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The knowledge that the persistent infection with high-risk (HR) human papillomavirus (HPV) is the etiological factor in the development of cervical cancer has led to the development of the HPV DNA detection methods as well as the prophylactic vaccine against the most common HR-HPV types, HPV 16 and 18. Despite HPV vaccination, cervical cancer screening will remain the main preventive measure for both vaccinated and non-vaccinated women, but the nature of screening and management of women with cervical disease is being adapted to the new technologies. Although, HPV DNA detection is more sensitive that cytology, its specificity is lower, since most HPV infections are transient. Therefore, other methods are considered to improve the management of women with cervical disease. Typing of HPV DNA and viral load measurements are still used for research purposes only. Detection of viral oncogene E6/E7 transcripts, which is the marker of the productive infection, is a promising tool for follow-up of HPV DNA-positive women. The detection of p16INK4a over-expression, as an indirect test of E6/E7 expression, is used for confirmation of cervical neoplasia. Despite the lack of standardization, the detection of p16INK4a is useful in clinical settings, however its reproducibility in the management of low-grade and borderline cases is low. Future perspectives include the determination of the methylation status of several cellular genes that could predict the progression of the disease.

The situation of cervical cancer prevention in South-East Europe is hardly documented, in spite of the fact that it encloses the most affected countries of Europe. We estimated the number of cases of cervical cancer, the number of deaths from this malignancy and the corresponding rates for 11 countries located in South-East Europe, in the period 2002–2004. Each year, approximately 9,000 women develop cervical cancer and about 4,600 die from the disease in this subcontinent. The most affected country is Romania with almost 3,500 cases and more than 2,000 deaths per year. High world-age standardised mortality rates (>7.5 [expressed per 100,000 women-years]) are observed in 7 countries: FYROM (7.6), Moldova (7.8), Bulgaria (8.0), Bosnia & Herzegovina (8.0), Albania (9.8), Serbia & Montenegro (10.1) and Romania (13.0). A matter of concern is the increasing mortality rate, in younger women, in the countries with the highest burden of cervical cancer. Thus, appropriate cervical cancer prevention programmes should be set up without delay in this part of Europe.

The infection with Human papillomavirus (HPV) is the necessary cause for cervical cancer. There are at least 15 High-Risk (HR) HPV types that are significantly associated with progression of cervical intraepithelial neoplasia to cervical cancer. Since previous studies showed that the prevalence of HPV in cervical cancers varies among different geographic regions, we wanted to investigate the prevalence of HPV types in Croatia, especially low abundant HR HPV types. By means of consensus primers directed polymerase chain reaction (PCR), we analysed cervical DNA samples of 2,136 Croatian women, mostly with abnormal cervical smears, in order to detect the presence of HPV. Type-specific primers were then used to determine Low-Risk (LR) HPV types 6/11 and HR HPV types 16, 18, 31, 33, 45, 52 and 58. Out of 2,136 specimens, 1,255 (58.8%) were positive for HPV. More than half of positive samples were typed (64.5%) and 35.5% still remained untyped. Multiple HPV infections were found in 10.3% of the cases. The most prevalent type, including both single and multiple infections, was HPV 16 with the prevalence of 15.9%, followed by HPV types 31, 6/11, 33, 18, 52, 45 and 58 with 8.7%, 7.1%, 4.5%, 3.8%, 2.3%, 1.2% and 1.1%, respectively. The significant increase of frequency from Low-grade Squamous Intraepithelial Lesions (LSIL) to High-grade Squamous Intraepithelial Lesions (HSIL) was observed for HR HPV types 16, 18, 31 and 33 but not 45, 52 and 58. The frequency of unknown HPV types was almost the same in cervical specimens of women with LSIL and those with HSIL, 19.8% and 21.1%, respectively. The prevalence of HPV infection rate decreased significantly with patient age from 68.5% (age group 12 to 24 years) to 38.8% (age group 45 to 54 years). But, in women aged 55 or older the overall prevalence increased to 56.6%. Our results indicate that prevalence of HR HPV types in Croatia is similar to other countries. We suggest that HPV positive women in Croatia should be closely monito

Opportunistic screening based on the Pap smear has been undertaken in Croatia since 1953. However, cervical cancer remains an important health problem in Croatia when compared to European countries with organised screening programmes. In Croatia, in addition to screening based on well established cytology, Human papillomavirus (HPV) testing is widely used as secondary test as a triage to borderline cytology and as a follow-up after treatment of severe cervical lesions. Many different approaches for HPV testing arose in Croatia over the last decade depending on the needs of each medical institution involved. Presently, there is an urgent need for better networking between the laboratories, the implementation of quality assessment and the adaptation of a uniform system of referring to and reporting of HPV testing. In conclusion, the best possible organisation for HPV testing would be essential for implementation of HPV testing as primary screening test in Croatia, an thus ultimately and hopefully, the more successful cervical cancer control.

Cervical cancer remains a significant source of disease and death in Europe. However, we now have the means to prevent virtually every case of cervical cancer through comprehensive, population-based, organised cervical cancer prevention programmes that effectively integrate cervical screening with the new technologies and vaccines that are now available. Given the potential health benefits of these programmes in reducing disease incidence and mortality, their establishment is now an ethical imperative for all European countries.