Final analysis of a 14-year long-term follow-up study of the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in women from four nordic countries.

BACKGROUND

The quadrivalent human papillomavirus (qHPV) vaccine prevented vaccine HPV type-related infection and disease in young women in the 4-year FUTURE II efficacy study (NCT00092534). We report long-term effectiveness and immunogenicity at the end of 14 years of follow-up after enrollment in FUTURE II.

METHODS

Young women (16-23 years of age) from Denmark, Iceland, Norway, and Sweden who received three qHPV vaccine doses during the randomized, double-blind, placebo-controlled FUTURE II base study were followed for effectiveness for an additional ≥10 years through national registries. Tissue samples including but not limited to those collected during organized cervical cancer screening programs were obtained from regional biobanks to be adjudicated for histopathology diagnosis and tested for HPV DNA. The observed incidence of HPV16/18-related high-grade cervical dysplasia (primary outcome) was compared with recent historical background incidence rates in an unvaccinated population. Serum was collected at years 9 and 14 to assess antibody responses.

FINDINGS

No cases of HPV16/18-related high-grade cervical dysplasia were observed in the per-protocol effectiveness population (

INTERPRETATION

Vaccination of young women with qHPV vaccine offers durable protection against HPV16/18-related high-grade cervical dysplasia for ≥12 years, with a trend toward continued protection through 14 years post-vaccination, and induces sustained HPV6/11/16/18 antibody responses for up to 14 years post-vaccination. There was no evidence of waning immunity, suggesting no need for a booster dose during that period.

FUNDING

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Informations de copyright

© 2020 Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). SKK reports research grants from MSD during the conduct of the study through her affiliating institute and personal fees from MSD outside the submitted work. MN reports research grants from MSD Norway through her affiliating institute during the conduct of the study and outside the scope of this study. KS reports research grants from MSD to her institution for the present work on HPV vaccination in Sweden and research grants to her institution for other register-based studies on HPV vaccination in Sweden. JD reports grants from MSD during the conduct of the study and grants from Genomica outside the submitted work. LT reports that her affiliating institution (ICS) received research grants from MSD Denmark ApS during the conduct of the study. CM reports unrestricted research grants through his affiliating institution from MSD during the conduct of the study. SB reports that her host institution received research grants from MSD Norway during the conduct of the study. EE reports that his affiliating institute received grants from MSD Norway during the conduct of the study. MH reports working on clinical trials sponsored by MSD during the conduct of the study. ÁIÁ has received grants from MSD during the conduct of the study. KB, KF, and IG have nothing to disclose. SWS has received grants from MSD for pathology review of biopsies during the conduct of the study. OB, TG, AL, JBM, DR, YSY, CB, and AS are current or former employees of MSD and may own stock or stock options in Merck & Co., Inc., Kenilworth, NJ, USA.