Indication for GARDASIL 9

GARDASIL 9 is a vaccine indicated in females 9 through 26 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 26 years of age for the prevention of anal cancer caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant) does not eliminate the necessity for girls to continue to undergo recommended cervical cancer screening later in life. Recipients of GARDASIL 9 should not discontinue anal cancer screening if it has been recommended by a health care professional.

GARDASIL 9 has not been demonstrated to provide protection against diseases from vaccine HPV types to which a person has previously been exposed through sexual activity.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, and anal cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, and anal cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58.

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

Select Safety Information for GARDASIL®9 9 (Human Papillomavirus 9-valent Vaccine, Recombinant)

GARDASIL 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following HPV vaccination. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion.

Safety and effectiveness of GARDASIL 9 have not been established in pregnant women.

The most common (≥10%) local and systemic adverse reactions in females were injection-site pain, swelling, erythema, and headache. The most common (≥10%) local and systemic reactions in males were injection-site pain, swelling, and erythema.

The duration of immunity of GARDASIL 9 has not been established.

There was an increase in injection-site swelling reported at the injection site for GARDASIL 9 when administered concomitantly with Menactra and Adacel. The majority of injection-site swelling adverse experiences were reported as being mild to moderate in intensity.


Dosage and Administration for GARDASIL 9

GARDASIL 9 should be administered intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh.

  • For individuals 9 through 14 years of age, GARDASIL 9 can be administered using a 2-dose or 3-dose schedule. For the 2-dose schedule, the second dose should be administered 6–12 months after the first dose. If the second dose is administered less than 5 months after the first dose, a third dose should be given at least 4 months after the second dose. For the 3-dose schedule, GARDASIL 9 should be administered at 0, 2 months, and 6 months.
  • For individuals 15 through 26 years of age, GARDASIL 9 is administered using a 3-dose schedule at 0, 2 months, and 6 months.

Before administering GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant), please read the Prescribing Information. The Patient Information also is available.

1. de Sanjose S, Quint WGV, Alemany L, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048–1056.
2. de Sanjose S, Alemany L, Ordi J, et al. Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva. Eur J Cancer. 2013;49(16):3450–3461.
3. Alemany L, Saunier M, Tinoco L, et al. Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples. Eur J Cancer. 2014;50(16):2846–2854.
4. Alemany L, Saunier M, Alvarado-Cabrero I, et al. Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide. Int J Cancer. 2015;136(1):98–107.
5. Joura EA, Ault KA, Bosch FX, et al. Attribution of 12 high-risk human papillomavirus genotypes to infection and cervical disease. Cancer Epidemiol Biomarkers Prev. 2014;23(10):1997–2008.
6. Garland SM, Steben M, Sings HL, et al. Natural history of genital warts: analysis of the placebo arm of 2 randomized phase III trials of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine. J Infect Dis. 2009;199(6):805–814.
7. Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer. 2012;131(10):2349–2359.
8. Centers for Disease Control and Prevention (CDC). Vaccine storage and handling. In: Atkinson W, Hamborksy J, Stanton A, et al, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th rev ed, 2nd printing. Washington, DC: Public Health Foundation; 2012:Appendix C.
9. Centers for Disease Control and Prevention (CDC). Vaccine administration. In: Atkinson W, Hamborksy J, Stanton A, et al, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th rev ed, 2nd printing. Washington, DC: Public Health Foundation; 2012:Appendix D.
10. Centers for Disease Control and Prevention (CDC). Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2015;64(11):300–304.
11. Centers for Disease Control and Prevention (CDC). Recommended immunization schedule for persons aged 0 through 18 years — United States, 2016. http://www.cdc.gov/vaccines/
schedules/downloads/child/0-18yrs-child-combined-schedule.pdf. Accessed June 3, 2016.
12. Centers for Disease Control and Prevention (CDC). Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014;63(RR-5):1–30.
13. Finer LB, Philbin JM. Sexual initiation, contraceptive use, and pregnancy among young adolescents. Pediatrics. 2013;131(5):1–6.
14. Data available on request from Merck Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package VACC-1163821-0000.
15. Centers for Disease Control and Prevention (CDC). Addressing parents' top questions about HPV vaccine. http://www.cdc.gov/vaccines/who/teens/for-hcp-tipsheet-hpv.pdf. Updated January 2016. Accessed February 10, 2016.
16. Centers for Disease Control and Prevention (CDC). HPV vaccine information for clinicians. http://www.cdc.gov/hpv/
hcp/need-to-know.pdf. Updated November 2015.
Accessed February 10, 2016.
17. National Foundation for Infectious Diseases (NFID). Call to action: HPV vaccination as a public health priority. http://www.nfid.org/homepage/additional-offerings/hpv-call-to-action.pdf. Published August 2014. Accessed February 11, 2016.
18. Centers for Disease Control and Prevention (CDC). Human papillomavirus vaccination coverage among adolescents, 2007–2013, and postlicensure vaccine safety monitoring, 2006–2014—United States. MMWR Morb Mortal Wkly Rep. 2014;63(29):614–624.
19. American Academy of Family Physicians (AAFP). Strong recommendation to vaccinate against HPV is key to boosting uptake. http://www.aafp.org/news/health-of-the-public/20140212hpv-vaccltr.html. Published February 12, 2014. Accessed February 11, 2016.
20. Data available on request from Merck Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package VACC-1096399-0000.

Efficacy of GARDASIL 9

Original 4 HPV types

Established efficacy for HPV Types 6, 11, 16, and 18

Efficacy against diseases caused by HPV Types 6, 11, 16, and 18 was inferred from non-inferiority by comparisons of geometric mean titers (GMTs) for GARDASIL 9 vs GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

In clinical studies of young men and women 16 to 26 years of age naïve to HPV Type 6, 11, 16, or 18, efficacy of GARDASIL wasa:

  • Cervical cancer
    HPV 16- and 18-related CIN 2/3 or AIS
    98% efficacy
  • Vulvar/vaginal cancer
    HPV 16- and 18-related VIN 2/3 and VaIN 2/3
    100% efficacy
  • Anal cancer
    HPV 6-, 11-, 16-, and 18-related AIN 2/3
    75% efficacy
  • Genital warts
    HPV 6- and 11-related
    89% efficacy in males
    99% efficacy in females

See efficacy for additional 5 HPV types >

Study results for data above:

  • Cervical: 2 CIN 2/3 or AIS cases in the group receiving GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] (n=8,493) vs 112 cases in the group receiving placebo (n=8,464) [95% CI, 93.5–99.8]
  • Vulvar/Vaginal: no VIN 2/3 or VaIN 2/3 cases in either group receiving GARDASIL (n=7,772) vs 10 cases in the VIN 2/3 group receiving placebo (n=7,744) [95% CI, 55.5–100.0], and 9 cases in the VaIN 2/3 group receiving placebo (n=7,744) [95% CI, 49.5–100.0]
  • Anal: 3 AIN 2/3 cases in the male group receiving GARDASIL (n=194) vs 13 cases in the male group receiving placebo (n=208) [95% CI, 8.8–95.4]
  • Genital Warts: 3 genital warts cases in the male group receiving GARDASIL (n=1,394) vs 28 cases in the male group receiving placebo (n=1,404) [95% CI, 65.3–97.9], and 2 genital warts cases in the female group receiving GARDASIL (n=6,932) vs 189 cases in the female group receiving placebo (n=6,856) [95% CI, 96.2–99.9]

aStudy Design: Efficacy of GARDASIL was assessed in 5 AAHS-controlled, double-blind, randomized clinical studies evaluated 24,596 individuals (20,541 girls and women 16 to 26 years of age and 4,055 boys and men 16 to 26 years of age at enrollment). Subjects received all 3 vaccinations within 1 year of enrollment, had no major deviations from the study protocol, were naïve to the relevant HPV type(s) (Types 6, 11, 16, and 18) prior to dose 1, and remained PCR negative to the relevant HPV type(s) through 1 month postdose 3 (Month 7).

AAHS=amorphous aluminum hydroxyphosphate sulfate.
AIN=anal intraepithelial neoplasia.
AIS=adenocarcinoma in situ.

Additional 5 HPV types

Demonstrated clinical efficacy against 5 more HPV types

In a worldwide clinical study of young women 16 to 26 years of age naïve to HPV Type 31, 33, 45, 52, or 58a:

  • Cervical cancer CIN 2/3, AIS
    Vulvar cancer VIN 2/3
    Vaginal cancer VaIN 2/3
    97% efficacy
    HPV 31-, 33-, 45-, 52-, and 58-related
  • One case in group receiving GARDASIL 9 (n=6,016) vs 30 cases in
    group receiving GARDASIL® [Human Papillomavirus Quadrivalent
    (Types 6, 11, 16, and 18) Vaccine, Recombinant] (n=6,017)
    [95% CI, 80.9–99.8]

See efficacy for additional 4 HPV types >

aStudy Design: Efficacy of GARDASIL 9 in 16- to 26-year-old women was assessed in an active comparator-controlled, double-blind, randomized clinical study that included a total of 14,204 women (GARDASIL 9=7,099; GARDASIL=7,105). Subjects were followed up with a median duration of 40 months (range 0 to 64 months) and efficacy was measured starting after the Month 7 visit. Efficacy was evaluated in subjects who received all 3 vaccinations within 1 year of enrollment, had no major deviations from the study protocol, were naïve to the relevant HPV type(s) prior to dose 1, and remained PCR negative to the relevant HPV type(s) through 1 month postdose 3 (Month 7).

AIN=anal intraepithelial neoplasia.
AIS=adenocarcinoma in situ.
CIN=cervical intraepithelial neoplasia.
PCR=polymerase chain reaction.
VaIN=vaginal intraepithelial neoplasia.
VIN=vulvar intraepithelial neoplasia.

Other Clinical End Points

Data for other clinical end pointsa

In a worldwide clinical study of young women 16 to 26 years of age naïve to HPV Type 31, 33, 45, 52, or 58a:

93% efficacyagainst HPV 31-, 33-, 45-, 52-, and 58-related ASC-US HR-HPV positive or worse Pap abnormality
Thirty-five cases in group receiving GARDASIL 9 (n=5,881) vs 462 cases in group receiving GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] (n=5,882) [95% CI, 89.7–94.8]
97% efficacyagainst HPV 31-, 33-, 45-, 52-, and 58-related biopsy
Seven cases in group receiving GARDASIL 9 (n=6,016) vs 222 cases in group receiving GARDASIL (n=6,017) [95% CI, 93.6–98.6]
88% efficacyagainst HPV 31-, 33-, 45-, 52-, and 58-related definitive therapyb
Four cases in group receiving GARDASIL 9 (n=6,012) vs 32 cases in group receiving GARDASIL (n=6,014) [95% CI, 65.7–96.0]

aStudy Design: Efficacy of GARDASIL 9 in 16- to 26-year-old women was assessed in an active comparator-controlled, double-blind, randomized clinical study that included a total of 14,204 women (GARDASIL 9=7,099; GARDASIL=7,105). Subjects were followed up with a median duration of 40 months (range 0 to 64 months) and efficacy was measured starting after the Month 7 visit. Efficacy was evaluated in subjects who received all 3 vaccinations within 1 year of enrollment, had no major deviations from the study protocol, were naïve to the relevant HPV type(s) prior to dose 1, and remained PCR negative to the relevant HPV type(s) through 1 month postdose 3 (Month 7).

bIncluding loop electrosurgical excision procedure (LEEP) and conization.

ASC-US=atypical squamous cells of undetermined significance.
HR=high-risk.

Indication for GARDASIL 9

GARDASIL 9 is a vaccine indicated in females 9 through 26 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 26 years of age for the prevention of anal cancer caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant) does not eliminate the necessity for girls to continue to undergo recommended cervical cancer screening later in life. Recipients of GARDASIL 9 should not discontinue anal cancer screening if it has been recommended by a health care professional.

GARDASIL 9 has not been demonstrated to provide protection against diseases from vaccine HPV types to which a person has previously been exposed through sexual activity.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, and anal cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, and anal cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58.

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

Select Safety Information for GARDASIL®9 9 (Human Papillomavirus 9-valent Vaccine, Recombinant)

GARDASIL 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].

Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following HPV vaccination. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion.

Safety and effectiveness of GARDASIL 9 have not been established in pregnant women.

The most common (≥10%) local and systemic adverse reactions in females were injection-site pain, swelling, erythema, and headache. The most common (≥10%) local and systemic reactions in males were injection-site pain, swelling, and erythema.

The duration of immunity of GARDASIL 9 has not been established.

There was an increase in injection-site swelling reported at the injection site for GARDASIL 9 when administered concomitantly with Menactra and Adacel. The majority of injection-site swelling adverse experiences were reported as being mild to moderate in intensity.


Dosage and Administration for GARDASIL 9

GARDASIL 9 should be administered intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh.

  • For individuals 9 through 14 years of age, GARDASIL 9 can be administered using a 2-dose or 3-dose schedule. For the 2-dose schedule, the second dose should be administered 6–12 months after the first dose. If the second dose is administered less than 5 months after the first dose, a third dose should be given at least 4 months after the second dose. For the 3-dose schedule, GARDASIL 9 should be administered at 0, 2 months, and 6 months.
  • For individuals 15 through 26 years of age, GARDASIL 9 is administered using a 3-dose schedule at 0, 2 months, and 6 months.

Before administering GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant), please read the Prescribing Information. The Patient Information also is available.

VACC-1206510-0000 03/17