The first quadrivalent human papillomavirus vaccine (HPV4) was licensed in the United States in 2006 (Gardasil, Merck & Co., Inc.).1 It contains viral proteins from HPV types 18, 16, 11, and 6, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts.2 The vaccine is licensed for use in females ages 9 to 26 years for the prevention of cervical, vulvar, and vaginal precancerous lesions and cancer, and for the prevention of anogenital warts.1 It was recently licensed in the United States for the prevention of anogenital warts in males, as it has been in other countries.2,3
HPV and cancer: Quantifying the threat
Human papillomavirus (HPV) is responsible for cancers at several anatomical sites, including the cervix, anus, oral mucosa, vulva, vagina, and penis.1 The rate of cervical cancer in the United States has declined markedly since the introduction of screening programs using cervical cytology testing.1 This decline has been predominantly in squamous cell carcinomas, not adenocarcinomas, which are located in the endocervix and harder to detect.1
There are still around 12,000 cases of cervical cancer diagnosed each year in the United States, for an incidence of 8.1/100,000 women, and 3924 cervical cancer-related deaths.1 In addition, 7% to 10% of the 50 million cervical cytology tests done each year require some form of follow-up. Of these, 2 million to 3 million findings requiring follow-up are atypical squamous cells of undetermined significance (ASC-US) and 1.25 million are low-grade squamous intraepithelial lesions.1
There were more than 4000 cases of anal cancer recorded in 2003, a rate of 1.6/100,000 in women and 1.3/100,000 in men. In contrast to the trend in cervical cancer rates, anal cancer rates are increasing.4 It is not known how many incident cases of genital and anal warts there are annually, but some estimates place the number as high as 1 million. Lifetime cumulative risk has been estimated at 10%.5
Global morbidity and mortality from HPV is considerable, with 500,000 cases of cervical cancer and 260,000 cervical cancerrelated deaths reported worldwide in 2005.2 Rates are highest in developing countries in Latin America, Africa, and Asia.2
The vaccine is effective in women
HPV4 has proven to be highly effective in women ages 15 to 26 who have not been previously infected with the HPV types in the vaccine. Effectiveness has been 98% to 100% after 3 to 5 years in these women, using such end points as moderate and severe cervical intraepithelial neoplasia (CIN2 and CIN3), endocervical adenocarcinoma in situ (AIS), anogenital warts, and vulvar and vaginal intraepithelial neoplasia.1,2,6 These trials are ongoing.
Efficacy among women with current or past HPV infection is less certain. Studies of this question have included only small numbers and the confidence intervals have been large and included 0. In intention-to-treat studies, efficacy has been 39% to 46% for prevention of CIN2 or 3 and AIS caused by HPV 16 and 18, 69% for prevention of HPV 16/18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine type-related warts.1
Who should be vaccinated?
According to the June 2006 recommendations of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), immunization with 3 doses of HPV4 should be routine for girls between the ages of 11 and 12. Vaccination may be started in girls as young as age 9 and can also be done for females between the ages of 13 and 26.1 The ACIP recommendations are summarized in TABLE 1.
The World Health Organization (WHO) qualifies its recommendations a bit. “Routine HPV vaccination,” notes WHO, “should be included in national immunization programs provided that:
- prevention of cervical cancer or other HPV-related diseases, or both, constitutes a public health priority,
- vaccine introduction is programmatically feasible,
- sustainable financing can be secured, and
- the cost effectiveness of vaccination strategies in the country or region are considered.”2
WHO also says the vaccine is most effective prior to HPV infection and that, based on the age of initiation of sexual activity, the target population is most likely to be females 9 to 13 years of age. WHO does not recommend vaccination in males.2
In the United States, most professional organizations, including the American Academy of Family Physicians, have adopted recommendations in line with those of ACIP. One exception is the American Cancer Society (ACS), which takes issue with ACIP’s recommendations for the 19- to 26-year age group. The ACS position is that the evidence is insufficient to recommend for or against routine use of the HPV vaccine for this age group.7