Cervical Cancer Burden and Prevention Activities in Europe

Cervical cancer is generally defined as a disease of disparity. This is due to marked differences in the incidence and mortality of cervical cancer between the developed and developing world. As a continent, Europe is not an exception. Cervical cancer in Europe is a true example of inequality—an almost straight line can be drawn for the incidence and mortality between Western and Eastern Europe. Usually, Western Europe is considered as a developed world. The countries of Eastern Europe (including Central European countries) as well as the former Soviet Union countries (including Central Asian countries) are referred to as “countries in transition” (Table 1). However, most of them in the international reports are still regarded as “developing countries.” This article describes cervical cancer epidemiology and cancer control efforts including screening and vaccination in Europe. It compares and contrasts prevention efforts in different parts of Europe.

A total of 54,517 new cases of cervical cancer cases and 24,874 deaths were reported in Europe in 2008 (1). Both incidence and mortality rates, age-standardized to the world standard million population are generally higher in Central and Eastern Europe and former Soviet Union countries than in Western Europe.

The overall incidence rate of cervical cancer in Europe is 10.6 per 100,000. The analysis between different parts of Europe shows more than doubled incidence rates in Central/Eastern Europe (14.9/100,000) when compared with Western Europe (6.9/100,000). Average incidence rates in Northern and Southern Europe are similar (8.4/100,000 and 8.1/100,000, respectively).

The highest incidence rates are currently reported in Romania and FYR Macedonia (23.9/100,000 and 22.0/100,000, respectively; Fig. 1). The lowest rates are observed in Malta (2.1/100,000), Switzerland (4.0/100,000), Greece (4.1/100 000), and Finland (4.5/100,000). Cumulative risk for getting the disease in Eastern Europe is 4 to 5 times higher than in Western and Nordic countries (Table 2).

In 1993, European Union (EU) was formally established as an economic and political confederation of member states. Today, EU consists of 27 sovereign Members States and includes most of Central and Eastern European countries.

Within EU, the incidence rates of cervical cancer are generally lower than in the rest of Europe (2). However, the differences between old and new EU members are substantial. The burden of cervical cancer is particularly high in the new member states, which geographically and historically belong to eastern part of Europe (Fig. 2).

In most Eastern European countries, the incidence rates are more than 20 per 100,000, in some regions and some age groups are reaching 40 per 100,000 (Romania, Serbia). Incidence rates above 13 per 100,000 are observed in Russia and countries of the former Soviet Union, with Armenia (17.3/100,000) and Moldova (17/100,000) ranking the first in the region (1, 3).

Comparing the latest Globocan report (2008) with the previous one (2002), the incidence of cervical cancer in Europe has not changed (11.05 to 10.6 per 100,000 women in 2002 and 2008, respectively), whereas mortality decreased for 10% (from 5.0 to 4.5 per 100,000 women; refs. 1, 4). Meanwhile, the age-adjusted incidence rate of cervical cancer in United States decreased from 7.7 per 100,000 women in 2002 to 5.7 per 100,000 women in 2008 (4). According to SEER Cancer Statistics Review, since 1975, the age-adjusted incidence rate of cervical cancer in United States has decreased from 14.8 per 100,000 women to 6.6 in 2008 (5).

Cancer incidence statistics from early periods in certain registries are inflated by shortcomings in the registration, which is why mortality trends may better reflect changes in burden from cervical cancer, over the time.

In EU, corrected age-standardized cervical cancer mortality rates have decreased significantly over the past decades in the old member states and continue to decrease, whereas in Eastern Europe and in the Baltic states, they are decreasing at a lower intensity (Czech Republic, Poland), remaining constant at a high rate (Estonia, Slovakia) or even increasing (Bulgaria, Latvia, Lithuania, Romania; ref. 6).

Generally, in all Eastern European and former Soviet Union countries, the incidence has been increasing during last decade (7). In Russia, the number of patients with a newly diagnosed cancer increased by 4.6% from 2000 to 2005 (8). In Belarus, cervical cancer incidence increased from 14.3 per 100,000 in 1997 to 17.2 per 100,000 in 2006 (9).

The trends in incidence of cervical cancer largely reflect coverage and quality of screening, as well as the exposure to risk factors.

The prevalence of human papillomavirus (HPV) infection differs within Europe, being in close correlation with the incidence of cervical cancer. In most EU countries, the age-standardized prevalence of high-risk HPV types in women with normal cytology, aged 30 to 64 years, ranges between 2% and 10%, being the lowest in Spain (1.2%) and Netherlands (4.6%). In the other countries, such as France and Belgium, the prevalence is more than 12% showing sustained elevated levels in women aged >35 years with the most prevalent HPV types being 16 and 18 (10). A recent study conducted in Moscow, Russia, has shown the overall HPV prevalence in screening population of 13.4% (<25 years, 42%; 25–30 years, 28.8%; >30 years, 11.1%). The most frequent HPV types were HPV 16 (32.5%), HPV 31 (17.0%), HPV 52 (13.1%), and HPV 56 (12.8%; ref. 11). In general, prevalence rate reported in Eastern Europe (21.4%) is comparable with rates of sub-Saharan Africa (24%) and even higher than those in Latin America (16%) with the most common high-risk HPV types being not only HPV16 and HPV 18 but also HPV 31, HPV 33, and HPV 39 (12).

Early onset of sexual life (in Russia, 13.5% girls start sexual relations before the age of 15 and by the age of 17, 47.8% adolescents are sexually active; refs. 11, 13) and high proportion of young female smokers (age, 13–15 years) in Eastern Europe (ranging from 8.2% in FYR Macedonia to 39.2% in Bulgaria; ref. 14) are important contributing factors to the onset of the disease. 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.

Overviews on incidence and mortality trends for cervical cancer have indicated close correlation to the intensity of organized screening. In the populations where the screening quality and coverage have been high, these efforts have markedly reduced the incidence of invasive cervical cancer (15).

The EU currently recommends to start screening between the age of 20 to 30 years and to extend it to 60 to 65 years, with a 3- or 5-year screening interval. Cancer screening should be offered only through population-based, organized screening programs, with quality assurance at all levels (16). Although a population-based policy for screening has been adopted by several EU member states, at the moment, key elements of the comprehensive recommendations on program implementation are not fulfilled by many European countries (Table 3; ref. 17).

Substantial reductions in incidence and mortality, observed in United Kingdom, Finland and Iceland, correlated with the level of implementation of organized screening (18). The best example is Finland where organized screening was already established in the 1960s and where age-standardized corrected mortality rates have dropped by 80% over the last 45 years (19). It was estimated from an age period cohort model that without screening, standardized cervical cancer mortality, in 2003–2007 in Finland, would have been 6 times higher (20).

Opportunistic screening also resulted in a reduction of cervical cancer incidence and mortality in other countries such as France or Austria (21).

Among the new member states, only Slovenia has the nationally organized screening program from 2003. The coverage reached even 82.1% in the first 5-year period after the implementation. Consequently, the incidence of cervical cancer in Slovenia decreased for 40% in the period from 2003 to 2009. Although Hungary also implemented organized screening in 2004, the country is still struggling with low coverage of target population in organized settings and more than 60% attendance outside the program (17).

Other new member countries (Czech Republic, Poland, Estonia, Lithuania, and Latvia) have already established at least partially functioning organized screening programs but are dealing with several important obstacles, such as low coverage (less than 20%) of target population within the program (22). Although cervical cancer is recognized as the most urgent public health care problem in Romania, the screening infrastructure in the country is insufficient and financial resources are less than 10% of the necessary amount (17).

Cervical cancer prevention in non-EU Eastern European countries, Russia, and other countries of the former Soviet Union relies on opportunistic screening. This type of screening has been characterized by high coverage in younger and very low coverage in middle-aged and older women. Screening of selected groups of women employed in large companies is conducted annually by many regional hospitals. This approach, however, has had small effect on morbidity and mortality.

The opportunistic screening is based on the decision of individual woman to visit gynecologist for any reason. The cost of annual smear is covered by health care insurance in most of Eastern European countries. This means that for any reason, women comes to gynecologist, she should be offered Pap smear. Such a system relies on awareness of women about cervical cancer, which is generally low (23). In countries where women are well informed about the importance of screening, the coverage in opportunistic screening is reaching 70% (Belgium, France, Slovenia), but in countries where the knowledge is relatively poor, not more than 20% of women visit gynecologist regularly (Table 3).

The implementation of organized screening has started in all countries of former Yugoslavia. Proposed age to start screening varies from 20 to 30 years, with the age to stop screening being between 55 and 69 years. A 3-year screening interval is implemented in all countries and women are screened mainly by conventional cytology, with small proportion of women screened by liquid-based cytology in Croatia and FYR Macedonia. Unfortunately, there are no published data on cervical cancer screening practice in Albania.

After cytology was introduced in the Soviet Union, in Leningrad Region, in 1964, the prevalence of invasive cervical cancer decreased from 31.61 to 8.13 per 100,000 women, during the following decade (24). Later, such system of opportunistic screening beginning from the age of 18 years with no upper age limit has been expanded to the whole country, and to a certain extent, is still maintained in the Russian Federation, Ukraine, Republic of Belarus, Moldova, and to much lesser degree in Armenia, Azerbaijan, and Georgia. However, these opportunistic screening programs that are currently in place are not sufficient.

The national strategies on cervical cancer prevention are under development in all these countries (25). Screening procedures, follow-up, and treatment services are provided free of charge to all eligible women and are covered through mandatory health care insurance. Although prevention programs are not yet available in many locations (Armenia, Azerbaijan), some well-organized pilot programs of organized screening were initiated (such as in Tbilisi, Georgia) with the plan for expansion to the whole country.

In conclusion, there are large variations in cervical cancer screening policies, coverage, and quality of screening across Europe. Being the member of EU is helpful but has no direct consequence on the efficacy of the cervical screening. The European cervical cancer screening guidelines (16) were prepared for all European countries (not only for EU members), but many of them failed in implementation (including Germany, currently the economically leading European country). On contrast, some of non-EU countries (Norway, Switzerland, Iceland) achieved good results in screening for cervical cancer.

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, availability of resources and infrastructure (Table 3). However, continued unavailability of population-based, systematically organized screening programs to women who may benefit from screening remains to be the major obstacle in control of cervical cancer in Europe.

The implementation of organized programs to vaccinate adolescent girls against HPV infection is an important strategy for the prevention of cervical cancer. As summarized in Table 4, almost all European countries have approved both HPV vaccines, have national recommendations, and offer vaccines covered by health care insurance for target group of females and given on demand. Most of EU member countries have decided to introduce HPV vaccination into their national immunization schedule or have started the decision-making process with a recommendation favoring introduction (26). Yet, only a few of them have actually implemented HPV vaccination in their national immunization program and currently provide routine vaccination free of charge to the primary target population.

The vaccination was successfully implemented through compulsory school-based programs, with the excellent coverage (>90%) in United Kingdom and Norway (27).

In Slovenia, HPV vaccination is conducted in school health care service network, reaching the coverage for 3 doses of 55.0% for the school year 2010–2011. In Latvia, HPV vaccination is conducted in local public health care centers and school health care services. In Romania, a national school-based program to vaccinate females aged 11 was first launched in 2008 but was stopped at the end of year 2011 due to negative public reaction, lack of proper communication, and resulting in low coverage in target population which did not reach 5%. Most of other countries offer free vaccination to the primary target population, with different coverage rates (Portugal, 89%; Netherlands, 50%; Greece, 9%; Table 4). In contrast to other European countries, in Finland where cervical cancer is effectively controlled by the national screening program, the authorities decided to run a long-term prospective study to evaluate the bivalent HPV vaccine in a randomized community trial, before any decision on national program is made (28).

In Central and East Europe, both HPV prophylactic vaccines are registered in all countries except Montenegro. However, only FYR Macedonia actually integrated the HPV vaccination in its national immunization program and currently provides routine vaccination free of charge to primary target population. The coverage for 3 doses in FYR Macedonia increased from 36.5% for the school year 2009–2010 to 67% for the school year 2009–2010.

In Russia, HPV vaccination has been implemented in some regional immunization programs and more than 20,000 girls have been vaccinated. However, is not included in national immunization program. The initiation of the HPV vaccination program in Moscow region showed a lack of knowledge about HPV, among adolescents, parents, and teachers. Immunization was often negatively perceived by the society as a potential encouragement for adolescents to initiate sexual activity. Only in Ukraine, HPV vaccination is now in the process of implementation in the immunization calendar. There are regional or pilot vaccination programs in Moldova, Georgia, Belarus and no national data about HPV immunization programs in Armenia and Azerbaijan.

The key reasons for lack of implementation of HPV vaccination on national level in majority of European countries are high vaccine cost, financial constraints, and negative public perception. In summary, the HPV vaccines are being delivered to the low-incidence populations that already have extensive cervical cancer screening programs, whereas the high-incidence countries have not implemented vaccination programs.

It has been almost 10 years since the Council of EU started to focus the attention to problem of breast, cervical, and colorectal cancer screening (29). Despite of well-defined screening policy, by 2007, only 8 countries had organized screening.

European Guidelines for Quality Assurance in Cervical Cancer Screening have been initiated in the Europe Against Cancer Program (16). It established the principles of organized population-based screening and stimulated numerous pilot projects. It is hoped that these guidelines will have a greater impact on countries in which screening programs are still lacking and in which opportunistic screening has been preferred in the past. As a result, today 16 countries and 9 regions have nationally organized population-based screening programs in Europe.

Among all preventive public health care interventions, high coverage of the target population with cytology screening and HPV vaccines is essential to achieve maximum reduction of cancer cases. Therefore, to obtain the maximum coverage and future visible benefit, immunization programs targeting adolescents before exposure to HPV should be preferred and population-based. Also, effective communication strategies must be adopted.

The resolution of the problem of cervical cancer in Europe will not be a matter of further scientific research but rather the implementation of public health care programs. All European countries must be encouraged to implement these programs as a priority. Substantially higher dimension of this public health care problem in the Eastern Europe requires special attention and possibly unique approach. Redesigning the service and changing attitudes in public, medical profession, and government will be the main ways to improve current unsatisfactory cervical cancer outcomes at our continent.

M. Poljak has Honoraria from Speakers Bureau from Abbott, Merck and Co., and Roche and is a Consultant/Advisory Board member for Abbott, GlaxoSmithKline, Roche, and Merck and Co. No potential conflicts of interests were disclosed by the other authors.

Conception and design: V. Kesic, M. Poljak, S. Rogovskaya

Development of methodology: V. Kesic

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): M. Poljak, S. Rogovskaya

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): V. Kesic, M. Poljak

Writing, review, and/or revision of the manuscript: V. Kesic, M. Poljak, S. Rogovskaya

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): S. Rogovskaya

Collection of data from various countries mentioned: S. Rogovskaya

International Agency for Research on Cancer has kindly granted the authors permission for print and electronic rights to use data from GLOBOCAN available at http://globocan.iarc.fr.