(Published May 2013)
Background Information on HPV Vaccines
- In June 2006, the FDA approved the quadrivalent vaccine for HPV 6, 11, 16, and 18 (Gardasil), manufactured by Merck and Co., Inc., for use in females ages 9 to 26.
- In November 2006, the HPV quadrivalent vaccine was included in the Vaccines for Children Program, a federally funded vaccine program that provides vaccines for free to both children and adolescents through their 19th birthday who are uninsured or underinsured.
- In 2007, the Advisory Committee on Immunization Practices (ACIP), a CDC advisory committee, released recommendations for using the HPV vaccine. ACIP recommended routine vaccination of girls ages 11 to 12 and catch-up vaccination for girls and young women ages 13 to 26. The vaccination series can be started as young as age 9.
- In October 2009, the FDA approved the bivalent vaccine for HPV 16 and 18 (Cervarix), manufactured by GlaxoSmithKline, for use in females ages 10 to 25. In 2011, the approval for Cervarix was extended to girls as young as age 9.
- In October 2011, ACIP recommended routine use of the quadrivalent HPV vaccine (Gardasil) for boys ages 11 to 12 as well as males ages 13 to 21 who have not yet been vaccinated. Males ages 22 to 26 may also be vaccinated. The vaccination series can be started as young as age 9.
|Table 5: Comparison of HPV Vaccines1-12|
|Targeted HPV types||6, 11, 16, 18||16, 18|
|HPV-related diseases potentially prevented||Cervical cancer and precancer, vulvar and vaginal cancer and precancer, penile, anal, and oropharyngeal cancers, low-grade lesions.
External genital warts.
|Cervical cancer and precancer, vulvar and vaginal cancer and precancer, penile, anal, and oropharyngeal cancers, low-grade lesions.|
|Indication||Females ages 9 to 26 for prevention of cervical cancer; cervical, vaginal, vulvar, and cancer precursors; and genital warts related to the four HPV types targeted by the vaccine.
Males ages 9 to 26 years for prevention of anal cancer and anal cancer precursors and genital warts.
Data are not available on the efficacy for prevention of penile and oropharyngeal
|Females ages 9 to 25 for prevention of cervical cancer and cervical cancer precursors.|
|Dosing and administration||Intramuscular injection of three separate 0.5-mL doses at 0, 2, and 6 months.||Intramuscular injection of three separate 0.5-mL doses at 0, 1, and 6 months.|
|Efficacy||Among young women (ages 16–26 years) who previously had not been exposed to any of the four HPV types in the vaccine:
In men (ages 16 to 26 years) not previously exposed to the four HPV types in the vaccine, there was 90% vaccine efficacy in preventing genital warts and 75% efficacy in preventing anal precancers.
|Among young women (ages 15–25 years) who previously had not been exposed to either of the two HPV types in the vaccine:
100% efficacy in preventing CIN3+ caused by the targeted HPV types
|Most common adverse events||Syncope (fainting), injection site pain and redness, dizziness, nausea, headache. Itchiness at the injection site and mild or moderate fever have also been reported.
To reduce fainting, prescribing information recommends that patients remain seated for 15 minutes after vaccination.
|Syncope (fainting), injection site pain and redness, dizziness, nausea, headache.
To reduce fainting, prescribing information recommends that patients remain seated for 15 minutes after vaccination.
|Other adverse events||Rates of serious adverse events similar between placebo and treated groups in clinical trials; vaccine-related serious adverse events occurred in 0.1% of more than 29,000 female and male participants.
Since 2006, 6% of all reports described serious adverse events. No current evidence suggests that the HPV vaccine caused the adverse events.
|Low rates of events in more than 30,000 females in clinical trials.
Rates of serious adverse events similar between placebo and treated groups in clinical trials; no subject withdrawals due to serious adverse events.
*ITT = intention-to-treat. ITT analysis includes all subjects who begin treatment,
whether or not they complete the study.
Frequently Asked Questions
The answers to these questions are based on information from ACIP and CDC.2,10
What is the target age for the vaccine? According to ACIP recommendations, the target age is 11 to 12 years old for routine vaccination of females, although the series can be started as young as age 9.
What about missed vaccines? If the schedule for either HPV vaccine is interrupted, the vaccine series does not need to be restarted. If the interruption occurs after the first dose, the second dose should be administered as soon as possible, and the second and third doses should be separated by an interval of at least 12 weeks. If only the third dose is delayed, it should be administered as soon as possible.
Can a female start the series with one vaccine and finish with another vaccine? When feasible, the same vaccine should be used throughout the series. If a provider does not know what vaccine was used for the first dose, either vaccine can be used to complete the series and provide protection against HPV 16 and 18. Fewer than three doses of the quadrivalent vaccine may provide less protection against HPV 6 and 11 and therefore less protection against genital warts.
Does it make sense for a female older than 12 to be vaccinated? “Catch-up” vaccines can be given to females ages 13 to 26 who were not previously vaccinated or who did not complete the full series. Vaccinating a woman who has already been sexually active also could offer some benefit. Even if she is already sexually active, she may not have been exposed yet to the HPV types against which the vaccines offer protection. Although the vaccine may not provide full protection, it may provide some benefit.
Who should not receive the vaccine? According to ACIP recommendations, the HPV vaccine should not be administered to:
- Children below the age of 9 years.
- Pregnant women. Both vaccines are designated as Pregnancy Category B; their use has not been associated with adverse outcomes of pregnancy or adverse events to the developing fetus. However, because data on vaccination in pregnancy are limited, it is recommended that vaccination be postponed until after delivery. If a woman has started the series and has been found to be pregnant, she should discontinue the series and recommence after delivery.
- Individuals with a history of immediate hypersensitivity to any vaccine component or to yeast.
- Individuals with anaphylactic latex allergy should not be given prefilled syringes of the bivalent HPV vaccine. Single-dose vials of the bivalent vaccine contain no latex.
Administration should be delayed in individuals with moderate or severe acute illnesses (although it can be administered to individuals with minor acute illnesses, such as diarrhea or mild upper respiratory infection). The vaccine CAN be administered to immunocompromised individuals; however, efficacy might be less than that in immunocompetent individuals.
How does previous HPV exposure affect the efficacy of the vaccine? The HPV vaccines are preventive rather than therapeutic. The vaccines are effective in preventing HPV-related disease associated with HPV types to which an individual has not yet been exposed. It is not effective in preventing infection with HPV types to which an individual has already been exposed.
Why shouldn’t I test for HPV status before vaccination? Pap testing and screening for HPV are not needed before vaccination. Many women have not been exposed to all HPV types present in the vaccines, making pretesting an unnecessary and additional burden and expense.
My patients don’t understand why they need to continue cervical cancer screening after vaccination. What should I tell them? It is important for females who receive the HPV vaccine to continue with regular cervical cancer screening for three reasons:
- The vaccines do not protect against all of the HPV types that cause cervical cancer. Rather, the vaccines protect against HPV types that are responsible for 70% of cervical cancers.
- An individual may be at risk for HPV-related disease if she was infected with a high-risk type of HPV before vaccination.
- An individual who does not complete the vaccine series may not receive the full benefits of the vaccine and thus may be at risk for HPV-related disease.
Do the vaccines provide cross-protection to other HPV types? Research has shown that both vaccines offer some cross-protection against other HPV types.13,14 At this time, however, Cervarix and Gardasil are indicated only for protection against disease caused by the vaccine relevant HPV types—16 and 18 in both vaccines and 6 and 11 in Gardasil.
Does the quadrivalent vaccine provide protection against external genital warts? Yes. In a combined analysis of three clinical trials, the efficacy of the quadrivalent vaccine was 98.9% against external genital warts that were associated with the HPV types included in the quadrivalent vaccine.4
Does the HPV vaccine help treat existing disease? No. Because HPV vaccines are preventive rather than therapeutic, they are not effective against existing disease, including existing HPV infection, cervical cytological abnormalities, and external genital warts. It is important to note that there is no evidence that the vaccines exacerbate existing disease. Young women who have had HPV infection and cervical treatment may be vaccinated, as it is not likely that they have been infected by all of the vaccine relevant types.
When counseling a patient about HPV vaccination, make sure your patient understands these points before leaving your office or clinic:
Patient Education Fact Sheet: Understanding HPV Vaccines
- Harper DM, Ranco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet. 2006;367(9518):1247-55.
- Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER; Centers for Disease Control and Prevention; Advisory Committee on Immunization Practices. Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2007;56(RR-2):1-24.
- Pedersen C, Petaja T, Strauss G, et al. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant. J Adolesc Health. 2007;40:564-71.
- Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356(19):1928-43.
- Dunne EF, Markowitz LE, Chesson H, et al. Centers for Disease Control and Prevention; Advisory Committee on Immunization Practices. Recommendations on the Use of Quadrivalent Human Papillomavirus Vaccine in Males—Advisory Committee on Immunization Practices (ACIP), 2011. MMWR. 2011;60(50):1705-8.
- Food and Drug Administration. Gardasil vaccine safety: Information from CDC and FDA on the safety of Gardasil vaccine. Available at: www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm179549.htm. Accessed June 30, 2012.
- Food and Drug Administration. Package Insert for Gardasil. Available at: www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM111263.pdf. Accessed June 30, 2012.
- Food and Drug Administration. Package Insert for Cervarix. Available at: www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM186981.pdf. Accessed June 30, 2012.
- Centers for Disease Control and Prevention. Frequently Asked Questions About HPV Vaccine Safety. Available at: www.cdc.gov/vaccinesafety/Vaccines/HPV/hpv_faqs.html. Accessed June 30, 2012.
- Centers for Disease Control and Prevention. HPV Vaccine Information for Clinicians – Fact Sheet. Available at: www.cdc.gov/std/HPV/STDFact-HPV-vaccine-hcp.htm. Accessed June 30, 2012.
- Centers for Disease Control and Prevention. FDA Licensure of Bivalent Human Papillomavirus Vaccine (HPV2, Cervarix) for Use in Females and Updated HPV Vaccination Recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR. 2010:59(20);626-9.
- Lehtinen M, Paavonen J, Wheeler CM, et. al. HPV PATRICIA Study Group. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomized, double-blind PATRICIA trial. Lancet Oncol. 2012:13(1):89-99.
- Wheeler CM, Castellsague X, Garland SM, et. al. HPV PATRICIA Study Group. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomized, double-blind PATRICIA trial. Lancet Oncol. 2012:13(1):100-10.
- Brown DR, Kjaer SK, Sigurdsson K, et al. The impact of quadrivalent human papillomavirus (HPV; types 6,11,16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naïve women aged 16-26 years. J Infect Dis. 2009;199(7):926-35.