Human Papillomavirus Vaccines—Vaccinate and Catch Up!
the US (27 % completing the three-dose regimen in 2009) to high rates in the UK (70.6 %), Flanders (85 %), and Australia (83 %).12–15
Reliable data
Recent data from Australia, which launched a national HPV vaccination program in 2007 for all girls and women ages 12–26 years, already show the effects of mass HPV vaccination, with reduced high-grade cervical abnormalities and genital warts.17,18
from developing countries are lacking. The most successful programs in the UK, Flanders, and Australia administer vaccinations through publically funded school-based clinics. However, opportunistic vaccination, which depends on the initiative of parents or healthcare providers, as in the Netherlands, results in a much lower uptake (49.9 %).16
Major problems
in many countries arise because of less organized healthcare delivery infrastructures, the current high cost of vaccines, no experience of school-based vaccination delivery, and other factors such as a lack of knowledge among adolescents and their parents on the effects and safety of the vaccines, and a lack of awareness of the burden of HPV-related diseases. Some religious or ethnic groups may not be willing to accept vaccination programs because HPV infections are sexually transmitted. Furthermore, adverse media coverage of cases of post-vaccination casualties has affected the uptake of HPV vaccines in some developed countries. It is clear that widespread education about HPV and the vaccines is the cornerstone of a successful vaccination program. Physicians are largely responsible for administering HPV vaccines because they are the principal drivers of preventive healthcare behaviors, including screening and vaccination, at the individual level. However, political authorities need to organize programs that reach the maximum number of people in the target population at the lowest cost. Central purchasing of vaccines leads to competitive pricing, while the reduction of detection, colposcopy procedures, and treatment of screening abnormalities saves costs. Furthermore, it is essential to continuously monitor the uptake of vaccines in the target population and to measure the effects of HPV vaccination through screening registries.
The benefit of catch-up vaccination should not be underestimated, although the uptake of catch-up HPV vaccination worldwide is less than in the young primary target age group. Older girls and young women who are not in the target age groups of school-based, health center, or community-based organized programs should have the opportunity to be vaccinated at low cost, which is totally, or at least partially, refunded by the government or the health insurance system. Competitive pricing of HPV vaccines for this catch-up population again will lead to lower costs for the community. Delivery of HPV vaccines in older girls occurs most effectively through school-based programs, as demonstrated in the UK and Australia, where consecutive rounds of HPV vaccination are organized for female students aged 17–18 years. Although HPV vaccines are not preventive when the individual is already infected by a vaccine HPV type, this does not mean that sexually active women carry a high risk of being infected. In both large Phase III clinical trials of HPV vaccines, more than three-quarters of the study population between 15 and 26 years of age (who were nearly all sexually active) were vaccine type DNA-negative at enrolment.5,6
Less than 0.5 % of the population were
infected with all vaccine types and being vaccinated did not protect against disease in this minority group. HPV vaccines were equally effective in people who were seropositive (having measurable serum antibodies induced by a humoral immune reaction following a natural
US OBSTETRICS & GYNECOLOGY
HPV infection) and those who were seronegative and DNA negative. Seropositive women in the placebo groups were not protected against new vaccine type infection or cervical intraepithelial neoplasia (CIN) caused by the vaccine types, while vaccinated women were fully protected. The majority of sexually active girls and women between 15 and 26 years of age are therefore equally good candidates for HPV vaccination as preadolescent girls who are not sexually active. As these women are older, the impact of HPV vaccination on reducing the number of women with genital warts, screening abnormalities, colposcopies, and treatment procedures will only be measurable in a few years.
In Victoria, Australia in 2007 a population-wide HPV vaccination program was launched for all girls and women aged 12–26 years. Three years after the introduction of the program, a 38 % decrease in the incidence of biopsy-proven high-grade cervical abnormalities (CIN grade 2 or worse, or adenocarcinoma in situ) was recorded in girls younger than 18 years.17
age of 18 years, or two years after the onset of sexual activity. Based on the 80 % coverage of school-based HPV vaccination in the UK, Cuzick and colleagues used their model to calculate a 51 % reduction in CIN grade 3 after seven years in Scotland and Wales, where cervical screening begins at age 20 years, and after 12 years in England, where screening starts at age 25 years.19
Australia’s cervical screening starts at the
It will take one or more
decades before the reduction in the burden of cervical cancer will be seen. Given the real burden of screening abnormalities, like financial cost, psychological stress, physical discomfort of follow-up smears, colposcopies, and the potential obstetrical consequences of excisional procedures on the cervix, the benefit of a significant reduction in screening abnormities as a result of HPV vaccination will be seen long before the reduction of cervical cancer incidence and mortality. Therefore, efforts to administer HPV vaccines to all young women, at least up to the age of 26, are of the utmost importance to reduce the costs and disadvantages of cervical screening and all cervical and non-cervical HPV-related diseases. From a healthcare point of view, vaccinating a target population of older women is less cost effective, but for individual women older than 26 years, HPV vaccination still offers the opportunity for protection against HPV-related diseases. A Phase III clinical trial of Gardasil has shown equally effective protection against new HPV 6, 11, 16, and 18 infections and genital HPV-related lesions in women aged 24–45 years compared with younger women aged between 16 and 26 years.7 New data on Cervarix show it provides strong protection against anal HPV 16 and 18 infection in women aged between 18 and 25 years, particularly among women who are HPV naïve at the time of vaccination.20
These findings indicate the potential role of HPV vaccines in the reduction of non-genital cancers, like anal cancer.
The present HPV vaccines do not cover all oncogenic HPV types, and therefore cannot replace cervical cancer screening. Vaccinated women need to be screened, but screening modalities such as first age of screening, screening test procedure, and interval periods between tests need to be reconsidered. Based on a series of prospective trials, primary HPV screening and secondary triage with cytology or other molecular tests for (persistent) high-risk HPV-positive women may become a cost-effective new way to prevent more
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