Tamás Sápy

The prognostic significance of HPV‐16 genome status of the lymph nodes, the integration status and p53 genotype in HPV‐16 positive cervical cancer: a long term follow up

Objective Prognostic evaluation of HPV‐16 genome status of the pelvic lymph nodes, the integration status of HPV‐16 and p53 codon 72 polymorphism in cervical cancer.

Novel human polyomaviruses in pregnancy: Higher prevalence of BKPyV, but no WUPyV, KIPyV and HPyV9

BACKGROUND Immunosuppression due to pregnancy may lead to higher susceptibility to infections and reactivation of latent infections, such as BK polyomavirus (BKPyV). There is lack of information about the prevalence of novel human polyomavirus 9 (HPyV9), WU (WUPyV) and KI (KIPyV) during pregnancy. OBJECTIVES To study whether pregnancy results in higher prevalence of HPyV9, WUPyV, KIPyV and their correlation with BKPyV. STUDY DESIGN Plasma, urine and throat swab samples from 100 pregnant and 100 non pregnant women were screened for the presence of WUPyV, KIPyV, HPyV9 and BKPyV by PCR. RESULTS No WUPyV DNA was detected in plasma, urine and respiratory samples from pregnant and non pregnant women. KIPyV DNA was found in two plasma samples from non pregnant women (2%) and not detected in other samples from neither pregnant nor non pregnant women. HPyV9 DNA was determined in all sample types of pregnant and non pregnant women, respectively. There were no significant differences between pregnant and non pregnant women in HPyV9 DNA frequencies for plasma (2% vs. 6%), urine (3% vs. 2%) and respiratory samples (2% vs. 2%). Prevalence of BKPyV in urine samples was significantly higher (p=0.039) in pregnant women (13%) then in non pregnant women (4%); co infection with KIPyV and/or HPyV9 was not detected. CONCLUSIONS In contrast with BKPyV, infection with WUPyV, KIPyV and HPyV9 was not detected more frequently during pregnancy. To the best of our knowledge HPyV9 was detected first in respiratory samples in our study.

Investigation of the occurrence of torque tenovirus in malignant and potentially malignant disorders associated with human papillomavirus

In a previous pilot study, a significantly poorer outcome of laryngeal cancer was found in patients co‐infected with human papillomavirus (HPV) and genogroup 1 torque tenovirus (TTV). The present study aimed to collect data on the overall prevalence of TTVs on the prevalence of genogroup 1 TTV in two other malignancies associated with HPV, oral squamous cell cancer and cervical cancer, and in oral and cervical premalignant lesions (oral lichen planus, oral leukoplakia, cervical atypia). Oral samples from all patients were accompanied with a sample from the healthy mucosa. The overall prevalence of TTV was significantly higher both in oral squamous cell cancer and cervical cancer compared with other patient groups or with the respective controls. The prevalence of genogroup 1 TTV was significantly higher in lesions of oral squamous cell cancer and oral lichen planus, but not in lesions of oral leukoplakia (24.6%, 10.1%, and 4.5%, respectively), compared with the prevalence in the oral cavity of controls (1.4%). Co‐infection rates with genogroup 1 TTV and HPV were significantly higher in oral squamous cell cancer than in controls, oral lichen planus or oral leukoplakia patients (12.3%, 0.0%, 6.7%, and 4.5%, respectively). The prevalence of genogroup 1 TTV in all cervical samples were comparable. These data suggest that genogroup 1 TTV may be associated specifically with some head and neck mucosal disorders, but disproves a (co)carcinogenic role in oral cancer or cervical cancer as well as an association with HPV or with malignancies associated with HPV. J. Med. Virol. 81:1975–1981, 2009.

Poor clinical outcome in early stage cervical cancer with human papillomavirus-18 positive lymph nodes

Epidemiologic and molecular studies have proven that human papillomavirus (HPV) plays an important role in the development of cervical cancer. However, the role of the virus in the progression of the disease, i.e. in the development of lymph node metastasis and in the adverse clinical outcome is poorly understood. We have been using the polymerase chain reaction (PCR) to study the presence and typing of human papillomavirus DNA since 1980 in cervical cancers and pelvic lymph nodes from the same patients. Out of the series of 47 cervical cancer patients we focused on four women (age: 41, 33, 35 and 56 years) in this article. The follow-up of these patients revealed early recurrences of the disease (7, 7, 17, 22 months) with very short survival (9, 10, 21, 24 months). Although we detected HPV-18 positivity both in the cervical tumors and in the regional lymph nodes too in all four cases, lymph nodes were negative by routine hystology in case of the three young patients (21, 33, 35 years of age). Our observations suggest that HPV type 18 positive cervical cancer patients, despite negative histological findings in the lymph nodes should be consider as a subpopulation for poor outcome especially in the young age group (p=0,022, Fishers exact test).

Meiotic segregation study of a novel t(3;6)(q21;q23) in an infertile man using fluorescence in situ hybridization (FISH)

Male carriers with balanced reciprocal translocations can produce a variable proportion of unbalanced gametes resulting in reproductive failures. The presence of a structural rearrangement may induce an interchromosomal effect. This is characterized by abnormal bivalents not involved in the reorganization thereby yielding non-disjunction, which would present as aneuploid spermatozoa for these chromosomes. In the present case report segregation analysis of the sperm and investigation of interchromosomal effect were carried out using cytogenetic and fluorescence in situ hybridization (FISH) analysis on blood lymphocytes. The karyotype of the patient was 46,XY,t(3;6)(q21;q23). During sperm segregation analysis a total of 2,002 sperms were evaluated, of which 46.8% showed normal/balanced (alternate segregation mode) and 53.2% of sperm showed an abnormal signal pattern. A significant difference in the frequency of the estimated number of chromosome anomalies was observed in the translocation carrier when compared to the normozoospermic group (P < 0.0001) and the oligozoospermic group (P < 0.0001). Meiotic segregation analysis of sperm together with aneuploidy assessment for X, Y, and 17 chromosomes using FISH allows for the determination of a reproductive prognosis in male balanced translocation carriers and can be used for appropriate genetic counseling.

PREVALENCE OF HUMAN HERPESVIRUS 6A AND 6B DURING PREGNANCY

The aim of the present study was to assess the frequency of human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) infection during pregnancy. 100-100 blood samples were collected from pregnant and non-pregnant women, then nucleic acid was isolated from both plasma and leukocytes fraction. Nested and real-time PCR were used to detect and differentiate HHV-6A and HHV-6B DNA and to determine viral loads. Reverse transcription PCR (RT-PCR) for HHV-6 U79/80 mRNA was performed in order to reveal active HHV-6 replication.HHV-6A and HHV-6B active infections were not detected in blood samples neither from pregnant nor from non-pregnant women. Frequency of HHV-6B and HHV-6A latency did not show difference between the studied groups (15% vs. 16%). HHV-6B latency was dominant in both studied groups (14/15 and 15/16). Beside these results, in leukocyte samples of one pregnant and three non-pregnant women high HHV-6A viral loads (1.28 × 10⁵ - 5.07 × 10⁵ GEq / 1.5 × 10⁶ leukocytes) were detected, and viral DNA was also found in plasma samples. Although RT-PCR did not confirm virus replication, but chromosomal integration was also not proved unequivocally, the number of 0.08-0.33 HHV-6 copy / 1 leukocyte refers more to postnatal infection.

Citogenetic and molecular genetic studies in infertility in East Hungary

INTRODUCTION In developed countries 10-15% of the couples are affected by infertility. In half of them genetic factors can be identified. AIMS We studied genetic alterations in infertility in Hungarian patients. METHODS Cyogenetic analyses were performed in 195 females and 305 males. In 17 females FMR1 mutations, in 150 males Y microdeletions, and aneuploidy were studied in the sperm of 28 males. In a carrier male sperm meiotic segregation was studied. RESULTS The most common aberrations in females were X chromosome aneuploidia and inversion (3.6%), while the same in males Klinefelter-syndrome (3.3%) and autosomal translocations (2%). In two females FMR1 premutation was found. While Y microdeletions were identified only in azoospermic and severe oligozoospermic men, partial microdeletions could also be detected in normozoospermic males. A higher aberration rate was found in cases with abnormality in both the number and motility of sperm. In a male patient with 46,XY,t(3;6)(q21;q23) karyotype, 53.2% of spem carried unbalanced chromosome assortment. CONCLUSIONS Knowledge of abnormalities may help in genetic counseling and choosing the most effective reproduction technique.

Onkofertilitás és kezelési lehetőségei. Irodalmi áttekintés

Absztrakt: A rosszindulatu daganatos betegsegek műtetes, sugar-, kemo- es biologiai terapias kezelese karos hatassal lehet a fiatal betegek kesőbbi fertilis kepessegeire. A javulo gyogyulasi eselyek mellett egyre nagyobb hangsulyt kap a betegek hosszu tavu eletminősege, igy a tulelesen tul jovőbeli fertilitasuk megőrzese is celkent fogalmazodik meg. Az onkologiai es fertilitasmegtartasi torekveseket az onkofertilitas kifejezes foglalja ossze. Ez alatt nemcsak specialis nőgyogyaszati műteti eljarasokat ertunk, hanem olyan beavatkozasokat is, amelyek az ivarsejtek, a nemi szervek vagy az embrio konzervalasat celozzak. Az onkofertilitas mint kifejezes az Amerikai Egyesult Allamokban szuletett, de napjainkban mar az egesz vilagon interdiszciplinaris tudomanyteruletkent egyre nagyobb teret hoditva valik egyre tobb szakember specialis erdeklődesi teruleteve. A klasszikus onkologiai es nőgyogyaszati szubspecialitasok mellett az onkofertilitas ismeretanyaga is olyan szintre emelkedik, amelynek naprakesz tudasa az...