Cervical Cancer as a Public Health Issue – What Next?

Cervical cancer is the second most common cancer in women worldwide. There are about 60,000 newly detected cases and 30,000 deaths annually in Europe, with the highest incidence reported from Eastern Europe countries. According to data from the National Institute of Public Health, in Croatia the incidence of cervical cancer was 14.9/100,000 in 2006, ranking eighth most common malignancy in women. Croatia has a lower incidence of the disease compared to many countries of Central and Southeast Europe. A large study carried out in 1995 by the International Agency for Research on Cancer, which included cervical cancer material collected from 22 countries all over the world revealed HPV genome in 99.7% of cases. Efficient methods of cervical cancer detection and screening methods for identification of precancerous lesions (conventional Pap smear) are available. Cervical cancer prevention programs should include education (of health care providers and women), stressing the benefits of screening, the age of the peak cervical cancer incidence, and the signs and symptoms of precancerous lesions and invasive disease. The aim of screening actions is to detect precancerous lesions that may lead to cancer if left untreated. Screening can only be effective if there is a well-organized system of follow up, diagnosis and treatment. Cervical cytology, or Papanicolaou (Pap) testing, has for decades been a cornerstone of cervical cancer screening. According to recent guidelines issued by the World Health Organization Regional Office for Europe, the primary task of the public health system is the introduction of secondary prevention through properly organized screening programs. Launching the national immunization program is only possible in the countries with well-organized secondary prevention programs and in those that can afford it

Distribution of human papillomavirus genotypes in women with high-grade cervical intraepithelial lesions and cervical carcinoma and analysis of human papillomavirus-16 genomic variants

Aim To analyze the distribution of high-risk human papil - lomavirus (HR-HPV) genotypes and the diversity of HPV16 genomic variants in Croatian women with high-grade squamous intraepithelial lesions (HSIL) and cervical carci - noma. Methods Tissue biopsy specimens were obtained from 324 women with histopathologically confirmed HSIL or cervical carcinoma, 5 women with low-grade SIL, and 49 women with negative histopathology. HR-HPV DNA was detected with Ampliquality HPV-type nucleic-acid hybrid - ization assay, which identifies 29 different HPV genotypes. HPV-16 genomic variants were analyzed by an in-house se - quencing. Results The most common HPV type in women with HSIL was HPV-16, detected in 127/219 (57.9%) specimens. HPV16 was also the dominant type in squamous cell cervical carcinoma (46/69 or 66.7%) and in adenocarcinoma (18/36 or 50.0%). Out of 378 patients, 360 had HR-HPV (282 sin - gle infections and 79 multiple infections), 3 (0.8%) patients had low-risk HPV, and 15 (4%) tested negative. HPV-16 vari - ants were determined in 130 HPV-16 positive specimens, including 74 HSIL and 46 carcinoma specimens. In HSIL specimens, 41 distinct variants were found, 98.6% belong - ing to the European branch and 1.4% belonging to the African branch. In cervical carcinoma specimens, 95% isolates grouped in 41 variants belonging to the European branch, one isolate (2.5%) belonged to the North American, and one (2.5%) to the Asian-American branch. Conclusion HPV-16, mainly belonging to the European branch, was the most frequent HPV genotype in women from Croatia with histologically confirmed HSIL and cervi - cal cancer

PHARMACOLOGICAL COST-BENEFIT ANALYSIS OF VACCINATION OF ADOLESCENTS BY CERVARIX

Karcinom vrata maternice u svijetu je drugi po učestalosti u žena. U Hrvatskoj je na osmome mjestu zastupljenosti. Ova vrsta karcinoma je bolest mlađih žena. Cervikalne intraepitelijalne neoplazije i karcinom vrata maternice su povezani su s trajnom infekcijom visoko onkogenim sojevima HPV-a. Cijena liječenja bolesti ovisi o njenom stadiju. Cjepivo Cervarix, primijenjeno u još spolno neaktivnih djevojčica i djevojaka, je u multinacionalnim dvostruko slijepim randomiziranim studijama pokazalo svoju visoku učinkovitost u stvaranju cirkulirajućih protutijela u serumu te smanjenju prevalencije HPV infekcije, preinvazivnih lezija i karcinoma vrata maternice. Cjepivo Cervarix također smanjuje prevalenciju trajne infekcije HPV-om u spolno aktivnih žena. Korištenjem matematičkih modela, uz visoku učinkovitost cjepiva od 100%, predviđa se 60–75% smanjenje morbiditeta i mortaliteta od karcinoma vrata maternice. Analizom izravnih troškova liječenja karcinoma vrata maternice i neizravnih troškova te kvalitetom života i usporedbom s cijenom cijepljenja u Hrvatskoj bi se godišnje moglo uštedjeti oko 50 milijuna kuna.Cervical carcinoma is the second most fequent female carcinoma in the world. In Croatia it took the 8th place. Cervical intraepithelial neoplasms and cervical carcinoma are related to permanent infection caused by high oncogenic type of HPV. The cost of treatment and therapy depends on grade of disease. In multinational double blinded randomised studies Cervarix vaccine has demonstrated its high efficiency in production of circulating serum antibodies, and the decrement of prevalence of HPV infection, preinvasive lesions and cervical carcinoma when applied in sexually not active adolescents. Cervarix vaccine also decreases the prevalence of permanent infections caused by HPV in sexually active women. Using mathematical models and considering high vaccine efficiency, it is predicted decrease of morbidity and mortality due to cervical carcinoma by 60–75%. When direct and indirect costs of therapy of cervical carcinoma and life quality were compared to cost of vaccination by Cervarix, it could be saved more than 50 milions of kunas in Croatia annually

Molecular analysis of human papillomaviruses and HPV 16 variants in patients with high-grade cervical intraepithelial lesion and cervical carcinoma

Cilj istraživanja bio je analizirati distribuciju HR-HPV tipova u bolesnica s HSIL i karcinomom vrata maternice, te utvrditi učestalost HPV 16 genomskih inačica u premalignim i malignim promjenama. HPV-DNA je izolirana iz 373 uzorka pacijentica s HSIL i karcinomom vrata maternice. Najčešći tip u HSIL bio je HPV 16 (57,9%), zatim HPV 31, HPV 33, HPV 58, HPV 52, HPV 18 i HPV 45 (12,8%, 6,8%, 6,4%, 5,9%,4,6% i 3,2%). HPV 16 je bio dominantan u karcinomu pločastih stanica (66,7%), ostali tipovi su bili: HPV 31, HPV 45, HPV 18 i HPV 33 (14,5%, 7,2%, 7,2% i 5,8%) uzorka. U adenokarcinomu HPV 16 bio je u 50,0%, HPV 18 u 41,7% a HPV 45 u 5,6% uzoraka. Određene su HPV16 inačice za 130 HPV16 pozitivnih uzoraka. U 74 uzorka HSIL-a pronađena je 41 inačica, 98,6% pripadalo je europskoj grani, a jedna (1,4%) afričkoj grani. Promatrajući uzorke karcinoma, 95% izolata svrstano u 41 varijantu pripadalo je europskoj grani, jedan izolat (2,5%) u Sjeverno Američkoj i jedan (2,5%) azijsko-američkoj grani. HPV 16 je bio dominantan. HPV 16 varijante dominantno pripadaju europskoj grani bez obzira na patohistološku dijagnozu. Sveobuhvatnim cijepljenjem devetvalentnim HPV cjepivom mogla bi se prevenirati 91,5% premalignih i malignih llezija vrata maternice u Hrvatskoj.The aim of the study was to analyze the distribution of HR-HPV types in patients with HSIL and cervical carcinoma and to determine the incidence of HPV 16 genomic variants in premalignant and malignant changes. HPV-DNA was isolated from 373 samples from patients with HSIL and cervical carcinoma. The most common type in HSIL was HPV 16 (57.9%), followed by HPV 31, HPV 33, HPV 58, HPV 52, HPV 18 and HPV 45 (12.8%, 6.8%, 6.4%, 5.9%, 4.6% and 3.2%). HPV 16 was dominant in squamous cell carcinoma (66.7%), other types were: HPV 31, HPV 45, HPV 18 and HPV 33 (14,5%, 7,2%, 7,2% and 5,8%). In adenocarcinoma HPV 16 was in 50.0%, HPV 18 in 41.7% and HPV 45 in 5.6% samples. HPV16 variants were determined for 130 HPV16 positive samples. In 74 HSIL samples 41 variants were found, 98.6% belonged to the European branch, one (1.4%) to the African branch. Observing carcinoma samples, 95% isolates grouped in 41 variants belonged the European branch, one isolate (2.5%) the North American, and one (2.5 %) the Asian-American branch. HPV 16 was dominant. HPV 16 variants dominantly belong to European branch regardless of pathohistological diagnosis. Comprehensive vaccination with the nine-valent HPV vaccine could prevent 91.5% of premalignant and malignant cervical lesions in Croatia

Cervical cancer as a public health issue - what next? [Karcinom cerviksa kao javnozdravstveni problem - kako dalje?]

Cervical cancer is the second most common cancer in women worldwide. There are about 60,000 newly detected cases and 30,000 deaths annually in Europe, with the highest incidence reported from Eastern Europe countries. According to data from the National Institute of Public Health, in Croatia the incidence of cervical cancer was 14.9/100,000 in 2006, ranking eighth most common malignancy in women. Croatia has a lower incidence of the disease compared to many countries of Central and Southeast Europe. A large study carried out in 1995 by the International Agency for Research on Cancer, which included cervical cancer material collected from 22 countries all over the world revealed HPV genome in 99.7% of cases. Efficient methods of cervical cancer detection and screening methods for identification of precancerous lesions (conventional Pap smear) are available. Cervical cancer prevention programs should include education (of health care providers and women), stressing the benefits of screening, the age of the peak cervical cancer incidence, and the signs and symptoms of precancerous lesions and invasive disease. The aim of screening actions is to detect precancerous lesions that may lead to cancer if left untreated. Screening can only be effective if there is a well-organized system of follow up, diagnosis and treatment. Cervical cytology, or Papanicolaou (Pap) testing, has for decades been a cornerstone of cervical cancer screening. According to recent guidelines issued by the World Health Organization Regional Office for Europe, the primary task of the public health system is the introduction of secondary prevention through properly organized screening programs. Launching the national immunization program is only possible in the countries with well-organized secondary prevention programs and in those that can afford it

Validation of the Croatian Version of the 8-Item Overactive Bladder Questionnaire (OAB-V8)

Objectives: The present study was conducted with the aim to translate, adapt, and validate the 8-item Overactive Bladder Questionnaire (OAB-V8) in Croatia. ----- Methods: This study included a total of 58 female patients with OAB and 66 healthy women. The translation to Croatian followed standardized procedure. All eligible participants completed OAB-V8 at inclusion and 2 weeks after to assess test-retest reliability. Cronbach α coefficient was calculated to assess internal consistency. ----- Results: Our study demonstrated high internal consistency for all items at both visits (Cronbach α between 0.799 and 0.847), with stable internal consistency reliability across items during the 2-week period. However, the exception is the item "waking up at night to urinate," which significantly changed during the 2-week period. Intraclass correlation for OAB-V8 items ranged from 0.810 to 1.0, with Spearman correlations greater than 0.9 for all items (P < 0.01). There were strong significant correlations between frequency of urination during daytime and uncomfortable and sudden urge to urinate, and between nocturia and waking up at night. Discriminative validity showed statistically significant score differences between patients and the control group. ----- Conclusions: The Croatian version of the OAB-V8 was successfully translated, adapted, and validated so the questionnaire is now ready for use as a reliable tool for initial screening and assessing patients with OAB in everyday Croatian clinical practice