By Sandra Adams Fryhofer M.D., MACP, FRCP
On Feb 1, 2016, President Obama announced “Moonshot,” a new billion-dollar national initiative “to eliminate cancer as we know it.” In his announcement, the President predicted 1.6 million new cancer cases and 600,000 deaths in the United States in 2016. He discussed recent advances in cancer treatment, including using immunotherapy to activate the immune system against cancer. (1)
The details of this initiative also revealed cutting-edge research opportunities in cancer vaccine development. The human papilloma virus (HPV) vaccine was specifically mentioned as an ex-ample of future success in preventing cervical and other cancers. (1) These are laudable goals, but current trends in HPV vaccine coverage suggest many are missing this cancer-preventing opportunity. (2)
The HPV Virus and Cancer
HPV, the human papilloma virus, is linked to cervical, vulvar and vaginal cancer in females, penile cancer in males, and both anal and oropharyngeal cancer in both genders. (3,4)
There are more than 100 different types of HPV virus strains identified. At least 40 of these types can infect the genital area. There are low-risk and high-risk types. The low-risk types include types 6 and 11 that cause genital warts and recurrent respiratory papillomatosis. (3) The high-risk types are linked to cancer: cervical, vulvar and vaginal cancer in females, penile cancer in males, and both anal and oropharyngeal cancer in both genders. High-risk HPV strains include types 16, 18, 31, 33, 45, 52 and 58, which are included in some or all of the available vaccines. (3)
Differences in Coverage
There are three HPV vaccines currently available: a bivalent vaccine, 2vHPV vaccine (covers 16, 18) brand name Cevarix made by GSK and FDA approved in 2009 (5); a quadrivalent vaccine, 4vHPV vaccine (covers 6, 11, 16, 18), brand name Gardasil (6) by Merck and FDA approved in 2006; and a nonavalent vaccine, 9vHPV vaccine (covers 6, 11, 16, 18 plus 31, 33, 45, 52, 58), brand name Gardasil 9 (7), also made by Merck and FDA approved in December 2014.
All three HPV vaccines, the 2valent (v), the 4v, and the new 9 valent vaccine, provide cancer protection against HPV types 16 and 18, which cause about 64 percent of HPV-related cancers overall (an estimated 21,300 cases of cancer each year). The cancer-causing potential of these two strains (16, 18) is similar for males and females. (8) Types 16 and 18 cause 63 percent of all HPV-related cancers in males and 65 percent of all HPV-related cancers in females (8) as well as 66 percent of all cervical cancers.(8)
The 4v and 9v vaccines also protect against types 6 and 11, which cause 90 percent of all cases of anogenital warts. (8) The newer 9v vaccine covers five additional strains, which are linked to 10 percent of HPV-related cancers overall (about 3,400 cancer cases each year) but with important gender differences. (8) The five additional strains are linked to 14 percent of HPV-related cancers in females, including 15 percent of cervical cancers, but only 4 percent of HPV-related cancers in males. (8) Thus, the 9v vaccine provides triple additional protection for females.
HPV Vaccination Recommendations
ACIP recommends adolescents begin the HPV vaccine series routinely starting at age 11 or 12. Catch up vaccination should continue through age 26 for all females, through age 21 for all males, and through age 26 for immunocompromised males, including those with HIV and for men who have sex with men. Any of the three vaccines can be used to start, continue or complete the series for females, but only the 4v and 9v vaccines are options for males. (8)
At the February 2016 ACIP meeting, Merck, maker of both the 4v and 9v HPV vaccines, an-nounced production and distribution of the HPV 4v vaccine will halt at the end of 2016.
Many physicians (and parents) may wonder about additional vaccination with HPV 9. If a child has already completed a bivalent or quadrivalent vaccination series, should they receive additional vaccination with the 9vHPV vaccine?
That’s a good question, but it is NOT answered or addressed in the 2016 ACIP Adult Immunization schedule or its footnotes. However, guidance on the ACIP website does clarify: “There is NO ACIP recommendation for additional 9-v HPV vaccine doses” for anyone that’s already completed bivalent or quadrivalent vaccination series. (9) However, studies show no serious safety concerns with additional nine valent vaccination other than higher rates of injection site swelling and redness.(9) So the decision for additional vaccination is in the physician’s and parents’ hands.
Dispelling HPV Vaccine Myths
The HPV virus is sexually transmitted, with an estimated 6.2 million new infections (pre-HPV vaccine era) each year. (3) HPV vaccines are prophylactic vaccines, which means they must be given before exposure to the virus strain to be effective.(3) Studies show that immune response to the vaccine is best when given at younger ages. (8) That’s why it is recommended to be given at age 11-12 (but can be given as early as age 9). (8)
HPV vaccines are cancer-preventing vaccines, not “sex vaccines.” A recent study in Pediatrics confirmed that HPV vaccination was not associated with riskier sexual behaviors: vaccination will not cause your children to have sex. (10)
Most of us hope that our children will have marital sex and give us grandchildren. Although we can help shape our own children’s behaviors, we don’t know and cannot control the past behaviors of the person they choose to marry. (The number of lifetime and recent sexual partners is the most consistent predictor of HPV infection.) So think of this vaccine as cancer protection insurance for your child.
You can’t get an HPV infection from the vaccine. The vaccine does not contain any viral DNA whatsoever, so there is no way to become infected with the virus by getting the vaccine. (3)
You don’t need a pregnancy test before getting the vaccine, but the vaccine should NOT be given to women who are pregnant or are planning to get pregnant soon. ACIP says the vaccine may be given to nursing moms. (3)
The vaccine is not meant to be a treatment for HPV infection (3), and women must still get regular cervical cancer screening beginning at age 21. (11)
New Evidence the Vaccine Seems to be Working
A study recently published in the journal Pediatrics and spearheaded by Dr. Laurie Markowitz demonstrates the effectiveness of the vaccine. HPV infection rates among 14- to 19-year-old girls for the four HPV types covered in the 4v HPV vaccine dropped 63 percent from 11.4 per-cent in 2006 (pre-vaccine era) to 4.3 percent in 2009-2012 (post-vaccine). (12)
Unfortunately, findings from the most recent National Health Interview Survey (NHIS) in 2014 revealed disappointing HPV vaccination coverage rates for adults age 19-26. Only 40.2 percent of females and 8.2 percent of males had received at least one HPV vaccine dose.(2) Much greater protection could be achieved if all kids were vaccinated with this cancer-preventing vaccine.
This is a prophylactic vaccine. Don’t let your kids or patients miss the window of opportunity for protection. Don’t underestimate the power of your recommendation. A recent study showed that women age 19-26 were overwhelmingly more likely to receive a HPV vaccination if it was recommended by their physician. (13) Encourage your patients, your family members and your friends to make sure their kids get vaccinated against HPV. These cancers can be eliminated if all kids receive this cancer-preventing vaccine.
1. FACT SHEET: Investing in the National Cancer Moonshot, White house website. Available at https://www.whitehouse.gov/the-press-office/2016/02/01/fact-sheet-investing-national-cancer-moonshot, Accessed on March 23, 2016.
2. Williams WW, Lu PJ, O’Halloran A, et al. Surveillance of Vaccination Coverage Among Adult Populations- United States, 2014. MMWR Morb Mortal Wkly Rep. 2016; 65(1):1-36.
3. Markowitz L, Dunne E, Saraiya M, Lawson H, Chesson H, Unger E, Quadrivalent Hu-man Papillomavirus Vaccine: Recommendations of ACIP, MMWR, March 23, 2007, Vo1 56, #RR02 FDA Licensure of Quadrivalent Human Papillomavirus Vaccine (HPV4, Gardasil) for Use in Males and Guidance from the Advisory Committee on Immunization Practices (ACIP), MMWR, May 28, 2010 / 59(20);630-632.
4. Quadrivalent Human Papillomavirus Vaccine (HPV4, Gardasil) for Use in Males and Guidance from ACIPMMWR, May 28, 2010, Vo1 59, #20 Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5920a5.htm, Accessed on March 23, 2016.
5. Cevarix package insert, FDA website. Available at http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM186981.pdf, Accessed on March 23, 2016.
6. Gardasil package insert, FDA website, Available at http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM111263.pdf, Accessed on March 23, 2016.
7. Gardasil 9 package insert, Merck website, Available at http://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_pi.pdf, Accessed on March 23, 2016.
8. Petrosky E, Bocchini JA, Hariri S, Chesson H, Curtis CR, Saraiya M, et al. Use of 9-Valent Human Papillomavirus (HPV) Vaccine: Updated HPV Vaccination Recommenda-tions of the Advisory Committee on Immunization Practices MMWR. 2015;64(11);300-304.
9. Supplemental information and guidance for vaccination providers regarding use of 9-valent HPV vaccine. CDC webiste, Available at http://www.cdc.gov/hpv/downloads/9vhpv-guidance.pdf, Accessed on March 23, 2016.
10. Mayhew A, Kowalczyk Mullins T, Ding L, Rosenthal S, Zimet G, Morrow C, Kahn J, Risk Perceptions and Subsequent Sexual Behaviors After HPV Vaccination in Adoles-cents, Pediatrics 2014;133:1-8, Available at http://pediatrics.aappublications.org/content/pediatrics/early/2014/01/28/peds.2013-2822.full.pdf, Accessed on March 23, 2016.
11. Cervical Cancer Screening, ACOG website , Available at http://www.acog.org/Patients/FAQs/Cervical-Cancer-Screening, Accessed on March 23, 2016.
12. Markowitz L, Liu G, Hariri S, Steinau M, Dunne E, Unger E, Prevalence of HPV After Introduction of the Vaccination Program in the United States, Pediatrics 2016;137(2):e20151968, Available at http://pediatrics.aappublications.org/content/pediatrics/early/2016/02/19/peds.2015-1968.full.pdf, Accessed on March 23, 2016.
13. Rosenthal SL, Weiss TW, Zimet GD, Ma L, Good MB, Vichnin MD Predictors of HPV vaccine uptake among women aged 19-26: importance of a physi-cian’s recommendation. Vaccine. 2011 Jan 29;29(5):890-5. doi: 10.1016/j.vaccine.2009.12.063. Epub 2010 Jan 5.