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Issue 1189: June 17, 2015

Ask the Experts: CDC Experts Answer Your Questions

The questions and answers in this edition of IAC Express, all related to human papillomavirus (HPV) vaccination, first appeared in the May 2015 issue of Needle Tips.

IAC extends thanks to our experts, medical officer Andrew T. Kroger, MD, MPH; and nurse educator Donna L. Weaver, RN, MN. Both are with the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC).

Questions and Answers 
Q: Which types of HPV are most likely to cause disease?

A: Of the annual average of 26,900 HPV-related cancers in the United States, approximately 64% are attributable to HPV 16 or 18 (65% for females; 63% for males; approximately 21,300 cases annually), which are included in all three HPV vaccines. Approximately 10% are attributable to HPV types 31, 33, 45, 52, and 58 (14% for females; 4% for males; approximately 3,400 cases annually), which are included in the 9-valent HPV vaccine. HPV type 16, 18, 31, 33, 45, 52, or 58 account for about 81% of cervical cancers in the United States. Approximately 50% of cervical precancers (CIN2 or greater) are caused by HPV 16 or 18 and 25% by HPV 31, 33, 45, 52, or 58. HPV 6 or 11 cause 90% of anogenital warts (condylomata) and most cases of recurrent respiratory papillomatosis. More information about HPV and HPV-related cancers is available in the 2014 HPV ACIP statement at

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Q: Are healthcare personnel at risk of occupational infection with HPV?

A: Occupational infection with HPV is possible. Some HPV-associated conditions (including anogenital and oral warts, anogenital intraepithelial neoplasias, and recurrent respiratory papillomatosis) are treated with laser or electrosurgical procedures that could produce airborne particles. These procedures should be performed in an appropriately ventilated room using standard precautions and local exhaust ventilation. Workers in HPV research laboratories who handle wildtype virus or “quasi virions” might be at risk of acquiring HPV from occupational exposures. In the laboratory setting, proper infection control should be instituted including, at minimum, biosafety level 2. Whether HPV vaccination would be of benefit in these settings is unclear because no data exist on transmission risk or vaccine efficacy in this situation.

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Q: Please summarize information about Merck’s new 9-valent HPV vaccine (9vHPV, Gardasil 9).

A: 9vHPV contains the four HPV types in 4vHPV (Gardasil; 16, 18, 6, and 11) and 5 additional "high risk" types (31, 33, 45, 52, and 58). It was licensed by the U.S. Food and Drug Administration (FDA) on December 10, 2014. 9vHPV is approved for use in females 9 through 26 years and males 9 through 15 years (Merck has subsequently submitted clinical trial data to the FDA for males 16 through 26 years of age). 9vHPV has the same schedule as 4vHPV (three intramuscular doses spaced 0, 1–2, and 6 months apart). In a clinical trial comparing 9vHPV to 4vHPV, 9vHPV reduced the risk of disease caused by the 5 additional strains by 97%. ACIP states that clinicians can administer either 4vHPV or 9vHPV to males through age 26 years to complete the HPV vaccine series.

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Q: With the availability of 9vHPV, has the ACIP changed its recommendations for HPV vaccines?

A: The ACIP recommendations for HPV vaccination have not changed. ACIP recommends that routine HPV vaccination be initiated for females and males at age 11 or 12 years. The vaccination series can be started as early as age 9 years. Vaccination is also recommended for females aged 13 through 26 years and for males aged 13 through 21 years who have not been vaccinated previously or who have not completed the 3-dose series. In addition, vaccination is recommended for men age 22 through age 26 years who 1) have sex with men or 2) are immunocompromised as a result of infection (including HIV), disease, or medication. Other males 22 through 26 years of age may be vaccinated at the clinician’s discretion.

Vaccination of females is recommended with 2vHPV (Ceravix, GlaxoSmithKline), 4vHPV (as long as this formulation is available), or 9vHPV. Vaccination of males is recommended with 4vHPV (as long as this formulation is available) or 9vHPV. Ideally, HPV vaccine should be administered before potential exposure to HPV through sexual contact.

All 3 HPV vaccines should be given as a 3-dose schedule, with the second dose given 1 to 2 months after the first dose and the third dose 6 months after the first dose.

The 2014 ACIP recommendations are available at (covers 2vHPV and 4vHPV), and the newly released 2015 ACIP recommendations (published March 27, 2015) are at, pages 300–304 (covers 9vHPV).

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Q: Can an HPV vaccine series begun with 2vHPV or 4vHPV be completed with 9vHPV?

A: Yes. Any available HPV vaccine may be used to continue or complete the series for females. 9vHPV or 4vHPV may be used to continue or complete the series for males. However, receiving fewer than 3 doses of 4vHPV or 9vHPV may provide less protection against genital warts caused by HPV types 6 and 11 than the usual 3-dose series. There are no data on the efficacy of the 5 additional HPV types included in 9vHPV if the person receives fewer than 3 doses.

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Q: Does ACIP recommend revaccination with 9vHPV for patients who previously received a series of 2vHPV or 4vHPV?

A: ACIP has not recommended routine revaccination with 9vHPV for persons who have completed a series of another HPV vaccine. There are data that indicate revaccination with 9vHPV after a series of 4vHPV is safe. Clinicians should decide if the benefit of immunity against 5 additional oncogenic strains of HPV is justified for their patients.

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Q: Is 9vHPV included in the Vaccines For Children (VFC) program?

A: Yes.

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Q: Do women and men whose sexual orientation is same-sex need HPV vaccine?

A: Yes. HPV vaccine is recommended for females and males regardless of their sexual orientation.

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Q: If a dose of HPV vaccine is significantly delayed, do I need to start the series over?

A: No, do not restart the series. You should continue where the patient left off and complete the series.

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Q: To accelerate completion of the HPV vaccine series, can doses be given at 0, 1, and 4 months?

A: No, there is no accelerated schedule for completing the HPV vaccine series. You should follow the recommended schedule of 0, 1–2, and 6 months.

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Q: What are the minimum intervals between doses of HPV vaccine?

A: Minimum intervals are used when patients have fallen behind on their immunization schedule or when they need their dosing schedule expedited (for example, if there is imminent travel). The minimum interval between the first and second doses of HPV vaccine is 4 weeks. The minimum interval between the second and third dose is 12 weeks. ACIP recommends an interval of 24 weeks between the first and third dose. However, the third dose can be considered to be valid if it was separated from the first dose by at least 16 weeks and from the second dose by at least 12 weeks.

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Q: If HPV vaccine is given subcutaneously instead of intramuscularly, does the dose need to be repeated?

A: Yes. No data exist on the efficacy or safety of HPV vaccine given by the subcutaneous route. All data on efficacy and duration of protection are based on a 3-dose series given on the approved schedule and administered by the intramuscular route. In the absence of data on subcutaneous administration, the Centers for Disease Control and Prevention (CDC) and the manufacturers recommend that a dose of HPV vaccine given by any route other than intramuscular should be repeated. There is no minimum interval between the invalid (subcutaneous) dose and the repeat dose.

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Q: If a patient has been sexually active for a number of years, is it still recommended to give HPV vaccine or to complete the HPV vaccine series?

A: Yes. HPV vaccine should be administered to people who are already sexually active. Ideally, patients should be vaccinated before onset of sexual activity; however, patients who have already been infected with one or more HPV types still get protection from other HPV types in the vaccine that have not been acquired.

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Q: I read that HPV vaccination rates are still low. What can we do as providers to improve these rates?

A: Coverage levels for HPV vaccine are improving but are still inadequate. Results from the CDC’s 2013 National Immunization Survey-Teen (NIS-Teen) indicate that HPV vaccination rates in girls age 13 through 17 years increased between 2012 and 2013. Just over 57% of girls age 13 through 17 years had started the series that they should have completed by age 13 years and 38% had completed the series. In 2013, 35% of boys age 13 through 17 years had received one dose but only 14% had received all three recommended doses. A summary of the 2013 NIS-Teen survey is available at, pages 625–633.

Providers can improve uptake of this life-saving vaccine in two main ways. First, studies have shown that missed opportunities are a big problem. Up to 88% (depending on year of birth) of girls unvaccinated for HPV had a healthcare visit where they received another vaccine such as Tdap, but not HPV. If HPV vaccine had been administered at the same visit, vaccination coverage for one or more doses could be 91% instead of 57%. Second, the 2013 NIS-Teen data show that not receiving a healthcare provider’s recommendation for HPV vaccine was one of the five main reasons parents reported for not vaccinating their daughters and the number one reason for not vaccinating their sons.

CDC urges healthcare providers to increase the consistency and strength of how they recommend HPV vaccine, especially when patients are age 11 or 12 years. The following resources can help providers with these conversations. For more detailed information about HPV vaccination strategies for providers, visit

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Q: If a 30-year-old female patient insists that she wants to receive HPV vaccine, can I give it to her?

A: HPV vaccine is not FDA-licensed for use in women older than age 26 years. Studies have shown that the vaccine is safe in women age 27 years and older. ACIP does not recommend the use of this vaccine outside the FDA licensing guidelines unless the series was started but not completed by age 26 years. Clinicians may choose to administer HPV vaccine off-label to men and women age 27 years or older.

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Q: What adverse events can be expected following HPV vaccine?

A: In clinical trials involving more than 35,000 subjects, the most common adverse event was injection site pain, which was reported in 58% to 90% of recipients (depending on vaccine and dose number). Other local reactions, such as redness and/or swelling, were reported in 30% to 40% of recipients. Local reactions were reported more frequently among 9vHPV recipients than among 4vHPV recipients, probably because of the larger amount of aluminum adjuvant present in 9vHPV. Systemic reaction, such as fever, headache, and fatigue, were reported by 2% to 50% of recipients (depending on vaccine and dose number). These symptoms generally occurred at about the same rate in vaccine and placebo recipients.

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How to submit a question to Ask the Experts

IAC works with CDC to compile new Ask the Experts Q&As for our publications based on commonly asked questions. We also consider the need to provide information about new vaccines and recommendations. Most of the questions are thus a composite of several inquiries.

You can email your question about vaccines or immunization to IAC at

As we receive hundreds of emails each month, we cannot guarantee that we will print your specific question in the Ask the Experts feature. However, you will get an answer.

You can also email CDC's immunization experts directly at There is no charge for this service.

If you have a question about IAC materials or services, email

Please forward these Ask the Experts Q&As to your co-workers and suggest they subscribe to IAC Express.

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About IZ Express

IZ Express is supported in part by Grant No. 1NH23IP922654 from CDC’s National Center for Immunization and Respiratory Diseases. Its contents are solely the responsibility of and do not necessarily represent the official views of CDC.

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Editorial Information

  • Editor-in-Chief
    Kelly L. Moore, MD, MPH
  • Managing Editor
    John D. Grabenstein, RPh, PhD
  • Associate Editor
    Sharon G. Humiston, MD, MPH
  • Writer/Publication Coordinator
    Taryn Chapman, MS
    Courtnay Londo, MA
  • Style and Copy Editor
    Marian Deegan, JD
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    Laurel H. Wood, MPA
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    Kayla Ohlde

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