By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a supplemental application to expand the indication for human papillomavirus 9-valent vaccine (HPV-9) to include men and women 27-45 years of age. HPV-9, a noninfectious recombinant vaccine, is distributed as Gardasil 9. The vaccine covers nine HPV types that are responsible for 90% of HPV-related cancers. Previously, the vaccine was approved for males and females 9-26 years of age.1
HPV-9 is indicated for women 9-45 years of age to prevent anal, cervical, vaginal, and vulvar cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58; genital warts (acuminate, condyloma) caused by HPV types 6 and 11; and dysplastic or precancerous lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. These include cervical intraepithelial neoplasia (CIN) grade 2/3 and cervical adenocarcinoma in situ (AIS); anal intraepithelial neoplasia (AIN) grades 1, 2, and 3; CIN grade 1; vulvar intraepithelial neoplasia (VIN) grades 2 and 3; and vaginal intraepithelial neoplasia grades 2 and 3.2
HPV-9 is indicated for men 9-45 years of age to prevent anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; genital warts (acuminate, condyloma) caused by HPV types 6 and 11; dysplastic or precancerous lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and AIN grades 1, 2, and 3.
Recommended dose for patients age 9-14 years: a two-dose regimen (initially and six to 12 months later) or a three-dose regimen (initial and two to six months).2 For patients 15-45 years of age, a three-dose regimen is recommended. HPV-9 is available as a single-dose vial or prefilled syringe (0.5 mL).
The FDA’s supplemental approval of HPV-9 expands the coverage of nine HPV types up to age 45 for men and women, thus potentially expanding the eradication of HPV-associated cancers.
While the vaccine protects against the types of HPV that cause oropharyngeal cancer, effectiveness in preventing this common cancer in men has not been established and is not approved for preventing this cancer.3 Preliminary data suggest a lower prevalence of oral infections of HPV types covered by the vaccine.3 The persistence of immune response to HPV-9 has not been established.3
The efficacy of HPV-9 for its expanded indication was based on a study of HPV-4 in 3,253 women 27-45 years of age.2 The study comprised two phases: a base study and a long-term study extension. In the base study, there was a median follow-up of 3.5 years after the three-dose regimen. Women were randomized to HPV-4 or adjuvant control. The endpoint was a combined outcome of HPV 6-, 11-, 16-, or 18-related persistent infection, genital warts, vulvar and vaginal dysplastic lesions of any grade, CIN of any grade, AIS, and cervical cancer. Vaccine efficacy was 87.7%, driven primarily by reduction of persistent infection. Efficacy against genital warts or cervical dysplasia was 95%.
In the extension phase (median of 8.9 years; n = 600), no cases of CIN or genital warts were observed. Effectiveness in men was inferred from data in women and immunogenicity data in men (n = 150) 27-45 years of age.
In a cross-study analysis, the ratio of geometric mean titer ranged from 0.72 to 0.82 for those 27-45 years of age relative to those 16-26 years of age. HPV-9 has been shown to be noninferior to HPV-4 in terms of immune response to HPV types 6, 11, 16, and 18 and 88-99% effective in preventing the additional five HPV types vs. HPV-4.
Based on data collected between 2011 and 2015, about 42,700 new cases of HPV-associated cancer occurred in the United States each year.4 Cervical cancer was most common among women and oropharyngeal cancer among men. The authors of the National Health and Nutrition Examination Survey 2013-2014 reported the prevalence of vaccine type HPV among women 18-59 years of age was 5.5%.5 In contrast, the prevalence in men in the same age range was 15.1%.6 The expanded indication widens the eligible population for vaccination against HPV-associated cancers. However, one concerning finding was that among vaccine-eligible men, only 10.7% were vaccinated vs. 31.5% of eligible women.7 Significant progress in eradication can be accomplished only if the expanded indication is coupled with a higher vaccination rate.7 The cost for a three-dose regimen is $614.61.
- U.S. Food & Drug Administration. FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old. Available at: . Accessed Oct. 23, 2018.
- Gardasil 9 Prescribing Information, Merck & Co, Inc., October 2018. Available at: . Accessed Oct. 23, 2018.
- U.S. Department of Health and Human Services. United States Cancer Statistics Data Brief, August 2018. Available online at: . Accessed Oct. 23, 2018.
- National Cancer Institute. HPV vaccination linked to decreased oral HPV infections. Available at: . Accessed Oct. 23, 2018.
- Berenson AB, Hirth JM, Chang M. Change in human papillomavirus prevalence among U.S. women aged 18-59 years, 2009-2014. Obstet Gynecol 2017;130:693-701.
- Han JJ, Beltran TH, Song JW, et al. Prevalence of genital human papillomavirus infection and human papillomavirus vaccination rates among US adult men: National Health and Nutrition Examination Survey (NHANES) 2013-2014. JAMA Oncol 2017;3:810-816.
- Han JJ, Tarney CM, Song J. Variation in genital human papillomavirus infection prevalence and vaccination coverage among men and women in the USA. Future Oncol 2017;13:1129-1132.