PPA News

Posted by: Brandy Zeller on Jul 2, 2015

By: Erin Tibbetts, PharmD candidate and Kelly L. Matson, BSNutr, PharmD

Human Papillomavirus 9-valent Vaccine and Food and Drug Administration (FDA) Indications

On December 10, 2014, the U.S. FDA approved the 9-valent human papillomavirus (HPV) vaccine (9vHPV, Gardasil 9) for prevention of cervical, vulvar, vaginal and anal cancer as well as for prevention of genital warts.1 9vHPV includes the four types covered by the quadrivalent HPV vaccine, 4vHPV (types 6, 11, 16 and 18), with additional coverage of types 31, 33, 45, 52 and 58.2 Expanded coverage provided by the new vaccine is expected to reduce cancer caused by HPV types 31, 33, 45, 52 and 58 by 13% and all HPV-related cancer by over 90%.3 In clinical trials, more than 99% of participants seroconverted for the 9 types found in 9vHPV; the immune response to the 4 types found in 4vHPV was noninferior when comparing the two vaccines.4

9vHPV is indicated in females aged 9 to 26 years for prevention of cervical, vulvar, vaginal and anal cancer caused by types 16, 18, 31, 33, 45, 52 and 58 as well as prevention of genital warts caused by types 6 and 11.2 In addition, 9vHPV is indicated for prevention of cervical intraepithelial neoplasia grade 2/3, cervical adenocarcinoma in situ, cervical intraepithelial neoplasia grade 1, vulvar intraepithelial neoplasia grades 2 and 3, vaginal intraepithelial neoplasia grades 2 and 3 and anal intraepithelial neoplasia grades 1, 2 and 3.2 9vHPV is also indicated in males aged 9 to 15 years for prevention of anal cancer caused by types 16, 18, 31, 33, 45, 52 and 58, for prevention of genital warts caused by types 6 and 11, and for prevention of anal intraepithelial neoplasia grades 1, 2 and 3.2

Dosing Schedule

Routine vaccination should begin between the ages of 11 and 12 years in both males and females. 9vHPV is a three-dose series supplied as a 0.5 mL intramuscular injection. The second dose should be given 2 months after the first dose. The third and final dose of 9vHPV should be given 6 months after the first dose. If doses are given later than the recommended schedule, the next dose should be given as soon as possible and the series does not need to be started over again.4

Advisory Committee on Immunization Practices (ACIP)

Recommendations In February 2015, ACIP developed recommendations for use of 9vHPV.4 Vaccination should be routinely initiated in males and females at 11 or 12 years of age but may begin as early as 9 years of age. Females who are unvaccinated or who have not completed the 3-dose series should be vaccinated between ages 13 and 26 years. Males aged 13 through 21 years who are unvaccinated or who have not completed the 3-dose series should also be vaccinated. 9vHPV vaccination is recommended through age 26 years in men who have sex with men or who are immunocompromised.4 If a patient has previously received 4vHPV without completing the series, it may be continued or completed with either 4vHPV or 9vHPV, if available, in both males and females. Additionally, females may complete the series with the 2vHPV vaccine. The efficacy of 9vHPV is unknown if the complete 3-dose series is not given. Vaccination should not be delayed based on availability of 9vHPV and efforts should be made to continue on schedule. 4

Side Effects and Additional Warnings

The most common side effects associated with 9vHPV in clinical trials were pain, swelling and erythema at the injection site.4 Less common side effects include headache, fever, nausea, dizziness and fatigue. Injection site reactions were more common in clinical trials for 9vHPV than in trials for 4vHPV; however, these reactions were transient and largely minor to moderate in intensity.2, 4 Five serious adverse events that were determined to be vaccine-related occurred in almost 14,000 vaccinations with 9vHPV: these events included pyrexia, allergy to vaccine, asthmatic crisis, headache and tonsillitis.2

Contraindications to 9vHPV include hypersensitivity to yeast or to a previous dose of 4vHPV or 9vHPV.2 Patients should be observed for 15 minutes following vaccination as syncope may occur leading to fall or injury.2

Safety after Vaccination with 4vHPV or Concomitant Vaccination with MCV4 and Tdap

A clinical trial to establish safety of 9vHPV following 4vHPV reported similar safety profiles between patients who had previously received 4vHPV and patients who had never received a HPV vaccination. The time between doses varied between 12 and 36 months. The most notable finding was an increase in injection site swelling and erythema following 9vHPV administration in patients who previously received 4vHPV. 2

The safety of concomitant vaccination with Menactra (MCV4) and Adacel (Tdap) was also studied. Injection site reactions were similar between the concomitant and non-concomitant groups. Swelling was observed more in patients receiving concomitant vaccinations. Furthermore, simultaneous administration did not decrease antibody response to any of the vaccines.2

Additional Information for Patients

Vaccination against HPV does not replace the recommended annual cervical cancer screenings which should begin at age 21 years.4 Anal screening, if recommended by a health care provider, should also be continued. 9vHPV does not provide protection for disease caused by previous exposure to HPV or any other sexually transmitted diseases, so it is important for patients to use protection during sexual intercourse.2 HPV vaccine is not recommended for use in pregnant women; if pregnancy occurs during the 3-dose series, the remainder of the series should be completed after pregnancy ends.4


1. U.S Food and Drug Administration. FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV. 10 December 2014. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm426485.htm. Accessed 2015 May 23.

2. Gardasil 9 (Human Papillomavirus 9-valent Vaccine) [package insert]. Merck Sharp & Dohme Corp; Whitehouse Station (NJ): February 2015.

3. Saraiya M, Unger ER, Thompson TD, Lynch CF, Hernandez BY, Lyu CW, et al. US Assessment of HPV Types in Cancers: Implications for Current and 9-valent HPV Vaccines. J Natl Cancer Inst. 2015; 107(6) djv086doi:10.1093/jnci/djv086.

4. Petrosky E, Bocchini JA, Hariri S, Chesson H, Curtis CR, Saraiya M, et al. 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): 300-4.