HPV Vaccination

Full update September 2022

Human papillomavirus (HPV) is the most common sexually transmitted infection in Canada and the US.1-3 Most HPV infections are asymptomatic and resolve without intervention. However, some HPV infections lead to significant morbidity, including precancer and cancer in both females and males.2,4 HPV vaccination rates remain low, with just over half of teenagers fully vaccinated for HPV.3,5 The FAQ below answers questions about HPV vaccination and includes a few talking points to ease concerns and improve vaccination rates.

Question

Answer/Pertinent Information

Who should be vaccinated against HPV?

Gardasil 9 is FDA- and Health Canada-approved in males and females nine to 45 years of age.6-8

Cervarix (Canada only) is Health Canada-approved in females nine to 45 years of age.9

Ideally start the series between the ages of 11 and 12 years (for females and males).10,11

  • Consider starting the series in patients as young as nine years.6,10-12
  • In Canada, age for beginning the HPV series typically depends on provincial/territorial programs (which vary), but most programs are for administration in grade six or seven (i.e., age 11 or 12 years).13,14
  • Routine and catch-up vaccinations are recommended through age 26 years, for males and females.12,15
  • Can consider discussing HPV vaccination with unvaccinated adults between 27 and 45 years, who are most likely to benefit (e.g., patients who anticipate a new sexual partner in the future, especially those with few sexual partners in the past). Though HPV vaccination appears safe in adults over 26 years, benefits are less pronounced than in younger patients.12
    • Modeling data suggests that HPV vaccination may prevent more HPV-related cancers in adolescents or young adults (NNT ~ 200) compared to adults vaccinated between 27 and 45 years (NNT ~ 6,500).12
  • Regardless of the original vaccine used to start the series (i.e., previously available Gardasil or Cervarix [Canada only]), feel comfortable using Gardasil 9 to complete the series for both females and males.16
  • When possible, use the same vaccine to the complete a vaccine series. However, if necessary, any available HPV vaccine can be used to complete the vaccine series. Note that Cervarix (Canada only) is not approved for use in males.2
  • Per US labeling, Gardasil 9 is contraindicated in patients with a severe hypersensitivity to yeast (a component in US and Canadian formulations).6

How should HPV vaccine doses be given?

Administer 0.5 mL of the HPV vaccine as an intramuscular injection.2

  • Gardasil 9 should be given in the upper arm or middle to upper outer thigh.6,17 
  • Cervarix (Canada only) should be given in the upper arm (i.e., deltoid).9

Patients should be observed for 15 minutes after administration, due to a risk of fainting.2,6

When are the two-dose and three-dose series appropriate?

The two-dose series is recommended for males and females up to 14 years.2,6,10

  • Provides a similar immune response to the three-dose series given to patients 15 years and older.6
  • Gardasil 9 should be given at 0 and six months OR at 0 and 12 months.2,6
  • Cervarix (Canada only) should be given at 0 and six months.2
  • Ensure a minimum of five months between the two doses.6,18
    • If the second dose is given less than five months after the first dose, the patient should then be given a third dose. The third dose should be administered six to 12 months after the first dose, and at least three months after the second dose, to ensure response.16

The three-dose series (doses at 0, 2, and 6 months for Gardasil 9; doses at 0,1, and 6 months for Cervarix [Canada only]) is recommended for:

  • patients 15 years or older starting the vaccine series.6,10 If the patient received their first dose when they were nine to 14 years, a two-dose schedule (with at least six months between doses) can be used to finish the series.
  • patients up to 14 years (as an optional alternative to the two-dose series).2,6,8
  • patients with immunocompromising conditions (e.g., cancer, HIV).2,18 Note that immunocompromised patients may have a reduced response.2,6
  • immunocompetent HIV-infected patients.2

For the three-dose series, there must be at least one month between the first two doses, at least three months between the second and third doses, and at least six months between the first and third doses.2

It is not necessary to restart the two- or three-dose series if more than the recommended time lapses between doses.2,18 Complete the vaccination series, starting right where the patient left off.18

How well is Gardasil 9 tolerated?

Expect adverse effects to be more common in females compared to males.6

Injection-site pain, redness, and swelling are the most common (~90% of females, ~65% of males) adverse effects, but are usually mild.2,6,13,17

Headache is the next most common adverse effect (~10%).6

Systemic adverse events (e.g., fatigue, myalgia, fever, nausea) have been reported. However, rates do not seem to differ from the control groups.2,6,17

  • Experts believe fainting with HPV vaccination is the result of getting an injection, not from the vaccine ingredients. Fainting has been reported after administration of almost all vaccines.19

What does the HPV vaccine protect against?

Gardasil 9 covers HPV strains 6, 11, 16, 18, 31, 33, 45, 52, and 58.6,8

  • Gardasil 9 protects against:6,8
    • anal and genital warts caused by HPV strains 6 and 11.
    • precancerous or dysplastic lesions caused by vaccine-covered strains.
    • cervical, vulvar, vaginal, anal, oropharyngeal, and other head and neck cancers caused by HPV strains 16, 18, 31, 33, 45, 52, and 58.6,8
  • Vaccination with Gardasil 9 could prevent more than 90% of HPV-caused cancers.20

Cervarix (Canada only) covers HPV strains 16 and 18.9,21

  • Cervarix is indicated to protect against cervical cancer (squamous cell and adenocarcinoma) by preventing precancerous or dysplasia lesions caused by HPV strains 16 and 18.9

Note that the now discontinued Gardasil vaccine covered HPV strains 6, 11, 16, and 18.21

What are some suggested talking points with patients and parents?

 

Discuss the benefits of vaccination with patients and their parents/caregivers. See our Vaccine Adherence: Addressing Myths and Hesitancy algorithm for additional ways to improve vaccination rates and overcome barriers.

  • Vaccination appears most effective (for HPV infection, genital warts, precancerous lesions) when given prior to becoming sexually active in males and females under the age of 26 years.6
    • For older females up to 45 years of age, vaccination may be about 47% effective for HPV infection, genital warts, and precancerous lesions regardless of prior HPV exposure or about 88% effective in those without prior HPV exposure [Evidence Level A-1].22
    • Modeling data suggests that HPV vaccination may prevent more HPV-related cancers in adolescents and young adults (NNT ~ 200) compared to adults vaccinated between the ages of 27 and 45 (NNT ~ 6,500).12

Ask parents/caregivers and/or patients about their concerns.

Recommend vaccination at a young age to ensure immunity before becoming sexually active.23

  • Close skin-to-skin sexual touching can spread the virus, making early vaccination important.1,13
  • Feel comfortable that HPV vaccination does not increase sexual activity or promiscuity.24

There is insufficient evidence that HPV vaccination causes:

  • anaphylaxis25
  • complex regional pain syndrome (CRPS)26
  • fertility issues26
  • Guillain-Barré26
  • postural orthostatic tachycardia syndrome (POTS)26
  • syncope25
  • venous thromboembolism and stroke25

Avoid use during pregnancy, due to lack of data.26

  • If a woman becomes pregnant during the vaccine series, delay future injections until after delivery.18

HPV vaccination can be given while breastfeeding.26

How much do the HPV vaccines cost?

Gardasil 9 costs about $270 (US) or $185 (Canada) per dose.a

Cervarix costs about $110 (Canada) per dose.a

US: Check with insurers to verify coverage.

  • Expect vaccinations to be covered for most patients between the ages of nine and 26 years. With updated CDC guidance, reimbursement may include vaccination for males and females up to 45 years.27

Canada: All provinces and territories offer HPV vaccines at no cost as part of school vaccination programs. Some insurance providers may cover HPV vaccines.28

Abbreviations: HPV = human papillomavirus, NNT = number to treat.

  1. Pricing based on wholesale acquisition cost (WAC). US medication pricing by Elsevier, accessed September 2022.

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.

Level

Definition

Study Quality

A

Good-quality patient-oriented evidence.*
  1. High-quality randomized controlled trial (RCT)
  2. Systematic review (SR)/Meta-analysis of RCTs with consistent findings
  3. All-or-none study

B

Inconsistent or limited-quality patient-oriented evidence.*
  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study

C

Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56.  https://www.aafp.org/pubs/afp/issues/2004/0201/p548.html.]

References

  1. CDC. Genital HPV infection – fact sheet. April 12, 2022. https://www.cdc.gov/std/hpv/stdfact-hpv.htm. (Accessed September 7, 2022).
  2. Government of Canada. Canadian Immunization Guide. Human papillomavirus (HPV). September 23, 2021. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-9-human-papillomavirus-vaccine.html#p4c8a1. (Accessed September 7, 2022).
  3. Bird Y, Obidiya O, Mahmood R, et al. Human Papillomavirus Vaccination Uptake in Canada: A Systematic Review and Meta-analysis. Int J Prev Med. 2017 Sep 14;8:71.
  4. CDC. Morbidity and Mortality Weekly Report (MMWR): human papillomavirus-associated cancers – United States, 2008-2012. Updated August 24, 2017. https://www.cdc.gov/mmwr/volumes/65/wr/mm6526a1.htm. (Accessed September 7, 2022).
  5. American Cancer Society. Half of US teens getting HPV vaccinations. August 29, 2019. https://www.cancer.org/latest-news/half-of-us-teens-getting-hpv-vaccinations.html. (Accessed September 7, 2022).
  6. Product information for Gardasil 9. Merck & Co. Whitehouse Station, NJ 08889. June 2020.
  7. FDA. FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old. October 5, 2018. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622715.htm. (Accessed September 7, 2022).
  8. Product monograph for Gardasil 9. Merck Canada. Kirkland, QC H9H 4M7. April 2022.
  9. Product monograph for Cervarix. GlaxoSmithKline. Mississauga, ON L5N 6L4. February 2019.
  10. CDC. CDC recommends only two HPV shots for younger adolescents. October 20, 2016. https://www.cdc.gov/media/releases/2016/p1020-hpv-shots.html. (Accessed September 7, 2022).
  11. CDC. Catch-up immunization schedule for children and adolescents who start late or who are more than 1 month behind. February 17, 2022. https://www.cdc.gov/vaccines/schedules/hcp/imz/catchup.html. (Accessed September 7, 2022).
  12. Meites E, Szilagyi PG, Chesson HW, et al. Human Papillomavirus Vaccination for Adults: Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019 Aug 16;68(32):698-702.
  13. Salvadori MI. Human papillomavirus vaccine for children and adolescents. Paediatr Child Health. 2018 Jul;23(4):262-265.
  14. Government of Canada. Provincial and territorial routine and catch-up vaccination schedule for infants and children in Canada. July 2022. https://www.canada.ca/en/public-health/services/provincial-territorial-immunization-information/provincial-territorial-routine-vaccination-programs-infants-children.html. (Accessed September 7, 2022).
  15. Government of Canada. Not just for kids: an adult guide to vaccination. May 3, 2022. https://www.canada.ca/en/public-health/services/publications/healthy-living/just-kids-adult-guide-vaccination.html. (Accessed September 7, 2022).
  16. Petrosky E, Bocchini JA, Hariri S, et al. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2015 Mar 27;64(11):300-4.
  17. Joura EA, Giuliano AR, Iversen OE, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015 Feb 19;372(8):711-23.
  18. Immunization Action Coalition. Ask the experts: human papillomavirus (HPV). January 18, 2022. http://www.immunize.org/askexperts/experts_hpv.asp. (Accessed September 7, 2022).
  19. CDC. Fainting (syncope). August 25, 2020. http://www.cdc.gov/vaccinesafety/concerns/fainting.html. (Accessed September 7, 2022).
  20. CDC. Cancers caused by HPV are preventable. November 1, 2021. https://www.cdc.gov/hpv/hcp/protecting-patients.html. (Accessed September 7, 2022).
  21. Canada Communicable Disease Report. Tunis MC, Deeks, SL. Summary of the National Advisory Committee on Immunization’s updated recommendations on human papillomavirus (HPV) vaccines: nine-valent HPV vaccine and clarification of minimum interval between doses in the HPV immunization schedule. July 7, 2016. https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2016-42/ccdr-volume-42-7-july-7-2016/ccdr-volume-42-7-july-7-2016-we-stop-measles-2.html. (Accessed September 7, 2022).
  22. Castellsague X, Munoz N, Pitisuttithum P, et al. End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age. Br J Cancer. 2011 Jun 28;105(1):28-37.
  23. CDC. Human papillomavirus (HPV): answering parents’ questions about HPV vaccination. November 1, 2021. https://www.cdc.gov/hpv/hcp/answering-questions.html. (Accessed September 7, 2022).
  24. Bednarczyk RA, Davis R, Ault K, et al. Sexual activity-related outcomes after human papillomavirus vaccination of 11- to 12-year-olds. Pediatrics. 2012 Nov;130(5):798-805.
  25. World Health Organization. Safety of HPV vaccines. https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/topics/human-papillomavirus-vaccines/safety. (Accessed September 7, 2022).
  26. CDC. Questions about HPV vaccine safety. July 15, 2020. https://www.cdc.gov/vaccinesafety/vaccines/hpv/hpv-safety-faqs.html#A2. (Accessed September 7, 2022).
  27. BlueCross BlueShield of North Carolina. Blue Cross NC expands age range coverage for Gardasil. August 16, 2019. https://www.bluecrossnc.com/provider-news/blue-cross-nc-expands-age-range-coverage-gardasil. (Accessed September 7, 2022).
  28. Government of Canada. Update on the recommended Human Papillomavirus (HPV) vaccine immunization schedule. March 10, 2016. https://www.canada.ca/en/public-health/services/publications/healthy-living/update-recommended-human-papillomavirus-vaccine-immunization-schedule.html. (Accessed September 7, 2022).

Cite this document as follows: Clinical Resource, HPV Vaccination. Pharmacist’s Letter/Prescriber’s Letter. September 2022. [380927]