Vaccination saves lives

Olga FEDOTOVA, Remedium magazine No. 5-2007.

Sad statisticsEvery year, about 470,000 new cases of breast cancer are registered on the planet, which is 14.2% of all malignant neoplasms in women.

Every two minutes in the world, one woman dies from cervical cancer. More than 270,000 women die from this pathology annually[Ferlay J].

Cervical cancer is a significant problem for the healthcare of the Russian Federation. In 2004, 12700 women with this disease were registered, which is about 5% of all malignant tumors and 31% of malignant neoplasms of the female genital organs. In recent years, there has been a trend of an increase in the incidence of cervical cancer in women in the age group up to 29 years, where the increase in this indicator from 1993 to 2002 amounted to 150%. There is also a high proportion of the advanced stages of the disease – more than 40%. Hence the high mortality rate – more than 6,000 women annually, in other words, in Russia 16 women die from cervical cancer every day. It is too early to talk about a pandemic, but if urgent measures are not taken, then by 2030, according to WHO representative Peter Boyle, the number of oncological diseases in the world will double.

HPV prefers youngEven the ancients said: identifying the cause of the disease is the first step on the path to healing.

Cervical cancer (cervical cancer) is one of the few malignant neoplasms whose etiology is scientifically proven. Over the past two decades, it has been established that the occurrence of precancerous conditions is directly related to the human papillomavirus (HPV), which is detected in almost all patients with precancerous conditions and breast cancer. About 100 types of HPV are known, 15 of them are oncogenic and can cause cervical cancer or precancerous changes. Globally, more than 70% of cases of cervical cancer are caused by infection with HPV types 16 and 18. It has been established that up to 80% of women are infected with HPV during their lifetime and in 50% of cases with oncogenic strains. "Studies show that most women become infected with the papilloma virus throughout their lives, and up to 82% of them become infected within 2 years after their sexual debut, mainly young girls and women," says S.I.Rogovskaya, MD, a researcher at the Scientific Center of Obstetrics, Gynecology and Perinatology. – The peculiarity of the virus is that it does not enter the blood, but is found only in the epithelial tissues of the skin and mucous membranes. Therefore, activation of the immune system in response to infection does not always occur. Even in patients with severe cervical cancer, antibodies are almost not detected in the blood. But even if antibodies are still present in the blood, their level is very low and is not able to provide long-term reliable protection against cancer. HPV persists in the epithelium for a long time and, when exposed to risk factors, sooner or later leads to the development of cancer of the cervix and other organs."

Vaccination against HPV infection - mission against breast cancerThe evidence that cervical cancer is a consequence of HPV infection has put it in a number of diseases potentially preventable with vaccination.

Scientists were faced with the task of creating an effective vaccine against the human papillomavirus, and therefore against cervical cancer. And they were created: the quadrivalent Gardasil vaccine (Gardasil, MSD) and the GlaxoSmithKline bivalent candidate vaccine against breast cancer. GSK's phase III clinical trial program for a candidate vaccine against cervical cancer is going well, and currently, more than 30,000 women are participating in the study in 25 countries around the world.

"The principles of vaccine development and production are the highest system of quality standards, strict adherence to international norms and requirements, national laws, responsive response to the needs of healthcare systems," Svetlana Ivanovna continues. – The process of creating a vaccine against HPV took more than 15 years and was extremely difficult, because so far this virus does not reproduce and is not grown on artificial media, so its study is difficult. HPV capsid proteins L1 and L2, which have the highest immunogenicity, were chosen as the target for the preventive vaccine. The essence of the vaccine's action is to slow down the production of HPV and prevent the formation of its critical concentration for the onset of the disease. During vaccination, cellular memory is stimulated, thanks to which, in future contact with the pathogen-antigen, the process of new production of neutralizing antibodies is started, which is important for creating long-term immunity.

Clinical research is a necessary component of the study, development and production of any drug or vaccine. Medical research involving people as subjects is carried out only by persons with scientific qualifications, under the supervision of a competent clinician and complies with generally accepted scientific principles, based on in-depth knowledge of scientific literature and other sources of information."

An interesting fact is that the creation of HPV vaccines is regarded as one of the most significant achievements of modern science. It is no coincidence that the American magazine TIME included the creation of this vaccine in the list of the 10 most important scientific and technological discoveries of 2006.

Protection level – maximumVaccines for the prevention of breast cancer have shown promising results in large-scale randomized placebo-controlled double-blind trials in many European countries, including Russia, with the participation of 60,000 adolescent girls and young women.

It has been indisputably proven that the effectiveness of vaccines to prevent severe breast cancer is approaching 100%. And although the maximum observation period is 5 years, doctors consider this period to be quite sufficient to unambiguously assess the effectiveness of vaccines: it is during this time that cervical intraepithelial neoplasia develops – and it becomes clear whether a person will get sick or not. In general, the level of confidence in the vaccine among specialists is very high. Suffice it to say that among the women who took part in the vaccine study, there were many medical workers themselves – doctors and nurses who have constant contact with infections and understand the need for protection like no one else.

Gardasil vaccine has already been registered in the European Union, USA, Canada, Russia, etc., and in the USA and Australia it is included in the National vaccination calendars, it is given to all girls aged 11 years. The registration of a candidate vaccine against breast cancer by GSK is expected to be completed in the near future.

A distinctive feature of GSK's candidate vaccine against breast cancer is the presence in its composition of a new adjuvant ASO4, which significantly enhances the immune response. According to clinical studies, the new adjuvant will contribute to the development of a longer and more pronounced immune response (immunogenicity). In addition, when GSK's candidate vaccine against breast cancer is introduced, there is a cross-reaction when antibodies are produced not only to HPV types 16 and 18, which provides protection against 70% of cases of cervical cancer, but also to HPV types 31 and 45, and this makes the range of protection even wider. It is important to note that the vaccine is exclusively preventive, preventive in nature and is not intended for use for medicinal purposes. It should be administered to uninfected HPV women, and to girls even before the onset of sexual activity.

Three whalesEffectiveness, safety and accessibility are the three pillars, the three main characteristics that, ideally, any modern drug or vaccine should possess.

According to the data presented by the American Association for Cancer Research in April 2007, GSK's candidate vaccine against breast cancer has demonstrated 100% effectiveness in preventing precancerous changes caused by 16, 18 types of HPV with a protection duration of more than 5 years. "These new findings from a large–scale completed study are amazing for both those working in the field of breast cancer prevention and for all women," says Dr. Stanley Gall, lead researcher and professor of obstetrics, gynecology and women's health at the University of Louisville, Kentucky. "Demonstrating 100% efficacy and a sustained immune response for more than 5 years is a significant contribution to understanding the possibilities of vaccination to prevent breast cancer and precancerous changes."

To date, more than 16,000 women have received at least one dose of GSK's candidate cervical cancer vaccine in clinical trials. The data from the completed clinical trials showed no differences in the frequency of serious adverse events after the appointment of a candidate vaccine against cervical cancer from GSK compared with placebo. The new ASO4 adjuvant system has been introduced to more than 30,000 patients both in clinical trials of the cervical cancer vaccine and as part of other candidate and licensed GSK vaccines with an acceptable level of safety.

As for the third principle – ensuring the availability of the drug, its implementation is still ahead and depends not so much on the developer company as on the organizers of healthcare. The pricing structure will be supported by the “vaccine availability model”, which takes into account the availability of the healthcare system, the ability of the private sector to purchase the vaccine directly, and the possibility of government assistance for a segment of society in need of it.

Who owns the information…At the same time, according to the Deputy Director for Science of the Center of Obstetrics, Gynecology and Perinatology, Doctor of Medical Sciences V.N.Prilepskaya, Russian obstetricians and gynecologists are still insufficiently informed about HPV infection and the possibilities of vaccination of cervical cancer.

A survey of 164 gynecologists organized by the Center showed that although most of them (89%) have an idea about the etiological role of HPV in the genesis of breast cancer, only 10% of them know about the possibility of an HPV test and 28% about preventive vaccination. Of course, all respondents expressed their willingness to learn and receive new information. Therefore, the manual for doctors "Prevention of cervical cancer" prepared by a group of leading Russian specialists (MEDpress-inform, 2007) was received with great interest.

Another, this time multicenter study "Women's Awareness of women's health", conducted in 10 leading European countries in 2006 with the participation of 4,500 women, shows that only 2% of them know that cervical cancer causes infection with the HPV virus. And if in Finland, France and Germany 89-90% of women are covered by screening, then in Romania – in 30%, and in Russia, according to some data, about 17%. It is not surprising that the mortality rate from breast cancer in our country is much higher than in other countries.

It all starts with screeningThe role of cervical screening – the examination of all women in order to identify and timely treat precancerous changes in the cervix – obstetricians and gynecologists have not questioned for a long time.

Regular screening can reduce the risk of developing breast cancer by 80%. However, in Russia, the frequency of detection of cervical pathologies during preventive examinations does not exceed 25%, and in the last 10 years their effectiveness has not significantly increased.

It is clear that the screening test should be simple, non-invasive, sensitive and specific, safe, inexpensive and affordable. Along with traditional and well-studied methods of examination, modern laboratory science offers new screening technologies, such as liquid cytology, HPV testing, computer diagnostics, etc. "The choice of the test depends on many factors: the organization of the healthcare system and its financial capabilities, the training of specialists, the availability of laboratories and modern equipment and other priority health needs. Therefore, it is very important to develop and present to the medical community a modern state program for the prevention of breast cancer on the basis of evidence-based medicine. Of course, the screening program itself will not be able to eradicate HPV infection, which remains the main cause of cervical cancer, but it is the results of screening examination of women from 18-20 years of age that will make it possible to form risk groups for which targeted preventive measures should be carried out, including vaccination, thereby contributing to a decrease in the incidence of breast cancer"- Vera Nikolaevna Prilepskaya believes.
In the Nordic countries, state gynecological screening programs have been implemented since the early 1960s, and centralized management of cancer registries is better established there than anywhere else. Vaccination, together with screening programs, can further reduce the risk of developing cervical cancer compared to the use of screening alone, as well as significantly reduce the number of detected cases of cervical pathology and require follow-up.

To be continued?The creation of a vaccine for the prevention of breast cancer is considered by many leading scientists to be the greatest achievement of mankind.

Cervical cancer is an important health problem that is a psychological and social burden for women all over the world. Vaccinoprophylaxis gives hope for a reduction in individual and public costs. The introduction of vaccine prophylaxis in conjunction with screening programs will significantly reduce the incidence of breast cancer. The creation of the next generations of vaccines will pursue the goal of protection against additional oncogenic HPV types and combine significant coverage of oncogenic HPV types with the longest duration of protective effect. In fact, we are now at the beginning of a very important path – a change in ideology in solving the most urgent problem of the fight against breast cancer. But we will not be able to assess the positive effects of large-scale vaccination until 20-30 years later, when we actually see a real reduction in morbidity and mortality from a dangerous HPV-associated disease. And only if the state authorities classify cervical cancer vaccination as a priority area and include the vaccine in the National Vaccination Calendar, a solution to the problem of breast cancer can be feasible.

Portal "Eternal youth" www.vechnayamolodost.ru
15.04.2008