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, prophylactic HPV vaccination is expected to be effective in preventing these cancers, which has not been achieved by cytology-based cervical screening. Trial data suggest that HPV-based screening is also effective in preventing adenocarcinoma 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. The efficacy of vaccination is likely to enable less intensive screening of vaccinated women in the future.
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. 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. Gardasil9 9-valent recombinant vaccine is also available and offers coverage against five additional HPV types (HPV 31/33/45/52/58).
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. 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, and beyond five years for the quadrivalent vaccine and up to six years for the 9-valent vaccine.
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.
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. 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. Marked reductions in observed frequency of genital warts  and overall declines of low- and high-grade cervical cytological abnormalities of at least 30% have been reported. A 17% decline in histologically confirmed cervical pre-cancerous lesions in the 25-29 year olds has been reported in Victoria.
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.
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. 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. 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.
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. 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. 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).
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 associated impacts on women (including adverse obstetric outcomes). Phase I trials are currently underway to develop therapeutic treatment strategies and may become clinically available in the near future.
Prevention of other cancers
Studies of the potential impact of the prophylactic vaccines on other cancers that are caused by HPV infection are ongoing.
- International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 2007 Feb 15;120(4):885-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17131323.
- FUTURE I and II Study Group, Ault KA, Joura EA, Kjaer SK, Iversen OE, Wheeler CM, et al. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine. Int J Cancer 2011 Mar 15;128(6):1344-53 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20949623.
- Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014 Feb 8;383(9916):524-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24192252.
- Smith MA, Canfell K. Projected impact of HPV vaccination and primary HPV screening on cervical adenocarcinoma: Example from Australia. Papillomavirus Res 2017 Jun;3:134-141 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28720447.
- Simms KT, Smith MA, Lew JB, Kitchener HC, Castle PE, Canfell K. Will cervical screening remain cost-effective in women offered the next generation nonavalent HPV vaccine? Results for four developed countries. Int J Cancer 2016 Dec 15;139(12):2771-2780 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27541596.
- Goldie SJ, O'Shea M, Diaz M, Kim SY. Benefits, cost requirements and cost-effectiveness of the HPV16,18 vaccine for cervical cancer prevention in developing countries: policy implications. Reprod Health Matters 2008 Nov;16(32):86-96 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19027626.
- Stanley M, Lowy DR, Frazer I. Chapter 12: Prophylactic HPV vaccines: underlying mechanisms. Vaccine 2006 Aug 31;24 Suppl 3:S3/106-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16949996.
- National Centre for Immunisation Research and Surveillance. Human papillomavirus (HPV) vaccines for Australians. Sydney: NCIRS; 2018 Available from: http://www.ncirs.edu.au/assets/provider_resources/fact-sheets/human-papillomavirus-hpv-fact-sheet.pdf.
- Future II Study Group, Ault KA. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet 2007 Jun 2;369(9576):1861-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17544766.
- HPV PATRICIA Study Group, Paavonen J, Naud P, Salmerón J, Wheeler CM, Chow SN, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 2009 Jul 25;374(9686):301-14 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19586656.
- Muñoz N, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, et al. Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women. J Natl Cancer Inst 2010 Mar 3;102(5):325-39 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20139221.
- Lu B, Kumar A, Castellsagué X, Giuliano AR. Efficacy and safety of prophylactic vaccines against cervical HPV infection and diseases among women: a systematic review & meta-analysis. BMC Infect Dis 2011 Jan 12;11:13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21226933.
- Roteli-Martins CM, Naud P, De Borba P, Teixeira JC, De Carvalho NS, Zahaf T, et al. Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother 2012 Mar;8(3):390-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22327492.
- FUTURE I/II Study Group, Dillner J, Kjaer SK, Wheeler CM, Sigurdsson K, Iversen OE, et al. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. BMJ 2010 Jul 20;341:c3493 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20647284.
- Huh WK, Joura EA, Giuliano AR, Iversen OE, de Andrade RP, Ault KA, et al. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial. Lancet 2017 Nov 11;390(10108):2143-2159 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28886907.
- National HPV Vaccination Program Register. Coverage Data. [homepage on the internet] Melbourne: Victorian Cytology Service; [cited 2017]. Available from: http://www.hpvregister.org.au/research/coverage-data.
- Garland SM, Kjaer SK, Muñoz N, Block SL, Brown DR, DiNubile MJ, et al. Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience. Clin Infect Dis 2016 Aug 15;63(4):519-27 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27230391.
- Drolet M, Bénard É, Boily MC, Ali H, Baandrup L, Bauer H, et al. Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 2015 May;15(5):565-80 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25744474.
- Machalek DA, Garland SM, Brotherton JML, Bateson D, McNamee K, Stewart M, et al. Very Low Prevalence of Vaccine Human Papillomavirus Types Among 18- to 35-Year Old Australian Women 9 Years Following Implementation of Vaccination. J Infect Dis 2018 Apr 23;217(10):1590-1600 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/29425358.
- Chow EP, Read TR, Wigan R, Donovan B, Chen MY, Bradshaw CS, et al. Ongoing decline in genital warts among young heterosexuals 7 years after the Australian human papillomavirus (HPV) vaccination programme. Sex Transm Infect 2015 May;91(3):214-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25305210.
- Smith MA, Liu B, McIntyre P, Menzies R, Dey A, Canfell K. Trends in genital warts by socioeconomic status after the introduction of the national HPV vaccination program in Australia: analysis of national hospital data. BMC Infect Dis 2016 Feb 1;16:52 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26829924.
- Donovan B, Franklin N, Guy R, Grulich AE, Regan DG, Ali H, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis 2011 Jan;11(1):39-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21067976.
- Brotherton JML, Malloy M, Budd AC, Saville M, Drennan KT and Gertig DM. Effectiveness of less than three doses of quadrivalent human papillomavirus vaccine against cervical intraepithelial neoplasia when administered using a standard dose spacing schedule: Observational cohort of young women in Australia. Papillomavirus Research 2015 [cited 2018];1:56-73 Abstract available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891730/pdf/main.pdf.
- Brotherton JM, Gertig DM, May C, Chappell G, Saville M. HPV vaccine impact in Australian women: ready for an HPV-based screening program. Med J Aust 2016 Mar 21;204(5):184-184e1 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26985843.
- McGregor S, Saulo D, Brotherton JML, Liu B, Phillips S, Skinner SR, et al. Decline in prevalence of human papillomavirus infection following vaccination among Australian Indigenous women, a population at higher risk of cervical cancer: The VIP-I study. Vaccine 2018 Jul 5;36(29):4311-4316 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/29880245.
- Ali H, Donovan B, Wand H, Read TR, Regan DG, Grulich AE, et al. Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data. BMJ 2013 Apr 18;346:f2032 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23599298.
- Smith MA, Liu B, McIntyre P, Menzies R, Dey A, Canfell K. Fall in genital warts diagnoses in the general and indigenous Australian population following implementation of a national human papillomavirus vaccination program: analysis of routinely collected national hospital data. J Infect Dis 2015 Jan 1;211(1):91-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25117753.
- Machalek DA, Chow EP, Garland SM, Wigan R, Cornall AM, Fairley CK, et al. Human Papillomavirus Prevalence in Unvaccinated Heterosexual Men After a National Female Vaccination Program. J Infect Dis 2017 Jan 15;215(2):202-208 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27815379.
- Chow EPF, Machalek DA, Tabrizi SN, Danielewski JA, Fehler G, Bradshaw CS, et al. Quadrivalent vaccine-targeted human papillomavirus genotypes in heterosexual men after the Australian female human papillomavirus vaccination programme: a retrospective observational study. Lancet Infect Dis 2017 Jan;17(1):68-77 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27282422.
- Brisson M, Bénard É, Drolet M, Bogaards JA, Baussano I, Vänskä S, et al. Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models. Lancet Public Health 2016 Nov;1(1):e8-e17 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/29253379.
- Lowy DR, Schiller JT. Prophylactic human papillomavirus vaccines. J Clin Invest 2006 May;116(5):1167-73 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16670757.
- Budd AC, Brotherton JM, Gertig DM, Chau T, Drennan KT, Saville M. Cervical screening rates for women vaccinated against human papillomavirus. Med J Aust 2014 Sep 1;201(5):279-82 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25163380.
- Brotherton J, Gertig D, Chappell G, Rowlands L, Saville M. Catching up with the catch-up: HPV vaccination coverage data for Australian women aged 18-26 years from the National HPV Vaccination Program Register. Commun Dis Intell Q Rep 2011 Jun;35(2):197-201 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22010515.
- Brotherton JM, Liu B, Donovan B, Kaldor JM, Saville M. Human papillomavirus (HPV) vaccination coverage in young Australian women is higher than previously estimated: independent estimates from a nationally representative mobile phone survey. Vaccine 2014 Jan 23;32(5):592-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24316239.
- Giles M, Garland S. Human papillomavirus infection: an old disease, a new vaccine. Aust N Z J Obstet Gynaecol 2006 Jun;46(3):180-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16704468.
- Yang A, Farmer E, Wu TC, Hung CF. Perspectives for therapeutic HPV vaccine development. J Biomed Sci 2016 Nov 4;23(1):75 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27809842.
- Brinkman JA, Caffrey AS, Muderspach LI, Roman LD, Kast WM. The impact of anti HPV vaccination on cervical cancer incidence and HPV induced cervical lesions: consequences for clinical management. Eur J Gynaecol Oncol 2005;26(2):129-42 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15857016.
- Kyrgiou M, Athanasiou A, Paraskevaidi M, Mitra A, Kalliala I, Martin-Hirsch P, et al. Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. BMJ 2016 Jul 28;354:i3633 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27469988.