By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved a 9-valent human papillomavirus (HPV) vaccine. The new vaccine covers five more types of HPV than the previous vaccine and protects against 90% of the HPV strains that cause cervical cancer.1 The new vaccine is marketed by Merck as Gardasil®9.

INDICATIONS

HPV-9 vaccine is indicated in girls and women ages 9 through 26 years of age for the prevention of cervical, vulvar, vaginal, and anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; and genital warts by HPV types 6 and 11.2 It is also indicated for the prevention of precancerous or dysplastic lesions (cervical, vulvar, anal, and vaginal intraepithelial neoplasia (CIN, VIN, AIN, VaIN) and cervical adenocarcinoma (AIS). HPV-9 is also indicated in boys ages 9-15 years to prevent anal cancer, genital warts, and precancerous or dysplastic lesions (anal intraepithelial neoplasia).

DOSAGE

The recommended dose is one injection (0.5 mL) intramuscularly, with follow-up injections at 2 and 6 months. HPV-9 can be given concomitantly with meningococcal vaccine (Menactra) and Tdap (Adacel). HPV-9 is supplied as a single-dose vial or prefilled syringe.

POTENTIAL ADVANTAGES

The relative contributions increase the overall coverage for cervical cancer-causing strains to 90% wordwide and to 95% in North America.1

POTENTIAL DISADVANTAGES

The duration of immunity has not been established.2 The most frequent adverse events are injection site pain (72-90%), injection site swelling (27-49%), and injection site erythema (25-42%).2 Injection site reactions appear to be more frequent in girls and women than boys. Injection site reactions were numerically higher for HPV-9 vs. HPV-4. Syncope may occur, so observation for 15 minutes after administration is recommended.

COMMENTS

The clinical studies with HPV-9 were based on the efficacy of HPV-4.2 In a large study in girls and women ages 16-26 years (n = 14,204) who were naïve to the relevant HPV types, HPV-9 was compared to HPV-4. The primary endpoint was efficacy for the five additional HPV types (31, 33, 45, 52, and 58) at the 7-month visit. HPV-9 showed > 90% efficacy against cervical, vaginal, and vulvar cancers, cervical intraepithelial neoplasia, HPV-related vulvar or vaginal disease, HPV-related persistent infection, abnormal Pap test, HPV-related biopsy, and 88% protection against definitive therapy (loop electrosurgical excision procedure and conization) related to the five HPV types. Effectiveness against the four previous HPV types were considered noninferior based on comparable geometric mean titers (GMTs) between HPV-9 and HPV-4. The effectiveness in girls and boys ages 9-15 years were inferred from GMTs.2 For all nine HPV types, the GMTs were 2-3-fold higher for the younger population relative to girls/women ages 16-26 years.2 In subjects previously vaccinated with HPV-4, seropositivity was 98% or higher with HPV-9. Anti-HPV titers for types 31,33, 45, 52, and 58 were 25-63% of the titer seen in previously unvaccinated subjects.2 The clinical relevance of this observation is not known.

CLINICAL IMPLICATIONS

HPV-9 vaccine provides additional coverage for about 20% of cervical cancers and 25%-30% of cervical precancers (CIN1, and CIN2/3) compared to the previous HPV vaccine.3 The recommendation for use of HPV-9 will be considered at the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practice meeting in February 2015.4 The wholesale cost is $489 for three doses.

REFERENCES

  1. Serrano B, et al. Infectious Agents and Cancer 2012;7:38.
  2. Gardasil 9 Prescribing Information. Merck and Company December 2014.
  3. http://www.cdc.gov/vaccines/acip/meetings/downloads/slides-oct-2013/03-HPV-luxembourg.pdfAccessed 12/20/14.
  4. http://aapnews.aappublications.org/content/early/2014/12/11/aapnews.20141211-1.full.pdf+html. Accessed 12/20/14.