Human papillomavirus vaccines launch a new era in cervical cancer prevention.(Public Health--Perspectives on HPV)

In 2006, the first vaccine against human papillomavirus (HPV) infection, Gardasil (Merck Frosst), was approved for use in Canada. A second vaccine, Cervarix (GlaxoSmith Kline), is currently undergoing regulatory review by Health Canada. Both vaccines are designed with the goal of preventing cervical cancer. This article provides an overview of HPV infection and the HPV vaccines, Gardasil and Cervarix.

HPV epidemiology and disease outcomes

HPV is one of the most common sexually transmitted infections. (1) The global age-standardized prevalence of HPV among women varies by location, ranging from 1.4% in Spain to 25.6% in Nigeria. (2) In Canada, although the prevalence varies by location, age, ethnic background and risk, (3) the most comprehensive population-based data indicate that the age-adjusted prevalence of HPV (all types) is 16.8% and that the prevalence of HPV types 16 and 18 is 10.6% and 3.5% respectively. (4) The highest prevalence rates are among women under 20 years of age (all HPV types 26.9%, all high-risk types 20.6%, high-risk HPV types 16 and/or 18 16.7%). (4) Factors that are predictors of HPV infection are presented in Box 1.

 
Box 1: Examples of the factors that 
predict human papillomavirus (HPV) 
infection (3,5,6) 
 
Exposure factors 
 
* Increased number of sexual 
partners 
 
* Early age of first intercourse 
 
* Never being married 
 
Endogenous factors 
 
* Oral contraceptive use 
 
* Immunosuppression secondary to 
infection or therapy 
 
Cervical microenvironment factors 
 
* Sexually transmitted infections 

The HPV family consists of over 100 DNA viruses. There are about 40 types of HPV that can infect the genital tract. (7) These viruses are divided into 2 groups (high or low risk) based on their oncogenic potential. The epidemiologic evidence that links HPV infection with cervical cancer includes data from case series, case-control and cohort studies. (8) In a large case series of 1000 cervical cancer cases in 22 countries, HPV DNA was detected in 99.7% of specimens. (8) Case-control studies in 22 countries (sponsored by the International Agency for Research on Cancer) demonstrated consistently high odds ratios (ORs) for the risk of cervical cancer associated with persistent HPV infection (squamous cell carcinoma OR 90.0, adenocarcinoma OR 81.3). (8) In a 10-year cohort study of 20 810 women, the cumulative incidence of cervical intraepithelial neoplasia (grade 3) among women positive for HPV type 16 was 17.2% (95% confidence interval [CI] 11.5%-22.9%), and the incidence among women positive for HPV type 18 was 13.6% (95% CI 3.6%-23.7%). However, the risk among women who tested positive for high-risk HPV types other than types 16 and 18 was 3.0% (95% CI 1.9%-4.2%). The 10-year incidence of cervical intraepithelial neoplasia (grade 3) among women negative for oncogenic high-risk HPV infections was 0.8% (95% CI, 0.6%-1.1%). (9) This study provides a conservative estimate of risk, given the aggressive management of grade 1 and 2 cervical intraepithelial neoplasia lesions among the trial cohort. In addition to the epidemiologic evidence, the biologic mechanism of HPV carcinogenesis has been clearly delineated. (8)

Globally, HPV types 16 and 18 account for 65%-77% of cervical cancers. HPV types 16 and 18 account for 41%-57% of high-grade cervical squamous intraepithelial lesions, 15%-32% of low-grade squamous intraepithelial lesions and 8%-19% of atypical squamous cells of undetermined significance. (10) Six HPV genotypes (types 31, 33, 35, 45, 52 and 58) account for an additional 20% of cervical cancers worldwide. (10)

HPV infections are also associated with other genitourinary cancers (e.g., anal, penile, vaginal, vulvar), head and neck cancers (e.g., conjunctivae, mouth, oropharynx, larynx) and nonmalignant diseases (e.g., genital warts, recurrent respiratory papillomatosis). (8,10-13) Of genital warts, 90%-100% of cases are caused by HPV types 6 and 11, although 20%-50% of lesions may be coinfected with high-risk types of HPV. (12) The International Agency for Research on Cancer has declared certain high-risk HPV genotypes, including HPV types 16 and 18, as group 1 carcinogens and has declared low-risk HPV types 6 and 11 as possible carcinogens (group 2b).11

Infection with a high-risk type of HPV is a necessary, but not sufficient, cause of cervical cancer. The development of a precancerous lesion (squamous intraepithelial lesion) from a persistent HPV infection can take from 1 to 10 years, and the development of invasive cervical cancer can take an additional 10 years. (14) Thus, there is a long lag period from infection to invasive disease. Cofactors that contribute to disease progression include a history of smoking, long-term use of oral contraceptives, high parity and sexually transmitted infections. (8)

The global annual incidence of cervical cancer ranges from 56.9/100 000 in Zimbabwe to less than 10/100 000 in developed countries including Canada, Switzerland and the Netherlands (Figure 1). (13) Each year in Canada there are about 1300 cases of cervical cancer and about 400 deaths attributed to this disease. (15) The lifetime risk of cervical cancer…