Human Papilloma Virus Vaccine: Get the Facts

In June 2013,[1] the Centers for Disease Control and Prevention (CDC) announced that the prevalence of the deadliest human papillomavirus (HPV) infections in teenage girls had been reduced by half between 2003 and 2010.[2] The reason, according to the CDC, was the 2006 introduction of the HPV vaccine GARDASIL (a second HPV vaccine, CERVARIX, was approved in 2009).

The success of the vaccine in curtailing HPV infections occurred despite the fact that only one-third of teenage girls in the U.S. had received the full three courses of the vaccine.[3] By comparison, vaccination rates in other developed countries, such as the U.K., Denmark[4] and several Canadian provinces[5] exceed 80 percent. CDC Director Dr. Thomas Frieden used the study as a clarion call for the medical and public health communities to ramp up vaccination efforts and reach the remaining two-thirds of unvaccinated girls (and far higher proportion of unvaccinated boys).[6]

Several factors may be responsible for the unusually low U.S. vaccination rates. Unlike other developed countries, the U.S. does not guarantee universal health insurance, which may have prevented many parents from seeking vaccination for their children. (Federal and state programs guaranteeing free vaccinations to low-income families ameliorated this somewhat, and the federal Affordable Care Act, once fully implemented, mandates health insurers to cover vaccinations of all recommended age groups at no additional cost to patients.)[7] Because the HPV vaccines are intended to prevent a sexually transmitted disease, some parents may associate them with promiscuity and may be reluctant to vaccinate their children.[8] Finally, the safety of the vaccines has been publicly questioned since their approvals, with high-profile figures such as 2012 presidential candidate Michele Bachmann suggesting that the vaccines may cause “mental retardation.”[9]

Know the facts about the HPV vaccines to determine if you or someone you know should get vaccinated.

What is HPV?

HPV is the most common sexually transmitted infection.[10] Four strains, or types, of the virus are most commonly implicated in human disease: types 6, 11, 16 and 18. Types 6 and 11 are the most common causes of genital and anal warts,[11] and types 16 and 18 are the most common causes of cervical cancer.[12] HPV types 16, 18 and other “high-risk” strains also are associated with most cancers of the vulva, vagina, anus and mouth/throat, and a significant proportion of penile cancers.[13]

Approximately 12,000 women are diagnosed with, and 4,000 die from, cervical cancer in the U.S. each year.[14] At any one time, approximately 1 percent of sexually active adults in the U.S. have visible genital warts.[15]

Do I have HPV?

According to the CDC, nearly all sexually active persons become infected with at least one strain of HPV at some point in their lives.[16] Approximately 79 million Americans are currently infected with the virus, and 14 million are newly infected every year.[17] Most people infected with HPV remain asymptomatic and are thus unaware of their infection.[18]

Testing for HPV infection is not recommended on a routine basis and is only approved to test for cancer-causing HPV strains in women 30 years of age and older undergoing a Pap smear and in all women with possible precancerous lesions on cervical exam.[19]

Is HPV curable?

In most people, HPV infections resolve on their own, with the body clearing the virus naturally. The CDC estimates that about 70 percent of new HPV infections clear within one year, and 90 percent clear within two years.[20] However, about 10 percent of women infected with cancer-associated HPV strains will have persistent infections that put them at risk for cervical cancer years down the road.[21]

What vaccines are approved to prevent infection?

There are two different vaccines approved by the Food and Drug Administration (FDA) to prevent HPV infections: GARDASIL (quadrivalent vaccine, which protects against four strains of HPV), approved in 2006,[22] and CERVARIX (bivalent vaccine, which protects against two strains of HPV), approved in 2009.[23]

GARDASIL is approved to prevent cervical, vulvar, vaginal and anal cancer and precancerous changes due to infection with the HPV strains 16 and 18, and to prevent genital warts due to infection with HPV strains 6 and 11, in girls and women 9 to 26 years of age. GARDASIL also is approved for the prevention of anal cancer and precancerous changes and genital warts due to infection with the same HPV strains in boys and men 9 to 26 years of age.[24]

CERVARIX is indicated only to prevent cervical cancer and precancerous changes due to HPV 16 and 18 in girls and women 9 to 25 years of age.[25] It is not approved to protect against the HPV strains 6 and 11 and is not approved in males.

GARDASIL is, by far, the more commonly administered vaccine, accounting for 99 percent of all HPV vaccinations administered in the U.S.[26]

Who should be vaccinated?

The CDC recommends that all girls ages 11 to 12 years old receive the three courses of either GARDASIL or CERVARIX and all boys ages 11 to 12 receive GARDASIL. [27]Vaccination can begin as early as age 9. Teenage and young women up to age 26 and men up to age 21 should get “catch-up” vaccinations if they had not already received the vaccine when they were younger.[28] In addition, gay and bisexual men of all ages and men and women up to age 26 with compromised immune systems (such as those with HIV infection/AIDS) should receive the vaccine.

What if I already have HPV?

Neither GARDASIL nor CERVARIX protect against complications from previously acquired HPV infections.[29],[30] Because so many people over age 26 have been sexually active and already exposed to at least one strain of HPV by their late 20s, the CDC does not recommend routine vaccination for those over 26 years of age.[31]

Are the vaccines safe?

Concerns have been raised that the HPV vaccine leads to serious side effects. The safety of the two vaccines was evaluated in large pre-approval clinical trials comprising tens of thousands of subjects.[32],[33] Both vaccines were found to be very safe, with only a few, mostly minor, side effects.[34]

Most people will experience pain, swelling and/or redness around the injection site.[35] In a small number of patients (fewer than two cases per million administered doses),[36] the vaccines can cause an anaphylactic allergic reaction, which can be fatal if untreated. The HPV vaccine should always be administered under the supervision of a health care professional, with treatments readily available in case of such a reaction.

A small number of people also may get light-headed or faint after receiving any injection, including the HPV vaccine, with fainting more commonly experienced by adolescents.[37] Sometimes, fainting can result in muscle jerking that may be mistaken for a seizure but is in fact a harmless bodily reflex that can occur after fainting.[38] Because fainting can result in falls and injuries, patients should be seated or lying down during HPV vaccination and refrain from standing up unsupported for about 15 minutes after the vaccination.[39]

Some vaccines can induce an immune response from the body, known as autoimmune syndromes, in which vaccine particles prompt the body to produce antibodies that end up targeting the body’s own tissues. This is very rare and usually occurs a few weeks after vaccination. Examples include a neurological syndrome called Guillain-Barre syndrome, a very rare complication of some vaccines.[40] Concerns have been raised that the HPV vaccine may cause similar reactions. However, the rate of autoimmune syndromes was identical in those receiving HPV vaccine and placebo in the clinical trials conducted prior to approval.[41],[42]

Adverse events reported to the FDA since GARDASIL’s approval are consistent with those seen prior to approval, with no new side effects identified through March 2013.[43]

Are the vaccines effective?

The GARDASIL and CERVARIX vaccines are both extremely effective in preventing HPV infections in those not previously exposed to the virus. Four clinical trials of GARDASIL were performed prior to its 2006 approval.[44] Among the more than 8,000 females ages 16 to 26 years of age[45] who received three vaccine doses and had no evidence of HPV infection before completing the vaccine series, GARDASIL prevented 100 percent of HPV 16- or 18-related precancerous cervical abnormalities and early localized forms of cervical cancer.[46] Data from three of the four trials indicated that GARDASIL also prevented 99 percent of genital warts related to HPV 6, 11, 16 and 18.

CERVARIX was evaluated in a clinical trial comprising more than 18,000 females aged 15 to 25 years.[47] The vaccine prevented 93 percent of precancerous cervical abnormalities and early localized forms of cervical cancer in subjects who had received three vaccine doses and had no evidence of prior HPV infection.[48]

The effectiveness of the vaccines in females is further suggested by the dramatic decline in HPV infections in teenage girls since the introduction of GARDASIL in 2006 and CERVARIX in 2009,[49] identified in the CDC study.[50] Though no one can say for sure how much of this decline is due to the introduction of the vaccine in 2006, infection rates had been stable before 2006.[51] Because cancers caused by the HPV infection usually do not occur until many years after infection,[52] noticeable declines in cervical and other cancer rates related to the HPV vaccine will not be evident for years or even decades from now.

A clinical trial involving 4,055 men and boys aged 16 through 26 showed GARDASIL’s effectiveness.[53] In subjects who received three vaccine doses and had no evidence of HPV infection before completing the vaccine series, GARDASIL prevented 89 percent of genital warts related to HPV 6, 11, 16 and 18, as well as a similar percentage of genital warts related to HPV 6 and 11.

Because there were too few occurrences of penile, groin and anal precancerous lesions in the clinical trial, the vaccine’s effectiveness in preventing cancer in males could not be definitively evaluated. In a substudy of 598 men who have sex with men in the trial who received all three vaccine doses without evidence of HPV infection until the last dose, GARDASIL seemed to have prevented 74 to 77 percent of anal precancerous lesions, consistent with its effectiveness in preventing cancers in females.

Can I stop getting pap smears after vaccination?

No. All women who receive the HPV vaccine should continue to undergo regular pap smears to screen for precancerous changes and early cancer of the cervix. Though the vaccine is very effective overall, a small number of vaccinated women will become infected with HPV strains 16 or 18 (those included in the vaccine). In addition, some women may already have been unknowingly infected with these HPV strains prior to being vaccinated. Finally, a small percentage of cervical cancers are due to HPV types other than 16 and 18. For all of these reasons, all women ages 21 to 65 years (with the exception of those who have had their cervix removed in a total hysterectomy and do not have a history of high-grade precancerous cervical lesions or cervical cancer) must continue to have pap smears on a regular basis, regardless of vaccination history.[54]

Conclusion

Both GARDASIL and CERVARIX are safe and effective in preventing a number of potentially fatal cancers in women, with GARDASIL also effective in preventing genital warts in both girls and boys. Serious side effects from the vaccines are rare, and many of the serious safety concerns raised in the media have thus far been largely unfounded.

The CDC estimates that at the current, low vaccination rates, the HPV vaccine will prevent 45,000 cervical cancer cases and 14,000 deaths in girls now aged 13 and younger over the course of their lifetimes. Increasing the rate to 80 percent would prevent an additional 53,000 cancers and almost 17,000 deaths.[55]

If you or someone you know falls within the recommended age range for vaccination and has not yet been vaccinated, a prompt visit to a health care professional is recommended to determine whether HPV vaccination should be initiated. For more information on the HPV vaccine for young women, visit www.cdc.gov/std/hpv/stdfact-hpv-vaccine-young-women.htm. 

References

[1] Centers for Disease Control and Prevention (CDC). New study shows HPV vaccine helping lower HPV infection rates in teen girls. June 19, 2013. http://www.cdc.gov/media/releases/2013/p0619-hpv-vaccinations.html. Accessed September 5, 2013.

[2] Markowitz LE, Hariri S, Lin C, et al. Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003-2010. J Infect Dis. 2013 Aug 1;208(3):385-93.

[3] Tavernise S. The New York Times. HPV vaccine is credited in fall of teenagers’ infection rate. June 19, 2013. http://www.nytimes.com/2013/06/20/health/study-finds-sharp-drop-in-hpv-infections-in-girls.html?hp&_r=1&. Accessed September 5, 2013.

[4] Ibid.

[5] Nature editorial. Active protection. July 18, 2013. 499: 253. http://www.nature.com/news/active-protection-1.13387. Accessed September 13, 2013.

[6] CDC. New study shows HPV vaccine helping lower HPV infection rates in teen girls. June 19, 2013. http://www.cdc.gov/media/releases/2013/p0619-hpv-vaccinations.html. Accessed September 5, 2013.

[7] Kaiser Family Foundation. The HPV vaccine: Access and use in the U.S. June 17, 2013. http://kff.org/womens-health-policy/fact-sheet/the-hpv-vaccine-access-and-use-in/. Accessed October 1, 2013.

[8] Tavernise S. The New York Times. HPV vaccine is credited in fall of teenagers’ infection rate. June 19, 2013. http://www.nytimes.com/2013/06/20/health/study-finds-sharp-drop-in-hpv-infections-in-girls.html?hp&_r=1&. Accessed September 5, 2013.

[9] ABC News. Michele Bachmann's HPV vaccine safety and 'retardation' comments misleading, doctors say. Gann C. September 14, 2011. http://abcnews.go.com/Health/Wellness/michele-bachmanns-hpv-vaccine-safety-retardation-comments-misleading/story?id=14516625. Accessed September 13, 2013.

[10] CDC. Human papillomavirus: What is HPV? http://www.cdc.gov/hpv/whatishpv.html. Accessed September 5, 2013.

[11] CDC. VPD surveillance manual, 5th edition, 2011. Chapter 5: Human papillomavirus. http://www.cdc.gov/vaccines/pubs/surv-manual/chpt05-hpv.pdf. Accessed September 20, 2013.

[12] Ibid.

[13] Ibid.

[14] CDC. HPV vaccine - questions & answers. How common are the health problems caused by HPV? http://www.cdc.gov/vaccines/vpd-vac/hpv/vac-faqs.htm. Accessed September 5, 2013.

[15] Ibid.

[16] CDC. Genital HPV infection - fact sheet. How common are HPV and health problems caused by HPV? http://www.cdc.gov/std/HPV/STDFact-HPV.htm#a5. Accessed September 5, 2013.

[17] CDC. Genital HPV infection - fact sheet. How common are HPV and health problems caused by HPV? http://www.cdc.gov/std/HPV/STDFact-HPV.htm#a5. Accessed September 5, 2013.

[18] CDC. Genital HPV infection - fact sheet. What is genital HPV infection? http://www.cdc.gov/std/HPV/STDFact-HPV.htm#a5. Accessed September 5, 2013.

[19] CDC. VPD surveillance manual, 5th edition, 2011. Chapter 5: Human papillomavirus. http://www.cdc.gov/vaccines/pubs/surv-manual/chpt05-hpv.pdf. Accessed September 20, 2013.

[20] CDC. Quadrivalent human papillomavirus vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP). March 23, 2007. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm. Accessed September 13, 2013.

[21] CDC. Basic information about HPV-associated cancers. http://www.cdc.gov/cancer/hpv/basic_info/. Accessed September 20, 2013.

[22] GARDASIL label. Revised 03/2013. http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf. Accessed September 12, 2013.

[23] CERVARIX label. Revised 08/2012. http://us.gsk.com/products/assets/us_cervarix.pdf. Accessed September 12, 2013.

[24] GARDASIL label. Revised 03/2013. http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf. Accessed September 12, 2013.

[25] CERVARIX label. Revised 08/2012. http://us.gsk.com/products/assets/us_cervarix.pdf. Accessed September 12, 2013.

[26] CDC. Human papillomavirus vaccination coverage among adolescent girls, 2007–2012, and postlicensure vaccine safety monitoring, 2006–2013 — United States. MMWR Weekly July 26, 2013 / 62(29);591-595. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6229a4.htm#tab2. Accessed October 1, 2013.

[27] CDC. Recommended immunization schedule for persons age 0 through 18 years. United States, 013. http://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-schedule.pdf. Accessed September 10, 2013.

[28] CDC. HPV vaccines. http://www.cdc.gov/hpv/vaccine.html. Accessed September 6, 2013.

[29] GARDASIL label. Revised 03/2013. http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf. Accessed September 12, 2013.

[30] CERVARIX label. Revised 08/2012. http://us.gsk.com/products/assets/us_cervarix.pdf. Accessed September 12, 2013.

[31] CDC. HPV vaccine information for clinicians - fact sheet. http://www.cdc.gov/std/hpv/stdfact-hpv-vaccine-hcp.htm. Accessed September 17, 2013.

[32] CERVARIX label. Revised August 2012. 6.1 Clinical Studies Experience.

[33] GARDASIL label. Revised March 2013. 6.1 Clinical Trials Experience.

[34] Food and Drug Administration. FDA safety summaries of GARDASIL, http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM111287.pdf, and CERVARIX, http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM237976.pdf. Accessed October 22, 2013.

[35] CDC . GARDASIL: Quadrivalent human papillomavirus vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP). March 23, 2007. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm#tab7. Accessed September 13, 2013.

CERVARIX: CDC MMWR. FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP). May 28, 2010 / 59(20);626-629. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5920a4.htm. Accessed September 13, 2013.

[36] Gee J, Naleway A, Shui I, et al. Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink. Vaccine. 2011 Oct 26;29(46):8279-84.

[37] CDC. Frequently asked questions about syncope after vaccination. Who is more likely to experience fainting after immunization? http://www.cdc.gov/vaccinesafety/Concerns/syncope_faqs.html. Accessed September 5, 2013.

[38] Medical knowledge.

[39] CDC. Frequently asked questions about syncope after vaccination. Can fainting and related injury after immunization be prevented? http://www.cdc.gov/vaccinesafety/Concerns/syncope_faqs.html. Accessed September 5, 2013.

[40] CDC. Guillain-Barré Syndrome (GBS). http://www.cdc.gov/flu/protect/vaccine/guillainbarre.htm. Accessed September 17, 2013.

[41] GARDASIL label. Revised March 2013. 6.1 Clinical Trials Experience.

[42] CERVARIX label. Revised August 2012. 6.1 Clinical Studies Experience.

[43] CDC. Human papillomavirus vaccination coverage among adolescent girls, 2007–2012, and postlicensure vaccine safety monitoring, 2006–2013 — United States. MMWR Weekly July 26, 2013 / 62(29);591-595. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6229a4.htm#tab2. Accessed October 1, 2013.

[44] CDC. MMWR; March 23, 2007 / 56(RR02);1-24. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm#tab3. Accessed September 16, 2013.

[45] Ibid.

[46] Ibid.

[47] CDC. MMWR Weekly; May 28, 2010 / 59(20);626-629. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5920a4.htm. Accessed September 16, 2013.

[48] Ibid.

[49] For approval dates, see page 1 of GARDASIL and CERVARIX labels.

[50] Markowitz LE, Hariri S, Lin C, et al. Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003-2010. J Infect Dis. 2013 Aug 1;208(3):385-93.

[51] Tavernise S. The New York Times. HPV vaccine is credited in fall of teenagers’ infection rate. June 19, 2013. http://www.nytimes.com/2013/06/20/health/study-finds-sharp-drop-in-hpv-infections-in-girls.html?hp&_r=1&. Accessed September 5, 2013.

[52] Medical knowledge.

[53] CDC. MMWR. 60(50);1705-1708. Recommendations on the use of quadrivalent human papillomavirus vaccine in males — Advisory Committee on Immunization Practices (ACIP), 2011 Weekly. December 23, 2011. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6050a3.htm. Accessed September 16, 2013.

[54] USPSTF. Screening for cervical cancer. March 2012. http://www.uspreventiveservicestaskforce.org/uspstf11/cervcancer/cervcancerrs.htm. Accessed September 17, 2013.

[55] Tavernise S. The New York Times. HPV vaccine is credited in fall of teenagers’ infection rate. June 19, 2013. http://www.nytimes.com/2013/06/20/health/study-finds-sharp-drop-in-hpv-infections-in-girls.html?hp&_r=1&. Accessed September 5, 2013.