Prevention

Following HPV infection being determined as necessary for the development of cervical cancer, vaccines have been developed to prevent infection with some high-risk types of HPV. Vaccination offers the potential to further the decrease in cervical cancer incidence and mortality rates that have been seen since the introduction of National Cervical Screening Program, particularly among groups with lower participation. As nearly 80% of adenocarcinomas are associated with HPV 16/18,^[1] prophylactic HPV vaccination is expected to be effective in preventing these cancers,^[2] which has not been achieved by cytology-based cervical screening. Trial data suggest that HPV-based screening is also effective in preventing adenocarcinoma^[3] and so the combination of HPV vaccination and HPV-based screening in Australia is expected to reduce adenocarcinoma incidence by more than 50% if incidence rates remain steady or observed trends continue.^[4] The efficacy of vaccination is likely to enable less intensive screening of vaccinated women in the future.^[5]

Internationally, prophylactic vaccination could have the 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.^[6] Moreover, given the prevalence of HPV infection worldwide, the development of a therapeutic vaccine is a priority.

Vaccines to prevent HPV infection

Three prophylactic HPV vaccines have been developed commercially and are currently used in Australia. Cervarix is a bivalent HPV 16/18 vaccine developed by GlaxoSmithKline. Gardasil, developed by Merck and Co. Inc., is a quadrivalent HPV 16/18/6/11 L1 virus-like particles vaccine.^[7] Gardasil9 9-valent recombinant vaccine is also available and offers coverage against five additional HPV types (HPV 31/33/45/52/58).^[8]

For further information about registered use of HPV vaccines see Policy context.

Studies 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.^{[9][10][11][12]} Therefore it is recommended vaccines are provided before sexual activity commences. Current generation vaccines do not have a therapeutic effect in those already infected with HPV.

The duration of protection conferred has been shown in clinical trials to be over 8.4 years for the bivalent vaccine,^[13] and beyond five years for the quadrivalent vaccine^[14] and up to six years for the 9-valent vaccine.^[15]

Based on current knowledge, 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.

For further information about HPV vaccine safety and efficacy, as well as dosage and administration, please refer to the Australian Immunisation Handbook.

National HPV Vaccination Program

In Australia, the National HPV Vaccination Program targets the vaccine to girls and boys aged 12 to 13 years, typically in the first year of high school. National HPV vaccination data report high coverage rates for girls and boys.^[16]

For further information about the National HPV Vaccination Program see Policy context.

In the short term, the impact of the HPV quadrivalent vaccine has decreased the prevalence of HPV 6/11/16/18 cervical/vaginal infections, genital warts, low- and high-grade cytological abnormalities in females targeted by worldwide national vaccination programs.^[17][18] The effectiveness of the vaccination program in Australia is reflected in the 92% decrease in prevalence of HPV 6/11/16/18 infections in young women in nine years, including a reduction of 87% in unvaccinated women.^[19] Marked reductions in observed frequency of genital warts [20][21][22] and overall declines of low- and high-grade cervical cytological abnormalities of at least 30% have been reported.^[23] A 17% decline in histologically confirmed cervical pre-cancerous lesions in the 25-29 year olds has been reported in Victoria.^[24]

In Indigenous women, the impact of the vaccination program has also been observed with a 94% reduction in vaccine-targeted HPV types in vaccinated girls.^[25]

In addition to the strong herd effects seen in young unvaccinated women, there are also multiple studies demonstrating herd protection effects in young men from the initially female-only HPV vaccination program, via substantial declines in genital warts and HPV infections.^{[26][27][28][29]} Herd protection effects are expected to increase even further in the future as a result of the high coverage achieved in boys since they have been included in the National HPV Vaccination Program.^[30] The expected long-term impact is a reduction in the incidence of cervical cancer and associated mortality. Taken together, expected short-term and long-term effects translate to a reduction in treatment costs as well as psychological and medical morbidity.^[31]

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 participate in the renewed National Cervical Screening Program. 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. Victorian data from 2010-2011 suggested that young women who were vaccinated were less likely to screen than those who were unvaccinated.^[32] 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.

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 HPV test, cancer registries and the vaccination program, to evaluate the vaccination program's effect on cervical cancer burden in Australia.

The Register commenced operations in June 2008, the year after the introduction of the National HPV Vaccination Program.^[33] This delay between the program starting and the register being operational, and the fact that notification of doses to the Register from community providers was not mandatory, means that Register data almost certainly underestimates doses delivered to women vaccinated in the community-based catch-up program (aged 18-26 in 2007).^[33][34]

Therapeutic vaccine

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.^[35] 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.^[36] Recent studies confirm the potential of therapeutic vaccines to enable regression of the most prevalent high-risk genotypes of HPV.^[36]

Therapeutic vaccines have the potential to provide less invasive and disfiguring treatment options for women with pre-existing HPV lesions,^[37] and to decrease treatment costs and associated impacts on women (including adverse obstetric outcomes).^[38] Phase I trials are currently underway to develop therapeutic treatment strategies and may become clinically available in the near future.^[36]

Prevention of other cancers

Studies of the potential impact of the prophylactic vaccines on other cancers that are caused by HPV infection are ongoing.