- Email: [email protected]
Quadrivalent human papillomavirus vaccine: Updated recommendations for males
Vaccine update
Quadrivalent human papillomavirus vaccine: Updated recommendations for males Chelsie B. Heesch and Mary S. Hayney
Human papillomavirus (HPV) causes 6.2 million infections in the United States each year, making it the most common sexually transmitted infection. Persistent infection with HPV can lead to genital warts and cancers of the cervix, penis, anus, vagina, and vulva. Approximately 7,000 HPV type 16– and 18–associated cancers occur in males each year, including anal, oropharyngeal, and penile cancers.1 In addition, an estimated 250,000 cases of genital warts caused by HPV types 6 and 11 occur in males per year in the United States. The quadrivalent HPV vaccine (HPV4; Gardasil—Merck & Co., Inc.) is highly effective in preventing genital warts in males and has recently demonstrated efficacy in the preventing grade 2 or 3 anal intraepithelial neoplasia (AIN2/3), which are precursors of anal cancer.2 Until recently, vaccination efforts for HPV have focused on routine immunization of females, although the incidence of HPV infection is similar for males and females.2 Routine immunization of males will result in fewer HPV infections and related cancers. This article provides a summary of the current literature supporting the use of HPV4 in males and recommendations regarding the use of HPV vaccines in general. Currently in the United States, two HPV vaccines are available. The bivalent HPV vaccine (HPV2; Cervarix— GlaxoSmithKline) is directed against HPV types 16 and 18. HPV4 is directed against HPV types 6, 11, 16, and 18. HPV types 6 and 11 are responsible for the majority of the cases of genital warts, whereas types 16 and 18 result in most HPV-associated cancers in males and most cervical cancers in females.1,3–5 HPV2 is licensed for females aged 10 to 25 years, whereas HPV4 is licensed for males and females aged 9 to 26 years. Both vaccines are highly effective for
preventing cervical cancer. In addition, HPV4 prevents genital warts caused by the vaccine types in both males and females. HPV4 is also effective in preventing vaginal and vulvar cancer in females and anal cancer in both males and females.1,3–5 In October 2011, the Advisory Committee on Immunization Practices (ACIP) changed from stating that males aged 11 to 12 years may be vaccinated with HPV4 to an explicit recommendation for the routine immunization of males aged 11 to 12 years with HPV4.1 This update in ACIP vaccine recommendations was prompted by additional clinical information showing HPV4 to be effective in preventing AIN among men who have sex with men (MSM). A substudy evaluated the efficacy of HPV4 in preventing AIN in 598 healthy MSM aged 16 to 26 years.6 The vaccine was determined to be 77.5% effective (95% CI 39.6–93.3) in preventing AIN2/3 and 73% effective in preventing AIN1 (16.3–93.4) caused by HPV types 6, 11, 16, and 18 in study participants who were seronegative at initiation of the trial and received all three doses of vaccine. MSM are at a higher risk for infection with HPV, genital warts, and anal cancer.1 The incidence of cancers associated with HPV is higher among MSM,
and the rate of anal cancer among MSM continues to rise.1,6 HPV4 is effective in reducing the rate of AIN2/3 among MSM. Vaccination with HPV4 may reduce the rate of anal cancer, and therefore HPV4 is particularly important for use among MSM. Upon updating the HPV4 vaccine recommendation, ACIP also considered information on HPV4 prevention of infection with HPV types 6, 11, 16, and 18 in males. The supporting study included 4,055 males aged 16 to 26 years.2 One month after the third dose of HPV4, 97.5% of the participants seroconverted to all four types of HPV in the vaccine. The vaccine was determined to be 90.4% effective in preventing genital warts caused by the vaccine types among participants who received all three doses and who were seronegative upon initiation of the trial (95% CI 61.2–94.4). The study found the vaccine to be safe with no serious vaccine-related adverse events reported. The primary mode of transmission of genital HPV is sexual intercourse.3 Although condom use decreases HPV transmission, it is not very effective.7 The prevalence of HPV is higher among those with multiple sex partners.3 Many adolescents have had multiple sexual partners and are sexually active at a young age. According to the National Survey of Family Growth, males aged 15 to 19 years had a median of 1.8 female sexual partners in their lifetime, whereas males aged 20 to 24 years had an average of 4.1 female sexual partners in their lifetime.8 According to the Youth Risk Behavior Surveillance, 8.4% of males had sexual intercourse before the age of 13 years; this rate was even higher among those in 9th
Send your immunization questions to the JAPhA Contributing Editors who coordinate the Vaccine Update column: n Mary S. Hayney, PharmD, BCPS, Associate Professor of Pharmacy, School of Pharmacy, University of Wisconsin, Madison (mshayney@ pharmacy.wisc.edu)
John D. Grabenstein, PhD, Director of Scientific Affairs, Merck Vaccine Division ([email protected])
n
This article is supported by a Cooperative Agreement provided by the Centers for Disease Control and Prevention (CDC) entitled “Pharmacists: Connecting, Communicating and Collaborating for Improved Community Health” (1U66 IP000114). The opinions expressed in this article do not represent the viewpoints of the CDC.
Journal of the American Pharmacists Association
www. japh a. or g
M a r /A p r 2012 • 52:2 •
JAPhA • 289
Vaccine update
Table 1. Adolescent (age 13–17 years) immunization rates: United States, 2009 Vaccine Tdap Meningococcal HPV (females, at least one dose) HPV (females, complete series) HPV (males)
Immunization rate % 56 63 44 27 1
Abbreviations used: HPV, human papillomavirus; Tdap, tetanus–diphtheria–acellular pertussis. Source: reference 10.
grade (33.6%) and even higher among those in 12th grade (59.6%).9 The vaccine offers protection against the HPV types to which a person has not been exposed previously. Therefore, for the vaccine to be most effective, it should be administered before sexual activity has begun or as soon as possible thereafter. The benefit of vaccination decreases with an increasing number of sexual partners, as the likelihood of prior infection increases. Vaccination of males aged 13 to 21 years who have not been vaccinated or who have not completed all three doses of the HPV4 series is also recommended. In addition, males aged 21 to 26 years may receive HPV4. Routine vaccination with HPV4 for MSM through age 26 years is also recommended. These new recommendations replace the previous statement from ACIP in October 2009 that males aged 9 to 26 years may receive the vaccine. ACIP recommendations for use of the HPV vaccine in females have not changed.1,4 Females aged 11 or 12 years are recommended to receive HPV4 or HPV2. Females aged 13 to 26 years who have not been vaccinated or who have not completed all three doses of the series are recommended to receive the vaccine. Both the HPV2 and HPV4 series are administered on the same schedule. The vaccination schedule is a three-dose series for both males (HPV4 only) and females (HPV2 or HPV4); the second dose is administered 1 to 2 months after the first dose and the third dose 6 months after the first dose. The HPV vaccine series may be ini290 • JAPhA • 5 2 : 2 • M a r /A p r 2012
tiated during an individual’s routine annual visit to his or her primary care provider, but the series could be completed using pharmacy-based immunization services. Take advantage of the visit to administer all vaccines that the individual may need. Although vaccination coverage has increased over the past several years among adolescents aged 13 to 17 years, coverage remains low (Table 1).10 Four routine vaccinations are recommended for adolescents: meningococcal conjugate, Tdap (tetanus–diphtheria– acellular pertussis), HPV, and influenza. Communication among health professionals, providing patients with personal immunization record cards, and use of the immunization registry will be critical to avoiding overimmunization or incomplete immunization. All immunizers should recall prior vaccine recipients who have not completed the vaccine series. Appointments and reminder phone calls are good options.11 Consider asking male patients whether you can send his parents or him a text message reminder.12 Appropriate use of this vaccine has great public health potential to reduce the cancer burden in the United States. To protect males and females against HPV and the diseases associated with HPV, it is important to begin routine vaccination in both males and females at age 11 to 12 years according to the most recent recommendations from ACIP.1,3,4 Chelsie B. Heesch Student pharmacist Mary S. Hayney, PharmD, MPH, FCCP, BCPS Professor of Pharmacy [email protected] School of Pharmacy University of Wisconsin–Madison doi: 10.1331/JAPhA.2012.12511
3. Centers for Disease Control and Prevention. Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2007;56:1–23. 4. Centers for Disease Control and Prevention. 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). MMWR Morb Mortal Wkly Rep. 2010;59:626–9. 5. Centers for Disease Control and Prevention. FDA licensure of quadrivalent human papillomavirus vaccine (HPV4, Gardasil) for use in males and guidance from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2010;59:630–2. 6. Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med. 2011;365:1576–85. 7. Winer RL, Hughes JP, Feng Q, et al. Condom use and the risk of genital human papillomavirus infection in young women. N Engl J Med. 2006;354:2645–54. 8. Chandra A, Mosher WD, Copen C, Sionean C. Sexual behavior, sexual attraction, and sexual identity in the United States: data from the 2006–2008 National Survey of Family Growth. Accessed at www.cdc.gov/nchs/nsfg/new_nsfg.htm, February 5, 2012. 9. Centers for Disease Control and Prevention. Youth risk behavior surveillance: United States, 2009. MMWR Morb Mortal Wkly Rep. 2010;59:1–142. 10. Centers for Disease Control and Prevention. National, state, and local area vaccination coverage among adolescents aged 13-17 years: United States, 2009. MMWR Morb Mortal Wkly Rep. 2010;59:1018–23.
1. Centers for Disease Control and Prevention. Recommendations on the use of quadrivalent human papillomavirus vaccine in males: Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011;60:1705–8.
11. Centers for Disease Control and Prevention. Improving influenza and pneumococcal polysaccharide, and hepatitis B vaccination coverage among adults aged <65 years at high risk: a report on recommendations of the Task Force on Community Preventative Services. MMWR Morb Mortal Wkly Rep. 2005;54:1–11.
2. Giuliano AR, Palefsky JM, Goldstone S, et al. Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med. 2011;364:401– 11.
12. Clark SJ, Butchart A, Kennedy A, Dombkowski KJ. Parents’ experiences with and preferences for immunization reminder/recall technologies. Pediatrics. 2011;128:e1100–5.
References
www.j aph a. or g
Journal of the American Pharmacists Association
Quadrivalent human papillomavirus vaccine: Updated recommendations for males Chelsie B. Heesch and Mary S. Hayney
Human papillomavirus (HPV) causes 6.2 million infections in the United States each year, making it the most common sexually transmitted infection. Persistent infection with HPV can lead to genital warts and cancers of the cervix, penis, anus, vagina, and vulva. Approximately 7,000 HPV type 16– and 18–associated cancers occur in males each year, including anal, oropharyngeal, and penile cancers.1 In addition, an estimated 250,000 cases of genital warts caused by HPV types 6 and 11 occur in males per year in the United States. The quadrivalent HPV vaccine (HPV4; Gardasil—Merck & Co., Inc.) is highly effective in preventing genital warts in males and has recently demonstrated efficacy in the preventing grade 2 or 3 anal intraepithelial neoplasia (AIN2/3), which are precursors of anal cancer.2 Until recently, vaccination efforts for HPV have focused on routine immunization of females, although the incidence of HPV infection is similar for males and females.2 Routine immunization of males will result in fewer HPV infections and related cancers. This article provides a summary of the current literature supporting the use of HPV4 in males and recommendations regarding the use of HPV vaccines in general. Currently in the United States, two HPV vaccines are available. The bivalent HPV vaccine (HPV2; Cervarix— GlaxoSmithKline) is directed against HPV types 16 and 18. HPV4 is directed against HPV types 6, 11, 16, and 18. HPV types 6 and 11 are responsible for the majority of the cases of genital warts, whereas types 16 and 18 result in most HPV-associated cancers in males and most cervical cancers in females.1,3–5 HPV2 is licensed for females aged 10 to 25 years, whereas HPV4 is licensed for males and females aged 9 to 26 years. Both vaccines are highly effective for
preventing cervical cancer. In addition, HPV4 prevents genital warts caused by the vaccine types in both males and females. HPV4 is also effective in preventing vaginal and vulvar cancer in females and anal cancer in both males and females.1,3–5 In October 2011, the Advisory Committee on Immunization Practices (ACIP) changed from stating that males aged 11 to 12 years may be vaccinated with HPV4 to an explicit recommendation for the routine immunization of males aged 11 to 12 years with HPV4.1 This update in ACIP vaccine recommendations was prompted by additional clinical information showing HPV4 to be effective in preventing AIN among men who have sex with men (MSM). A substudy evaluated the efficacy of HPV4 in preventing AIN in 598 healthy MSM aged 16 to 26 years.6 The vaccine was determined to be 77.5% effective (95% CI 39.6–93.3) in preventing AIN2/3 and 73% effective in preventing AIN1 (16.3–93.4) caused by HPV types 6, 11, 16, and 18 in study participants who were seronegative at initiation of the trial and received all three doses of vaccine. MSM are at a higher risk for infection with HPV, genital warts, and anal cancer.1 The incidence of cancers associated with HPV is higher among MSM,
and the rate of anal cancer among MSM continues to rise.1,6 HPV4 is effective in reducing the rate of AIN2/3 among MSM. Vaccination with HPV4 may reduce the rate of anal cancer, and therefore HPV4 is particularly important for use among MSM. Upon updating the HPV4 vaccine recommendation, ACIP also considered information on HPV4 prevention of infection with HPV types 6, 11, 16, and 18 in males. The supporting study included 4,055 males aged 16 to 26 years.2 One month after the third dose of HPV4, 97.5% of the participants seroconverted to all four types of HPV in the vaccine. The vaccine was determined to be 90.4% effective in preventing genital warts caused by the vaccine types among participants who received all three doses and who were seronegative upon initiation of the trial (95% CI 61.2–94.4). The study found the vaccine to be safe with no serious vaccine-related adverse events reported. The primary mode of transmission of genital HPV is sexual intercourse.3 Although condom use decreases HPV transmission, it is not very effective.7 The prevalence of HPV is higher among those with multiple sex partners.3 Many adolescents have had multiple sexual partners and are sexually active at a young age. According to the National Survey of Family Growth, males aged 15 to 19 years had a median of 1.8 female sexual partners in their lifetime, whereas males aged 20 to 24 years had an average of 4.1 female sexual partners in their lifetime.8 According to the Youth Risk Behavior Surveillance, 8.4% of males had sexual intercourse before the age of 13 years; this rate was even higher among those in 9th
Send your immunization questions to the JAPhA Contributing Editors who coordinate the Vaccine Update column: n Mary S. Hayney, PharmD, BCPS, Associate Professor of Pharmacy, School of Pharmacy, University of Wisconsin, Madison (mshayney@ pharmacy.wisc.edu)
John D. Grabenstein, PhD, Director of Scientific Affairs, Merck Vaccine Division ([email protected])
n
This article is supported by a Cooperative Agreement provided by the Centers for Disease Control and Prevention (CDC) entitled “Pharmacists: Connecting, Communicating and Collaborating for Improved Community Health” (1U66 IP000114). The opinions expressed in this article do not represent the viewpoints of the CDC.
Journal of the American Pharmacists Association
www. japh a. or g
M a r /A p r 2012 • 52:2 •
JAPhA • 289
Vaccine update
Table 1. Adolescent (age 13–17 years) immunization rates: United States, 2009 Vaccine Tdap Meningococcal HPV (females, at least one dose) HPV (females, complete series) HPV (males)
Immunization rate % 56 63 44 27 1
Abbreviations used: HPV, human papillomavirus; Tdap, tetanus–diphtheria–acellular pertussis. Source: reference 10.
grade (33.6%) and even higher among those in 12th grade (59.6%).9 The vaccine offers protection against the HPV types to which a person has not been exposed previously. Therefore, for the vaccine to be most effective, it should be administered before sexual activity has begun or as soon as possible thereafter. The benefit of vaccination decreases with an increasing number of sexual partners, as the likelihood of prior infection increases. Vaccination of males aged 13 to 21 years who have not been vaccinated or who have not completed all three doses of the HPV4 series is also recommended. In addition, males aged 21 to 26 years may receive HPV4. Routine vaccination with HPV4 for MSM through age 26 years is also recommended. These new recommendations replace the previous statement from ACIP in October 2009 that males aged 9 to 26 years may receive the vaccine. ACIP recommendations for use of the HPV vaccine in females have not changed.1,4 Females aged 11 or 12 years are recommended to receive HPV4 or HPV2. Females aged 13 to 26 years who have not been vaccinated or who have not completed all three doses of the series are recommended to receive the vaccine. Both the HPV2 and HPV4 series are administered on the same schedule. The vaccination schedule is a three-dose series for both males (HPV4 only) and females (HPV2 or HPV4); the second dose is administered 1 to 2 months after the first dose and the third dose 6 months after the first dose. The HPV vaccine series may be ini290 • JAPhA • 5 2 : 2 • M a r /A p r 2012
tiated during an individual’s routine annual visit to his or her primary care provider, but the series could be completed using pharmacy-based immunization services. Take advantage of the visit to administer all vaccines that the individual may need. Although vaccination coverage has increased over the past several years among adolescents aged 13 to 17 years, coverage remains low (Table 1).10 Four routine vaccinations are recommended for adolescents: meningococcal conjugate, Tdap (tetanus–diphtheria– acellular pertussis), HPV, and influenza. Communication among health professionals, providing patients with personal immunization record cards, and use of the immunization registry will be critical to avoiding overimmunization or incomplete immunization. All immunizers should recall prior vaccine recipients who have not completed the vaccine series. Appointments and reminder phone calls are good options.11 Consider asking male patients whether you can send his parents or him a text message reminder.12 Appropriate use of this vaccine has great public health potential to reduce the cancer burden in the United States. To protect males and females against HPV and the diseases associated with HPV, it is important to begin routine vaccination in both males and females at age 11 to 12 years according to the most recent recommendations from ACIP.1,3,4 Chelsie B. Heesch Student pharmacist Mary S. Hayney, PharmD, MPH, FCCP, BCPS Professor of Pharmacy [email protected] School of Pharmacy University of Wisconsin–Madison doi: 10.1331/JAPhA.2012.12511
3. Centers for Disease Control and Prevention. Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2007;56:1–23. 4. Centers for Disease Control and Prevention. 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). MMWR Morb Mortal Wkly Rep. 2010;59:626–9. 5. Centers for Disease Control and Prevention. FDA licensure of quadrivalent human papillomavirus vaccine (HPV4, Gardasil) for use in males and guidance from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2010;59:630–2. 6. Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med. 2011;365:1576–85. 7. Winer RL, Hughes JP, Feng Q, et al. Condom use and the risk of genital human papillomavirus infection in young women. N Engl J Med. 2006;354:2645–54. 8. Chandra A, Mosher WD, Copen C, Sionean C. Sexual behavior, sexual attraction, and sexual identity in the United States: data from the 2006–2008 National Survey of Family Growth. Accessed at www.cdc.gov/nchs/nsfg/new_nsfg.htm, February 5, 2012. 9. Centers for Disease Control and Prevention. Youth risk behavior surveillance: United States, 2009. MMWR Morb Mortal Wkly Rep. 2010;59:1–142. 10. Centers for Disease Control and Prevention. National, state, and local area vaccination coverage among adolescents aged 13-17 years: United States, 2009. MMWR Morb Mortal Wkly Rep. 2010;59:1018–23.
1. Centers for Disease Control and Prevention. Recommendations on the use of quadrivalent human papillomavirus vaccine in males: Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011;60:1705–8.
11. Centers for Disease Control and Prevention. Improving influenza and pneumococcal polysaccharide, and hepatitis B vaccination coverage among adults aged <65 years at high risk: a report on recommendations of the Task Force on Community Preventative Services. MMWR Morb Mortal Wkly Rep. 2005;54:1–11.
2. Giuliano AR, Palefsky JM, Goldstone S, et al. Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med. 2011;364:401– 11.
12. Clark SJ, Butchart A, Kennedy A, Dombkowski KJ. Parents’ experiences with and preferences for immunization reminder/recall technologies. Pediatrics. 2011;128:e1100–5.
References
www.j aph a. or g
Journal of the American Pharmacists Association