Quadrivalent human papillomavirus vaccine: Updated recommendations for males

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