<![CDATA[Interview with Elmar Joura]]>

1. After 14 years since HPV vaccines were first introduced in population- based public programs, what is your global balance?
We have seen after robust results of the extensive clinical trials that these vaccines also work in the real-life setting. Looking at the results of 14 countries with a national immunization program we clearly see that the vaccines are effective in preventing HPV infections and disease.^1,2 And just recently we got the final proof from Sweden that these vaccines prevent invasive cancer.³

2. What is the spectrum of diseases caused by HPV that could benefit from a generalized vaccination campaign?
These vaccines were initially developed to prevent cervical cancer and its precursors. Meanwhile, we know that in total 6 cancers- 5% of all cancers worldwide- can be prevented. Aside from cervical cancer, (HPV-related) vulvar and vaginal cancer in women, and penile cancer in men, anal and oropharyngeal cancer in both men and women can be prevented. Not to forget disease caused by low-risk types: genital warts, a disease with a lifetime risk of approximately 30% and a prevalence of 1%- not life threatening but a significant limitation in quality of life. And the rare respiratory papillomatosis, a terrible disease for those suffering from.

3. What is now the expected preventive impact in populations well vaccinated?
We have seen very soon after the start of HPV vaccination programs a decline in genital warts, since they break out a few weeks after infection. In the vaccinated cohorts, they are now almost eliminated. We have seen a decline in precancers of the cervix, and in the long run we can even eliminate invasive cervical cancer and other HPV-related cancers.^1-3 But this is the perspective for the next five decades, since oncogenesis is a slow process.

4. Is there a definite fraction of vaccination coverage that countries need to attain to secure herd protection?
We have seen that vaccination coverage is crucial and the higher the coverage the more effective is the national immunization program. We should aim to achieve a coverage of >70%. A gender-neutral approach certainly improves if not doubles the coverage- wherever it is feasible it should be implemented.

5. Other than the target populations for vaccination (typically girls up to 15 years of age) how do you envisage extending the indications to vaccinate adult women (i.e. to age 30-40)?
Australia has demonstrated with a broad catch-up up to the age of 26 that the disease reduction in the population is seen much earlier compared to countries only vaccinating one or two cohorts.¹ Efficacy of HPV vaccines has been demonstrated up to the age of 45 years and this certainly gives a good protection for the individual; in women over the age of 30 the combination of HPV testing and vaccination provides the best protection.⁴ And we could demonstrate that after treatment for HPV-related disease, HPV vaccination significantly reduces the risk of recurrent/subsequent disease.⁵ In Europe, the upper age limit for all HPV vaccines has been dropped. But in general, within the national immunization programs we have seen that the earlier we vaccinate the more effective the program is, the catch-up improves the result. The more people are vaccinated the less virus is circulating.

6. What is the expected safety record after more than 100 M individuals have been vaccinated?
The safety profile is excellent, WHO stated that these vaccines are extremely safe. Neurologic and autoimmune disease, often suspected to be caused by vaccines, has the same incidence in vaccinated and unvaccinated populations.

7. What is the incentive to include boys into the public programs?
Including boys into national immunization programs improves vaccination coverage, gives to males direct protection against HPV-related disease and provides protection to young men who have sex with men (MSM). They have a substantial risk for HPV- related disease and remain unprotected in a girls-only vaccination program.

8. How do you value the cervical cancer elimination campaign launched by WHO?
This is an important initiative of the most respected health organization and it gives us ambitious, but well defined goals. By 2030, 90% of girls under the age of 15 should be vaccinated and 70% of women aged 35 and 45 should be screened by HPV-testing. We have the tools to eliminate cervical cancer, we need the political will to achieve this goal.⁶

The first country which will reach the threshold set by WHO (4 cases/100,000 women- year) will be Australia in 2028. Then cervical cancer will stop to be a public health issue in this country.⁷

9. How has COVID-19 impacted into the HPV vaccination campaigns?
COVID-19 takes a lot of resources from the current prevention and screening programs.⁸ This certainly endangers women and also delays the process of elimination. Hopefully the awareness for viral infection and disease will increase and more facilities for viral testing will be available globally. This can improve the implementation of HPV vaccination and testing, the basis of elimination in the long run.

DISCLOSURE EAJ has received institutional grants and lecture fees from MSD and GSK.

References

1. Drolet M, Bénard É, Pérez N et al. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet. 2019;394:497-509. Available from: https://pubmed.ncbi.nlm.nih.gov/31255301/

2. Lei J, Ploner A, Elfström KM et al. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med 2020;383:1340-1348. Available from: https://pubmed.ncbi.nlm.nih.gov/32997908/

3. Giuliano AR, Joura EA, Garland SM et al. Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population. Gynecol Oncol 2019;154:110-117. Available from: https://pubmed.ncbi.nlm.nih.gov/30982556/

4. Bosch FX, Robles C, Díaz M et al. HPV-FASTER: broadening the scope for prevention of HPV-related cancer. Nat Rev Clin Oncol. 2016;13:119-32. Available from: https://pubmed.ncbi.nlm.nih.gov/26323382/

5. Jentschke M, Kampers J, Becker J et al. Prophylactic HPV vaccination after conization: A systematic review and meta-analysis. Vaccine. 2020;38:6402-6409. Available from: https://pubmed.ncbi.nlm.nih.gov/32762871/

6. Brisson M, Kim JJ, Canfell K et al. Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries. Lancet. 2020;395:575-590. Available from: https://pubmed.ncbi.nlm.nih.gov/32007141/

7. 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-e27. Available from: https://pubmed.ncbi.nlm.nih.gov/30291040/

8. Ciavattini A, Delli Carpini G, Giannella L et al. European Federation for Colposcopy (EFC) and European Society of Gynaecological Oncology (ESGO) joint considerations about human papillomavirus (HPV) vaccination, screening programs, colposcopy, and surgery during and after the COVID-19 pandemic. Int J Gynecol Cancer. 2020;30:1097-1100. Available from: https://ijgc.bmj.com/content/30/8/1097

ARTICLES INCLUDED IN HPW SPECIAL ISSUE ON HPV VACCINES:

L Baandrup, P Valentiner-Branth, SK Kjaer. HPV Vaccination Crisis and Recovery: The Danish Case.

B Huber, RBS Roden, R Kirnbauer. L2-based Human Papillomavirus Vaccines: Current Status And Potential.

M Drolet, M Brisson. Population-level Impact and Herd Effects of HPV Vaccination Programs in High-Income Countries: Real-life Data.

SM Garland, GL Murray, DA Machalek. Prevention of HPV-Related Diseases Following 4-Valent Vaccination in Australia.

M Kane, M Stanley. Pre-school HPV Immunization?

PM Kotulka, A Luxembourg, A Shaw. Challenges in HPV Vaccine Development and Supply.

R Cameron, K Cuschieri, K Roy. Prevention of HPV Infection and Associated Disease Following Bivalent HPV Vaccination in Scotland.

QY Yan, MJ González-Méndez, YL Qiao. Current Status of HPV Vaccine in China.

L Xu, SM Garland, M Arbyn. Efficacy of HPV Vaccination To Prevent Vulvar and Vaginal Precancer.

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Elmar A Joura, MD
Associate Professor of Gynecology, Head of Colposcopy and Vulvar Services, Department of Obstetrics and Gynecology, Medical University of Vienna, General Hospital and Comprehensive Cancer Center Vienna.
elmar.joura@meduniwien.ac.at

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