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Human Papillomavirus (HPV) © NIAID

Years ago, I came across the case of an acquaintance who had cancer, which, as it later turned out, was caused by the human papillomavirus (HPV). Fortunately, it was a story with a happy ending, but that does not apply to everyone.

Human papillomavirus is the name given to a group of 200 known viruses. It is now known that almost all sexually active people develop HPV infections in the course of their lives. Around half of them have a high-risk type of the virus. HPV can infect the skin, the genital area and the throat. Scientists assume that precursor forms of HPV type 16 have most likely infected all archaic human populations, at least since Homo Erectus.

In 90 per cent of cases, the body itself controls the infection. The immune system usually removes HPV from the body within one or two years without leaving any lasting consequences. However, experts estimate that high-risk HPV infections cause around 5 per cent of all cancers worldwide, particularly cervical cancer, but also other types of cancer in both men and women. In 2019, for example, HPV caused an estimated 620,000 cases of cancer in women and 70,000 cases of cancer in men, according to the WHO. ‘Cervical cancer was the fourth leading cause of cancer and cancer-related deaths in women in 2022, with about 660,000 new cases and about 350,000 deaths worldwide’. The highest incidence of cervical cancer in women is in sub-Saharan Africa (24 per cent), followed by Latin America and the Caribbean (16 per cent), Eastern Europe (14 per cent) and Southeast Asia (14 per cent). (Source: www.WHO.int )

In men, there are very different forms of HPV depending on sexual predisposition, with throat or penile cancer being the most common.

Condoms help to prevent HPV, but do not offer complete protection as they do not cover the entire genital skin. However, the introduction of the HPV vaccine was a big step forward in the fight against this disease. However, we must realise that HPV vaccines do not treat HPV infections or diseases, but can prevent them from developing.

Effective screening and treatment of precancerous lesions can also be an effective means of preventing HPV cervical cancer. Screening tests are used to check for the presence of disease while symptoms are not yet present and aim to find precancerous lesions if they are present.

The mortality rate for HPV-related diseases is considerable, particularly for cervical cancer in low and middle-income countries. Despite medical efforts, cervical cancer remains a significant public health problem in Europe. In 2020, cervical cancer was the ninth most common cancer in women on the continent, with around 58,169 new cases and 25,989 deaths. (Source: www.hpvworld.com )

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Comprehensive HPV vaccination has the potential to significantly reduce the incidence and mortality rates of these cancers. In countries with high vaccination coverage, there has already been a reduction in HPV infections and precancerous lesions, which will ultimately lead to lower cancer mortality.

Although the benefits of this vaccine have already been proven, the uptake of vaccination varies widely around the world and depends on numerous factors and conditions, from medical infrastructure and economic conditions to cultural beliefs, social awareness and also government policies and health programmes. The critical importance of vaccination and the need for coordinated international efforts at various levels to maximise its benefits and uptake must be emphasised.

The vaccine against the human papillomavirus is relatively new, especially when compared to many other vaccines available in the world today that have saved lives and led to the eradication of many diseases. Smallpox, poliomyelitis, diphtheria, tetanus or rubella have been eradicated or significantly reduced thanks to mass immunisation.

The link between HPV and cervical cancer was first clearly established in the early 1980s through the careful studies of the German virologist Harald zur Hausen, who discovered that certain HPV strains are responsible for cervical cancer. He was later awarded the Nobel Prize for Medicine for this discovery.

However, the development of an HPV vaccine only began in the 1990s. Scientists focused on developing a vaccine that could prevent infection with the most common HPV strains known to cause cancer.

The first HPV vaccine, Gardasil, was developed by Merck & Co and approved by the US Food and Drug Administration (FDA) in June 2006. Gardasil is directed against HPV types 16 and 18, which are responsible for most cases of cervical cancer. According to the manufacturer Merck & Co, the HPV vaccines do not contain live viruses or viral DNA, so they cannot cause cancer or other HPV-related diseases.

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The Gardasil and Cervarix HPV-vaccines © diariofarma

A second HPV vaccine, Cervarix, was developed by GlaxoSmithKline and approved by the FDA in October 2009.

In 2014, Gardasil 9, a new and improved vaccine that protects against nine HPV types (6, 11, 16, 18, 31, 33, 45, 52 and 58), was authorised. This enhanced protection aims to cover additional strains that cause cervical cancer and other types of cancer. The HPV vaccines should first be given to all children aged 9 to 14 years before they become sexually active, usually in one or two doses, and then to young adults. The HPV vaccine is no longer recommended for adults over the age of 45, as it is assumed that most adults of this age have already been exposed to HPV.

Since the introduction of HPV vaccines, large-scale national immunisation programmes have been implemented in many countries, leading to a significant reduction in infections and related diseases and an improvement in overall health. The World Health Assembly adopted the Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. On this occasion, several general goals were declared, including the vaccination of 90 per cent of girls up to the age of 15 with HPV vaccines.

One hundred and forty-three countries worldwide have included the HPV vaccine in their national immunisation agenda by the end of 2023. The proportion of girls vaccinated with a single dose of HPV is currently estimated at 27 per cent.

In April 2007, Australia introduced a national, government-funded vaccination programme against human papillomavirus for the first time. In the US, HPV infections responsible for associated cancers have decreased by 88 per cent in teenage girls and 81 per cent in young adult women since HPV vaccination was first recommended in 2006. (Source: www.cdc.gov) As part of the US Healthy People 2030 programme, a target was set for 80 percent of American teenagers to receive the full HPV vaccination, but this rate is currently stagnating at about 63 percent.

In October 2023, Nigeria announced the inclusion of the vaccine against human papillomavirus in its routine immunisation system. This is expected to reach 7.7 million girls – the largest number in a single HPV vaccination in the African region, considering that the disease is the third most common cancer in the country.

According to the World Health Organisation, HPV vaccination rates in Asia are much lower (between 4 and 2 percent).

In Europe, the WHO estimates that coverage of the HPV vaccination programme for women will have reached 32 by 2022, although there are significant differences between the individual programmes in the various European countries. The same organisation reports that today 40 out of 54 countries in Europe have national HPV vaccination programmes for girls. Boys, on the other hand, are currently only included in national HPV vaccination programmes in ten of the 27 EU countries and eight other European countries.

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A young girl being vaccinated © Wikicommons

According to the European Centre for Disease Prevention and Control (ECDC), Portugal has one of the highest HPV vaccination rates among EU countries, with a particularly high vaccination coverage rate among adolescent girls. The high vaccination rates in this country are attributed to strong public health initiatives, school vaccination programmes and widespread public acceptance of the vaccine.

Both my son and daughter were vaccinated against HPV free of charge before the age of 15, while residing in Germany, and Austria has announced that HPV vaccination will be free for everyone aged 9 to 30 from 1 July 2024.

The United Kingdom introduced its HPV vaccination programme in 2008, and a study published in 2021 predicts that cervical cancer rates could fall by 90 per cent in the vaccinated population, representing great potential for the future eradication of HPV-related cancers. The Swedish HPV vaccination programme, which was introduced in 2010, has also led to a significant reduction in HPV infections. In France, the HPV vaccination rate among girls aged 11 to 19 has risen steadily since the programme was introduced in 2007. Today, an estimated 46 per cent of the target population has been vaccinated with one dose and 37 per cent have received the full HPV vaccination. (Source www.hpvcentre.net) At the other end of the spectrum, Bulgaria has one of the lowest HPV vaccination rates among EU countries due to limited public awareness, a hesitant attitude towards vaccine and less comprehensive public health initiatives.

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© projectperch.eu

The European Partnership for HPV Contrast – PERCH – was launched in 2022 as a joint action project by the European Health and Digital Executive Agency (HaDEA). It consists of 18 European countries and 34 partner organisations and aims to jointly promote HPV vaccination, optimise data collection to monitor vaccination coverage and impact over the next ten years, support Member States in the effective implementation of national HPV vaccination strategies and raise awareness of HPV-related diseases among target groups (adolescent girls and boys).

It should be clear by now that mass vaccination against HPV is having a major impact on reducing HPV-related cancers. Although this has already been seen in several countries with robust vaccination programmes, it will take more time to see the most significant results and benefits due to the long latency period between HPV infection and the development of related cancers.

In the short term (5-10 years), a decline in HPV infections can be observed in the vaccinated population groups. In the medium term (10-15 years), a decrease in precancerous lesions can be observed. As a logical consequence, the incidence of HPV-related cancers will decrease in 15-20 years as the vaccinated population increases. There are already countries such as Australia, which is now a world leader in HPV vaccination and hopes to eliminate cervical cancer as a public health problem by 2035.

So, while some benefit from HPV vaccination can be seen in the first decade, the most dramatic declines in cancer rates will not be seen until the next 15 to 20 years as vaccinated populations continue to age. To achieve these long-term results, continued high vaccination coverage rates and solid public health efforts are needed.

Although no nation has yet completely eradicated HPV-related cancers, there are many countries where the number of HPV infections and precancerous lesions has decreased significantly thanks to successful mass vaccination programmes. These countries underline the effectiveness of mass vaccination programmes in reducing HPV-related health problems. Continued vaccination efforts combined with screening and public health initiatives promise to drastically reduce and possibly eradicate HPV-related cancers in the future.

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The widespread HPV vaccination is also proving to be a much more economical alternative. The cost of vaccinating a person is significantly lower than the cost of treating a case of HPV-related cancer. The cost per HPV vaccine dose varies, but in high-income countries it is usually around EUR 150-200 per dose, whereas the cost of treating cervical cancer, for example, can range from EUR 20,000 to EUR 50,000 per patient in the early stages and up to EUR 150,000 or more in the advanced stages.

For every euro spent on HPV vaccination, several euros can be saved on cancer treatment and the related healthcare costs. One could say that for governments, mass vaccination against HPV is very cost-effective compared to the treatment of HPV-related cancers. The initial investment in vaccination programmes can lead to significant long-term savings in healthcare costs associated with the treatment of these cancers.

Whichever way we look at things, implementing HPV vaccination programmes can be a crucial step towards reducing the prevalence of HPV infection and the associated burden of cervical and other HPV-related cancers. Countries such as Australia and Portugal have demonstrated the profound impact of widespread vaccination through significant declines in HPV-related disease. Continued efforts to increase vaccine coverage, raise public awareness and support global immunisation initiatives are crucial to further these successes. By prioritising HPV vaccination, we can move closer to a future where HPV-related cancers are a rarity, which will ultimately save countless lives and improve public health worldwide.

alexandra.paucescu@europe-diplomatic.eu

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