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. 2020 Jun 20:23:100401.
doi: 10.1016/j.eclinm.2020.100401. eCollection 2020 Jun.

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

Susanne K Kjaer  1 , Mari Nygård  2 , Karin Sundström  3 , Joakim Dillner  3 , Laufey Tryggvadottir  4 , Christian Munk  5 , Sophie Berger  2 , Espen Enerly  2 , Maria Hortlund  3 , Ágúst Ingi Ágústsson  6 , Kaj Bjelkenkrantz  7 , Katrin Fridrich  8 , Ingibjorg Guðmundsdóttir  9 , Sveinung Wergeland Sørbye  10 , Oliver Bautista  11 , Thomas Group  11 , Alain Luxembourg  11 , J Brooke Marshall  11 , David Radley  11 , Yi Shen Yang  11 , Cyrus Badshah  11 , Alfred Saah  11
Affiliations

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

Susanne K Kjaer et al. EClinicalMedicine. .

Abstract

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 (N = 2121; 24,099·0 person-years of follow-up) during the entire study. Vaccine effectiveness of 100% (95% CI 94·7-100) was demonstrated for ≥12 years, with a trend toward continued protection through 14 years post-vaccination. Seropositivity rates at study conclusion were >90% (HPV6/11/16) and 52% (HPV18) using competitive Luminex immunoassay, and >90% (all four HPV types) using the more sensitive IgG Luminex immunoassay.

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.

Keywords: Cervical intraepithelial neoplasia; Human papillomavirus; Long-term follow-up; Quadrivalent hpv vaccine.

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Conflict of interest statement

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.

Figures

Fig 1:
Fig. 1
Participant disposition. LTFU=long-term follow-up. qHPV=quadrivalent human papillomavirus. *Nordic participants who received placebo in the base study are not included in this report.
Fig 2:
Fig. 2
Control chart analysis of effectiveness of qHPV vaccine against HPV16/18-related CIN2 or worse in the PPE population (A) and HNRT population (B). Shaded areas are intervals with insufficient follow-up time to declare statistical significance. CIN=cervical intraepithelial neoplasia. HNRT=HPV-naïve to relevant type. HPV=human papillomavirus. PPE=per-protocol effectiveness. qHPV=quadrivalent human papillomavirus.
See this image and copyright information in PMC

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