The case for HPV immunization

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Practice Alert

The case for HPV immunization

J Fam Pract. 2009 December;58(12):660-664

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References

1. Centers for Disease Control and Prevention. Quadrivalent human papillomavirus vaccine: Recommendations of the Advisory Committee on Immunization Practices. March 23, 2007. Available at: http://www.cdc.gov/mmwr/pdf/rr/rr5602.pdf. Accessed November 3, 2009.

2. World Health Organization. Human papillomavirus vaccines. WHO position paper. Weekly Epidemiological Record. 2009;84(15):118-131.Available at: http://www.who.int/wer/2009/wer8415.pdf. Accessed October 27, 2009.

3. U.S. Food and Drug Administration. October 16, 2009 Approval letter—Gardasil. Available at: www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm186991.htm. Accessed October 31, 2009.

4. Johnson LG, Madeleine MM, Newcomer LM, et al. Anal cancer incidence and survival; the surveillance, epidemiology and end results experience, 1973-2000. Cancer. 2004;101:281-288.

5. Trottier H, Franco EL. The epidemiology of genital human papillomavirus infection. Vaccine. 2006;24:1-15.

6. Rambout L, Hopkins L, Hutton B, et al. Prophylactic vaccination against human papillomavirus infection and disease in women: a systematic review of randomized controlled trials. CMAJ. 2007;177:469-479.

7. Saslow D, Castle PE, Cox JT, et al. American Cancer Society guideline for human papillomavirus vaccine use to prevent cervical cancer and its precursors. CA Cancer J Clin. 2007;57:7-28.

8. Centers for Disease Control and Prevention. Vaccination coverage among adolescents aged 13-17 years, United States 2007. MMWR Morb Mortal Wkly Rep. 2008;57:1100-1103.

9. Fisher R, Darrow DH, Tranter M, et al. Human papillomavirus vaccine: recommendations, issues and controversies. Curr Opin Pediatr. 2008;20:441-445.

10. Gerend MA, Magloire ZF. Awareness, knowledge and beliefs about human papillomavirus in a racially diverse sample of young adults. J Adolesc Health. 2008;42:237-242.

11. Advisory Committee on Immunization Practices: summary report, October 22-23, 2008, Atlanta, Ga. Available at: http://www.cdc.gov/vaccines/recs/ACIP/downloads/min-oct08.pdf. Accessed April 27, 2009.

12. Daley M. HPV vaccination practices. A national survey of physicians 18 months post licensure. Presentation at the October 2008 ACIP meeting. Available at: http://cdc.confex.com/cdc/nic2009/webprogram/Paper18003.html. Accessed November 3, 2009.

13. Slade BA, Leidel L, Vellozzi C, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA. 2009;302:750-757.

14. Meeting of the Advisory Committee on Immunization Practices; October 21-22, 2009; Atlanta, Ga.

TABLE 1
ACIP HPV4 recommendations¹

Routinely vaccinate girls between the ages of 11 and 12 years with 3 doses of the HPV4 vaccine. The series can start in those as young as 9 years.
Provide catch-up vaccination of females between the ages of 13 and 26 who have not been previously vaccinated.
Avoid unnecessary testing: Neither Pap testing nor HPV screening is needed before vaccination.
Don’t hesitate to administer the HPV4 vaccine with other age-appropriate vaccines.
Follow the vaccine recommendations even if your patient has an abnormal Pap test, a positive HPV DNA test, or genital warts. Keep in mind that vaccination does not change recommendations for cervical cancer screening.

ACIP, Advisory Committee on Immunization Practices

Some doubts among parents and physicians

Recent national vaccine survey data show that only 25% of females ages 13 to 17 had received 1 or more doses of HPV4 vaccine.⁸ Young women appear to be interested in the vaccine and in possibly receiving it, but they tend to underestimate their risk of contracting HPV.^9,10 Some parents are concerned that the vaccine may encourage risk-taking behavior.¹¹ Physicians report that some parents fear the vaccine is too new to be fully evaluated and are concerned that insurance may not cover the cost of the 3-shot series.¹²

FAST TRACK

Close to 90% of family physicians and 98% of pediatricians administer the HPV4 vaccine in their practices.

Physician attitudes toward the vaccine are generally positive. Close to 90% of family physicians and 98% of pediatricians administer the vaccine in their practices. Eighty percent strongly recommend it to 13- to 15-year-olds, and 50% recommend it to 11- to 12-year-olds.

A small minority of family physicians has misconceptions regarding the vaccine:

15% believe an HPV test should be ordered before vaccination
19% believe the vaccine should not be given to those diagnosed with HPV
31% believe a pregnancy test should be ordered before administering the vaccine.¹²

Safety concerns, minor and major

Clinical trials conducted by the vaccine manufacturer demonstrated slightly higher rates of some systemic adverse reactions in the vaccinated group compared with placebo groups (TABLE 2). Data on adverse reactions at the injection site also showed somewhat higher percentages in the vaccine group. These trials were not large enough to detect severe, rare adverse reactions.

The CDC and the US Food and Drug Administration (FDA) collaboratively operate a passive reporting system, the Vaccine Adverse Events Reporting System (VAERS), as a way of conducting surveillance for these rare events. The manufacturer is required to report suspected adverse events to VAERS, but providers and consumers can also report any suspected adverse events.

There are problems with VAERS. Because it is a passive system, some adverse events may not be reported. At the same time, some events reported by consumers and physicians may be coincidental occurrences not caused by the vaccine. To complicate matters further, patients often receive more than 1 vaccine at the same time, so that attributing any particular adverse reaction to a single vaccine is problematic. These imperfections in VAERS should lead to caution in interpreting reports received on any 1 vaccine.

A recent article published in the Journal of the American Medical Association (JAMA) described the reports on the HPV4 vaccine received by the VAERS for the first 2½ years after licensure.¹³ Slightly more than 23 million doses had been distributed during this time, and 12,424 adverse events were reported. The most common were syncope (1847), dizziness (1763), nausea (1170), headache (957), and injection site reactions (926). Of all these reported events, 772 reactions were classified as serious, and 32 vaccine recipients died. Investigation of the deaths revealed that the mean time from vaccine to the death was 47 days, the deaths were caused by a variety of underlying conditions, and 4 deaths remained unexplained.

The only 2 serious adverse events that appeared to occur more frequently than background rates were venous thrombotic events, at 1 per 500,000 doses, and syncope, at a rate of 8.2 per 100,000 doses. The syncopal events were concentrated among the 11- to 18-year-olds and resulted in 293 falls and 200 head injuries. The authors of the JAMA article caution about attributing any cause and effect to the venous thromboembolism findings because of the high rates of oral contraceptive use in this age group, which increases the risk of this condition. Studies are ongoing to try to sort out these issues.

TABLE 2
HPV4 systemic adverse events in females, ages 9-23 years¹

Adverse events occurring 1 to 15 days post-vaccination	HPV4 recipients (N=5088)	Placebo recipients (N=3790)
Pyrexia	13.0%	11.2%
Nausea	6.7%	6.6%
Nasopharyngitis	6.4%	6.4%
Dizziness	4.0%	3.7%
Diarrhea	3.6%	3.5%
Vomiting	2.4%	1.9%
Myalgia	2.0%	2.0%
Cough	2.0%	1.5%
Toothache	1.5%	1.4%
Upper respiratory tract infection	1.5%	1.5%
Malaise	1.4%	1.2%
Arthralgia	1.2%	0.9%
Insomnia	1.2%	0.9%
Nasal congestion	1.1%	0.9%