HPV Vaccines

S. Dobson, MD

Division of Infectious and Immunological Diseases, Department of Pediatrics, University of British Columbia; BC Children’s Hospital, Vancouver, BC, Canada

Background

In 2006, a quadrivalent HPV vaccine was approved for use in Canada, the first of two vaccines for human papillomavirus (HPV) prevention. The second is a bivalent vaccine that is currently undergoing regulatory review by Health Canada. The efficacy of both vaccines heralds a new era in the prophylactic treatment of cervical cancer. Consequently, provincial ministries of health are beginning to formulate immunization programs for pre-adolescent girls.

Facts About HPV

• Over 100 human papillomavirus (HPV) types have been described, 40 of which infect the genital tract.¹
  • They infect differentiating epithelial cells of skin or mucosae.
• Almost all cervical cancers can be traced to infection with at least 13 oncogenic HPV types.
  • HPV 16 and 18 (high risk types) contribute to 70% of cervical cancers.1,2
  • These vaccines provide an opportunity to prevent this cancer by immunization against the high risk (HR) HPV types.
• For oncogenic potential, the viral genome integrates itself into the host cell genome and then develops a persistent infection. This infection, which must persist for years, in combination with co-existing factors, permits the progression to cancer.³
• In Canada, there are approximately 1,300 cases and 400 deaths from cervical cancer annually.¹ Lifetime risk of cervical cancer for Canadian females is 0.7% or 1 in 138 women.1 This is in spite of over 50 years of screening through Pap testing.¹

In addition to the high risk types, there are other HPV types:

• HPV 6 and 11 are low risk (LR) for causing cancer, but they cause 90% of genital warts^1,4
  • Warty projections can occur anywhere on the genital skin surface, but they appear primarily on the vulva, penis and perianal skin.
  • Usually self-limited lesions in immunocompetent individuals that resolve within 12–24 months.
• Although squamous cell cancers of the mouth and oropharynx are rare, they have been associated with HPV.^1,5,6

Patient Questions

As a frontline physician, it would be sensible to consider the kinds of questions patients are likely to ask about these vaccines and to whom would recommendations be appropriate.

When is HPV acquired?

HPV is one of the most common sexually transmitted infections, with the highest prevalence in adolescents and young adults under the age of 25 years. The acquisition rate of HPV infection is high following the sexual debut of girls, with almost 40% being infected by some type of HPV within 2 years.1 It is estimated that up to 80% of women will develop an HPV infection at some time in their lives.¹

What are the vaccines?

• The quadrivalent HPV vaccine that acts against types 6, 11, 16 and 18 is given as a 0.5ml injection intramuscularly in 3 doses at 0, 2, and 6 months.
• A soon-to-be licensed bivalent vaccine that acts against types 16 and 18 is also administered in a 3-dose schedule at 0, 1, and 6 months.

What will the vaccines do?

• Clinical trials in women aged 16–26 years have found that both vaccines are at least 95% effective in preventing persistent HPV 16 and 18 infection.⁷
• They are almost 100% effective in preventing vaccine-type specific cervical cancer precursors in girls and young women not previously infected with these types.^2,7
• The quadrivalent vaccine is 97% effective in preventing vaginal and vulval intraepithelial neoplasia, and is 99% effective in preventing genital warts caused by HPV 6 and 11.¹
• Given to females prior to sexual debut, it is anticipated that up to 70% of cervical cancers could be prevented.^3,7

What might the vaccines do?

• Both vaccines appear to offer some cross protection against other closely related HPV types, such as 31, 45 and 52
  • Together these 3 types are estimated to cause another 12% of cervical cancers.8
  • It is not known how complete and durable this protection is.
• Evidence for efficacy in older women up to 45 years shows promise, providing these women have not already been infected by the HPV types in the vaccine.
• They may provide protection against infection for males. These trials are ongoing.

What won’t the vaccines do?

• They will not provide any therapeutic benefit if a patient has a pre-existing infection with the specific HPV types contained in the vaccines.
• Change cervical cancer screening recommendations.

Are these vaccines safe?

• Safety was established through placebo controlled trials.^2,7
  • For both vaccines, local injection site reactions, e.g., pain, were common (~ 93%); placebo was only 6%-8% lower.
  • There was no difference between vaccine and placebo groups in the frequency of systemic adverse events.
  • Serious adverse events were no more common in the vaccine group vs. the placebo group and none were considered vaccine related.
  • Use during pregnancy or in those who are immunocompromised has not been evaluated.

Conclusion

The National Advisory Committee on Immunization (NACI) recently released its recommendations for the use of the quadrivalent vaccine, which include:

• For use in females 9-26 years of age.
• Due to limited data, the quadrivalent vaccine is not recommended for females
• Although not recommended for women >26 years, these patients can be vaccinated following individual consultation.
  • Full recommendations can be viewed at: www.naci.gc.ca.

The recommendations for the use of the bivalent vaccine will be available following its approval in Canada.

References

1. Dobson S, et al. Canada Communicable Disease Report 33(ACS-2):1-31 (2007 Feb 15).
2. Future II Study Group. N Engl J Med 356(19): 1915-1927 (2007 May 10).
3. Munoz N, et al. Vaccine 24(Suppl 3):S1-10 (2006 Aug 21).
4. Bourcier M, et al. Skin Therapy Lett – FP ed 3(2):1-3 (2007 Jun).
5. Kumar B, et al. Int J Radiat Oncol Biol Phys 69(2 Suppl):S109-11 (2007).
6. Ernster JA, et al. Laryngoscope 117(12):2115-28 (2007 Dec).
7. Harper DM, et al. Lancet 364(9447):1757-65 (2004 Nov 13).
8. Dawar M, et al. CMAJ 177(5):456-61 (2007 Aug 28).