By Editt Nikoyan, MS, and Philip R. Fischer, MD, DTM&H

Editt Nikoyan is a student at the Mayo Clinic School of Medicine. Dr. Fischer is Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.

Ms. Nikoyan and Dr. Fischer report no financial relationships relevant to this field of study.

SYNOPSIS: The Centers for Disease Control and Prevention has changed its recommendation for the human papillomavirus vaccine administration from a routine three-dose series to a two-dose series for 9- to 14-year-old children.

SOURCE: Centers for Disease Control and Prevention. CDC recommends only two HPV shots for younger adolescents. Available at:

On Oct. 19, 2016, the CDC released a new recommendation that 9- to 14-year-olds receive only two doses of the human papillomavirus (HPV) vaccine at least six months apart. Those who start the vaccine series when they are older than 15 years of age will continue to need three doses. CDC and the Advisory Committee on Immunization Practices (ACIP) made this recommendation after a thorough review of studies indicating that two doses of HPV vaccine in 9- to 14-year-olds produce an immune response similar to or greater than the response in young adults older than 15 years of age who received three doses. CDC encourages physicians to begin implementing the two-dose series in their practices to protect their adolescent patients against HPV-associated cancers.


HPV is the most common sexually transmitted infection in the United States. Most HPV infections are self-limited and asymptomatic. However, cancerous HPV infections (largely types 16 and 18) cause approximately 30,700 new cases of cervical, penile, vulvar, vaginal, anal, and oropharyngeal cancers in the United States each year.1 In addition, noncancerous HPV infections (largely types 6 and 11) are the cause of almost all anogenital warts, as well as benign abnormalities of the cervix and recurrent respiratory papillomatosis (RRP).2

There are three HPV vaccines licensed in the United States: a bivalent vaccine (Cervarix), a quadrivalent vaccine (Gardasil), and a 9-valent vaccine (Gardasil 9). The bivalent and quadrivalent vaccines protect against 66% of cervical cancers, while the 9-valent vaccine protects against an additional 15% of cervical cancers. Previously, the scheduling of the HPV vaccine in the United States was to use the same vaccine product as a three-dose series of intramuscular injections within a six-month period, recommended routinely for boys and girls 11-12 years of age.3

The recommendation for a two-dose HPV vaccination schedule for younger adolescents should lead to higher completion rates than those achieved with the three-dose HPV vaccination schedule in the United States. According to a 2012 study, the proportion of patients who completed the series dropped significantly between 2006 and 2009. Across the 9- to 12-year-old, 13- to 18-year-old, and 19- to 26-year-old age groups, the proportion of initiators who completed the three-dose series dropped from approximately 44-57% in 2006 to 20-22% in 2009, with the steepest declines in completion among the 9- to 12-year-olds and 13- to 18-year-olds. However, the rates of initiation of the vaccine increased from 22.4% in 2006 to 48.9% in 2009, and the rates of completing the second dose remained relatively stable between 26.8% in 2006 to 29.7% in 2009.4 A 2014 study found barriers specific to the completion of the three-dose schedule, which included lack of insurance coverage, little contact with the medical system, and being unaware of or forgetting about the need for additional doses.5 Now with a two-dose schedule rather than a three-dose schedule, one less trip to the doctor for a vaccine injection means one less copayment or insurance deductible charge, saving the patient the added cost and time of a third dose, and subsequently incentivizing completion of the HPV vaccine series.

Cervical cancer is the fourth most common cancer in women worldwide, with an estimated 266,000 deaths and 528,000 new cases in 2012 alone. About 85% of this burden occurs in developing and underdeveloped countries, where it accounts for almost 12% of all female cancers.6 Since the licensure of the HPV vaccine in 2006, it has been shown to be highly effective, with up to a 90% reduction in infections, particularly when the vaccine has high coverage in a targeted population and is administered in younger adolescents, before HPV exposure.7 Regardless of the efficacy of the vaccine itself, however, there are several barriers to successful global impact, including the availability of national funding, individual access to healthcare facilities, engagement of families in the importance of immunization for both girls and boys, and mistrust or misunderstanding of healthcare workers about the purpose of the HPV vaccine.8 Despite the World Health Organization’s recommendation of the two-dose vaccine schedule rather than the three-dose vaccine schedule worldwide, which was implemented in 65 countries by the end of 2015, these barriers impede the successful universal adoption of the HPV vaccine.

In the United States, major barriers exist to reaching the Healthy People 2020 objective of increasing the HPV vaccination coverage of males and females by ages 13-15 to 80%. In 2015, only 27% of boys and 37% of girls had completed their HPV series by the age of 15. However, more than 80% of adolescents 13-15 years of age had received other routine vaccines for tetanus-diphtheria-pertussis (Tdap) and meningococcus. Parents reported not receiving the healthcare provider’s recommendation for the HPV vaccine as one of the main reasons for not vaccinating their sons and daughters.9 One less scheduled dose should alleviate some barriers, such as the cost and time. Providers, though, should improve their communication about the HPV vaccine to improve patient knowledge about the vaccine and the importance of the second dose. If HPV vaccines are administered at the same visit as when 11- to 12-year-olds receive their scheduled Tdap or meningitis vaccine, HPV vaccine coverage for one or more doses potentially could reach the Healthy People 2020 goal.


  1. Centers for Disease Control and Prevention. HPV and Cancer. Available at: Accessed Nov. 3, 2016.
  2. Saraiya M, Unger ER, Thompson TD, et al. US assessment of HPV types in cancers: Implications for current and 9-valent HPV vaccines.J Natl Cancer Inst 2015;107:1-12.
  3. Centers for Disease Control and Prevention. 2015 Sexually Transmitted Diseases Treatment Guidelines. Available at: Accessed Nov. 3, 2016.
  4. Hirth JM, Tan A, Wilkinson GS, Berenson AB. Completion of the human papillomavirus vaccine series among insured females between 2006 and 2009. Cancer 2012;118:5623-5629.
  5. Holman DM, Benard V, Roland KB, et al. Barriers to human papillomavirus vaccination among US adolescents: A systematic review of the literature. JAMA Pediatr 2014;168:76-82.
  6. World Health Organization. (2016, March 20). Human Papillomavirus (HPV). Available at: Accessed Oct. 29, 2016.
  7. Garland SM, Kjaer SK, Muñoz N, et al. Impact and effectiveness of the quadrivalent human papillomavirus vaccine: A systematic review of 10 years of real-world experience. Clin Infect Dis 2016;63:519-527.
  8. World Health Organization. HPV Vaccine Communication: Special Considerations for a Unique Vaccine, 2016 Update. Geneva, 2016.
  9. Reagan-Steiner S, Yankey D, Jeyarajah J, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years – United States, 2015. MMWR Morb Moral Wkly Rep 2015;65:850-858.