Vaccine Preventable Diseases

Human Papillomavirus

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Advisory Committee on Immunization Practices (ACIP) Recommendations

Adolescents and Adults
- All males and females without contraindications ages 11-12 years should receive two doses of HPV vaccine administered at least 6 months apart.
- Vaccination can be started as young as 9 years of age.
- Those who start the series after the age of 15 should receive three doses of HPV vaccine, with the second and third doses administered 1-2 months and 6 months after the first dose, respectively.
- If not previously vaccinated, catch-up vaccination is recommended for all males through age 21 and females through age 26.
- If doses are delayed there is no need to repeat doses since increasing the interval between doses is generally associated with enhanced immune responses [1, 2].

For More Information
ACIP recommendations: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/hpv.html
Immunization schedules: http://www.cdc.gov/vaccines/schedules/index.html
 

Disease 

HPV is a small DNA virus that is transmitted by direct contact with an infected person. Over 120 types of HPV have been identified, about 80 of which infect nonmucosal epithelium and 40 of which infect the mucosal and genital epithelium. Infection with one HPV type does not necessarily prevent later infection with another type. Genital HPV infection is generally transmitted via direct sexual contact, but can rarely be transmitted by nonsexual routes. Risk of transmission is reduced but not eliminated by using physical barriers such as condoms. HPV is the most common sexually transmitted infection in the U.S., with an estimated 79 million persons currently infected. 14 million new infections are estimated to occur each year, about half of which are in persons 15-24 years old. HPV infection often occurs very soon after onset of sexual activity, further illuminating the need for vaccination well prior to the onset of sexual activity. Infected mothers can transmit HPV to their infants during childbirth resulting in juvenile onset recurrent respiratory papillomatosis. Onset can occur at up to 18 years of age [3].

Although HPV infection is quite common, most infections are asymptomatic and resolve spontaneously. Possible clinical manifestations include anogenital warts, recurrent respiratory papillomatosis, cervical intraepithelial neoplasia (CIN), and cancer [1]. High-risk HPV types, including types 16, 18, 31, 45 and others, can cause high-grade cervical lesions and cancer, as well as vulvar, vaginal, penile, anal, and oropharyngeal cancers. HPV has been detected in 99% of cervical cancers (of which 70% are types 16 and 18), as well as 70% of vulvar and vaginal cancers (49-55% type 16), 91% of anal cancers (77% type 16), 72% of oropharyngeal cancer (61% type 16), and 40-50% of penile cancers [3]. Infection with several low-risk HPV types (such as types 6 and 11) can cause low-grade cervical cell abnormalities, anogenital warts, and laryngeal papillomas [1]. In the U.S. between 2006 to 2010, an average of 33,160 HPV-associated cancers were diagnosed annually, 62% were among females and 38% among males [3].

Vaccine

HPV vaccines are subunit vaccines using a recombinant HPV L1 major capsid protein as the vaccine antigen. These L1 proteins self-assemble into virus-like particles (VLP), which are both noninfectious and nononcogenic [1].

HPV vaccines include bivalent (abbreviation: 2vHPV; trade name: Cervarix®), quadrivalent (4vHPV; Gardasil®), and 9-valent (9vHPV; Gardasil 9®) vaccines. However, as of late 2016, only 9vHPV is being distributed in the U.S. 9vHPV includes HPV types 16, 18, 6, 11, 31, 33, 45, 52, and 58 [2].

Vaccine Effectiveness: HPV vaccines are very immunogenic, with at least 97.9% of vaccine recipients developing antibody responses to all the types included in their respective vaccines after completing the two-dose series. Estimates of efficacy against cervical intraepithelial neoplasia (CIN) after three doses have ranged from 93-97%, depending on the vaccine. 4vHPV efficacy against genital warts related to vaccine types after three doses was shown to be 99% in women and 88% in men. Studies comparing two doses to three doses and 9vHPV to 4vHPV have shown noninferior immunogenicity [1, 2, 4].

Vaccine Safety: Mild local reactions such as pain and swelling are the most common adverse reactions following HPV vaccination, reported in 20-90% of recipients [1]. Because syncope has been reported among adolescents receiving vaccinations, adolescent recipients should always receive the vaccine while sitting and not in view of others awaiting vaccination, and be observed for up to 15 minutes immediately after vaccination [5-8].

HPV vaccines are among the most rigorously studied vaccines for safety; except for very rare occurrences of anaphylaxis, no serious adverse events have been associated with HPV vaccination. Severe allergic reaction (e.g. anaphylaxis) to a previous dose or vaccine component is a contraindication to further HPV vaccination [1].

Contraindications and Precautions: Severe allergic reaction (e.g. anaphylaxis) to a previous dose or vaccine component is a contraindication to further HPV vaccination. 2vHPV is contraindicated for persons with anaphylactic latex allergy. 4vHPV and 9vHPV are contraindicated for persons with a history of immediate hypersensitivity to yeast. HPV vaccination is not recommended during pregnancy. Current moderate to severe acute illness is a precaution to any vaccination [1, 2, 4].

Considerations in Pregnancy: HPV vaccines are not routinely recommended in pregnancy due to limited available safety data. However, if a woman is discovered to be pregnant after receiving HPV vaccine, no intervention is indicated. The remaining doses in the series should be delayed until after the pregnancy [4].

Rates of adverse outcomes (e.g. spontaneous abortions, late fetal deaths, and congenital anomalies) among females reporting pregnancy during the HPV4 clinical trials were consistent between vaccine and placebo groups as well as with those in surveillance registries of women who received one or more doses during pregnancy. In addition, a postlicensure registry enrolled more than 2,800 females who received HPV vaccine within 1 month before their last menstrual period or anytime during pregnancy. The rates of spontaneous abortions and major birth defects among these women were not greater than those of a comparison unexposed population [3].

References

1. Epidemiology and Prevention of Vaccine-Preventable Diseases. Washington D.C.: Centers for Disease Control and Prevention; 2015.
2. 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 Morbidity and mortality weekly report 2016;65:1405-8.
3. Markowitz LE, Dunne EF, Saraiya M, et al. Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014;63:1-30.
4. Petrosky E, Bocchini JA, Jr., Hariri S, et al. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morbidity and mortality weekly report 2015;64:300-4.
5. Braun MM, Patriarca PA, Ellenberg SS. Syncope after immunization. Archives of pediatrics & adolescent medicine 1997;151:255-9.
6. Syncope after vaccination--United States, January 2005-July 2007. MMWR Morbidity and mortality weekly report 2008;57:457-60.
7. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and reports : Morbidity and mortality weekly report Recommendations and reports 2011;60:1-64.
8. Bernard DM, Cooper Robbins SC, McCaffery KJ, Scott CM, Skinner SR. The domino effect: adolescent girls' response to human papillomavirus vaccination. The Medical journal of Australia 2011;194:297-300.