Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Central and Eastern Europe.

We present a review of current cervical cancer screening practices, the implementation status of vaccination against human papillomaviruses (HPV) and available data concerning the burden of HPV infection and HPV type-specific distribution in 16 Central and Eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and the Former Yugoslav Republic (FYR) of Macedonia. Since published data were relatively scarce, two detailed surveys were conducted during August-October 2011 and in January 2013 to obtain relevant and updated information. The mean prevalence of HPV infection in 8610 women with normal cervical cytology from the region was 12.6%, with HPV16 being the most frequent HPV type. The overall HPV DNA prevalence in women with high-grade cervical lesions was 78.1%. HPV DNA was found in 86.6% of cervical cancers; the combined prevalence of HPV16/18 among HPV positive cases was 87.5%. The overall HPV DNA prevalence in genital warts and laryngeal papillomas was 94.8% and 95.2%, respectively, with HPV6 and HPV11 being the most frequent types. Opportunistic and organized cervical screening, mainly based on conventional cytology, is performed in nine and seven countries in the region, respectively, with the proposed age of the start of screening ranging from 20 to 30 years and the estimated coverage ranging from a few percent to over 70%. At least one of the current HPV prophylactic vaccines is registered in all Central and Eastern European countries except Montenegro. Only Bulgaria, Czech Republic, FYR Macedonia, Latvia, Romania and Slovenia have actually integrated HPV vaccination into their national immunization programme and currently provide routine vaccination free of charge to the primary target population. The key reasons for lack of implementation of HPV vaccination into the national immunization programme are high vaccine cost and negative public perception. 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.

Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Russian Federation, the Western countries of the former Soviet Union, Caucasus region and Central Asia.

Limited data are available on the burden of human papillomavirus (HPV) and its associated diseases in the Russian Federation, the Western Countries of the former Soviet Union (Belarus, Republic of Moldova, Ukraine), the Caucasus region and Central Asia (Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan). Both the incidence and mortality rate of cervical cancer are higher in these countries than in most Western European countries. In this article, we review available data on HPV prevalence and type distribution in women with normal cytology, women from the general population, cervical precancerous lesions and cervical cancer, as well as data on national policies of cervical cancer screening and HPV vaccination initiatives in these countries. Based on scarce data from the 12 countries, the high-risk HPV (hrHPV) prevalence among 5226 women with normal cytology ranged from 0.0% to 48.4%. In women with low-grade cervical lesions, the hrHPV prevalence among 1062 women varied from 29.2% to 100%. HrHPV infection in 565 women with high-grade cervical lesions ranged from 77.2% to 100% and in 464 invasive cervical cancer samples from 89.8% to 100%. HPV16 was the most commonly detected hrHPV genotype in all categories. As the HPV genotype distribution in cervical diseases seems to be similar to that found in Western Europe the implementation of HPV testing in screening programs might be beneficial. Opportunistic screening programs, the lack of efficient call-recall systems, low coverage, and the absence of quality assured cytology with centralized screening registry are major reasons for low success rates of cervical cancer programs in many of the countries. Finally, HPV vaccination is currently not widely implemented in most of the twelve countries mainly due to pricing, availability, and limited awareness among public and health care providers. Country-specific research, organized nationwide screening programs, registries and well defined vaccination policies are needed. 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.

Host gene expression profiling of cervical smear is eligible for cancer risk evaluation.

AIMS: Uterine cervical carcinoma (CC) is known to be a delayed consequence of human papillomavirus (HPV) infection. Considering the reported influence of HPV on host genome activity, we conceived an approach to capture human gene expression profiles corresponding to increased risks of carcinogenesis. METHODS: A sample set of 143 female participants included a 'control' group of 23, a 'pathology' group of 83 (cervical abnormalities of varied grade including 10 cases of CC), and a 'HPV carrier' group of 37 (infected but manifesting normal cytology). HPV detection, viral load measurements and gene expression profiling were performed by real-time PCR assays. RESULTS: Gradual increase in expression of proliferation markers and a decrease in expression of proapoptotic genes, some receptors, PTEN and PTGS2 were demonstrated for progressive grades of cervical intraepithelial neoplasia leading to cancer. All reported trends were statistically significant, for instance, correlation of gene expression values for MKI67, CCNB1 and BIRC5. A model was proposed that employed mRNA concentrations for genes MKI67, CDKN2A, PGR and BAX. Prompt distinction between the norm and the cancer, provided by initial calculation, suggested that positive values of the function could indicate the higher individual risks. Indeed, all patients assigned to high risk by calculation were HPV infected and showed elevated viral E6, E7 mRNA concentration known to be associated with CC onset. CONCLUSIONS: The research was concentrated on dynamical gene expression profiling upon pathological changes ultimately leading to CC. Differences of normalised mRNA concentrations were used for quantitative model design and its primary approbation.

Cervical cancer burden and prevention activities in Europe.

Cervical cancer is an important public health care problem in Europe. The overall incidence rate of cervical cancer in Europe is 10.6 per 100,000. However, within Europe, the incidence rates significantly differ, being lower in Western Europe where prevention programs are better developed. Significantly higher are the incidence and mortality rates in Central and Eastern Europe, being in close correlation to the intensity of organized screening. Human papillomavirus (HPV) vaccines are being delivered to the low-incidence populations that already have extensive screening programs, whereas the high-incidence countries have not implemented the vaccination programs yet. The resolution of the problem of cervical cancer control in Europe will be a matter of the implementation of public health care programs across the whole continent.

Effect of a levonorgestrel intrauterine system on women with type 1 diabetes: a randomized trial.

OBJECTIVE: Women with diabetes need safe, effective contraception. Although intrauterine devices provide superior contraception, concerns remain that progestin absorbed systemically from the levonorgestrel-releasing device may impair carbohydrate metabolism. To examine the effect of the levonorgestrel-releasing intrauterine system on glucose metabolism in diabetic women. METHODS: We randomly assigned 62 women with uncomplicated insulin-dependent diabetes mellitus to either a levonorgestrel-releasing or a copper T 380A intrauterine device. The primary outcome to assess glucose metabolism was glycosylated hemoglobin; fasting serum-glucose levels and daily insulin dose requirements over 12 months of observation were examined as well. RESULTS: Outcome data were available for 29 women using the levonorgestrel-releasing and 30 using the copper device. At 12 months, mean glycosylated levels were similar for women of the 2 groups (6.3%, standard deviation [SD] +/- 1.5 compared with 6.3%, SD +/- 1.3, respectively). The same was true for mean fasting-serum glucose levels (7.4 mM, SD +/- 4.2 compared with 7.5 mM, SD +/- 4.2) and daily insulin doses (35.1 units, SD +/- 12.8 compared with 36.4 units, SD +/- 9.0). No important differences were noted at either 6 weeks or 6 months. CONCLUSION: The levonorgestrel-releasing device had no adverse effect on glucose metabolism, even at the 6-week observation when systemic levels of levonorgestrel would have been higher than at later observations. Concern about a potential adverse effect of this contraceptive on glucose control is unwarranted, and its use in women with diabetes should be liberalized. LEVEL OF EVIDENCE: I.