You are on page 1of 3

Annals of Internal Medicine

men (MSM), especially if they are HIV-positive (25 to 100 per 100 000) (6).
FDA Licensing Distinctions Between HPV Vaccines

Adult Immunization 2012: Politics, Process, and Progress

his issue of Annals marks the sixth consecutive publication of the annual update of the Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule (1). For the rst time, the adult schedule and the schedule for children and adolescents (2) are designed to be combined. This editorial highlights the rationale behind key changes.






Recommendations by the committee do not become policy of the Centers for Disease Control and Prevention (CDC) until they are signed by the CDC Director and accepted by the Secretary of the U.S. Department of Health and Human Services. This allows for discretionary oversight (3). These recommendations are considered provisional until published in Morbidity and Mortality Weekly Report (1). Vaccine coverage mandated through the Affordable Care Act should increase access to vaccines but could further politicize this process. Budget concerns could delay, and even prevent, incorporation of ACIP recommendations, including those that also inuence insurance coverage in the private sector (4).

The HPV vaccine is a prophylactic vaccine. It is most effective if given before exposure to the virus. Immune response is more robust when the vaccine is administered to younger persons (9, 10). There are distinct differences in the U.S. Food and Drug Administrations (FDA) licensing for the 2 HPV vaccines currently available. The quadrivalent vaccine (HPV4 [Gardasil, Merck & Co., North Wales, Pennsylvania]) protects against types 6, 11, 16, and 18, and is FDA-approved for both females and males aged 9 to 26 years (9). The bivalent vaccine (HPV2 [Cevarix, GlaxoSmithKline, Research Triangle Park, North Carolina]) protects against types 16 and 18 but is FDA-approved only for females (10). Both vaccines prevent cervical cancer; however, only HPV4 is FDA-approved for prevention of vulvar, vaginal, and anal cancer. Efcacy of the HPV4 vaccine for anal intraepithelial neoplasia in MSM ranges from 50% to 78% (11). Only HPV4 protects against genital warts. Although the rationale for protection is certainly plausible, clinical HPV vaccine data are not available for oropharyngeal cancer, recurrent respiratory papillomatosis, or penile cancer (9, 10).
HPV Vaccination: Not Just for Girls




In October 2010, the ACIP adopted an evidencebased process modeled after the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) guidelines. The committee now evaluates quality of evidence, benets and harms, values and preferences of affected populations, and economic impact (5). Votes of the ACIP expanding routine human papillomavirus (HPV) vaccination to males and hepatitis B vaccination to young adult diabetics were the rst to use this approach.


HPV-Related Disease Burden


Human papillomavirus types 6 and 11 are associated with genital warts and recurrent respiratory papillomatosis; types 16 and 18 are linked to cervical, vaginal, vulvar, anal, penile, and oropharyngeal cancer (6 8). Rates of HPVrelated oropharyngeal cancer are increasing in men. Risk factors for both men and women include having multiple sex partners and engaging in oral sex. For men, having sex with other men is also a major risk factor (6 8). Anal cancer is on the rise, with 1600 new cases in women and 900 new cases in men each year. The overall rate and absolute number of anal cancer cases are higher in women (1.4 per 100 000) than in men (1 per 100 000). However, incidence is highest in men who have sex with

The committees recommendations for HPV vaccination differ from FDA licensing directives. The new, routine HPV4 vaccination recommendation for maleslike femalesstarts at age 11 years but stops short of gender parity. It extends routine vaccination to males only through age 21 years, whereas vaccinating females through age 26 years is established CDC policy. A subgroup of MSM, as well as immunocompromised and HIV-positive males, should be vaccinated through age 26 years (12). Extending HPV4 vaccine coverage to males is more cost-effective when female coverage rates are low; the 2010 National Immunization Survey data on teenagers show just that (13). Fewer than half (48.7%) of teenage girls has received at least one HPV vaccine dose; only about one third (32%) has received all three doses. Trends for increases in HPV vaccine coverage are also blunted (13). Evidence-based data review supports the cost-effectiveness of vaccinating young MSM, but targeted vaccination strategies may stigmatize individuals. Such strategies require self-identication of risk factors and thus may not be successful.




Hepatitis B vaccination is now routinely recommended for unvaccinated diabetic adults through age 59 years. This age cutoff was chosen on the basis of disease risk and cost-effectiveness. There is also a softer recom 2012 American College of Physicians 243


Adult Immunization 2012

mendation that, at physician discretion, hepatitis B vaccine may be administered to older diabetics. Diabetic patients aged 23 to 59 years have more than twice the risk for hepatitis B than people without diabetes. For diabetics aged 60 years or older, risk for hepatitis B was increased 1.5 times, but this increase was not statistically signicant (14). Nearly one third of patients older than age 65 years have type 2 diabetes (15). Ironically, this group was left out of routine vaccinationinitial discussions investigating the need for hepatitis B vaccination in diabetics began with recognition of outbreaks of hepatitis B infection in older patients in assisted-living facilities due to sharing blood glucosemonitoring equipment (16, 17). Although hepatitis B vaccine efcacy decreases somewhat with patient age, failing to offer vaccine leads to 100% susceptibility (that is, zero efcacy) (18).


The American College of Physicians has established its rst-ever Adult Immunization Technical Advisory Committee. The College has representation at all ACIP meetings and on many ACIP vaccine working groups. Vaccines are vital to ensuring our nations health. The newly released fourth edition of the ACP Guide to Adult Immunization (21) can help physicians incorporate and improve vaccination strategies in their own practices.
Sandra Adamson Fryhofer, MD Emory University Atlanta, GA 30309
Requests for Single Reprints: Sandra Adamson Fryhofer, MD, 1938

Peachtree Road, Suite 502, Atlanta, GA 30309.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline .org/authors/icmje/ M11-3040.


Tetanus, diphtheria, and acellular pertussis (Tdap) booster is designed to protect infants from pertussis. The practice of cocooning infants and young children by vaccinating family and household contacts (and health care personnel) is still recommended. The change is when to vaccinate pregnant mothers. Previous guidance stated that unvaccinated mothers should be given Tdap immediately postpartum; the new strategy begins protection even sooner: Tdap should be given during pregnancy, preferably after 20 weeks of gestation. Protective maternal antibodies then pass to the fetus. Further study is needed to ensure that maternal antibodies do not blunt the infants own immune response to pertussis vaccination (19).

Ann Intern Med. 2012;156:243-245.

1. Advisory Committee on Immunization Practices. Recommended Adult Immunization Schedule: United States, 2012. Ann Intern Med. 2012:156:211-7. 2. Centers for Disease Control and Prevention. Recommended immunization schedule for persons aged 0 18 yearsUnited States, 2012. MMWR. 2012;61. [Forthcoming] 3. Hinman AR, Orenstein WA, Schuchat A; Centers for Disease Control and Prevention (CDC). Vaccine-preventable diseases, immunizations, and MMWR1961-2011. MMWR Surveill Summ. 2011;60 Suppl 4:49-57. [PMID: 21976166] 4. Affordable Care Act and Immunization. Accessed at /factsheets/2010/09/affordable-care-act-immunization.html on 1 November 2011. 5. Ahmed F, Temte JL, Campos-Outcalt D, Schunemann HJ; ACIP Evidence Based Recommendations Work Group (EBRWG). Methods for developing evidence-based recommendations by the Advisory Committee on Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention (CDC). Vaccine. 2011;29:9171-6. [PMID: 21839794] 6. Moscicki AB, Palefsky JM. Human papillomavirus in men: an update. J Low Genit Tract Dis. 2011;15:231-4. [PMID: 21543996] 7. DSouza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356:1944-56. [PMID: 17494927] 8. Marur S, DSouza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11:781-9. [PMID: 20451455] 9. U.S. Food and Drug Administration. FDA Vaccine, Blood & Biologics: Gardasil. Accessed at Products/UCM094042 on 1 November 2011. 10. U.S. Food and Drug Administration. FDA Vaccine, Blood and Biologics: Cevarix. Accessed at on 1 November 2011. 11. Palefsky JM, Giuliano AR, Goldstone S, Moreira ED Jr, Aranda C, Jessen H, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med. 2011;365:1576-85. [PMID: 22029979] 12. Centers for Disease Control and Prevention (CDC). Recommendations on the use of quadrivalent human papillomavirus vaccine in malesAdvisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011;60:1705-8. [PMID: 22189893] 13. Centers for Disease Control and Prevention (CDC). National and state


Egg allergy is no longer a contraindication to inuenza vaccination. Data from at least 17 studies of more than 2600 egg-allergic patients have debunked concerns that traces of ovalbumin egg protein could trigger a serious allergic reaction. Egg-allergic patients must get the inactivated u shot because that is what has been studied. No skin tests are needed before vaccinating, and the entire vaccine dose can be given at one time. Patients should be observed for 30 minutes after receiving the vaccine (20). A new intradermal u formulation (Fluzone Intradermal, sano pasteur, Swiftwater, Pennsylvania) is now an option for adults aged 18 to 64 years. Its microinjector apparatus features an ultrane, 0.06-in needle that causes less pain on injection but induces more injection-site reactions. It is also 30% more expensive than prelled syringes. The dermal layer of skin is rich in dendritic cells that play a key role in triggering immune response (20).
244 7 February 2012 Annals of Internal Medicine Volume 156 Number 3

Adult Immunization 2012


nation coverage among adolescents aged 13 through 17 yearsUnited States, 2010. MMWR Morb Mortal Wkly Rep. 2011;60:1117-23. [PMID: 21866084] 14. Centers for Disease Control and Prevention (CDC). Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011;60:1709-11. [PMID: 22189894] 15. National Diabetes Information Clearing House (NDIC). National Diabetes Statistics, 2011: Fast Facts on Diabetes. Accessed at /dm/pubs/statistics/#fast on 1 November 2011. 16. Thompson ND, Perz JF. Eliminating the blood: ongoing outbreaks of hepatitis B virus infection and the need for innovative glucose monitoring technologies. J Diabetes Sci Technol. 2009;3:283-8. [PMID: 20144359] 17. Centers for Disease Control and Prevention (CDC). Notes from the eld: deaths from acute hepatitis B virus infection associated with assisted blood glucose monitoring in an assisted-living facilityNorth Carolina, August-October 2010. MMWR Morb Mortal Wkly Rep. 2011;60:182. [PMID: 21330968]

18. Hepatitis B vaccination for adults with diabetes policy considerations. Presented at a meeting of the Advisory Committee on Immunization Practices. Center for Disease Control and Prevention, Atlanta, Georgia, 27 October 2010. Available at -hepb-VaccAdultDiabetes.pdf. 19. Centers for Disease Control and Prevention (CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant aged 12 monthsAdvisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011;60: 1424-6. [PMID: 22012116] 20. Centers for Disease Control and Prevention (CDC). Prevention and control of inuenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011; 60:1128-32. [PMID: 21866086] 21. American College of Physicians. Guide to Adult Immunization: A TeamBased Manual. 4th ed. Philadelphia: American Coll Physicians; 2010.




Annals of Internal Medicine and the American College of Physicians recognize excellence among internal medicine trainees and junior investigators with annual awards for original research and scholarly review articles published in Annals in each of the following categories: Most outstanding article with a first author in an internal medicine residency program or general medicine or internal medicine subspecialty fellowship program Most outstanding article with a first author within 3 years following completion of training in internal medicine or one of its subspecialties Selection of award winners will consider the articles novelty; methodological rigor; clarity of presentation; and potential to influence practice, policy, or future research. Judges will include Annals Editors and representatives from Annals Editorial Board and the American College of Physicians Education/Publication Committee. Papers published in the year following submission are eligible for the award in the year of publication. First author status at the time of manuscript submission will determine eligibility. Authors should indicate that they wish to have their papers considered for an award when they submit the manuscript, and they must be able to provide satisfactory documentation of their eligibility if selected for an award. Announcement of awards for a calendar year will occur in January of the subsequent year. We will provide award winners with a framed certificate, a letter documenting the award, and complimentary registration for the American College of Physicians annual meeting. Please refer questions to Mary Beth Schaeffer at mschaeffer@acponline .org.

7 February 2012 Annals of Internal Medicine Volume 156 Number 3 245