Committee Opinion
Number 641, September 2015
(Published Electronically Ahead of Print on July 24, 2015)
(This Committee Opinion Replaces Committee Opinion Number 588)


Committee on Adolescent Health Care
Immunization Expert Work Group

This Committee Opinion reflects emerging clinical and scientific advances as of the date issued and is subject to change. This information should not be construed as dictating an exclusive course of treatment or procedure to be followed.


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Human Papillomavirus Vaccination

ABSTRACT: Human papillomavirus (HPV) is associated with the development of anogenital cancer (including cervical, vaginal, vulvar, penile, and anal), oropharyngeal cancer, and genital warts. Human papillomavirus vaccination can significantly reduce the incidence of anogenital cancer and genital warts. Despite the benefits of HPV vaccines, only approximately one third of girls in the recommended age group have received all three vaccines. Compared with other vaccines recommended in the same age bracket, HPV vaccination rates in the United States are unacceptably low. It is crucial that obstetrician–gynecologists and other providers educate parents and patients on the benefits and safety of HPV vaccination. The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend routine vaccination with HPV vaccine for girls and boys. The 9-valent HPV vaccine is recommended by the Advisory Committee on Immunization Practices and was licensed by the U.S. Food and Drug Administration in December 2014 for girls and boys aged 11–12 years.


Summary of Recommendations

  • It is crucial that obstetrician–gynecologists and other providers educate parents and patients on the benefits and safety of human papillomavirus (HPV) vaccination.
  • The Centers for Disease Control and Prevention (CDC) and the American College of Obstetricians and Gynecologists (the College) recommend routine vaccination with HPV vaccine for girls and boys. Despite this recommendation, only approximately 50% of girls aged 13–17 years in the United States have received at least one vaccine dose; only 33% have received all three doses.
  • The target age for vaccination is 11–12 years for girls and boys.
  • The 9-valent HPV vaccine has been added to the Advisory Committee on Immunization Practices (ACIP) recommendations for girls and boys at the target age of 11–12 years with catch-up for females and males through age 26 years if not vaccinated in the target age.
  • Testing for HPV DNA is not recommended before vaccination in any group and if the patient is tested for HPV DNA and the results are positive, vaccination is still recommended.

Human papillomavirus is associated with the development of anogenital cancer (including cervical, vaginal, vulvar, penile, and anal), oropharyngeal cancer, and genital warts. Of the more than 100 HPV genotypes, 13 have been shown to cause cervical cancer (1). Most cases of all HPV-associated cancer are caused by HPV genotypes 16 and 18 (2–4). In the United States, HPV genotypes 16 and 18 account for 66% of cases of cervical cancer and HPV genotypes 31, 33, 45, 52, and 58 account for an additional 15% of cases of cervical cancer (4). For cervical intraepithelial neoplasia (CIN) 2+, 50–60% of cases are caused by HPV genotypes 16 and 18 and 25% of cases are caused by HPV genotypes 31, 33, 45, 52, and 58 (5). Approximately 90% of cases of genital warts are caused by HPV genotypes 6 and 11 (6).

Despite cervical cytology screening in the United States, each year cervical cancer is diagnosed in more than 12,000 women and nearly 4,000 die from the disease. Additionally, nearly 2.8 million abnormal Pap test results are identified annually (7).

Human papillomavirus vaccination can significantly reduce the incidence of anogenital cancer and genital warts. Additionally, HPV vaccination may decrease the incidence of oropharyngeal cancer as well as maternal passage of HPV to infants, which results in recurrent laryngeal papillomatosis, although definitive prevention trials have not been completed for these two disease endpoints (8). In the United States, the prevalence of vaccine-type HPV decreased 56% among females aged 14–19 years between 2006 when the quadrivalent HPV vaccine was introduced and 2010 (9). Despite the benefits of HPV vaccines, only approximately one third of girls in the recommended age group have received all three vaccines. Compared with other vaccines recommended in the same age bracket, HPV vaccination rates in the United States are unacceptably low (10).

Human Papillomavirus Vaccines

The U.S. Food and Drug Administration (FDA) has approved three vaccines shown to be effective at preventing HPV infection. All three vaccines are given in a three-dose series with a schedule of 0, 1–2, and 6 months. The durability of the immune response (ie, how long protection lasts) is being monitored in various long-term studies, and there currently is no indication for a booster vaccine (11). The series does not need to be restarted if there is a delay in administration of the second or third dose.

  Although obstetrician–gynecologists are not likely to care for many patients in the initial HPV vaccination target group, they have the opportunity to educate mothers about the importance of vaccinating their children at the recommended age. Furthermore, obstetrician–gynecologists play a critical role in vaccinating adolescent girls and young women during the catch-up period. Vaccination is not associated with an earlier onset of sexual activity (12) or increased incidence of sexually transmitted infections (13).

Timing of Vaccination

The Advisory Committee on Immunization Practices and the College recommend HPV vaccination for girls and boys at the target age of 11–12 years as part of the adolescent immunization platform in order to help reduce the incidence of anogenital cancer and genital warts associated with HPV infection. Bivalent, quadrivalent, and 9-valent vaccines are recommended for females aged 9–26 years and quadrivalent and 9-valent vaccines are recommended for males aged 9–26 years. Human papillomavirus vaccination of girls at an earlier age (9–14 years versus 15–26 years) results in higher antibody levels. Although it is not known whether this more robust immune response correlates with greater vaccine efficacy, this may be another reason supporting earlier vaccination of girls aged 9–14 years. Earlier vaccination also is preferred because the vaccines are most effective when given before the onset of sexual activity and statistics show that one in three 9th graders and two in three 12th graders have engaged in sexual intercourse (13, 14).

In Sweden, vaccine effectiveness in preventing genital warts was 93% among girls vaccinated between ages 10 years and 13 years compared with 48% and 21% if vaccinated at ages 20–22 years and 23–26 years, respectively (15). All of these findings underscore the importance of vaccination at the target age (11–12 years) and before the onset of sexual activity. Although a reduced two-dose schedule is recommended by the World Health Organization (WHO) for those aged 9–13 years, this dosage schedule currently is not recommended by the ACIP or the College for any age.

Vaccination is recommended regardless of sexual activity or exposure to HPV. Although the vaccine may be less effective in sexually active individuals, it is expected that some benefit will be experienced because prior sexual exposure to all vaccine types is unlikely (16, 17). Vaccination is recommended even if the patient is tested for HPV DNA and the results are positive. Testing for HPV DNA is not recommended before vaccination in any group.

9-valent Human Papillomavirus Vaccine

The 9-valent HPV vaccine is recommended by ACIP and was licensed by the FDA in December 2014 for girls and boys aged 11–12 years. Catch-up vaccination for females and males through age 26 years is recommended for those not vaccinated at the target age of 11–12 years. In a phase III efficacy trial comparing the 9-valent HPV vaccine with the quadrivalent HPV vaccine among approximately 14,000 females aged 16–26 years, the 9-valent HPV vaccine had high efficacy for prevention of greater than or equal to CIN 2, vulvar intraepithelial neoplasia (VIN) 2 or 3, and vaginal intraepithelial neoplasia 2 or 3 due to HPV genotypes 31, 33, 45, 52, and 58 (see Table 1) (18). The antibody titer against HPV genotypes 6, 11, 16, and 18 was not reduced with the addition of the other five HPV genotypes (18).

Revaccination with the 9-valent HPV vaccine in individuals who previously completed the three-dose series with the quadrivalent HPV vaccine or the bivalent HPV vaccine currently is not a routine recommendation. If obstetrician–gynecologists or other providers do not know or do not have available the HPV vaccine product previously administered, or are in settings that are transitioning to the 9-valent HPV vaccine, any available HPV vaccine product may be used to continue or complete the series for females for protection against HPV genotypes 16 and 18; the 9-valent HPV vaccine or the quadrivalent HPV vaccine may be used to continue or complete the series for males (18).

Safety

Safety data for all three HPV vaccines are reassuring. According to the Vaccine Adverse Events Reporting System, more than 60 million doses of HPV vaccine have been distributed, and there are no data to suggest that there are any severe adverse effects or adverse reactions linked to vaccination (19). The 9-valent and quadrivalent vaccines had similar safety profiles, except that the 9-valent HPV vaccine had a higher rate of injection site swelling and erythema than the quadrivalent HPV vaccine, and the rate increased after each successive dose of the 9-valent HPV vaccine (18). Obstetrician–gynecologists or other providers should counsel patients to expect discomfort after vaccination and that such discomfort is not a cause for concern. Available data demonstrate no safety concerns in individuals who were vaccinated with the 9-valent HPV vaccine after having been vaccinated with the quadrivalent HPV vaccine (20). Anyone who has ever had a life-threatening allergic reaction to any component of the HPV vaccine, or to a previous dose of the HPV vaccine, should not get the vaccine. Obstetrician–gynecologists or other providers should assess patients for severe allergies, including an allergy to yeast. Individuals with a moderate or severe illness should wait until their illness improves before receiving a vaccine.

Uses and Efficacy of the Bivalent, Quadrivalent, and 9-valent Human Papillomavirus Vaccines

Considerations for Special Populations

Although HPV vaccination in pregnancy is not recommended, neither is routine pregnancy testing before vaccination. Available safety data regarding the inadvertent administration of the vaccine during pregnancy are reassuring (21, 22). Patients and obstetrician–gynecologists or other providers are encouraged to register women exposed to the 9-valent HPV vaccine around the time of conception or during pregnancy by contacting the manufacturer (20). Pregnancy registries for the quadrivalent HPV vaccine and bivalent HPV vaccine have been closed. Exposure to these vaccines can be reported by calling the manufacturer (23, 24). If a vaccine series is started and a patient then becomes pregnant, completion of the vaccine series should be delayed until that pregnancy is completed. Lactating women can receive any HPV vaccine because inactivated vaccines like HPV do not affect the safety of breastfeeding for mothers or infants (25).

The presence of immunosuppression, like that experienced in patients with human immunodeficiency virus (HIV) infection or organ transplantation, is not a contraindication to HPV vaccination. However, the immune response may be less robust in the immunocompromised patient (26).

Human papillomavirus vaccines are not currently licensed in the United States for women older than 26 years. Off-label use may be indicated on a case-by-case basis (27).

Patient Education and Vaccination Efforts

High rates of HPV vaccination will reduce the burden of HPV-related disease in the United States. Current vaccination rates are unacceptably low. Studies have shown that physicians’ recommendations play a crucial role in the acceptance of HPV vaccination by patients and parents of patients (28). It is crucial that obstetrician–gynecologists and other providers educate parents and patients on the benefits and safety of HPV vaccination and offer HPV vaccines in their offices.

According to the CDC, if health care providers increase HPV vaccination coverage to 80%, it is estimated that an additional 53,000 cases of cervical cancer could be prevented during the lifetime of those younger than 12 years (29). Furthermore, for every year that coverage does not increase, an additional 4,400 women will develop cervical cancer.

For More Information

These resources are for information only and are not meant to be comprehensive. Referral to these resources does not imply the American College of Obstetricians and Gynecologists’ endorsement of the organization, the organization’s web site, or the content of the resource. The resources may change without notice.

ACOG has identified additional resources on topics related to this document that may be helpful for ob-gyns, other health care providers, and patients. You may view these resources at: www.acog.org/More-Info/HPV.

References

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  2. Merck & Company, Inc. Gardasil® 9 (human papillomavirus 9-valent vaccine, recombinant): highlights of prescribing information. Whitehouse Station (NJ): Merck; 2014. Available at: http://www.fda.gov/downloads/Biologics BloodVaccines/Vaccines/ApprovedProducts/UCM426457.pdf. Retrieved June 9, 2015.
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