Nº 223
HPV eradication: targets for the century
Quote this article as:
IH Frazer & SM Garland (January 2023). HPV eradication: targets for the century. www.HPVWorld.com, 223
We have the tools, and WHO has given us a strategy for cervical cancer elimination within a century, by eradicating high-risk human papillomavirus (HRHPV) infections. As HRHPVs are human-specific and genetically stable, and there are now effective prophylactic vaccines (pillar 1 of the WHO strategy), high vaccine coverage should allow HPV eradication if we can achieve equitable vaccine distribution globally (Figure 1). Underpinning high coverage is education at all levels of the community, so that women in particular know and request vaccination of their children. The remaining challenges to achieving this goal (which are non-trivial) are 1) affordability, 2) access to vaccine supplies, and 3) development and implementation of national programs for distribution of prophylactic vaccines. With more vaccine manufacturing facilities coming online, supply and affordability should increase. Thus, it is reasonable to predict that through universal immunisation against oncogenic HPV infection, the eradication of HPV will be a reality globally in the next century. We have a huge challenge here as currently only 13% of age-eligible girls are fully vaccinated.1 Whilst HPV-related cervical disease has significantly decreased with high vaccine coverage, HPV-related diseases with longer incubation (particularly HPV-related oropharyngeal cancer) will take rather longer to disappear, likely 4-5 decades. Reduction in juvenile-onset recurrent respiratory papillomatosis may be a surrogate for what can realistically be achieved for oropharyngeal cancer. It is worth noting that eradicating other viruses (e.g. variola) required case spotting and ring-fencing through immunisation over a lengthy period. HPV testing is more complex than case spotting, and HPV infectivity lasts longer than for variola, so we will need to deploy extensive resources to eradicate HPV, particularly if we accept that not all immunised individuals achieve 100% resistance to the 8-10 known high-risk HPV infections.
.
With time, comprehensive cervical screening with high-precision HPV assays (pillar 2 of the WHO strategy for cervical cancer elimination) should enable cervical cancer elimination, assisted by increasing HPV infection elimination, but the challenge will remain to ensure timely access to treatment for those who test positive for HPV: better technologies for on-the-spot treatment and for record-keeping to allow sufficient follow up to ensure effective eradication of disease, will be required. Eventually, as predicted by modelling, current methods of cervical cancer screening will no longer be cost-effective,2 and cheaper and simpler local self-testing (akin to COVID-19 rapid antigen testing but more accurate) will be needed to ensure the ongoing effectiveness of screening until all HPV is gone.
.
Effective treatment of cervical cancer (pillar 3 of the WHO strategy for cervical cancer elimination) should follow the general improvement of medical care globally – a major challenge for the 21st century – and may also rely on better immunotherapy for HPV-associated cancers, as at least non-antigen specific immunotherapy targeting HPV-associated tumours should be achievable . With continued research, it should be possible to develop HPV-specific immunotherapy, once we better understand the inhibitory factors which prevent successful tumour elimination with immunotherapy that has proven effective in animal models of HPV infection.
DISCLOSURE
IF is a named inventor on patents describing the technology enabling HPV vaccines. SG has nothing to disclose.
References
1. Vorsters A, Bosch FX, M Poljak et al. HPV Prevention and Control – the way forward”. Preventive Medicine 2022, 156:106960. Available from: https://doi.org/10.1016/j.ypmed.2022.106960
2. Hall MT, Simms KT, Lew JB et al. The projected timeframe until cervical cancer elimination in Australia: a modelling study Lancet Public Health 2019; 4: e19–27. Available from: https://doi.org/10.1016/s2468-2667(18)30183-x
3. PATH. Projected and current national introductions, demonstration/ pilot projects, gender-neutral vaccination programs, and global HPV vaccine introduction maps (2006-2023). Updated 17 March 2023. Available from: https://media.path.org/documents/Global_Vaccine_Intro_Overview_Slides_Final_PATHwebsite_MAR_2022_qT92Wwh.pdf
This article is included in the HPW Special Issue Prevention of HPV-related diseases in Australia
Scientific coordinators:
Suzanne Garland, Dorothy Machalek, Cristyn Davies, Xavier Bosch
On behalf of the editorial team, we would like to thank all the authors who contributed to this special issue of HPW
HPW editors:
Marisa Mena, Patricia Guijarro
On behalf of the editorial team, we would like to thank all the authors who contributed to this special issue of HPW
OTHER ARTICLES IN THIS HPW SPECIAL ISSUE:
D Machalek, C Davies. Australia’s HPV Vaccination Program: 15 years of success
D Machalek, K Sharma, J Kaldor. Tracking the impact of HPV vaccination on infection prevalence to measure vaccination program success
E Chow, J McCloskey. HPV vaccination is highly effective at preventing genital warts
O McNally, R McBain, KL Talia. Prevention of vulvar, vaginal precancer and cancer
R Hillman, M Poynten. Prevention of anal cancer
D Novakovic, A Cheng. Prevention of recurrent respiratory papillomatosis with HPV vaccination
C Davies, SR Skinner. School-based vaccination is key to reducing HPV-related diseases
C Vujovich-Dunn, C Vajdic, R Guy. Enhancing Australian monitoring and evaluation systems to support equitable HPV vaccination
J Brotherton, M Saville, D Wrede. Prevention of cervical precancer and cancer
M Smith, L Whop, J Brotherton. Cervical cancer elimination: true success requires equity
IH Frazer & SM Garland (January 2023). HPV eradication: targets for the century. www.HPVWorld.com, 223
We have the tools, and WHO has given us a strategy for cervical cancer elimination within a century, by eradicating high-risk human papillomavirus (HRHPV) infections. As HRHPVs are human-specific and genetically stable, and there are now effective prophylactic vaccines (pillar 1 of the WHO strategy), high vaccine coverage should allow HPV eradication if we can achieve equitable vaccine distribution globally (Figure 1). Underpinning high coverage is education at all levels of the community, so that women in particular know and request vaccination of their children. The remaining challenges to achieving this goal (which are non-trivial) are 1) affordability, 2) access to vaccine supplies, and 3) development and implementation of national programs for distribution of prophylactic vaccines. With more vaccine manufacturing facilities coming online, supply and affordability should increase. Thus, it is reasonable to predict that through universal immunisation against oncogenic HPV infection, the eradication of HPV will be a reality globally in the next century. We have a huge challenge here as currently only 13% of age-eligible girls are fully vaccinated.1 Whilst HPV-related cervical disease has significantly decreased with high vaccine coverage, HPV-related diseases with longer incubation (particularly HPV-related oropharyngeal cancer) will take rather longer to disappear, likely 4-5 decades. Reduction in juvenile-onset recurrent respiratory papillomatosis may be a surrogate for what can realistically be achieved for oropharyngeal cancer. It is worth noting that eradicating other viruses (e.g. variola) required case spotting and ring-fencing through immunisation over a lengthy period. HPV testing is more complex than case spotting, and HPV infectivity lasts longer than for variola, so we will need to deploy extensive resources to eradicate HPV, particularly if we accept that not all immunised individuals achieve 100% resistance to the 8-10 known high-risk HPV infections.
.
With time, comprehensive cervical screening with high-precision HPV assays (pillar 2 of the WHO strategy for cervical cancer elimination) should enable cervical cancer elimination, assisted by increasing HPV infection elimination, but the challenge will remain to ensure timely access to treatment for those who test positive for HPV: better technologies for on-the-spot treatment and for record-keeping to allow sufficient follow up to ensure effective eradication of disease, will be required. Eventually, as predicted by modelling, current methods of cervical cancer screening will no longer be cost-effective,2 and cheaper and simpler local self-testing (akin to COVID-19 rapid antigen testing but more accurate) will be needed to ensure the ongoing effectiveness of screening until all HPV is gone.
.
Effective treatment of cervical cancer (pillar 3 of the WHO strategy for cervical cancer elimination) should follow the general improvement of medical care globally – a major challenge for the 21st century – and may also rely on better immunotherapy for HPV-associated cancers, as at least non-antigen specific immunotherapy targeting HPV-associated tumours should be achievable . With continued research, it should be possible to develop HPV-specific immunotherapy, once we better understand the inhibitory factors which prevent successful tumour elimination with immunotherapy that has proven effective in animal models of HPV infection.
DISCLOSURE
IF is a named inventor on patents describing the technology enabling HPV vaccines. SG has nothing to disclose.
References
1. Vorsters A, Bosch FX, M Poljak et al. HPV Prevention and Control – the way forward”. Preventive Medicine 2022, 156:106960. Available from: https://doi.org/10.1016/j.ypmed.2022.106960
2. Hall MT, Simms KT, Lew JB et al. The projected timeframe until cervical cancer elimination in Australia: a modelling study Lancet Public Health 2019; 4: e19–27. Available from: https://doi.org/10.1016/s2468-2667(18)30183-x
3. PATH. Projected and current national introductions, demonstration/ pilot projects, gender-neutral vaccination programs, and global HPV vaccine introduction maps (2006-2023). Updated 17 March 2023. Available from: https://media.path.org/documents/Global_Vaccine_Intro_Overview_Slides_Final_PATHwebsite_MAR_2022_qT92Wwh.pdf
This article is included in the HPW Special Issue Prevention of HPV-related diseases in Australia
Scientific coordinators:
Suzanne Garland, Dorothy Machalek, Cristyn Davies, Xavier Bosch
On behalf of the editorial team, we would like to thank all the authors who contributed to this special issue of HPW
HPW editors:
Marisa Mena, Patricia Guijarro
On behalf of the editorial team, we would like to thank all the authors who contributed to this special issue of HPW
OTHER ARTICLES IN THIS HPW SPECIAL ISSUE:
D Machalek, C Davies. Australia’s HPV Vaccination Program: 15 years of success
D Machalek, K Sharma, J Kaldor. Tracking the impact of HPV vaccination on infection prevalence to measure vaccination program success
E Chow, J McCloskey. HPV vaccination is highly effective at preventing genital warts
O McNally, R McBain, KL Talia. Prevention of vulvar, vaginal precancer and cancer
R Hillman, M Poynten. Prevention of anal cancer
D Novakovic, A Cheng. Prevention of recurrent respiratory papillomatosis with HPV vaccination
C Davies, SR Skinner. School-based vaccination is key to reducing HPV-related diseases
C Vujovich-Dunn, C Vajdic, R Guy. Enhancing Australian monitoring and evaluation systems to support equitable HPV vaccination
J Brotherton, M Saville, D Wrede. Prevention of cervical precancer and cancer
M Smith, L Whop, J Brotherton. Cervical cancer elimination: true success requires equity