THE FDA HAS licensed the human papillomavirus quadrivalent vaccine, Gardasil (HPV4), for use in males ages 9 to 26 for the prevention of genital warts caused by human papillomavirus (HPV) genotypes 6 and 11; anal cancer caused by HPV genotypes 16 and 18; and anal intraepithelial neoplasia grades 1, 2, and 3 caused by HPV genotypes 6, 11, 16, and 18.1,2 Before October 2009, HPV4 was approved for use in females of the same age, but marketed for the prevention of cervical cancer. Seventy percent of cervical cancers are caused by HPV 16 and 18.3
The Advisory Committee on Immunization Practices (ACIP) recommends HPV4 for routine use in females but doesn't recommend it for routine use in males.1 Opponents of HPV4 male vaccination argue that public health initiatives should be geared toward increasing immunization rates in young girls because females carry the greatest HPV-related disease burden. Studies have shown little benefit derived from including males in vaccination programs when female vaccination rates are high.4
Prevalence and impact of HPV
HPV is a sexually transmitted infection currently affecting over 20 million Americans. At least 50% of sexually active men and women will acquire it at some point in their lives.5 Ninety percent of HPV infections are cleared naturally within 2 years by the immune system. The remaining 10% of people with persistent infections are at increased risk for HPV-associated diseases, such as cancers and recurrent genital warts.6
Most studies have found the prevalence of HPV in men as high as those reported in women. HPV type 16 was the most common genotype. Men who have sex with men (MSM) are at the highest risk for HPV-associated diseases.1
Besides causing approximately 70% of cervical cancers, HPV 16 and 18 have been linked to vulvar, vaginal, penile, anal, and head and neck cancers. HPV 6 and 11 cause 90% of genital warts and most cases of respiratory papillomatosis.6 HPV4 specifically targets these four genotypes.7
HPV4 is most effective when given before exposure to HPV, so the goal is to immunize individuals before their first sexual contact. The recommendation is to administer the vaccine at age 11 or 12 because the incidence of sexual activity is lower in this age group than in teenagers and young adults.8,9
Men aren't exempt from HPV-related cancers. The incidence of anal cancer (1.4 per 100,000 men) is low compared to cervical cancer rates, but a female-only vaccination program would completely exclude MSM, who have the highest risk for anal cancers.1,10 A newer study cited by the ACIP provides evidence for the high efficacy of HPV4 against anal cancers in MSM.1
Although penile cancer in the United States accounts for less than 1% of new cancers in men, research suggests that HPV is the primary cause in up to 40% of these cancers worldwide.11 Head and neck cancers, which have a higher incidence in men, account for 3% of all malignancies in the United States.12 High percentages (68% to 86%) of HPV 16 are linked to oropharyngeal, oral, and laryngeal squamous cell carcinomas.13 A fourfold increased risk of head and neck squamous cell carcinomas has been found in individuals of both sexes who are positive for HPV 16 antibodies, even when controlling for smoking and drinking.14
Genital warts account for more than 500,000 diagnoses each year in the United States, with approximately 10% of adults developing them in their lifetime. Treatment is difficult and painful, with a high number of recurrences in the first 6 months.11
Several studies that suggest that male vaccination is cost-prohibitive make several assumptions. One is that female vaccination rates are or will reach 80% or more.4 While distribution of HPV4 is high (32 million in the United States), many people resist HPV4 immunization. Parents are concerned about vaccine safety and some believe it encourages sexual activity.15,16 The cost of HPV4 ($108 to $130 per dose) also serves as a barrier to high immunization rates.17
Another assumption is that the vaccine's duration of immunity is lifelong, but its long-term effectiveness is unknown at this time.4,7 Another concern is that most research only measures outcomes related to the incidence of carcinoma in situ, cervical cancer, and genital warts to estimate cost-effectiveness.9,18–20 More recent models have incorporated additional HPV-related disease outcomes to include both male and female noncervical cancers. When these other diseases are accounted for, male vaccination becomes more cost-effective.21
Educate and initiate
Additional research regarding the efficacy, duration of immunity, long-term outcomes, and cost-effectiveness of HPV4 are needed to determine the best vaccination strategy. You can tell your patients that
- HPV4 has been shown to be effective in preventing HPV 6, 11, 16, and 18-associated diseases, including most cervical cancers and genital warts.
- it's most effective when given before exposure to HPV.
- its adverse reaction profile is similar to other vaccines given to adolescents.22
Initiate a conversation with parents and your adolescent patients about sexuality, sexual intercourse, and safer sex practices. This open dialogue provides the perfect opportunity to educate them about their health and healthy decision-making.
1. 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
. 2010;59(20): 630–632.
2. Gardasil Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant. Prescribing information
3. Castle P, Cox JT. Recommendations for the use of the human papillomavirus vaccines
4. Petaja T, Keranen H, Karppa T, et al. Immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in healthy boys aged 10–18 years. J Adolesc Health
5. Centers for Disease Control and Prevention. Genital HPV infection—fact sheet
6. Cogliano V, Baan V, Straif K, et al. Carcinogenicity of human papillomaviruses. Lancet Oncol
7. Food and Drug Administration. Gardasil
8. Centers for Disease Control and Prevention. Immunization schedules
9. Gunther OP, Ogilive G, Naus M, et al. Protecting the next generation: What is the role of the duration of the human papillomavirus vaccine-related immunity? J Infect Dis
10. National Cancer Institute. SEER stat fact sheets: anal cancer
11. Alexander KA, Dempsey AF, Gillison ML, Palefsky JM. The disease burden of HPV. Infect Dis Children
12. Head and Neck Cancer Resource Center
13. Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev
14. Furniss CS, McClean MD, Smith JF, et al. Human papillomavirus 16 and head and neck squamous cell carcinoma. Int J Cancer
15. Chitale R. CDC report stirs controversy for Merck's Gardasil vaccine
16. HPV vaccine—what's a parent to do?.
17. Centers for Disease Control and Prevention. CDC vaccine price list
18. Brisson M, Van de Velde N, Boily MC. Economic evaluation of human papillomavirus vaccination in developed countries. Public Health Genomics
19. Dunne EF, Datta SD, Markowitz LE. A review of prophylactic human papillomavirus vaccines: Recommendations and monitoring in the US. Cancer
. 2008;113(10 suppl):2995–3003.
20. Jit M, Choi YH, Edmunds WJ. Economic evaluation of human papillomavirus vaccination in the United Kingdom. BMJ
21. Chesson H. Overview of cost-effectiveness models of male HPV vaccination in the United States
22. Slade BA, Leidel L, Vellozzi C, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA