Following HPV infection being determined as necessary for the for the development of cervical cancer, vaccines have been developed to prevent infection with high-risk types of HPV. Vaccination offers the potential to further the decrease in cervical cancer rates and deaths that has been seen with the introduction of screening programs, particularly among groups with lower participation in such programs.
By preventing infection with high risk HPV types 16 and 18 (and potentially other types) prophylactic vaccines could prevent up to 70% of cervical cancers. As nearly 80% of adenocarcinomas are associated with the most common HPV types, prophylactic HPV vaccination is expected to be effective in preventing these cancers, which has not been achieved by cervical screening.
Second-generation prophylactic vaccines that aim to prevent a greater number of HPV types are in development. The efficacy of vaccination is likely to enable less intensive screening of vaccinated women in the future.
Internationally, prophylactic vaccination could have greatest impact in developing countries that have the highest burden of HPV-related disease and lack organised screening programs, with the potential to prevent the deaths of millions of women in the next decade. Given the prevalence of HPV infection worldwide, the development of a therapeutic vaccine is a priority.
Vaccines to prevent HPV infection
Two prophylactic HPV vaccines have been developed commercially and are approved for use in Australia. Cervarix is a bivalent HPV 16/18 vaccine developed by GlaxoSmithKline. It is given as an intra-muscular injection in a three-dose course, generally at zero, one and six months. Gardasil, developed by Merck and Co. Inc., is a quadrivalent HPV 16/18/6/11 L1 VLP vaccine delivered by an intra-muscular injection at zero, two and six months. Both vaccines have been approved by the Therapeutic Goods Administration for use in Australia.
For maximum efficacy, prophylactic vaccines must be administered to individuals prior to HPV exposure. Current generation vaccines do not have a therapeutic effect in those already infected with HPV. It is recommended that HPV vaccines be provided before sexual activity commences. In Australia, the National Immunisation Program targets the vaccine to adolescent/pre-adolescent girls, aged 11 to 13 years.
For further information about registered use of HPV vaccines and the National Immunisation Program see Policy context.
Second-generation, expanded valency vaccines are currently in Phase III clinical trials. These vaccines aim to prevent a broad spectrum of HPV infections, increasing the proportion of cervical cancers that would be prevented.
Large-scale studies have shown the HPV vaccines to be safe and well tolerated.
Gardasil, the quadrivalent vaccine distributed via the National Immunisation Program, has been assessed as safe and effective by Australia’s Therapeutic Goods Administration and by the US Food and Drug Administration and the European Medicines Agency.
From the introduction of the National HPV Vaccination Program to June 2010 more than 6 million doses of Gardasil had been distributed and a very low number of adverse events following administration had been reported. The most common side effects after HPV vaccination are mild such as pain, swelling or redness at the injection site. Commonly reported events such as headache or feeling unwell may be equally common in people who have not received the vaccine, hence establishing a causal link to the vaccine is difficult. About one in five reported events were events associated with injection procedures generally, including dizziness, syncope (fainting) and panic attacks. A recent review of notifications of syncope following HPV vaccination in Australia found rates were similar to those reported internationally.
Anaphylaxis (severe allergic reaction) has occurred rarely following administration of Gardasil. The estimated rate of anaphylaxis following HPV vaccination in Australia is 2.6 per million. International studies show anaphylaxis occurs at similar rates (ranging from 0 to 3.5 per million doses) following administration of other vaccines to children and adolescents.
No other serious or unusual events have been causally related to the HPV vaccines in large-scale trials (with up to four years of follow-up) and clinical usage to date.
For further information about HPV vaccine safety and efficacy, as well as dosage and administration, please refer to the Australian Immunisation Handbook.
Results demonstrate that both the quadrivalent and bivalent vaccine are highly effective in preventing persistent infections and cervical disease associated with HPV types 16 and 18 when given to females who are not already infected with these HPV types. The quadrivalent vaccine confers additional protection against HPV 6/11-induced mucosal and cutaneous genital disease. Both vaccines have demonstrated some cross-protection against other HPV types, but further studies are needed to confirm the size of the impact and efficacy against diseases due to other HPV types.
The duration of protection conferred has been shown in clinical trials to be over 8.4 years for the bivalent vaccine, and beyond five years for the quadrivalent vaccine. Studies have measured the levels of neutralising antibodies against the targeted HPV types, but it is unknown whether antibody levels reflect clinical immunity and thus whether higher antibody levels will result in longer duration of protection.
Based on present knowledge, both HPV vaccines are anticipated to provide long-term protection against the high-risk HPV types, but ongoing monitoring is essential. If future research identifies waning protection, individuals who have been vaccinated will need to be recalled for a booster. The National HPV Vaccination Register was established to record details of all individual vaccinations in case such recall is required.
In the short term, the impact of the HPV vaccines is projected to be a reduction in cervical dysplasia, initially in young vaccinated cohorts, and this reduction will then impact older age groups as vaccinated cohorts begin to pass through the screening program. Following the introduction of population-wide HPV vaccination in Australia there has been a significant decline in new cases of genital warts in young women and a decrease in high-grade cervical lesions in girls under 18 years in Victoria. There has also been a decline in genital wart presentations in males presenting at sexual health clinics, suggesting herd immunity due to vaccination of girls and young women. These ecological data need to be validated by data linkage (so that individual-level information on vaccination and on outcomes can be examined), but are likely to be early markers of the impact of vaccination. The expected long-term impact is a reduction in the incidence of cervical cancer and associated mortality.
Recent studies have indicated that the HPV vaccination program in Australia has been effective in reducing cervical abnormalities. A Victorian-based study linking data between the Victorian Cervical Cytology Registry and the National HPV Vaccination Program Register calculated vaccine effectiveness against cervical abnormalities. Adjusted vaccine effectiveness was greatest for CIN3+ and adenocarcinoma in situ, at 48% for fully vaccinated women and 36% for women who received any dose of vaccine. A Queensland-based study of linked screening and vaccination data calculated a 3-dose vaccine effectiveness of 46% for histologically-confirmed high grade cervical abnormalities (CIN2, adenocarcinoma in situ or worse) and 34% effectiveness for other cervical abnormalities in women attending for their first cervical screening test. The corresponding adjusted numbers needed to vaccinate were 125 to prevent one confirmed high grade lesion and 22 to prevent one other abnormality.
Taken together, expected short-term and long-term effects translate to a reduction in treatment costs as well as psychological and medical morbidity.
As the vaccine does not protect against all types of HPV associated with cervical cancer, and may not be effective in women exposed to HPV prior to receiving the vaccine, vaccinated women should continue to have regular Pap tests. Confusion about the protection of HPV vaccination and the need for continuing participation in cervical screening has the potential to lessen compliance with cervical screening in the vaccinated population. Effective communication strategies will be required to ensure vaccinated women still participate in the National Cervical Screening Program.
It has been anticipated that, as the incidence of cervical abnormalities declines due to population-based HPV vaccination, screening strategies will change to reflect this. See Impact of HPV vaccination on screening.
HPV immunisation in males
Immunising males is expected to further reduce HPV infection rates in women through improved "herd immunity" – an overall reduction in infection rates across the wider community.
In July 2012, the Australian Government announced a plan to include boys on the National HPV Vaccination Program from 2013 . See Vaccination of boys in the Policy context section for more information.
Prevention of other cancers
Studies of the potential impact of the prophylactic vaccines on other cancers that are caused by HPV infection are ongoing.
For more information on the link between HPV and cancers other than cervical canver, see the section on HPV infection and cancer.
Maximising vaccine uptake
The impact of the HPV vaccination on future cervical cancer incidence and mortality will be influenced by uptake of the vaccine by the population. National HPV vaccination data for girls aged 15 in 2009 shows 70.8% of girls had completed the full course of the HPV vaccine. Evidence shows higher coverage is possible through similar school-based vaccination programs in the UK, demonstrating room for improved coverage rates.
The uptake of the HPV vaccines is influenced by the target population’s perceptions of benefits and risks as well as health professionals’ attitudes and advice. Therefore communication strategies targeting health professionals, parents, women and adolescents – which are sensitive to culture, religion and age – are required to support uptake.
Specific and targeted strategies are necessary to maximise uptake of HPV vaccination by girls in population groups that are at higher risk of cervical cancer and/or have low participation in cervical cancer screening, particularly Aboriginal and Torres Strait Islander women and women of culturally and linguistically-diverse backgrounds.
HPV vaccination has the greatest potential to reduce cervical cancer incidence and associated mortality in under-screened populations with a higher incidence of cervical cancer. There is a strong association between living in areas with a high average socioeconomic status and cervical screening, with the lowest screening rates evident in the in the most disadvantaged areas. Conversely, data from Victoria has shown that HPV vaccination coverage has a much less pronounced socioeconomic gradient, with coverage rates only slightly lower in women and girls from the most disadvantaged areas.
In Australia, Aboriginal and Torres Strait Islander women are over four times more likely to die of cervical cancer than non-Indigenous women. This higher risk is, in part, due to lower participation in the National Cervical Screening Program. Vaccinating Aboriginal girls and women has the ability to reduce the incidence of adenocarcinomas, and incidence of and mortality from cervical cancer. Effective prevention in this population will require a strong understanding of barriers to participation in the immunisation program.
National HPV Vaccination Program Register
The National HPV Vaccination Program Register is a collaboration of the Australian Department of Health and Ageing and the Victorian Cytology Service. It was established through a 2007 act of federal parliament to monitor and evaluate the vaccination program, by recording information about HPV vaccine doses administered in Australia. Its core functions are to:
- Record vaccination doses and key demographic information;
- Develop systems to support the completion of the three-dose vaccination schedule;
- Collect data to monitor and evaluate program participation rates; and
- Inform women when booster doses are required.
The Register will ultimately work towards developing systematic links between the Pap test, cancer registries and the vaccination program, to evaluate the vaccination program's effect on cervical cancer burden in Australia.
Second-generation prophylactic vaccines
Despite their efficacy and potential impact, there are some limitations to the current HPV vaccines, including the need for multiple doses, the lack of protection against some types of HPV that cause cervical cancer and, particularly for developing countries, the cost.
Several second-generation vaccines with expanded valency, providing protection against a broader range of HPV types – including a nonavalent (9 HPV targets) vaccine – are currently in Phase III clinical trials. If successful, such vaccines could prevent most potentially cancer-causing infections, preventing about 90% of cervical cancers. Once efficacy is established, the additional benefits of next generation vaccines will need to be weighed against the cost. Evaluation will also need to consider the potential to further extend the cervical screening interval and commencement age given the expected large-scale reduction in cervical abnormalities.
Worldwide it is estimated that there are about 100 million women infected with high-risk HPV types, and that 5 million women have persistent infections that may result in anogenital cancers. Prophylactic HPV vaccines are ineffective against pre-existing HPV infection, thus there is a need for therapeutic vaccines that can clear existing HPV infections, prevent the development and progression of lesions, and eliminate existing lesions and possibly cancers. Recent studies confirm the potential of therapeutic vaccines to enable regression of the most prevalent high-risk genotypes of HPV.
Therapeutic vaccines have the potential to provide less invasive and disfiguring treatment options for women with pre-existing HPV lesions, and to decrease treatment costs and psychosocial impacts on women. However such vaccines are at least 10 years from market.
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