Effectiveness, immunogenicity, and safety of the quadrivalent HPV vaccine in women and men aged 27–45 years

ABSTRACT

Among women aged 27–45 years, the quadrivalent human papillomavirus (qHPV; HPV6/11/16/18) vaccine was generally well tolerated, efficacious, and immunogenic in the placebo-controlled FUTURE III study (NCT00090220; n = 3253). The qHPV vaccine was also generally well tolerated and highly immunogenic in men aged 27–45 years who participated in the single-cohort mid-adult male (MAM) study (NCT01432574; n = 150). Here, we report results of a long-term follow up (LTFU) extension of FUTURE III with up to 10 years follow-up. To understand the relevance of the mid-adult women LTFU study in the context of mid-adult men vaccination, we report results from post-hoc, cross-study immunogenicity analyses conducted to compare immunogenicity (geometric mean titers; GMTs) at 1-month post-qHPV vaccine dose 3 in women and men aged 27–45 years versus women and men aged 16–26 years from prior efficacy studies. The qHPV vaccine demonstrated durable protection against the combined endpoint of HPV6/11/16/18-related high-grade cervical dysplasia and genital warts up to 10 years (median 8.9) post-dose 3 and sustained HPV6/11/16/18 antibody responses through approximately 10 years in women aged 27–45 years. Efficacy of qHPV vaccine in men aged 27–45 years was inferred based on the cross-study analysis of qHPV vaccine immunogenicity demonstrating non-inferior HPV6/11/16/18 antibody responses in men aged 27–45 years versus 16–26 years. In conclusion, durable effectiveness of the qHPV vaccine was demonstrated in women 27–45 years of age, and vaccine efficacy was inferred in men 27–45 years of age based on the serological results.

KEYWORDS:

• clinical trial
• effectiveness
• human papillomavirus
• immunogenicity
• mid-adult persons
• qHPV vaccine

Acknowledgments

The authors would like to thank the study participants and investigators, and Robert Kurman for contributions serving on the pathology panel. Rodney Finalle, Barbara Kuter, Vimalanand Prabhu, Miriam Reuschenbach, Kunal Saxena, and Christine Velicer, all of Merck & Co., Inc., Rahway, New Jersey, USA, reviewed and provided feedback on a draft of this manuscript.

Disclosure statement

IM: Ivette Maldonado has received grants through her institutions for board membership and study conduct.

MP: Manuel Plata has received grants through his institutions for study conduct and support for travel. He has also received honoraria from the Fundación Cardioinfantil.

MG: Mauricio Gonzalez has grants via his institution to serve as an investigator and colposcopist of FUTURE III study (Protocol 019).

AC: Alfonso Correa has no interests to declare.

CN: Claudia Nossa has no interests to declare.

AG: Anna R. Giuliano reports grant support from, and is an advisory board member for, Merck & Co., Inc.

EJ: Elmar Joura reports grants from Merck during the conduct of the study and personal fees from Merck Sharp & Dohme (MSD) outside the submitted work.

AF: Alex Ferenczy received consultation fees from MSD as a member of the Pathology Panel.

BR: Brigitte M. Ronnett is a consultant for MSD as part of the Pathology Panel.

MS: Mark H. Stoler has received personal fees from MSD, Roche, Becton Dickinson, and Inovio Pharmaceuticals as a consultant, all outside of the submitted work.

HJZ: Hao Jin Zhou is a former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock/stock options in the Company.

AJ: Amita Joshi is a former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock/stock options in the Company.

RD: Rita Das is a former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock/stock options in the Company.

OB: Oliver Bautista is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock/stock options in the Company.

TG: Thomas Group is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock/stock options in the Company.

AL: Alain Luxembourg is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock/stock options in the Company.

AS: Alfred Saah is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock/stock options in the Company.

UB: Ulrike Buchwald is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock/stock options in the Company.

Supplemental data

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2022.2078626

Additional information

Funding

Funding for this research was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Editorial support, under the direction of the authors, was provided by Erin Bekes, PhD, of CMC AFFINITY, a division of McCann Health Medical Communications Inc., Hackensack, New Jersey, USA, funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA, in accordance with Good Publication Practice (GPP3) guidelines.