Did HPV vaccination programs beat cervical cancer?
Dr. Volker Bischoff
Alcimed Great Explorer Oncology ♦ Freelance Business Coach for Scientists 📩 info@vbischoff-coaching.de
After a little more than one decade of the launch of HPV vaccination programs, countries are starting to have data demonstrating vaccine effectiveness and/or showing falls in targeted types, and cross protective types. The most discussed aspect has been the decrease of the cervical cancer cases and mortality. Australia is one of the main characters in this scenario, and aims to eliminate cervical cancer as a public health issue in the coming 20 years combining HPV vaccination and HPV-based cervical screening. Other countries like Scotland and Sweden are also promoting the effectiveness of the HPV vaccination. Even if this good news represent an important step for the global healthcare system, it is important to notice that these analyses are treating limited data and this phenomenon is still restrained to a specific group of countries.
What is HPV? And why is it strongly related to cervical cancer?
We all have heard this word once in our life, probably without knowing what it means. It stands for human papillomavirus and is the most common viral infection of the reproductive tract. What we mostly also do not know is that most sexually active women and men will be infected at some point in their life and that it will probably clear up without any intervention. (1)
A small proportion of infections with certain types of HPV can persist and progress to different forms of cancer. Cervical cancer is by far the most common HPV-related disease and the fourth most common cancer in women, with almost 570,000 cases in 2018. (2) In addition, HPV infections contribute to over 40% of oropharyngeal cancers and can be responsible for penile, vulvar and anal carcinomas. (3)
In order to understand the relation between HPV infections and cancers, we have to focus first on the virus. HPV is a double-stranded DNA virus with more than 150 identified genotypes, which are categorized into two groups: low-risk types, including HPV- 6/11/40/42/43/44/54/61 and -72, responsible for genital wart; and high-risk types HPV-16/18/31/35/39/45/51/52/56/58/66 and -68, cause of 99.7% of cervical cancer. More than 40 types are spread through direct sexual contact, resulting or not in infections. (3)
A persistent infection with high-risk HPVs results in lesions that can progress to malignant cancers. In the case where abnormal cells are found on the surface of the cervix, they are called cervical intraepithelial neoplasia (CIN). Depending on how abnormal the cells look and how much of the cervical tissue is affected, it can be classified on scale of 1 to 3. CIN 2 or CIN3 are more likely to become cancer if not treated. Treatments in these cases may include cryotherapy, loop electrosurgical procedure (LEEP), or cone biopsy to remove or destroy the abnormal tissue. (4)
The immune system is usually capable of recognizing and controlling the cells infected by high-risk HPV. However, in the case where the infected cells remain and continue to grow, an area of precancerous cells is formed. It takes 15 to 20 years for cervical cancer to develop in women with normal immune system, and only 5 to 10 in women with weakened immune systems, like those with untreated HIV infection. (1)
What are the existing vaccination methods?
As other immunizations, HPV vaccines stimulate the body to produce antibodies that, in future encounters with HPV, bind to the virus and prevent it from infecting cells. There are currently three commercially available HPV vaccines: Cervarix®, a bivalent HPV-16/18 vaccine; Gardasil®, a quadrivalent HPV-6/11/16/18 vaccine; and Gardasil®9, a nonavalent HPV-6/11/16/18/31/33/45/52/58 vaccine. These vaccines are based on virus-like-particles (VLP) that are formed by HPV surface components and that are not infectious because they lack the virus’ DNA. (4)
The vaccines are considered highly effective due to the strong immunogenic activity from the VLPs. The World Health Organization (WHO) recognizes that the three existing vaccines offer comparable immunogenicity, efficacy and effectiveness for the prevention of cervical cancer, which is mainly caused by HPV types 16 and 18. Therefore the choice should be made regarding the locally relevant data and on factors like the prevailing HPV-associated public health problem and the population for which the vaccine has been approved. (1)
Corresponding to prevention method for HPV infection, the vaccines do not prevent other sexually transmitted diseases, neither do they treat existing HPV infections or HPV-caused diseases. The vaccines should therefore be given before initial exposure to the virus, meaning before individuals begin sexual activity, and WHO-recommend primary target population is girls aged 9-14 years. Most countries that initiated their vaccination programs established this age range as priority, but also invested in catch-up initiatives for females older than 15 years and males. (1) (5)
What has been the outcome? What can we expect?
The HPV vaccine has been proving its effectiveness. Since the first licensure of HPV-vaccination in 2006, many countries have implemented publicly funded national vaccination programs for HPV, mainly high income countries. After proven decrease in incidence of HPV16 and HPV18 in the past 4 years, researchers are now analyzing the positive outcomes of these vaccines in regard of cervical cancer.
Australia, Scotland and Japan are examples of countries where the effects of the HPV vaccines have already been positively related to the decrease of cervical cancer. Australian researchers have lately declared that by combining their high-coverage vaccination and screening, cervical cancer could be considered eliminated as a public health problem in Australia within the next 20 years (threshold of four new cases per 100,000 women annually) (5). Furthermore, the International Papillomavirus Society declared that Australia has also achieved the greatest herd immunity against HPV. In herd immunity, vaccines provide some protection for those who are not vaccinated, because fewer germs are being transmitted from person to person.
Even if the situation is promising, not everyone benefits from these evolutions. Developing countries are still in disadvantage and their key obstacle is cost. In these countries, cervical cancer is the leading cause of cancer death in women. Therefore, the WHO’s International Agency of Research on Cancer is evaluating a potential low cost alternative for Gardasil®, made by a generic manufacturer, the Serum Institute of India. (8)
Another important factor to achieve the decrease, or elimination, of cervical cancer is the cervical screening. As the HPV vaccines do not cover all the high-risk HPVs, like HPV39, 51, 56 and -59, they can remain as causes for infections which may progress to a cancer. Also, when women are vaccinated after being infected by the virus, the infection can progress without their knowledge. (9)
Conclusion
The HPV vaccination can be considered a big step in the fight against HPV infections and, consequently, cervical cancer. However, while the developed nations are already noticing the positive effects of this technology, a lot has to be done in developing countries in order to achieve a comparable success. Furthermore, as in other fields, contradictions also exist regarding the effectiveness on the reduction of cervical cancer; mainly anti-vaccination campaigns remain against the HPV vaccines and refuse their positive results.
For now, it is important to continue the research to improve the effects of HPV vaccines and its alliance with cervical screening, in order to follow the Australian expectations to eliminate cervical cancer as a public health problem.
References
(1)World Health Organization. https://www.who.int
(2) International Agency for Research in Cancer. https://www.iarc.fr/
(3) Aleyo Chabeda, Romana J.R. Yanez, Renate Lamprecht, Ann E. Meyers, Edward P. Rybicki, Inga I. Hitzeroth, Therapeutic vaccines for high-risk HPV-associated diseases, Papillomavirus Research, Volume 5, 2018, Pages 46-58, ISSN 2405-8521,
(4) National Cancer Institut. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cancer
(5) The projected timeframe until cervical cancer elimination in Australia: a modelling study
(6) Ryo Konno, Hiroshi Konishi, Catherine Sauvaget, Yasuo Ohashi, Tadao Kakizoe, Effectiveness of HPV vaccination against high grade cervical lesions in Japan, Vaccine, Volume 36, Issue 52, 2018, Pages 7913-7915, ISSN 0264-410X
(8) Dyer Owen, Cervical cancer: deaths increase as HPV vaccine is underused, says WHO. BMJ;364 :1580
(9) Ährlund-Richter A, Cheng L, Hu YOO, Svensson M, Pennhag AAL, Ursu RG, Haeggblom L, Grün N, Ramqvist T,Engstrand L, Dalianis T and Du J (2019) Changes in Cervical Human Papillomavirus (HPV) Prevalence at a Youth Clinic in Stockholm, Sweden, a Decade After the Introduction of the HPV Vaccine. Front. Cell. Infect. Microbiol. 9:59.doi: 10.3389/fcimb.2019.00059