Use of a 2-Dose Schedule for Human Papillomavirus Vaccination — Updated Recommendations of the Advisory Committee on Immunization Practices
Weekly / December 16, 2016 / 65(49);1405–1408

Use of a 2-Dose Schedule for Human Papillomavirus Vaccination — Updated Recommendations of the Advisory Committee on Immunization Practices
Weekly / December 16, 2016 / 65(49);1405–1408
Elissa Meites, MD1; Allison Kempe, MD2,3; Lauri E. Markowitz, MD1 (View author affiliations)View suggested citation
Vaccination against human papillomavirus (HPV) is recommended to prevent HPV infections and HPV-associated diseases, including cancers. Routine vaccination at age 11 or 12 years has been recommended by the Advisory Committee on Immunization Practices (ACIP) since 2006 for females and since 2011 for males (1,2). This report provides recommendations and guidance regarding use of HPV vaccines and updates ACIP HPV vaccination recommendations previously published in 2014 and 2015 (1,2). This report includes new recommendations for use of a 2-dose schedule for girls and boys who initiate the vaccination series at ages 9 through 14 years. Three doses remain recommended for persons who initiate the vaccination series at ages 15 through 26 years and for immunocompromised persons.
HPV infection causes cervical, vaginal, and vulvar cancers in women; penile cancers in men; and oropharyngeal and anal cancers as well as genital warts in both men and women (3). Three HPV vaccines are licensed for use in the United States. All are noninfectious. Quadrivalent and 9-valent HPV vaccines (4vHPV and 9vHPV, Gardasil and Gardasil 9, Merck and Co, Inc., Whitehouse Station, New Jersey) are licensed for use in females and males aged 9 through 26 years (1). Bivalent HPV vaccine (2vHPV, Cervarix, GlaxoSmithKline, Rixensart, Belgium) is licensed for use in females aged 9 through 25 years (1). As of late 2016, only 9vHPV is being distributed in the United States. The majority of all HPV-associated cancers are caused by HPV 16 or 18, types targeted by all three vaccines. In addition, 4vHPV targets HPV 6 and 11, types that cause genital warts. 9vHPV protects against these and five additional types: HPV 31, 33, 45, 52, and 58. All three vaccines have been approved for administration in a 3-dose series at intervals of 0, 1 or 2, and 6 months. In October 2016, after considering new clinical trial results (4), the Food and Drug Administration (FDA) also approved 9vHPV for use in a 2-dose series for girls and boys aged 9 through 14 years (5). In October 2016, ACIP recommended a 2-dose schedule for adolescents initiating HPV vaccination in this age range. This report provides recommendations for use of 2-dose and 3-dose schedules for HPV vaccination.
During November 2015–October 2016, the ACIP HPV Vaccines Work Group held monthly telephone conferences to 1) review and evaluate the quality of the evidence assessing immunogenicity, efficacy, and postlicensure effectiveness of a 2-dose schedule; 2) consider benefits and harms of a 2-dose schedule; 3) weigh the variability in the values and preferences of patients and providers for a 2-dose schedule; and 4) examine health economic analyses. During teleconferences, summaries of findings were presented for Work Group discussion.
A systematic review was conducted to identify studies involving human subjects* that reported primary data on any important or critical health outcomes related to HPV vaccination† after 2 doses of 9vHPV, 4vHPV, or 2vHPV, administered at an interval of 0 and ≥6 months (±4 weeks) to persons aged 9 through 14 years. The review focused on this age group given available 2-dose trial data for 9vHPV (4). Immunogenicity outcomes of interest were seroconversion, geometric mean titers (GMTs), or antibody avidity. Studies were excluded if they lacked a comparison group in which efficacy of 3 doses of HPV vaccine against clinical endpoints was demonstrated in clinical trials (e.g., females aged 15 through 26 years).§ Evidence regarding a 3-dose schedule for HPV vaccine was reviewed previously (1,2).
Quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Detailed methods and GRADE tables can be found online (6). Other studies from the search and from the broader literature informed additional expert guidance that extended beyond the research question addressed formally via GRADE analysis (7). Evidence was reviewed by the Work Group, summarized, and publicly presented at the February and June 2016 A