associated HPV types than previously known,” says the paper’s last author Matti Lehtinen, researcher at the Department of Laboratory Medicine, Karolinska Institutet, and principal investigator at the Tampere University, Finland.
“The results also show that both quadrivalent and bivalent vaccines provide protection for a long time.”
Funding and Conflict of interest:
The study was financed by the Academy of Finland and the Finnish Cancer Foundation. Matti Lehtinen has received research funding from Merck and GlaxoSmithKline Biologicals through Tampere University. Joakim Dillner has received research funding from Merck through Karolinska Institutet. Martin Müller is developing a patent for an HPV vaccine produced at Loyola University in the USA and licensed by GlaxoSmithKline Biologicals and DKZF. Tim Waterboer is engaged as an advisor for MSD Sharpe & Dohme. There are no other reported conflicts of interest.
Sustainability of neutralizing antibodies induced by bi- or quadrivalent HPV vaccines correlates with efficacy, Felipe Colaço Mariz, Penelope Gray, Noemi Bender, Tiina Eriksson, Hanna Kann, Dan Apter, Jorma Paavonen, Emma Pajunen, Kristina M. Prager, Peter Sehr, Heljä-Marja Surcel, Tim Waterboer, Martin Müller, Michael Pawlita, Matti Lehtinen. Lancet Infectious Diseases, online 31 May 2021,
Sustained cross-reactive antibody responses after human papillomavirus vaccinations: Up to 12 years follow-up in the Finnish Maternity Cohort, Hanna Kann, Matti Lehtinen, Tiina Eriksson, Heljä-Marja Surcel, Joakim Dillner, Helena Faust. The Journal of Infectious Diseases, 3 October 2020,
For more information, please contact:
Matti Lehtinen, adjunct professor
Department of Laboratory Medicine, Karolinska Institutet and Tampere University
Mail: matti.lehtinen [at] tuni.fi (preferred), matti.lehtinen [at] ki.se
Photo: Erkki Karén