**6. Introduction of vaccination of adolescents against HPV infection in KhMAO-Ugra: problems and solutions**

The strategic direction of the development of modern health care in the Russian Federation is prevention and early detection of diseases, which contributes to more effective treatment and improvement of demographic indicators of public health. One of the most important preventive measures is vaccination, and today more than 30 diseases that cause serious damage to human health can be prevented with its help. Immunization prevents 2.5 million deaths per year across all age groups.

These facts indicate that the issues of prevention and treatment of HPVassociated diseases require a multidisciplinary approach, as they affect such specialists as gynecologists, oncologists, epidemiologists, pediatricians, immunologists, dermatologists, etc.

The World Health Organization has been recommending the inclusion of HPV vaccination in vaccination calendars around the world since 2009 [15]. The WHO and the United Nations Children's Fund (UNICEF) consider HPV vaccination a priority for national immunization programs. More than 60 countries have already introduced universal mass vaccination of girls; in a number of countries (the USA, Australia, Canada, Austria, New Zealand, etc.), boys are vaccinated along with girls.

To date, the Russian Federation has two documents regulating measures for the prevention of HPV-associated diseases.


Despite government HPV vaccination programs, female vaccination rates remain below targets in many countries [18, 19]. Models tend to demonstrate that vaccination of boys is most cost-effective if vaccination coverage of the female

**11**

*The Importance of the Problem of HPV-Associated Diseases in KhMAO-Ugra: Vaccination…*

population is at a suboptimal level (less than 50%) [20, 21]. The benefits of vaccinating adolescent boys are not only the prevention of HPV infection for the partner but also the prevention of cancer of the penis and anal canal and anogenital warts. Vaccination is the most effective investment in health care. The cost of treatment of one case of cervical cancer in the Russian Federation on average is \$3000 and the cost of vaccination with preventive vaccination Gardasil—\$235. With mass immunization of adolescents aged 12 years old, the pharmacoeconomic efficacy of vaccine introduction was calculated on a national scale, which showed the amount of prevented costs to be \$235,000,000, and in the first 5 years, only \$16,000,000

There are numerous publications confirming the pharmacoeconomic effective-

According to the instructions, the vaccine is approved for use in women aged 9 to 45 years old and in men aged 9 to 26 years old and can protect against diseases such as cervical cancer, vulvar cancer, vaginal cancer, anal cancer, and anogenital warts. Due to the fact that the human papillomavirus causes serious diseases in men, and screening methods for HPV-associated lesions of the anal canal and penis do not exist today, universal vaccination of adolescents of both sexes with quadrivalent HPV vaccine, the only one approved for use in boys, will achieve significant results in reducing the level of HPV-associated diseases and the rapid spread of

The primary target cohort for HPV vaccination is children and adolescents aged 9 to 13 years before sexual debut, as recommended by the World Health Organization. The WHO since 2009 recommends that vaccination against human papillomavirus be included in vaccination calendars of all countries of the world. The WHO and the United Nations Children's Fund consider HPV vaccination as a priority for national immunization programs. Sixty countries have already introduced universal mass vaccination of girls, and three countries (the USA, Australia,

At the moment, two HPV vaccines are registered in the Russian Federation: bivalent vaccine (Cervarix, contains antigens to 16 and 18 types of HPV) and quadrivalent vaccine (Gardasil, contains antigens 6, 11, 16, and 18 types of HPV). Bivalent HPV vaccine is used to prevent cancer and precancerous lesions of the cervix, vulva, and vagina. Quadrivalent HPV vaccine can protect not only from cervical, vulvar, and vaginal cancer but also from cancer of the anal canal and anogenital warts in women and men. The primary target cohort for HPV vaccination is adolescents aged 9–13 years old prior to sexual debut, as recommended by

The monitoring of epidemiological effectiveness is an integral part of HPV vaccination programs. In the long term, HPV vaccination can reduce the incidence and mortality from a number of cancers (cervical cancer, anal cancer, etc.), the prevention of which is a public health priority. Evaluation of the effectiveness of vaccination programs in the medium term is possible to reduce precancerous dysplasia

ness of HPV vaccination not only in computational models but also in real life

In 2013, the Research Institute of Childhood Infections of the FMBA conducted a pharmacoeconomical evaluation of the cost-effectiveness of vaccination of 12-year-old girls with a quadrivalent HPV vaccine in Russia. For the period of survival, taking into account both direct medical and indirect costs, the vaccine is characterized by a cost-effectiveness ratio equal to \$5800/QALY. When the gross domestic product of the Russian Federation was \$6000, vaccination of girls with a quadrivalent HPV vaccine in the Russian Federation is characterized by high cost efficiency and can be recommended for routine use in the Russian

*DOI: http://dx.doi.org/10.5772/intechopen.90668*

will be prevented by reducing genital warts [22].

[22–28].

population.

HPV infection in the world [29].

Canada) also vaccinate boys against HPV.

the World Health Organization [1].

### *The Importance of the Problem of HPV-Associated Diseases in KhMAO-Ugra: Vaccination… DOI: http://dx.doi.org/10.5772/intechopen.90668*

population is at a suboptimal level (less than 50%) [20, 21]. The benefits of vaccinating adolescent boys are not only the prevention of HPV infection for the partner but also the prevention of cancer of the penis and anal canal and anogenital warts.

Vaccination is the most effective investment in health care. The cost of treatment of one case of cervical cancer in the Russian Federation on average is \$3000 and the cost of vaccination with preventive vaccination Gardasil—\$235. With mass immunization of adolescents aged 12 years old, the pharmacoeconomic efficacy of vaccine introduction was calculated on a national scale, which showed the amount of prevented costs to be \$235,000,000, and in the first 5 years, only \$16,000,000 will be prevented by reducing genital warts [22].

There are numerous publications confirming the pharmacoeconomic effectiveness of HPV vaccination not only in computational models but also in real life [22–28].

In 2013, the Research Institute of Childhood Infections of the FMBA conducted a pharmacoeconomical evaluation of the cost-effectiveness of vaccination of 12-year-old girls with a quadrivalent HPV vaccine in Russia. For the period of survival, taking into account both direct medical and indirect costs, the vaccine is characterized by a cost-effectiveness ratio equal to \$5800/QALY. When the gross domestic product of the Russian Federation was \$6000, vaccination of girls with a quadrivalent HPV vaccine in the Russian Federation is characterized by high cost efficiency and can be recommended for routine use in the Russian population.

According to the instructions, the vaccine is approved for use in women aged 9 to 45 years old and in men aged 9 to 26 years old and can protect against diseases such as cervical cancer, vulvar cancer, vaginal cancer, anal cancer, and anogenital warts. Due to the fact that the human papillomavirus causes serious diseases in men, and screening methods for HPV-associated lesions of the anal canal and penis do not exist today, universal vaccination of adolescents of both sexes with quadrivalent HPV vaccine, the only one approved for use in boys, will achieve significant results in reducing the level of HPV-associated diseases and the rapid spread of HPV infection in the world [29].

The primary target cohort for HPV vaccination is children and adolescents aged 9 to 13 years before sexual debut, as recommended by the World Health Organization. The WHO since 2009 recommends that vaccination against human papillomavirus be included in vaccination calendars of all countries of the world. The WHO and the United Nations Children's Fund consider HPV vaccination as a priority for national immunization programs. Sixty countries have already introduced universal mass vaccination of girls, and three countries (the USA, Australia, Canada) also vaccinate boys against HPV.

At the moment, two HPV vaccines are registered in the Russian Federation: bivalent vaccine (Cervarix, contains antigens to 16 and 18 types of HPV) and quadrivalent vaccine (Gardasil, contains antigens 6, 11, 16, and 18 types of HPV). Bivalent HPV vaccine is used to prevent cancer and precancerous lesions of the cervix, vulva, and vagina. Quadrivalent HPV vaccine can protect not only from cervical, vulvar, and vaginal cancer but also from cancer of the anal canal and anogenital warts in women and men. The primary target cohort for HPV vaccination is adolescents aged 9–13 years old prior to sexual debut, as recommended by the World Health Organization [1].

The monitoring of epidemiological effectiveness is an integral part of HPV vaccination programs. In the long term, HPV vaccination can reduce the incidence and mortality from a number of cancers (cervical cancer, anal cancer, etc.), the prevention of which is a public health priority. Evaluation of the effectiveness of vaccination programs in the medium term is possible to reduce precancerous dysplasia

*Human Papillomavirus*

dermatologists, etc.

along with girls.

prevention of HPV-associated diseases.

men from 9 to 26 years [16].

dose immunization (0–6 months) [17].

never use barrier contraception.

**KhMAO-Ugra: problems and solutions**

debut at the age of 16 and younger. About 14.6% of them had the first sexual contact at the age of 15, 10.4% from 13 to 14 years old, 31.2% from 17 years old, and 16.7% from 18 years old. About 66.7% of them had 1 sexual partner; every third (33.3%) sexually active teenager under the age of 18 had 2 or more sexual partners. For contraception, 57% of respondents use a condom, 29%—combined oral contraceptives. Only 23.5% of adolescents are regularly protected from sexual infections, 27%

**6. Introduction of vaccination of adolescents against HPV infection in** 

The strategic direction of the development of modern health care in the Russian Federation is prevention and early detection of diseases, which contributes to more effective treatment and improvement of demographic indicators of public health. One of the most important preventive measures is vaccination, and today more than 30 diseases that cause serious damage to human health can be prevented with its help. Immunization prevents 2.5 million deaths per year across all age groups. These facts indicate that the issues of prevention and treatment of HPVassociated diseases require a multidisciplinary approach, as they affect such specialists as gynecologists, oncologists, epidemiologists, pediatricians, immunologists,

The World Health Organization has been recommending the inclusion of HPV vaccination in vaccination calendars around the world since 2009 [15]. The WHO and the United Nations Children's Fund (UNICEF) consider HPV vaccination a priority for national immunization programs. More than 60 countries have already introduced universal mass vaccination of girls; in a number of countries (the USA, Australia, Canada, Austria, New Zealand, etc.), boys are vaccinated

To date, the Russian Federation has two documents regulating measures for the

1. "Federal clinical guidelines for the management of patients with anogenital (venereal) warts," Russian society of dermatovenerologists and cosmetologists, (Moscow, 2015). For the prevention of diseases associated with HPV, two vaccines are registered in the Russian Federation: bivalent and quadrivalent. The bivalent HPV vaccine is used to prevent cancer and precancerous diseases of the cervix, vulva, and vagina in women aged 9 to 45 years. Quadrivalent HPV vaccine is used for the prevention of cancer and precancerous changes of the cervix; vulva cancer, vagina cancer, and anal cancer; and anogenital warts in women from 9 to 45 years, as well as anal cancer and anogenital warts in

2. "Federal clinical guidelines for HPV vaccine prevention," Union of Pediatricians of Russia (Moscow, 2016). These clinical guidelines regulate two vaccination regimens. Standard scheme: girls/women from 14 to 45 years old and boys/men from 14 to 26 years old—three doses (0–2–6 months). Alternative scheme: girls and boys from 9 to 13 years old—it is possible to carry out two-

Despite government HPV vaccination programs, female vaccination rates remain below targets in many countries [18, 19]. Models tend to demonstrate that vaccination of boys is most cost-effective if vaccination coverage of the female

**10**

and in the short term (2–4 years from the beginning of the program)—to reduce the prevalence of anogenital warts. Experience with national HPV vaccination programs has shown that maximum coverage can be achieved with school-based vaccination, as recommended by the WHO.

Since 2007, 27 regional programs of primary prevention of HPV-associated diseases have been implemented in Russia, which indicates the importance of protection against HPV infection.

A decrease in the incidence of anogenital warts in the general population has been recorded in the USA, Australia, New Zealand, Belgium, Sweden, and Germany. For example, in Australia, 4 years after the introduction of vaccination, there were the almost complete disappearance of anogenital warts in the population of young women and almost 40% reduction in precancerous lesions of the cervix in young women. The rate of decline was clearly correlated with vaccination coverage. The greatest effect was observed in countries with high coverage (70–85%) [26, 27, 30–33].

The experience of such regions as KhMAO, where the vaccination calendar is constantly being improved and the result is evaluated, can be an example for other regions and become one of the arguments for expanding the national calendar of preventive vaccinations.

The regional HPV vaccination program for adolescent girls in KHMAO was launched in 2009. In the process of introducing the vaccination program, we faced a number of difficulties and objections, which were mainly related to the lack of awareness of pediatricians and parents, and a lot of myths and negative reviews on the Internet and in the media.

We studied the opinions of parents and doctors on the vaccine prevention of HPV-associated diseases. Our goal was to raise awareness among parents and health-care providers and to assess the impact of anti-vaccine advocacy on the population in order to develop a program of further interventions to improve vaccination adherence.

The results of the opinion study of 358 people demonstrated that parents are extremely poorly aware of the problem of HPV infection, the associated risks, and the possibility of preventing diseases caused by HPV with vaccines. Only 21% of respondents know about the HPV problem and 31% have heard about vaccination. Only 49% of parents believe that it is necessary to vaccinate, but only 9% of respondents are ready to vaccinate their children. About 69% of parents doubt the need for vaccination, 22% categorically refused. Also, parents do not have exact knowledge at what age and who needs to be vaccinated, 63% believe that only girls need to be vaccinated, and 35% believe that adolescents of both sexes need to be vaccinated. For explanations about vaccination, 31% will turn to a pediatrician and 15% to a gynecologist; 39% prefer to study reviews on the Internet, and only 12% will receive information on official websites about vaccination.

The results of the opinion study of 254 doctors showed better awareness, and 83% gave a positive answer about the risks of HPV infection and the possibilities of vaccination; the most informed were obstetricians and gynecologists. The majority of doctors (98%) support vaccination, but only 50% are ready to vaccinate their child, 36% of them doubt the effectiveness, and 14% are not sure about the safety of vaccines, which also indicates a lack of knowledge. Obstetricians and gynecologists showed the highest adherence to HPV vaccination (86%). The majority of doctors are ready to receive additional information on vaccination of HPV-associated diseases from official sources: when contacting a polyclinic 59%; a skin and venereal

**13**

*The Importance of the Problem of HPV-Associated Diseases in KhMAO-Ugra: Vaccination…*

we have developed lectures and presentations for medical professionals and parents; created a video about vaccination, which was demonstrated in children's polyclinics; and developed and published booklets, posters, and leaflets for the population. Meetings were held with parents and teachers and medical workers in schools of the city, which were organized with the assistance of the Department of Education of KhMAO-Ugra. The text of the voluntary informed consent for parents has been developed, which includes all necessary information about the risk of HPV-associated diseases, the vaccination program and the effectiveness of immunization, and contraindications and possible postvaccination reactions. The introduction of such voluntary informed consent has increased the commitment of health professionals and parents to vaccination and reduced the frequency of refusals. A "School of Health" is organized, where meetings with parents and schoolchil-

dren are held on a regular basis. The objectives of this school are the following:

• Advocate to motivate vaccination and provide information on the risks of HPV

• Expose myths in order to gain the trust of parents and counter anti-vaccine

• Persuade doubters on the example of highlighting the effectiveness of the regions where vaccination is carried out and familiarization with their own

Monitoring the effectiveness and safety of vaccines is an integral part of any vaccination program, which should be carried out both at the vaccination implementa-

Evaluation of the effectiveness of vaccination in the short term is traditionally carried out according to the incidence of genital warts, as the earliest marker of

HPV vaccination in the long term aims to reduce the incidence and mortality from cervical cancer, anal cancer, and other HPV-associated cancers. However, the introduction of a monitoring system, or register of vaccinated, will allow assessing not only the indicators of early effectiveness but also monitoring adverse events

Indicators such as a decrease in cases of genital warts or genital intraepithelial neoplasia in the vaccinated population will be recorded earlier than results in a decrease in HPV-associated cancers and may indicate the effectiveness of HPV vaccination. For monitoring it is necessary to have a register of vaccinated. The creation of the register of vaccinated will allow assessing the following parameters: indicators of early effectiveness and monitoring adverse events associated and not associated with vaccination. The introduction of the HPV register should be carried out at all levels, from doctors involved in vaccination to health administrators involved in

The information contained in the register will assess the following criteria for

experience of vaccination in previous years in the KhMAO

• Live stream on Instagram account "School of Health"

tologist, 9%; and on official websites about vaccination—47%.

dispensary, 21%; a pediatrician, 11%; an obstetrician-gynecologist, 28%, a derma-

To raise awareness of the population and the medical community in our region,

*DOI: http://dx.doi.org/10.5772/intechopen.90668*

infection and associated diseases

associated or not associated with vaccination.

evaluating strategies to improve the health of citizens.

the implementation of the HPV vaccination program:

agitation

tion stage and in the future.

HPV infection.

### *The Importance of the Problem of HPV-Associated Diseases in KhMAO-Ugra: Vaccination… DOI: http://dx.doi.org/10.5772/intechopen.90668*

dispensary, 21%; a pediatrician, 11%; an obstetrician-gynecologist, 28%, a dermatologist, 9%; and on official websites about vaccination—47%.

To raise awareness of the population and the medical community in our region, we have developed lectures and presentations for medical professionals and parents; created a video about vaccination, which was demonstrated in children's polyclinics; and developed and published booklets, posters, and leaflets for the population. Meetings were held with parents and teachers and medical workers in schools of the city, which were organized with the assistance of the Department of Education of KhMAO-Ugra. The text of the voluntary informed consent for parents has been developed, which includes all necessary information about the risk of HPV-associated diseases, the vaccination program and the effectiveness of immunization, and contraindications and possible postvaccination reactions. The introduction of such voluntary informed consent has increased the commitment of health professionals and parents to vaccination and reduced the frequency of refusals.

A "School of Health" is organized, where meetings with parents and schoolchildren are held on a regular basis. The objectives of this school are the following:


Monitoring the effectiveness and safety of vaccines is an integral part of any vaccination program, which should be carried out both at the vaccination implementation stage and in the future.

Evaluation of the effectiveness of vaccination in the short term is traditionally carried out according to the incidence of genital warts, as the earliest marker of HPV infection.

HPV vaccination in the long term aims to reduce the incidence and mortality from cervical cancer, anal cancer, and other HPV-associated cancers. However, the introduction of a monitoring system, or register of vaccinated, will allow assessing not only the indicators of early effectiveness but also monitoring adverse events associated or not associated with vaccination.

Indicators such as a decrease in cases of genital warts or genital intraepithelial neoplasia in the vaccinated population will be recorded earlier than results in a decrease in HPV-associated cancers and may indicate the effectiveness of HPV vaccination.

For monitoring it is necessary to have a register of vaccinated. The creation of the register of vaccinated will allow assessing the following parameters: indicators of early effectiveness and monitoring adverse events associated and not associated with vaccination. The introduction of the HPV register should be carried out at all levels, from doctors involved in vaccination to health administrators involved in evaluating strategies to improve the health of citizens.

The information contained in the register will assess the following criteria for the implementation of the HPV vaccination program:

*Human Papillomavirus*

30–33].

preventive vaccinations.

the Internet and in the media.

websites about vaccination.

cination adherence.

vaccination, as recommended by the WHO.

protection against HPV infection.

and in the short term (2–4 years from the beginning of the program)—to reduce the prevalence of anogenital warts. Experience with national HPV vaccination programs has shown that maximum coverage can be achieved with school-based

Since 2007, 27 regional programs of primary prevention of HPV-associated diseases have been implemented in Russia, which indicates the importance of

A decrease in the incidence of anogenital warts in the general population has been recorded in the USA, Australia, New Zealand, Belgium, Sweden, and Germany. For example, in Australia, 4 years after the introduction of vaccination, there were the almost complete disappearance of anogenital warts in the population of young women and almost 40% reduction in precancerous lesions of the cervix in young women. The rate of decline was clearly correlated with vaccination coverage. The greatest effect was observed in countries with high coverage (70–85%) [26, 27,

The experience of such regions as KhMAO, where the vaccination calendar is constantly being improved and the result is evaluated, can be an example for other regions and become one of the arguments for expanding the national calendar of

The regional HPV vaccination program for adolescent girls in KHMAO was launched in 2009. In the process of introducing the vaccination program, we faced a number of difficulties and objections, which were mainly related to the lack of awareness of pediatricians and parents, and a lot of myths and negative reviews on

We studied the opinions of parents and doctors on the vaccine prevention of HPV-associated diseases. Our goal was to raise awareness among parents and health-care providers and to assess the impact of anti-vaccine advocacy on the population in order to develop a program of further interventions to improve vac-

The results of the opinion study of 358 people demonstrated that parents are extremely poorly aware of the problem of HPV infection, the associated risks, and the possibility of preventing diseases caused by HPV with vaccines. Only 21% of respondents know about the HPV problem and 31% have heard about vaccination. Only 49% of parents believe that it is necessary to vaccinate, but only 9% of respondents are ready to vaccinate their children. About 69% of parents doubt the need for vaccination, 22% categorically refused. Also, parents do not have exact knowledge at what age and who needs to be vaccinated, 63% believe that only girls need to be vaccinated, and 35% believe that adolescents of both sexes need to be vaccinated. For explanations about vaccination, 31% will turn to a pediatrician and 15% to a gynecologist; 39% prefer to study reviews on the Internet, and only 12% will receive information on official

The results of the opinion study of 254 doctors showed better awareness, and 83% gave a positive answer about the risks of HPV infection and the possibilities of vaccination; the most informed were obstetricians and gynecologists. The majority of doctors (98%) support vaccination, but only 50% are ready to vaccinate their child, 36% of them doubt the effectiveness, and 14% are not sure about the safety of vaccines, which also indicates a lack of knowledge. Obstetricians and gynecologists showed the highest adherence to HPV vaccination (86%). The majority of doctors are ready to receive additional information on vaccination of HPV-associated diseases from official sources: when contacting a polyclinic 59%; a skin and venereal

**12**

