Epidemiology of cervical cancer in the Czech Republic

Dušek L.¹, Dvořák V.², Chroust K.¹, Májek O.¹, Mužík J.¹, Klimeš D.¹, Brabec P.¹, Pavlík T.¹, Michal M.³, Ondruš J.⁴

¹ Institute of Biostatistics and Analyses, Masaryk University, Brno; ² Czech Gynaecological and Obstetrical Society; ³ Biopticka Laborator, Ltd., Pilsen; ⁴ TOP GYN CENTER Ltd., Cytobioptic Laboratory, Ostrava

Introduction

Cervical carcinoma (CC) is a relatively common type of cancer in women worldwide, affecting over 500,000 women each year, and killing more than 270,000 women per year. Cervical cancer occurs mainly in developing countries, accounting for about 85% of cases worldwide. Human papilloma viruses (HPVs) are causative agents of the disease, and are typically transmitted through sexual contact. An aetiological connection was found between several HPV types and other malignant tumours in the anogenital region, as well as some head and neck cancers. Highly sensitive and specific molecular biology techniques have detected HPV in up to 90% of cervical carcinomas. The remaining 10% are HPV-negative carcinomas in which a higher risk of relapse of primary disease was documented (1, 2). The high-risk HPVs (particularly HPV 16 and HPV 18) inactivate the proteins p53 and p105Rb, thus inactivating the proliferation control (3, 4). HPV 16 and HPV 18 are responsible for more than 70% of all cervical carcinomas, while types 31 and 45 account for additional 10% of cases.

The aetiology of cervical cancer being known, effective prophylactic measures can be adopted. These involve population-based programmes of secondary prevention (screening programmes), which rely on regular preventive examinations to search for precancerous changes and to prevent the development of malignant tumours. And secondly, vaccination against HPV has been introduced relatively recently: the latest generation of preventive HPV vaccines is based on hollow virus-like particles (VLPs) assembled from recombinant HPV coat proteins. The vaccines target the most common high-risk HPVs which account for most cases of cervical cancer. Although the primary prevention of cervical cancer is the main objective of prevention efforts, the prospect of an entire elimination of the disease by vaccination is rather distant, at least one or two generations. Screening therefore remains the most effective as a weapon against cervical cancer (6).

Expected benefits of screening

Cervical carcinoma is a preventable disease, and a significant decrease in incidence and mortality can be expected as a result of population-based screening programme. Some authors suggest a decrease in mortality by up to 80%, provided that the screening programme is highly organized and the majority of target female population participate in it (7,8). On the contrary, non-organized prevention programmes provide much less protection against cervical cancer mortality, while the costs are higher (9). From this point of view, cervical carcinoma is similar to breast carcinoma and colorectal carcinoma, which are also preventable by the means of effective screening programmes. The term “organized screening” refers to a number of measures which need to be adopted in order to ensure a thorough quality check of all stages of the programme. In particular, these involve a timely and correct communication of examinations performed by the gynaecologists and involved laboratories. A transparent accreditation process for the laboratories is essential, and the same applies to the collection and analysis of relevant data. Information technology plays an important role; a screening programme can only be effective and successful if it is monitored and regularly assessed.

Genital HPV infections have been reported in all ethnic and socio-economic groups. HPV prevalence in the population ranges from 14 to 35 per cent; this estimate, however, is rather variable and depends on the demography of the population of interest. The incidence of HPV infection is reported to be highest in the 20-25 age group (prevalence up to 45%), logically followed by a first increase in cervical cancer incidence in the 25-29 age group. The second peak of the prevalence of HPV infection is in the 45-50 age group. In total, 50 to 80% of sexually active people are infected with at least one type of HPV in their lifetime (10). HPV infection itself, however, does not automatically mean that cervical carcinoma will develop. The development of cervical cancer is very slow and is determined by a persistent infection with a high-risk HPV. The primary HPV infection is asymptomatic in most cases (90% of women) and its clearance lasts 8-12 months. Dysplastic changes subsequently develop in about 10% of infected women, carcinoma in situ (CIS) develops in about 1%, and invasive cervical carcinoma affects less than 0.2% of infected women. The aetiopathogenesis of cervical carcinoma therefore provides enough space to apply prevention programmes.

Indeed, the epidemiology of cervical carcinoma worldwide is strongly influenced by the existence of effective screening programmes in individual countries (see Table 1). Very high incidence and mortality rates have been observed in developing countries which lack nationwide prevention programmes. On the other hand, cervical cancer incidence has been less than 10/100,000 women in countries with effective screening, such as Finland, Luxembourg, United States or France. Unfortunately, the Czech Republic still ranks among countries with a rather ineffective cervical screening programme. Similar incidence and mortality rates have been reported for Slovakia or Poland, for example.

Current situation in the Czech Republic

Long-term incidence of cervical cancer in the Czech population is relatively high, and the trend has been more or less stable over the last three decades (see Figure 1, Table 2), although the trend assessment in the late 1990s suggested a possible increase (11). From the mid-20th century, a reduction in cervical cancer incidence among Czech women was observed due to the establishment of cytology centres and prevention centres for gynaecological cancers (12). Nevertheless, since 1990, the incidence of cervical cancer has been fluctuating around 19-22/100,000 women and no further decrease has been observed. Although an opportunistic cervical cancer screening has been running in the Czech Republic since 1966, its effects have not been visible on the population level since early 1990s, probably due to a relatively small proportion of participating women (12). In 2000, the crude incidence rate was 20.0/100,000, while there were 19.1 new cases of cervical cancer per 100,000 women in 2005. The absolute number of new cases reported annually still exceeds 1000 (13).

High incidence of cervical carcinoma affects a wide spectrum of age categories, which further deepens social and ethical consequences. More than 30% of new cases of cervical carcinoma occur in women under 45. The Czech population not being an exception, the age-specific incidence starts to grow from 29 years on and reaches a peak at the age of 45-55 (see Figure 2). Unfortunately, mortality rates are relatively high in these age categories, which is partly due to the fact that almost 30% of patients are diagnosed in an advanced clinical stage 3 or 4 (Figure 1). Clinical stage is the most important prognostic factor in cervical carcinoma, as confirmed by available survival data for the Czech population (for treated patients only): the relative five-year survival in cervical cancer (regardless of clinical stages) reaches 74%; this number is obviously higher for patients diagnosed in clinical stage I or II (87.2%), and much lower for those diagnosed in stage III (48.5%) or even IV (10.2%). More than 400 Czech women die of cervical cancer each year.

Conclusion

The facts stated above give clear reasons for the promotion of population-based screening. Provided that clear rules are established for the organization of the screening, a decrease in mortality on population level can be expected, as demonstrated by the comparison of selected European countries on Figure 3 (15, 16, 17). This assumption is based on the experience from countries which launched an organized screening programme many years ago (18), and is also supported by some positive trends in the Czech population which were probably initiated by the opportunistic screening (19, 20). Data from the Czech National Cancer Registry are showing a slightly decreasing trend in mortality rates over the latest available period 2001-2005 (-2.1% per year; Figure 1).

Figure 1: Epidemiology of cervical cancer in the Czech Republic.

Figure 2: Epidemiology of cervical cancer in the Czech Republic – age-specific analyses (source of data: Czech National Cancer Registry, 2001–2005).

Figure 3: Mortality of cervical cancer in the Czech Republic in comparison with other countries.

Table 1: International comparison of cervical cancer epidemiology (GLOBOCAN study, 2002).

Table 2: Basic epidemiological characteristics of cervical cancer in the Czech Republic (source of data: Czech National Cancer Registry, year 2005).

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