Importance of addition of HPV DNA testing to the cytology based cervical cancer screening and triage of findings with p16/Ki67 immunocytochemistry staining in 35 and 45 years old women LIBUSE trial data analysis.

OBJECTIVE: The study evaluates results of 2-years follow-up of patients in ages 35-36 and 45-46, who are participating in the project LIBUSE, that deals with efficacy of HPV DNA and Pap smear co-testing and p16/Ki67 dual staining in the Czech national cervical screening. DESIGN: Prospective observational study. SETTING: Department of Obstetrics and Gynecology, General University Hospital and 1st Medical Faculty, Charles University, Prague. MATERIALS AND METHODS: Out of all women enrolled in the project LIBUSE only those who were at the beginning of the study 35-36 and 45-46 years old were sellected. Conventional Pap smear and HPV DNA test (Cobas 4800, Roche Diagnostics) had been collected at the baseline. Women were stratified according to their results in the three risk groups: 1. low-risk, 2. high-risk and 3. intermediate risk, who subsequently underwent p16/Ki67 dual staining. All high-risk patients and those with positive result of dual staing were refered to the expert colposcopy. The cases with biopsy proven precancers or cancers were considered as „positive findings“. RESULTS: Altogether 352 women meet the age requirements. In 26 (7.6%) women had been proven HPV DNA positivity and out of the them 9 cases were HPV 16/18 positive. Severe cytological abnormality was found only in one patient (0.3%), who was simultaneously HPV positive. Ten women (2.8%) were classified as high-risk and directly refered to colposcopy. Another 18 patients underwent p16/Ki67 dual staining and 4 positive cases were refered to colposcopy too. After one year further 9 patients were classified as intermediate risk and 6 more were identified after two years of follow-up. Within two years 9 more patient were refered to colposcopy. After the entire period of follow-up in 10 patients biopsy confirmed precancer lesions, none of them had invasive cancer. CONCLUSIONS: Addition of HPV DNA testing with selective HPV 16/18 genotyping to the cytology based screening significantly increases sensitivity and safety of our cervical screening program.

Correlation between integration of high-risk HPV genome into human DNA detected by molecular combing and the severity of cervical lesions: first results of the EXPL-HPV-002 study.

OBJECTIVES: The aim of the EXPL-HPV-002 study is to evaluate the integration of 14 high-risk HPV as a biomarker of the severity and the progression of cervical lesions. Such a „triage biomarker“ would help to reduce the number of unnecessary colposcopies, to avoid over-treatment of lesions that spontaneously regress and to better target the lesions requiring treatment. DESIGN: EXPL-HPV-002 is a prospective, open-label, single arm, GCP study conducted at 2 clinical sites in the Czech Republic. SETTINGS: Investigations centers: Private Gynecology Center, Brno; Gynecological and Obstetrical Clinic, Brno; Genotyping central lab: NRL for Papillomaviruses and polyomaviruses, IHBT, Prague; Histology Central reading: Aeskulab Pathology, Prague; Molecular combing HPV test: Genomic Vision, Bagneux. METHODS: From June 2016 to May 2018, 688 patients aged 25-65, referred to colposcopy after an abnormal Pap-smear, were enrolled in the study. Among them 60% were found HPV high-risk. The study is divided in two phases: 1. a cross-sectional phase using data collected at first visit (colposcopy images ± histology, pap-smear for HPV genotyping and molecular combing) to study the association between HPV integration status versus colposcopy and histology grades; 2. a longitudinal phase using data collected in follow-up visits: cytology at 6, 18 and 30 months and colposcopy ± histology at 12, 24 and 36 months. A pap-smear collected at 12, 24 and 36 months allows to perform genotyping and molecular combing. HPV integration status is analyzed in comparison with the evolution of lesions, viral clearance and HPV genotype. HPV genotyping and molecular combing were performed on pap-smear samples in central laboratories. Histology data were reviewed by central reading. RESULTS: The transversal phase of the study is achieved and shows that the HPV integration into the human DNA, monitored by molecular combing, can significantly differentiate normal subjects from women with cervical lesions or cancer. CONCLUSION: HPV integration into the host genome, monitored by Genomic Visions technology, is a reliable diagnostic biomarker that will greatly help clinicians to improve their medical decision tree.

[Nine-valent HPV vaccine - new generation of HPV vaccine]. / Nonavalentní HPV vakcína - nová generace ockování proti HPV.

OBJECTIVE: To evaluate current knowledge about new generation of HPV vaccine - nine-valent vaccine Gardasil9. DESIGN: Review article. RESULTS: The nine-valent vaccine against HPV 6/11/16/18/31/33/45/52/58 could improve efficacy of quadrivalent vaccine from 70 to 90 percent for cervical cancer. In addition this vaccine has covered around85-90% of HPV-related vulvar, vaginal and anal cancers. Efficacy and immunogenicity against HPV 6/11/16/18 is the same as for quadrivalent vaccine. Efficacy against HPV 31/33/45/52/58 associated lesions is 97%.

[Results of the Czech National Cervical Cancer screening programme]. / Výsledky Národního programu screeningu karcinomu delozního hrdla v Ceské republice.

INTRODUCTION: The nationwide Cervical Cancer Screening Programme in the Czech Republic was introduced in 2009. The aim of this article is to describe the results of this programme in the first few years after its transformation into a fully-fledged, organised programme. MATERIAL AND METHODS: During the first few years, a network of 37 accredited laboratories was stabilised, ensuring that examinations would be readily available across the Czech Republic. Although all women aged between 25 and 70 years fall within the target group of the current personalised invitation programme, women not in this age group are reimbursed for preventive screening examinations as well. The programme is equipped with an information support provided by the Institute of Biostatistics and Analyses of the Masaryk University, which runs the Cervical Cancer Screening Registry. RESULTS: Cervical cancer incidence and mortality rates in the Czech Republic have seen a significant decrease over the last decade. By the end of 2013, more than 11 million examinations were reported to the registry by the accredited laboratories, and more than 15,000 serious cervical lesions were detected. Analysis of the data from the registry makes it possible to monitor the quality of individual laboratories and the effectiveness of the entire programme. CONCLUSION: The promising start of the programme provides a strong argument for its continuation. The program--me has the potential to decrease cervical cancer incidence rates in the Czech Republic to values comparable with those reported by countries with advanced health care systems.

[Approach to population-based screening in the Czech Republic, methodology and first results of the personalised invitation of citizens to cancer screening programmes]. / Koncepce populacního screeningu v Ceské republice, metodika a první výsledky adresného zvaní obcanu do preventivních onkologických programu

In January 2014, a programme of personalised invitations was launched in the Czech Republic, with the objective of inviting insured persons to cancer screening programmes; namely breast cancer screening and cervical cancer screening in women, and colorectal cancer screening both in women and men. This programme aims at strengthening the current cancer prevention programmes, and to increase the currently inadequate participation of the target population in these programmes; therefore, personalised invitations are sent to citizens who have not participated in these programmes for several years and therefore at risk of developing a serious disease. The project is coordinated by the Czech Ministry of Health in cooperation with the expert medical societies involved (gynaecology, gastroenterology, gastrointestinal oncology, diagnostic radiology, general practice), representatives of health care payers, and other experts nominated by the Minister of Health. All health care payers invite their clients (insured persons) to preventive check-ups, covering all examinations needed. The project has been realised with the assistance of financial resources from EU funds. This article describes the methodology of personalised invitations which has been implemented nationwide, its data background, and the first results of the project in the first half of 2014, when almost 1.3 million Czech citizens were invited.

[Performance indicators in screening programmes]. / Indikátory kvality screeningových programu

Breast, colorectal and cervical cancer screening programmes make it possible to decrease the population mortality rates of these diseases. How-ever, complex standards of the quality of care must be introduced and followed in order to maintain a favourable ratio between the benefits and risks arising from population-wide screening programmes. Such programmes should be organized and population-based, ensuring that quality control is performed at all levels. This review introduces the system of quality control in the Czech cancer screening programmes, and provides specific examples of performance indicators that are usable and/ or being used in these programmes. Cancer screening programmes in the Czech Republic are equipped with a comprehensive information background which involves monitoring of the cancer burden in the population, monitoring of the screening process based on clinical data, and monitoring of the screening process based on administrative data. In particular, the specific performance indicators describe the success rate of take up of the target population, ability of the screening test to reveal (sensitivity) or to exclude (specificity) the screened condition, correct employment of subsequent diagnostic methods or treatment of detected cancers or precancerous lesions where applicable. In the Czech breast cancer screening programme, these indicators are routinely used in order to monitor the individual centres; in both colorectal and cervical cancer screening programmes, these indicators are used to monitor the entire programme, whereas the system of quality control for individual centres is under continuous development. A project of personalized invitations was launched in 2014, and its results are regularly evaluated in cooperation with the Czech National Reference Centre and the Ministry of Health of the Czech Republic.

[Prebioptic methods in the cervical cancer screening]. / Prebioptické metody pri screeningu karcinomu delozního hrdla.

OBJECTIVE: To evaluate the agreement between Pap smears, colposcopic findings and definitive excisional specimen in patients with abnormal Pap smears. DESIGN: Retrospective study. SETTING: Center of outpatient gynecology and primary care, Brno; Department of Obstetrics and Gynecology, University Hospital, Olomouc; Department of Medical Biophysics, Palacky University, Olomouc.Subjects and methods of the study: This retrospective study assessed the correlation between colposcopy and histopathology of woman who had abnormal Pap smears. Colposcopic chart review included participants from 2008 to 2012 who attended colposcopic clinic, center of outpatient gynecology care, Brno. RESULTS: One thousand nine hundred and twenty five patients screened by cytology, submitted to colposcopy and subjected to cone biopsy were selected. Cytopathological results were compared with colposcopic findings and results obtained on the basis of histological analyses of cone biopsy specimen. Agreement of cytology and histopathological diagnosis was in 1199 patients (62.3%). Agreement of colposcopic diagnosis and cervical pathology was matched in 1492 (93.5%). Agreement of colposcopy and cytology was found in 1022 pacientek (64.1%). False negatives of cytology in high grade lesions were in 36.4%. CONCLUSION: Strength of agreement between colposcopic diagnosis and cervical pathology was found to be very good while for cytology high percentage of false negative results was seen. Expert colposcopists and high quality standard cytopathologic and bioptic laboratories are necessary for nationwide cervical screening programmes. KEYWORDS: cervical cancer, colposcopy, oncological cytology, histology, CIN, cone biopsy.

[Role of prebioptic and bioptic methodsin the screening and diagnosis of cervical cancer]. / Prebioptické a bioptické metody pri screeningu a diagnostice karcinomu delozního hrdla.

OBJECTIVE: To describe the available prebioptical and bioptical methods used in screening and diagnosis of cervical cancer. DESIGN: Review article. SETTING: Center of outpatient gynecology and primary care, Brno; Department of Obstetrics and Gynecology, University Hospital, Olomouc.Subjects and methods of the study: In a review article there are outlines of the prebioptical investigative techniques and related diagnostics aim to detect, verificate and treat cervical lesions. It describes and compares various methods, including their mutual correlation. CONCLUSION: The oncological cytology, colposcopy and HPV testing have an irreplaceable role in diagnosis of cervical cancer. Appropriate combination gives us a chance to achieve high sensitivity in detection of severe lesions of the cervix.

[Epidemiology of genital warts in female population of Czech Republic]. / Epidemiologie genitálních bradavic mezi zenami v Ceské republice.

OBJECTIVE: The aim of study was to evaluate prevalence of genital warts in Czech Republic. SUBJECT: Multicentric prospective observation study. SETTING: HPV College. METHODS: During 6 month (February 2010 - July 2010) 20 private gynaecological centers in all Czech Republic were counting up the number of genital warts cases. Risk factors, therapy and knowledges about genital warts were evaluated. RESULTS: There were 637 patients with genital warts in cohort of 70 980 patients. The prevalence of genital warts was 0.89%. The most frequent risk factor was cigarette smoking in 37%. Main strategy for treatment were podophyllin local application and cold knife excision. CONCLUSION: The prevalence of genital warts in our study has shown importance for its prevention by rules of safety sex and HPV vaccination against HPV type 6 and 11.

[Genital warts and HPV vaccination]. / Genitální bradavice a HPV vakcinace.

OBJECTIVE: To present and overview of incidence of, and cost of care for, genital warts. SUBJECT: Review. SETTING: Department of Obstetrics and Gynecology, Palacky University and Faculty University, Olomouc; Office gynecology and primary care centre, Brno; Department of Obstetrics and Gynecology, Charles university in Prague-First Faculty of Medicine and General Faculty Hospital, Prague. METHOD: Literature review of incidence of, and cost of care for, genital warts in some european countries, North America and Australia. CONCLUSION: Genital warts exert a considerable impact on health services, a large proportion of which could be prevented through immunisation using the quadrivalent human papillomavirus vaccine.

Czech National Cancer Screening Programmes in 2010.

BACKGROUNDS: All three cancer screening programmes recommended by the Council of the EU are available to defined target age groups in the Czech Republic. Organized programmes for screening of breast, colorectal and cervical cancer have been initiated in the last decade. MATERIALS AND METHODS: A system for information support, as an essential component of organized screening programmes, has been implemented in all screening programmes. It comprises the Czech National Cancer Registry to monitor the cancer burden and population impact of the programmes, the National Reference Centre as a provider of nationwide insurance claims data, and the specialised databases of all three programmes, which collect information on screening, diagnostics and final diagnoses. RESULTS: Early diagnostics of malignant neoplasms and progress in therapy have helped to stabilize mortality, even in diagnoses with increasing incidence. The coverage of the Czech screening programmes has constantly been rising; however, it is still insufficient: 51.2%, 17.9% and 48.4% of the target population was covered at the end of 2008 in breast, colorectal and cervical screening programmes, respectively. In 2008, a total of 468,419 women underwent screening mammography and 2,128 tumours were detected (4.5 per 1,000 screened). According to the screening colonoscopy registry, more than 13,000 men and women underwent preventive colonoscopy in 2009, 4,085 patients were diagnosed with adenoma and 619 with colorectal cancer, mostly in the early stages. The information system for cervical screening was implemented in 2009 and has been running in pilot mode; the first results are expected at the end of 2010. CONCLUSION: The system for information support within organised cancer screening programmes enables monitoring of the performance of screening and diagnostic centres and thus helps to maintain continuous quality improvements, which are a necessary presumption for replicating the promising results of clinical trials. To achieve a substantial impact on population incidence and mortality, a large increase in test coverage in target populations will be necessary. The programmes should be transformed to a population-based form, which involves inviting all people in the target population to be screened.

[Screening of cervical cancer--theoretical background]. / Screening karcinomu delozního hrdla--teoretické predpoklady.

OBJECTIVE: To show the basic rules for creation of creening programme in case of cervical cancer's screening. DESIGN: Review article. SETTING: Centrum of gyneco-oncology prevention, Havírov. METHODS: Study of the current literature. CONCLUSION: Screening programme should be set up economic possibilities of state. It must cover all risk group. It should have high specificity and sensitivity. This test should be connected with diagnostic methods and appropriate therapy.

[Screening of cervical cancer--update]. / Screening karcinomu delozního hrdla--soucasný stav.

OBJECTIVE: Update screening of cervical cancer. DESIGN: Review article. SETTING: Out-patient Gynaecology and Primary Care Centre, Brno. METHODS: Study of the current literature. CONCLUSION: The persistent infection by human papillomavirus is a necessary condition for development of cervical cancer. Screening activity has an influence on it. Current screening is based on regular PAP smear. It should be evaluated by laboratory with accreditation and quality control. HPV test is too expansive for routine connection with screening for the most European countries.

[Recommendations for the treatment of tobacco dependence]. / Doporucení pro lécbu závislosti na tabáku.

This first Czech version of guidelines formulated by the working group of mentioned medical associations is based on current literature and international guidelines. They are aimed mainly on clinical medicine and on incorporation of this treatment into the health care system according to WHO recommendations. They should serve to the treatment of tobacco dependence at any level: during any contact with the smoking patient (short intervention), in specialised centres or for the health care providers or health system itself.

[Arthroscopic subacromial decompression.]. / Artroskopická subakromiální dekomprese.

Arthroscopic subacromial decompression is a generally recognized method of the treatment of the primary impingement sydrome and is one of the basic arthroscopic methods. The data in literature present 73-94 % of good and very good results. From May 1993 till June 1996 we treated at our clinic 40 patients with arthroscopic subacromial decompression of which 38 patients were followed up. The average period of follow-up is 3 years (2-5 years). All patients had clinical symptoms of impingement syndrome prior to operation. The patients who were indicated to resection of the lateral part of the clavicula and suture of the rotator cuff were not incorporated in the group. For the evaluation we used UCLA score after Ellman, the subjective satisfaction of patients was evaluated in detail. In 79 % the results after UCLA were good and very good (satisfactory). The most marked improvement was achieved in the evaluation of pain. 84 % of patients evaluated subjectively the result of the operation as good and very good. Worse evaluation on average was provided by patients who suffered the injury of the shoulder joint, patients already disabled before the surgery and women. The causes of unsatisfactory results in our group were the following: insuficient resection of acromion in 2 patients, persisting pain of acromioclavicular joint in 2 patients, non-diagnosed complete rupture of the rotator cuff in 1 patient, secondary impingement syndrome in 1 patient, CB syndrome in 1 patient and unclear cause of persisting complaints in 1 patient. Unsatisfactory results are caused by technical errors during the surgery and incorrect indications. The results can be improved by a careful clinical examination (acromioclavicular joint, stability, elimination of a secondary impingement), preliminary planning of the extent of resection of acromion according to radiographs (Y-projection, projections after Rockwood) and a correct evaluation of arthroscopic findings (lesion of labrum, SLAP, lesion of the rotator cuff). Key words: impingement syndrome, subacromial decompression, arthroscopy.

[SLAP Injuries - Superior Labrum Anterior Posterior.]. / Poranení SLAP - superior labrum anterior posterior.

From May to December 1996 the author treated at his Clinic five patients with injuries of the anchoring of the labrum superior and anchoring of the long head of the biceps. Snyder describes these injuries as SLAP -superior labrum anterior posterior. Only the development of arthroscopic technique provided new findings on these lesions. Anamnestic data and the clinical picture closely resemble the impingement syndrome. Here too irritation of the rotator cuff occurs but the cause is intraarticular. Theoretical work provides evidence that injuries of this type lead to reduction of the torsion rigidity of the shoulder joint reduced tension of the lower glenohumeral ligament. This along with chronic overburdening by so-called overhead activity creates prerequisites for the development of microinstability of the shoulder. This is why acromioplasty does not lead to improvement. As regards treatment a conservative procedure focused on correct conditioning of the brachial plexus dominates (in particular of the stabilizers of the scapula), administration of non-steroid anti-inflammatory drugs (NSAID), intraarticular corticoid administration, physical therapy, surgery is the last method of choice. Depending on the type of lesion it is recommended to treat the labrum superior and the tendon of the biceps, and depending on the degree of instability, the operation is supplemented by stabilization. Debridement of the rotator cuff is not always necessary, acromioplasty is performed when the acromion has shape II or III. The presented results are preliminary. In the first three patients the condition improved and at present they pursue sports as formerly. Another two patients still have rehabilitation treatment. Key words: SLAP lesion, superior labrum anterior posterior, microinstability, surgery of SLAP, arthroscopy, stabilization surgery and acromioplasty in the treatment of SLAP lesions.

Ectopic pregnancy in an uncommon location revealed by ultrasound.

We report the case of extrauterine intraovarian pregnancy of a young woman. The patient was preoperatively examined by ultrasound which revealed extrauterine pregnancy of the fourth lunar month. Histologically, intraovarian gravidity of four months was proven.

PIP: Reported is the case of a 36-year-old IUD user with an extrauterine intraovarian pregnancy that was revealed through ultrasonography. The patient presented with a slightly enlarged uterus and a 3-month history of amenorrhea. Sonography showed the uterus to be shifted to the right side with a nonhomogeneous cystic mass to its left. This mass was identified as the amnial cavity with a fetus of approximately 13 weeks' gestation. The IUD was extracted from the uterine cavity, and a D & C was performed. Laparotomy failed to show pathologic changes in the right Fallopian tube or ovary, but revealed a 12 cm diameter tumor growing from the left ovary and fixed to the uterine edge and cavum Douglasi. The abdominal cavity contained a small amount of liquid and coagulated blood. The cyst was ruptured during attempted luxation, and both amnial liquid and the 13 cm long fetus were drained away. Since the placenta had grown into the tissue of the deformed ovary, pregnancy extirpation and ovariectomy were performed. Also necessary, given the deformation of the Fallopian tube, was a salpingectomy.