Human Papillomavirus in 2019: An Update on Vaccines and Dosing Recommendations

By Salina Zhang and Pelin Batur, MD

About 12% of women worldwide are infected with human papillomavirus (HPV).1 Persistent HPV infection with high-risk strains such as HPV 6, 11, 16 and 18 cause nearly all cases of cervical cancer and some anal, vaginal, penile, and oropharyngeal cancers.2 An estimated 13,000 cases of invasive cervical cancer will be diagnosed this year in the United States alone.3

Up to 70% of HPV-related cervical cancer cases can be prevented with vaccination. A number of changes have been made to the vaccination schedule within the past few years—patients younger than 15 need only 2 rather than 3 doses, and the vaccine itself can be used in adults up to age 45.

Vaccination and routine cervical cancer screening are both necessary to prevent this disease3 along with effective family and patient counseling. Here, we discuss the most up-to-date HPV vaccination recommendations, current cervical cancer screening guidelines, counseling techniques that increase vaccination acceptance rates, and follow-up protocols for abnormal cervical cancer screening results.

Types of HPV vaccines

HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts.4 The US Food and Drug Administration (FDA) has approved 3 HPV vaccines:

• Gardasil 9 targets HPV types 6, 11, 16 and 18 along with 31, 33, 45, 52, 58—these cause 90% of cervical cancer cases and most cases of genital warts5—making it the most effective vaccine available; Gardasil 9 is the only HPV vaccine currently available in the United States.
• The bivalent vaccine (Cervarix) targeted HPV 16 and 18 only, and was discontinued in the United States in 2016.
• The quadrivalent HPV vaccine (Gardasil) targeted HPV 16 and 18 as well as 6 and 11, which cause most cases of genital warts; the last available doses in the United States expired in May 2017; it has been replaced by Gardasil 9.

The incidence of cervical cancer in the United States dropped 29% among 15- to 24-year-olds from 2003–2006 when HPV vaccination first started to 2011–2014.6

Vaccine dosing recommendations for primary prevention

The Advisory Committee on Immunization Practices (ACIP) revised its HPV vaccine schedule in 2016, when it decreased the necessary doses from 3 to 2 for patients under age 15 and addressed the needs of special patient populations.7 In late 2018, the FDA approved the use of the vaccine in men and women up to age 45. However, no change in guidelines have yet been made.

In females, the ACIP recommends starting HPV vaccination at age 11 or 12, but it can be given as early as age 9. A 2-dose schedule is recommended for the 9-valent vaccine before the patient’s 15th birthday (the second dose 6 to 12 months after the first).7 For females who initiate HPV vaccination between ages 15 and 45, a 3-dose schedule is necessary (at 0, 1 to 2, and 6 months).7,8

The change to a 2-dose schedule was prompted by an evaluation of girls ages 9 to 13 randomized to receive either a 2- or 3-dose schedule. Antibody responses with a 2-dose schedule were not inferior to those of young women (ages 16 to 26) who received all 3 doses.9 The geometric mean titer ratios remained noninferior throughout the study period of 36 months.

However, a loss of noninferiority was noted for HPV-18 by 24 months and for HPV-6 by 36 months.9 Thus, further studies are needed to understand the duration of protection with a 2-dose schedule. Nevertheless, decreasing the number of doses makes it a more convenient and cost-effective option for many families.

The recommendations are the same for males except for one notable difference: in males ages 21 to 26, vaccination is not routinely recommended by the ACIP, but rather it is considered a “permissive use” recommendation: i.e., the vaccine should be offered and final decisions on administration be made after individualized discussion with the patient.10 Permissive-use status also means the vaccine may not be covered by health insurance. Even though the vaccine is now available to men and women until age 45, many insurance plans do not cover it after age 26.

Children of either sex with a history of sexual abuse should receive their first vaccine dose beginning at age 9.7

Immunocompromised patients should follow the 3-dose schedule regardless of their sex or the age when vaccination was initiated.10

For transgender patients and for men not previously vaccinated who have sex with men, the 3-dose schedule vaccine should be given by the age of 26 (this is a routine recommendation, not a permissive one).8

References

1. Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, de Sanjosé S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis. 2010;202(12):1789-1799. doi:10.1086/657321
2. de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancer attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 2012; 13(6):607-615. doi:10.1016/S1470-2045(12)70137-7
3. American Cancer Society. Key statistics for cervical cancer. www.cancer.org/cancer/cervical-cancer/about/key-statistics.html. Accessed February 14, 2019.
4. Thaxton L, Waxman AG. Cervical cancer prevention: immunization and screening 2015. Med Clin North Am. 2015;99(3):469–477. doi:10.1016/j.mcna.2015.01.003
5. McNamara M, Batur P, Walsh JME, Johnson KM. HPV update: vaccination, screening, and associated disease. J Gen Intern Med. 2016;31(11):1360-1366. doi:10.1007/s11606-016-3725-z
6. Guo F, Cofie LE, Berenson AB. Cervical cancer incidence in young US females after human papillomavirus vaccine introduction. Am J Prev Med. 2018;55(2):197-204. doi:10.1016/j.amepre.2018.03.013
7. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65(49):1405-1408. doi:10.15585/mmwr.mm6549a5
8. Centers for Disease Control and Prevention (CDC). Supplemental information and guidance for vaccination providers regarding use of 9-valent HPV vaccine Information for persons who started an HPV vaccination series with quadrivalent or bivalent HPV vaccine. www.cdc.gov/hpv/downloads/9vhpv-guidance.pdf. Accessed February 14, 2019.
9. Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA. 2013;309(17):1793-1802. doi:10.1001/jama.2013.1625
10. Markowitz LE, Dunne EF, Saraiya M, et al; 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-05):1-30. pmid:25167164

Note: This article was originally published in the Cleveland Clinic Journal of Medicine.