- Email: [email protected]
Prevention of Cervical Cancer in Central and Eastern Europe and Central Asia: A Challenge for the Future
Vaccine 31S (2013) vii–ix
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Foreword
Prevention of Cervical Cancer in Central and Eastern Europe and Central Asia: A Challenge for the Future
Cervical cancer is frequently referred to as a disease of disparity. Europe is not an exception. This is clearly illustrated when comparing cervical cancer incidence and mortality between Western and Eastern Europe. The overall incidence rate of cervical cancer in Europe is 10.6/100,000 [1]. However, the incidence rates for Central and Eastern Europe are more than twice as high as in Western Europe (16.6 and 6.9/100,000 respectively—estimation for the year 2008) [1]. Fifteen countries with the highest incidence of cervical cancer in Europe belong to Central and Eastern Europe [1]. Some of the countries in these two regions have incidence rates over 20/100,000 (Romania, Bulgaria, the Former Yugoslav Republic (FYR) of Macedonia, Serbia and Lithuania), in some regions and some age groups reaching over 40/100,000. Cumulative risk for getting the disease before 75 years of age in Eastern Europe is 4–5 times higher when compared with Western and Nordic countries [1]. Higher incidence rates are also observed in Russian Federation and countries of the former Soviet Union (above 17/100,000 in Armenia and Republic of Moldova) with the highest rates being reported in Central Asia (Kazakhstan 19.1/100,000 and Kyrgyzstan 26.5/100,000) [1]. Additionally, there is an increasing trend of incidence and mortality from cervical cancer in several countries ([2] and Bray F et al., Vaccine, this issue [3]). This Regional Report describes HPV-related cancer epidemiology and cancer control efforts, including screening and vaccination, in Central and Eastern Europe and Central Asia (CEECA). It compares and contrasts prevention efforts in 28 countries from CEECA (Fig. 1). We defined Central and Eastern Europe as the region comprising 16 countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia, and FYR of Macedonia. The second region targeted comprises the Russian Federation, three Western Countries of the former Soviet Union: Belarus, Republic of Moldova and Ukraine, and 8 countries in the Caucasus region and Central Asia: Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. Several factors contribute to the regional differences in cervical cancer rates and their trends. Cancer of the cervix is related to sexual activity. Infection with oncogenic types of human papillomaviruses (HPV) is central to the etiology and considered to be the necessary (although not sufficient) etiological factor. The prevalence of HPV infection differs within Europe, being in close correlation with the incidence of cervical cancer. In Eastern Europe, the prevalence (21.4%) is much higher than in the other parts of Europe (Western Europe 9.0% and Northern Europe 10.0%). This rate is comparable with rates of Sub-Saharan Africa (24.0%), and 0264-410X/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.vaccine.2012.11.105
even higher than in Latin America (16.1%) with the most common high-risk (HR) HPV types in Europe identified not only as 16/18, but 31, 33 and 39 as well [4]. The risk of HPV acquisition in the region is high. A significant percentage of sexually active adolescents [5,6] and a high proportion of young female smokers (age range 13–15 years) in Eastern Europe (ranging from 6.2% in Montenegro to 39.2% in Bulgaria) [7] are important contributing factors to the onset of the disease. An emerging problem is the high prevalence of human immunodeficiency virus (HIV) infection, which, during the last decade in Eastern Europe and Central Asia, has increased by 250 percent [8]. Due to impaired immunity, certain gynecologic conditions, including HPV infection, are more common in HIV-positive women than HIV-negative women. Consequently, the risk for cervical intraepithelial neoplasia (CIN) is five times higher, and CIN is more severe and difficult to treat, in HIV-positive women [9]. When untreated, CIN more often progresses to cervical cancer, which is today one of HIV/AIDS defining diseases, in HIV-positive women [10]. However, differences in sexual behavior and HPV infection cannot entirely account for the geographic variation of the cervical cancer incidence. The most important factor is the availability of screening. Countries of CEECA share common problems in cervical cancer prevention, which is either inadequately organized or not organized at all. Through the past decade, trends in care for women with cervical cancer in these countries have been changing. Efforts are now focusing, first, on prevention and raising awareness of the disease and second, on early detection. European Guidelines for Quality Assurance in Cervical Cancer Screening established the principles of organized population-based screening [11]. However, such a policy has still not been adopted in all countries of Central and Eastern Europe. Only Slovenia has an effective nationally organized screening program with 82.1% coverage (2004–2008) and a consequent decrease in cervical cancer incidence of 40% for the period of 2003–2009. Hungary implemented organized screening in 2004, but is still struggling with low coverage of the target population in organized settings and higher attendance outside the program [12]. At least partially functioning organized cervical cancer screening programs have been established in Baltic countries (Estonia, Lithuania and Latvia), Czech Republic, and Poland. Common to all these countries are low coverage (less than 30%) of the target population within the program, insufficient screening infrastructure and low financial resources [12]. In other countries of CEECA, cervical cancer prevention still relies on opportunistic screening. This type of screening has been
viii
Foreword / Vaccine 31S (2013) vii–ix
Fig. 1. Countries included in the regional report “Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region”. List of included countries: Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, Montenegro, Poland, Republic of Moldova, Romania, Russian Federation, Serbia, Slovakia, Slovenia, Tajikistan, the Former Yugoslav Republic of Macedonia, Turkmenistan, Ukraine, and Uzbekistan.
characterized by high coverage in younger and very low coverage in middle-aged and older women (Poljak M et al. and Rogovskaya SI et al., Vaccine, this issue [13,14]). Screening of selected groups of women employed in large companies is performed annually by many regional hospitals. This approach, however, has had little effect on morbidity and mortality. Cervical cancer is recognized as the first identified virallyinduced cancer that affects women alone. Thus, primary prevention of cervical cancer is possible by introducing vaccination against HPV infection. In CEECA, at least one of the current HPV prophylactic vaccines is registered in all countries except Montenegro, Tajikistan and Turkmenistan, but most of the countries do not have national recommendations nor is the HPV vaccination included in national immunization programs. Only Bulgaria, Czech Republic, FYR Macedonia, Latvia, Romania and Slovenia have integrated HPV vaccination in their national immunization programs and currently provide routine vaccination free of charge to the primary target population (female/12 years of age), with coverage over 55% (Poljak M et al., Vaccine, this issue [13]). In Ukraine, HPV vaccination is now in the process of being implemented in the school-based immunization program. In Russian Federation, HPV vaccination has been incorporated in some regional immunization programs, resulting over 20,000 girls being vaccinated. There are pilot/donation programs in Republic of Moldova, Georgia, Uzbekistan and no national or pilot HPV immunization programs in Armenia and Azerbaijan at present (Rogovskaya SI et al., Vaccine, this issue [14]). The main problems regarding initiation of the HPV vaccination in CEECA are a lack of knowledge about HPV, negative public perception of the vaccine as a potential encouragement for adolescents to initiate sexual activity, and high cost of the vaccine. The most promising approach for the prevention of cervical cancer in the future seems to be a combination of HPV vaccination and screening [15]. Unfortunately, the high-incidence countries of CEECA have neither effective screening nor HPV vaccination programs. In this region, nationwide vaccination programs are not expected in the near future. For this reason, when HPV vaccines become available to the neediest populations of CEECA at affordable costs, efforts should be focused on secondary prevention strategies. In the past, screening programs based on cytology have been successful in reducing the incidence and mortality from cervical cancer [16]. However, an organized screening program based on the Pap test is a very complex and difficult public health service to
provide. Countries of CEECA have introduced cytology into clinical practice in early 60s and have since used it on an opportunistic basis. Infrastructure and resources in health care in these countries are not sufficient to build an effective program based on cytology. Even if the main barriers for organization of effective screening are overcome, the relatively low sensitivity of a single Pap test and a high rate of false negative results remain important shortcomings of cytology-based screening. As a result, cervical cancer still occurs in women who regularly undergo screening, even in countries with extensive screening programs [17]. With HPV infection now established as the causative agent in most cases of cervical cancer, it can be expected that screening for cervical cancer will be substantially changed in the near future. New, more sensitive techniques that would screen for HPV infection within a targeted population, rather than mass screening by cytology, would be desirable. Today, testing for HPV DNA is one of the most intensively studied alternatives to cervical cytology screening. Its role has already been established for the triage of Pap smears with atypical squamous cells of undetermined significance (ASCUS) and follow-up after treatment [18]. Although the role of HPV testing in primary screening has still not been clearly defined, many international, randomized controlled trials have yielded promising results [19–21]. HPV testing is more sensitive than cytology (especially in women aged ≥30 years), it may lengthen the interval between screenings and has better cost-effectiveness. The risk of developing high-grade lesions is reduced compared with cytology and the absolute rate of severe lesions after a negative HPV test is negligible [22]. A recently published cost-effectiveness analysis based on a Dutch microsimulation model concludes that “most European countries should consider switching from primary cytology to HPV screening for cervical cancer. HPV screening must, however, only be implemented in situations where screening is well controlled” [23]. Unfortunately, the high cost of internationally validated HPV tests prevents them from being incorporated into the screening practice in many low- and middle-income countries in CEECA, as presented by Poljak M et al., Vaccine, this issue [24]. The potential implementation of HPV-based screening would also require strict control of methodology, since most of HPV tests currently used in CEECA are not validated. At present in CEECA, decisions on the target age group and frequency of screening are usually made at the national level, on the basis of local incidence and prevalence of cancer, HPV prevalence, and availability of resources and
Foreword / Vaccine 31S (2013) vii–ix
infrastructure. For the implementation of HPV vaccination, different approaches have been chosen, based on the organization of each country’s health care system. Implementation of effective screening, along with accessible and effective treatment of precancerous lesions and immunization with prophylactic HPV vaccine, will be future challenges. But the main challenge will be to raise the awareness of cervical cancer and its prevention among general public, health care professionals and public health decision-makers in CEECA. The whole society should be mobilized to prepare the political will, the economic resources and the administrative infrastructure to control cervical cancer, because cervical cancer prevention is not just a problem of the medical profession. The incidence of cervical cancer clearly reflects how well society as a whole takes care of its women. This article forms part of a regional report entitled “Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region” Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in the field are presented in a separate monograph entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012. Acknowledgements The author expresses special thanks to Mario Poljak and Svetlana I. Rogovskaya for sharing the results of their own research of screening and HPV vaccination in Central/Eastern Europe and Central Asia. Disclosed potential conflicts of interest The author has disclosed no potential conflicts of interest. References [1] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available at: http://globocan.iarc.fr. (last accessed March 2013). [2] Arbyn M, Antoine J, Magi M, Smailyte G, Stengrevics A, Suteu O, et al. Trends in cervical cancer incidence and mortality in the Baltic countries, Bulgaria and Romania. Int J Cancer 2011;128:1899–907. [3] Bray F, Lortet-Tieulent J, Znaor A, Brotons M, Poljak M, Arbyn M. Patterns and Trends in Human Papillomavirus-Related Diseases in Central and Eastern Europe and Central Asia. Vaccine 2013;31S:H32–45. [4] Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch XF, de Sanjose S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 2010;202(12):1789–99. [5] Crochard A, Luyts D, di Nicola S, Gonc¸alves MA. Self-reported sexual debut and behavior in young adults aged 18-24 years in seven European countries: implications for HPV vaccination programs. Gynecol Oncol 2009;115(3 Suppl):S7–14. [6] Rogovskaya SI, Mikheyeva IV, Shipulina OU, Minkina GN, Podzolkova NM, Radzinsky VE. Prevalence of human papillomavirus infection in Russia. Epidemiology Vaccinoprophilaxis 2012;62:25–33. [7] World Health Organization. Report on the global tobacco Epidemic, 2008. The MPOWER package. Available at: www.who.int/tobacco/mpower/ mpower report full 2008.pdf.(last accessed March 2013). [8] UNAIDS Global Report. Facts sheet Eastern Europe and Central Asia. Available at: http://www.unaids.org/documents/20101123 FS eeca em en.pdf.(last accessed March 2013).
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[9] Denny L, Boa R, Williamson A-L, Allan B, Hardie D, Stan R, et al. Human papillomavirus infection and cervical disease in human immunodeficiency virus-1-infected women. Obstet Gynecol 2008;111:1380–7. [10] Denny LA, Franceschi S, de Sanjosé S, Heard I, Moscicki AB, Palefsky J. Human papillomavirus, human immunodeficiency virus and immunosuppression. Vaccine 2012;30(Suppl 5):F168–74. [11] Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, et al. European guidelines for quality assurance in cervical cancer screening (2nd ed.). Brussels, Luxembourg: European Community, Office for Official Publications of the European Communities;2008. [12] Nicula F, Anttila A, Neamtiu L, Zˇ akelj MP, Tachezy R, Chil A, et al. Challenges in starting organised screening programmes for cervical cancer in the new member states of the European Union. Eur J Cancer 2009;45: 2679–84. [13] Poljak M, Seme K, Maver PJ, Kocjan BJ, Cuschieri KS, Rogovskaya SI, et al. Human Papillomavirus Prevalence and Type-Distribution. Cervical Cancer Screening Practices and Current Status of Vaccination Implementation in Central and Eastern Europe. Vaccine 2013;31S:H59–70. [14] Rogovskaya SI, Shabalova IP, Mikheeva IV, Minkina GN, Podzolkova NM, Shipulina OY, et al. Human Papillomavirus Prevalence and Type-Distribution, Cervical Cancer Screening Practices and Current Status of Vaccination Implementation in the Russian Federation, the Western Countries of the former Soviet Union, Caucasus region and Central Asia. Vaccine 2013;31S:H46–58. [15] Lynge E, Rebolj M. Primary HPV screening for cervical cancer prevention: results from European trials. Nat Rev Clin Oncol 2009;6:699–706. [16] International Agency for Research on Cancer. Cervix cancer screening. IARC handbooks of cancer prevention, vol. 10. Lyon: IARC Press; 2005. p. 1–302. [17] Spence AR, Goggin P, Franco EL. Process of care failures in invasive cervical cancers: A systematic review and meta-analysis. Prev Med 2007;45:93–106. [18] Arbyn M, Ronco G, Meijer CJ, Naucler P. Trials comparing cytology with human papillomavirus screening. Lancet Oncol 2009;10:935–6. [19] Rijkaart DC, Berkhof J, van Kemenade FJ, Coupe VM, Rozendaal L, Heideman DA, et al. HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications. Br J Cancer 2012;106(5):975-81. [20] Kitchener HC, Almonte M, Thomson C, Wheeler P, Sargent A, Stoykova B, et al. HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial. Lancet Oncol 2009;10:672–82. [21] Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, Del Mistro A, et al. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol 2010 Mar;11(3):249-57. [22] Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, Munk C, et al. Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study. BMJ 2008;377: a1754. [23] de Kok IM, van Rosmalen J, Dillner J, Arbyn M, Sasieni P, Iftner T, et al. Primary screening for human papillomavirus compared with cytology screening for cervical cancer in European settings: cost effectiveness analysis based on a Dutch microsimulation model. BMJ 2012;344:e670. [24] Poljak M, Rogovskaya SI, Kesic V, Bray F, Berkhof J, Seme K, et al. Recommendations for Cervical Cancer Prevention in Central and Eastern Europe and Central Asia. Vaccine 2013;31S:H80–2.
Vesna Kesic Faculty of Medicine, University of Belgrade, Department of Obstetrics and Gynecology, Clinical Center of Serbia, Belgrade, Serbia Tel.: +381 11 366 36 44; +381 63 89 88 335, fax: +381 11 361 56 03. E-mail address: [email protected] 14 February 2012
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Foreword
Prevention of Cervical Cancer in Central and Eastern Europe and Central Asia: A Challenge for the Future
Cervical cancer is frequently referred to as a disease of disparity. Europe is not an exception. This is clearly illustrated when comparing cervical cancer incidence and mortality between Western and Eastern Europe. The overall incidence rate of cervical cancer in Europe is 10.6/100,000 [1]. However, the incidence rates for Central and Eastern Europe are more than twice as high as in Western Europe (16.6 and 6.9/100,000 respectively—estimation for the year 2008) [1]. Fifteen countries with the highest incidence of cervical cancer in Europe belong to Central and Eastern Europe [1]. Some of the countries in these two regions have incidence rates over 20/100,000 (Romania, Bulgaria, the Former Yugoslav Republic (FYR) of Macedonia, Serbia and Lithuania), in some regions and some age groups reaching over 40/100,000. Cumulative risk for getting the disease before 75 years of age in Eastern Europe is 4–5 times higher when compared with Western and Nordic countries [1]. Higher incidence rates are also observed in Russian Federation and countries of the former Soviet Union (above 17/100,000 in Armenia and Republic of Moldova) with the highest rates being reported in Central Asia (Kazakhstan 19.1/100,000 and Kyrgyzstan 26.5/100,000) [1]. Additionally, there is an increasing trend of incidence and mortality from cervical cancer in several countries ([2] and Bray F et al., Vaccine, this issue [3]). This Regional Report describes HPV-related cancer epidemiology and cancer control efforts, including screening and vaccination, in Central and Eastern Europe and Central Asia (CEECA). It compares and contrasts prevention efforts in 28 countries from CEECA (Fig. 1). We defined Central and Eastern Europe as the region comprising 16 countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia, and FYR of Macedonia. The second region targeted comprises the Russian Federation, three Western Countries of the former Soviet Union: Belarus, Republic of Moldova and Ukraine, and 8 countries in the Caucasus region and Central Asia: Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. Several factors contribute to the regional differences in cervical cancer rates and their trends. Cancer of the cervix is related to sexual activity. Infection with oncogenic types of human papillomaviruses (HPV) is central to the etiology and considered to be the necessary (although not sufficient) etiological factor. The prevalence of HPV infection differs within Europe, being in close correlation with the incidence of cervical cancer. In Eastern Europe, the prevalence (21.4%) is much higher than in the other parts of Europe (Western Europe 9.0% and Northern Europe 10.0%). This rate is comparable with rates of Sub-Saharan Africa (24.0%), and 0264-410X/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.vaccine.2012.11.105
even higher than in Latin America (16.1%) with the most common high-risk (HR) HPV types in Europe identified not only as 16/18, but 31, 33 and 39 as well [4]. The risk of HPV acquisition in the region is high. A significant percentage of sexually active adolescents [5,6] and a high proportion of young female smokers (age range 13–15 years) in Eastern Europe (ranging from 6.2% in Montenegro to 39.2% in Bulgaria) [7] are important contributing factors to the onset of the disease. An emerging problem is the high prevalence of human immunodeficiency virus (HIV) infection, which, during the last decade in Eastern Europe and Central Asia, has increased by 250 percent [8]. Due to impaired immunity, certain gynecologic conditions, including HPV infection, are more common in HIV-positive women than HIV-negative women. Consequently, the risk for cervical intraepithelial neoplasia (CIN) is five times higher, and CIN is more severe and difficult to treat, in HIV-positive women [9]. When untreated, CIN more often progresses to cervical cancer, which is today one of HIV/AIDS defining diseases, in HIV-positive women [10]. However, differences in sexual behavior and HPV infection cannot entirely account for the geographic variation of the cervical cancer incidence. The most important factor is the availability of screening. Countries of CEECA share common problems in cervical cancer prevention, which is either inadequately organized or not organized at all. Through the past decade, trends in care for women with cervical cancer in these countries have been changing. Efforts are now focusing, first, on prevention and raising awareness of the disease and second, on early detection. European Guidelines for Quality Assurance in Cervical Cancer Screening established the principles of organized population-based screening [11]. However, such a policy has still not been adopted in all countries of Central and Eastern Europe. Only Slovenia has an effective nationally organized screening program with 82.1% coverage (2004–2008) and a consequent decrease in cervical cancer incidence of 40% for the period of 2003–2009. Hungary implemented organized screening in 2004, but is still struggling with low coverage of the target population in organized settings and higher attendance outside the program [12]. At least partially functioning organized cervical cancer screening programs have been established in Baltic countries (Estonia, Lithuania and Latvia), Czech Republic, and Poland. Common to all these countries are low coverage (less than 30%) of the target population within the program, insufficient screening infrastructure and low financial resources [12]. In other countries of CEECA, cervical cancer prevention still relies on opportunistic screening. This type of screening has been
viii
Foreword / Vaccine 31S (2013) vii–ix
Fig. 1. Countries included in the regional report “Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region”. List of included countries: Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, Montenegro, Poland, Republic of Moldova, Romania, Russian Federation, Serbia, Slovakia, Slovenia, Tajikistan, the Former Yugoslav Republic of Macedonia, Turkmenistan, Ukraine, and Uzbekistan.
characterized by high coverage in younger and very low coverage in middle-aged and older women (Poljak M et al. and Rogovskaya SI et al., Vaccine, this issue [13,14]). Screening of selected groups of women employed in large companies is performed annually by many regional hospitals. This approach, however, has had little effect on morbidity and mortality. Cervical cancer is recognized as the first identified virallyinduced cancer that affects women alone. Thus, primary prevention of cervical cancer is possible by introducing vaccination against HPV infection. In CEECA, at least one of the current HPV prophylactic vaccines is registered in all countries except Montenegro, Tajikistan and Turkmenistan, but most of the countries do not have national recommendations nor is the HPV vaccination included in national immunization programs. Only Bulgaria, Czech Republic, FYR Macedonia, Latvia, Romania and Slovenia have integrated HPV vaccination in their national immunization programs and currently provide routine vaccination free of charge to the primary target population (female/12 years of age), with coverage over 55% (Poljak M et al., Vaccine, this issue [13]). In Ukraine, HPV vaccination is now in the process of being implemented in the school-based immunization program. In Russian Federation, HPV vaccination has been incorporated in some regional immunization programs, resulting over 20,000 girls being vaccinated. There are pilot/donation programs in Republic of Moldova, Georgia, Uzbekistan and no national or pilot HPV immunization programs in Armenia and Azerbaijan at present (Rogovskaya SI et al., Vaccine, this issue [14]). The main problems regarding initiation of the HPV vaccination in CEECA are a lack of knowledge about HPV, negative public perception of the vaccine as a potential encouragement for adolescents to initiate sexual activity, and high cost of the vaccine. The most promising approach for the prevention of cervical cancer in the future seems to be a combination of HPV vaccination and screening [15]. Unfortunately, the high-incidence countries of CEECA have neither effective screening nor HPV vaccination programs. In this region, nationwide vaccination programs are not expected in the near future. For this reason, when HPV vaccines become available to the neediest populations of CEECA at affordable costs, efforts should be focused on secondary prevention strategies. In the past, screening programs based on cytology have been successful in reducing the incidence and mortality from cervical cancer [16]. However, an organized screening program based on the Pap test is a very complex and difficult public health service to
provide. Countries of CEECA have introduced cytology into clinical practice in early 60s and have since used it on an opportunistic basis. Infrastructure and resources in health care in these countries are not sufficient to build an effective program based on cytology. Even if the main barriers for organization of effective screening are overcome, the relatively low sensitivity of a single Pap test and a high rate of false negative results remain important shortcomings of cytology-based screening. As a result, cervical cancer still occurs in women who regularly undergo screening, even in countries with extensive screening programs [17]. With HPV infection now established as the causative agent in most cases of cervical cancer, it can be expected that screening for cervical cancer will be substantially changed in the near future. New, more sensitive techniques that would screen for HPV infection within a targeted population, rather than mass screening by cytology, would be desirable. Today, testing for HPV DNA is one of the most intensively studied alternatives to cervical cytology screening. Its role has already been established for the triage of Pap smears with atypical squamous cells of undetermined significance (ASCUS) and follow-up after treatment [18]. Although the role of HPV testing in primary screening has still not been clearly defined, many international, randomized controlled trials have yielded promising results [19–21]. HPV testing is more sensitive than cytology (especially in women aged ≥30 years), it may lengthen the interval between screenings and has better cost-effectiveness. The risk of developing high-grade lesions is reduced compared with cytology and the absolute rate of severe lesions after a negative HPV test is negligible [22]. A recently published cost-effectiveness analysis based on a Dutch microsimulation model concludes that “most European countries should consider switching from primary cytology to HPV screening for cervical cancer. HPV screening must, however, only be implemented in situations where screening is well controlled” [23]. Unfortunately, the high cost of internationally validated HPV tests prevents them from being incorporated into the screening practice in many low- and middle-income countries in CEECA, as presented by Poljak M et al., Vaccine, this issue [24]. The potential implementation of HPV-based screening would also require strict control of methodology, since most of HPV tests currently used in CEECA are not validated. At present in CEECA, decisions on the target age group and frequency of screening are usually made at the national level, on the basis of local incidence and prevalence of cancer, HPV prevalence, and availability of resources and
Foreword / Vaccine 31S (2013) vii–ix
infrastructure. For the implementation of HPV vaccination, different approaches have been chosen, based on the organization of each country’s health care system. Implementation of effective screening, along with accessible and effective treatment of precancerous lesions and immunization with prophylactic HPV vaccine, will be future challenges. But the main challenge will be to raise the awareness of cervical cancer and its prevention among general public, health care professionals and public health decision-makers in CEECA. The whole society should be mobilized to prepare the political will, the economic resources and the administrative infrastructure to control cervical cancer, because cervical cancer prevention is not just a problem of the medical profession. The incidence of cervical cancer clearly reflects how well society as a whole takes care of its women. This article forms part of a regional report entitled “Comprehensive Control of HPV Infections and Related Diseases in the Central and Eastern Europe and Central Asia Region” Vaccine Volume 31, Supplement 7, 2013. Updates of the progress in the field are presented in a separate monograph entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012. Acknowledgements The author expresses special thanks to Mario Poljak and Svetlana I. Rogovskaya for sharing the results of their own research of screening and HPV vaccination in Central/Eastern Europe and Central Asia. Disclosed potential conflicts of interest The author has disclosed no potential conflicts of interest. References [1] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010. Available at: http://globocan.iarc.fr. (last accessed March 2013). [2] Arbyn M, Antoine J, Magi M, Smailyte G, Stengrevics A, Suteu O, et al. Trends in cervical cancer incidence and mortality in the Baltic countries, Bulgaria and Romania. Int J Cancer 2011;128:1899–907. [3] Bray F, Lortet-Tieulent J, Znaor A, Brotons M, Poljak M, Arbyn M. Patterns and Trends in Human Papillomavirus-Related Diseases in Central and Eastern Europe and Central Asia. Vaccine 2013;31S:H32–45. [4] Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch XF, de Sanjose S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 2010;202(12):1789–99. [5] Crochard A, Luyts D, di Nicola S, Gonc¸alves MA. Self-reported sexual debut and behavior in young adults aged 18-24 years in seven European countries: implications for HPV vaccination programs. Gynecol Oncol 2009;115(3 Suppl):S7–14. [6] Rogovskaya SI, Mikheyeva IV, Shipulina OU, Minkina GN, Podzolkova NM, Radzinsky VE. Prevalence of human papillomavirus infection in Russia. Epidemiology Vaccinoprophilaxis 2012;62:25–33. [7] World Health Organization. Report on the global tobacco Epidemic, 2008. The MPOWER package. Available at: www.who.int/tobacco/mpower/ mpower report full 2008.pdf.(last accessed March 2013). [8] UNAIDS Global Report. Facts sheet Eastern Europe and Central Asia. Available at: http://www.unaids.org/documents/20101123 FS eeca em en.pdf.(last accessed March 2013).
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Vesna Kesic Faculty of Medicine, University of Belgrade, Department of Obstetrics and Gynecology, Clinical Center of Serbia, Belgrade, Serbia Tel.: +381 11 366 36 44; +381 63 89 88 335, fax: +381 11 361 56 03. E-mail address: [email protected] 14 February 2012