September 01, 2013
4 min read

Moving forward with HPV vaccination

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HPV is primarily spread through sexual contact and presents a significant public health concern because certain high-risk types, particularly HPV-16 and HPV-18, are responsible for causing about 70% of all cervical cancers.

Additionally, these and other types are strongly associated with anal, vulvar, vaginal, penile, and head and neck cancers. The lower-risk types, HPV-6 and HPV-11, are more strongly associated with anogenital warts and almost never with invasive cancers. Two vaccines directed against the high-risk HPV types 16 and 18 are currently available and offer substantial protection against HPV-related cancers.

The first HPV vaccine to become available in the United States was a quadrivalent product (HPV4; Gardasil, Merck & Co), active against HPV types 6, 11, 16 and 18. The quadrivalent HPV vaccine received its initial FDA approval in 2006 and is currently indicated as a three-dose series (months 0, 1 and 6) for the prevention of HPV-related disease in both male and female patients aged 9 to 26 years. In 2009, a second HPV vaccine was approved for use. This bivalent product (HPV2; Cervarix, GlaxoSmithKline) is active against HPV types 16 and 18, also given as a three-dose series, is indicated only for HPV-related disease prevention in female patients aged 9 to 26 years.

Leah Steinke

Leah Steinke

Clinical efficacy data

The efficacy of preventing genital warts associated with HPV types 6, 11, 16 and 18 was found to be 89% in a study of more than 4,000 male patients completing a three-dose regimen of the quadrivalent HPV vaccine. Similar efficacy has been described among female patients: The bivalent HPV vaccine prevents 92.9% of cancerous lesions associated with HPV-16 and/or HPV-18, and 98.2% of lesions caused by HPV-6, HPV-11, HPV-16 and/or HPV-18 were prevented by the quadrivalent vaccine.

Antibody response appears to be significantly higher among patients aged 9 to 15 years undergoing HPV vaccination vs. patients aged 16 to 26 years. This data, compounded with the preference to complete vaccination before initiation of sexual activity, drives national recommendations to vaccinate those aged 11 to 12 years.

Practical considerations

Because it is made using Saccharomyces cerevisia, HPV4 should be not be given to patients with hypersensitivity reactions to yeast. Because the HPV2 prefilled syringes contain latex, they may cause reactions among latex-allergic patients. Syncope, sometimes accompanied by seizure-like activity, has been documented after vaccination. Thus, patient observation for 15 minutes after receiving an injection of either HPV vaccine is recommended. As HPV vaccination has not been studied and is not recommended for use in pregnant patients, manufacturers should be contacted in the event of a pregnant women being exposed to the vaccine for monitoring purposes. As neither the bivalent nor quadrivalent products are live vaccines, they may be given simultaneously with other live or inactivated vaccines. While studies do not exist to evaluate the interchangeability of the two vaccines and it is recommended that the same vaccine be used to complete the three-dose course, either vaccine may be used to complete the regimen and provide protection against HPV types 16 and 18.

Ethical discussions

As HPV is spread primarily through sexual contact, critics of the vaccine have expressed concerns that use may lead to increased promiscuity and threaten principles of sexual abstinence among adolescents. Additionally, debates regarding compulsory vaccination, which often draw controversy, have gained additional media interest in the setting of such ethical and religious objections. A recent report from the CDC found an increase in administration of at least one dose of HPV vaccine from 25.1% in 2007 to 53% in 2011; however, a failure to improve in 2012 was evidenced by a similarly low vaccination rate of 53.8%. Of parents choosing not to vaccinate their daughters, 19.1% stated that the vaccine was unnecessary, and 10.1% had the reason that their daughter was not sexually active.

National recommendations

The CDC Advisory Committee on Immunization Practices recommends routine administration of quadrivalent HPV vaccine to boys aged 11 to 12 years, and routine administration of either the bivalent or quadrivalent HPV vaccine to girls aged 11 to 12 years. The AAP closely follows ACIP guidance and recommends the routine administration of three doses of HPV vaccine to both boys and girls aged 11 to 12 years, and vaccination may start as young as 9 years. Female patients may receive either the bivalent or quadrivalent vaccine, whereas males should receive the quadrivalent vaccine only.

Although the AAP recommends that female patients aged 11 to 12 years who are not receiving the HPV vaccine should still receive it when aged 13 to 26 years, vaccination of older male patients is recommended only through age 21 years, on the basis of cost-efficacy models. However, men aged up to 26 years may still be vaccinated. An important exception is the population of men who have sex with men, for whom special efforts should be made to complete vaccination up to age 26 years.

Routine cervical cancer screening (Papanicolaou) continues to be recommended regardless of HPV vaccination status.

Future directions

Although the HPV2 and HPV4 vaccines are approved for a three-dose regimen only, the high cost and high efficacy of these agents have elicited interest in the feasibility of a reduced-dose regimen for cost containment and ease of administration. In a recent study investigating a two-dose regimen of quadrivalent HPV vaccine (given at months 0 and 6) in girls aged 9 to 13 years, antibody responses 1 month after completion of the two-dose regimen was noninferior to the three-dose regimen among girls in the same age group. However, this noninferiority was not maintained through 24 to 36 months for some genotypes, warranting future study before an alternative dosing schedule can be adopted.


AAP Committee on Infectious Diseases. Pediatrics. 2012;129;602-605.
CDC. MMWR. 2010;59:626-629.
CDC. MMWR. 2011;60:1705-1708.
CDC. MMWR. 2013;62:591-595.
Cervarix [package insert]. Research Triangle Park, NC: GlaxoSmithKline Biologicals; 2011.
Colgrove J. N Engl J Med. 2006;355:2389-2391.
Dobson SRM. JAMA. 2013;309:1793-1802.
Gardasil [package insert]. Whitehouse Station, NJ: Merck & Co.; 2011
Hwang LY, Moscicki AB. Human Papillomaviruses. In: Long SS, Pickering LK, Prober CG, eds. Principles and practice of pediatric infectious diseases, 4th Ed. Philadelphia, Pa: Elsevier Inc; 2012:1145-1149.
Kjaer SK. Cancer Prev Res. 2009;2:868-878.
Paavonen J. Lancet. 2009;374:301-314.

For more information:

Leah Steinke, PharmD, is a clinical pharmacist, specialist in infectious diseases, at Children’s Hospital of Michigan, Detroit.

Disclosure: Steinke reports no relevant financial disclosures.