SP-0489: HPV-transformation in the cervix and at non-cervical sites

Pla general d'un dels panells horitzontals sobre espais verds de Barcelona a l'exposició Ciutat. Barcelona projecta a l'Edifici Fòrum. Exposició sobre la planificació urbanística i arquitectònica de Barcelon

Genotoksični učinak kompleksa kvercetina i lantana na ljudske stanice karcinoma grla maternice

Quercetin is the main fl avonoid in diet with a potential in the treatment of cancer, cardiovascular, and neurodegenerative diseases. Due to its specifi c planar chemical structure, quercetin readily forms chelates with metalions. Complexes of bioactive compounds and metal ions such as lanthanum often show strong cytotoxic and antitumour properties. The aim of this study was to compare the genotoxic effects of the quercetin/lanthanum complex on human cervical carcinoma cells with compare it to the effects of free ligands, quercetin, and lanthanum alone. The quercetin/lanthanum complex showed considerable cytotoxicity in the concentration range of (100 to 1000) mmol mL-1 and exposure time of three hours. The complex also induced a dose-dependent pro-oxidative effects and the formation of single-strand and double-strand DNA breaks. Although we obtained promising results on the cell level, future experiments should answer whether the quercetin/lanthanum complex is cancer-specific and stable enough in physiological conditions to make a potential new antitumour drug.Kvercetin je jedan od najzastupljenijih flavonoida u prehrani. Zbog specifi čne kemijske strukture i bioloških svojstava jedan je od najproučavanijih flavonoida kao potencijalni lijek koji bi se rabio za liječenje kardiovaskularnih, neurodegenerativnih i tumorskih bolesti. Kvercetin zbog svoje planarne kemijske strukture vrlo lako stupa u interakciju s metalnim ionima te tvori kelate. Cilj ove studije bio je utvrditi potencijalni genotoksični učinak kompleksa kvercetina i lantana na ljudskoj staničnoj liniji karcinoma grla maternice i usporediti taj učinak s genotoksičnim učincima pojedinačnih spojeva, kvercetina i lantana. Istraživani kompleks izazvao je značajnu toksičnost u rasponu koncentracija od 100 mmol mL-1 do 1000 mmol mL-1 i u vremenu inkubacije od 3 sata. Kompleks je pokazao prooksidativnu aktivnost u ovisnosti o koncentraciji te je pri najvišim istraživanim koncentracijama izazvao lomove DNA. Ako bi u daljnjim istraživanjima kompleks kvercetina i lantana pokazao selektivno djelovanje prema stanicama raka i stabilnost u fiziološkim uvjetima, mogao bi se promatrati u svjetlu potencijalnog antitumorskog lijeka, što bi trebala rasvijetliti daljnja istraživanja

Prenatal diagnosis of Langer-Giedion Syndrome confirmed by bac s-on-beads technique

Langer-Giedion Syndrome (LGS), with characteristic phenotypic features including craniofacial dysmorphic signs, postnatal growth retardation and skeletal abnormalities, mental impairment, urogenital malformations and heart defects, is caused by partial deletions of the long arm of chromosome 8. We present a case of a female fetus with LGS. The diagnosis was molecularly proven with the BACs on Beads™ method at 32 weeks of gestation. To the best of our knowledge, prenatal recognition of that genetic defect had previously been made in only one case. Also, it has never been described before

Wyniki przesiewowych badań prenatalnych w materiale 2285 ciąż z rejonu Pomorza Zachodniego diagnozowanych w latach 2005-2006

Summary In the following paper we have presented the results of non-invasive and invasive prenatal diagnostic tests performed on 2285 pregnant women from the Western-Pomeranian Region between 2005 and 2006. Material and methods: Retrospective analysis of screening tests on 2285 pregnant women. Medical history, including age, weight, familial data pedigrees up to third degree relatives, accompanying diseases, gestational complications in the family, type, dosage and period of any drugs intake, was obtained. Sonographic screening and evaluation of maternal serum PAPP-A and betaHCG levels. Results: Screening tests identified 4.5% high-risk pregnancies in this group. 69% of the patients consented to invasive diagnosis. As a result, genetic anomalies were detected in 43.7% of cases. Significant differences in betaHCG levels correlated with oral gestagens intake and place of residence (coastal areas). Conclusion: Broad use of certified non-invasive methods of prenatal screening allow substansial reduction of invasive procedures with high levels of positive prediction. Medical drugs intake as well as place of inhabitation may influence on free betaHCG levels.Streszczenie Cel pracy: Celem pracy było przeanalizowanie wyników nieinwazyjnych i inwazyjnych badań prenatalnych przeprowadzonych w regionie zachodniopomorskim w latach 2005-2006. Materiał i metody: Analiza retrospektywna 2285 ciąż. Wywiad z uwzględnieniem 3 pokoleniowego rodowodu, badania ultrasonograficzne I trymestru wraz z testem podwójnym. Amniopunkcje ze standardową oceną kariotypu. Wyniki: Drogą badań przesiewowych wyłoniono 4,5% ciąż podwyższonego ryzyka, z których 69% poddało się amniopunkcji. Pozwoliło to na potwierdzenie w wysokim odsetku (43,7%) nieprawidłowości genetycznych. W badanej grupie ciężarnych zaobserwowano istotne zmiany w parametrach biochemicznych betaHCG zależne od przyjmowanych leków (gestageny) oraz od miejsca zamieszkania (okolice nadmorskie). Wnioski: Powszechne zastosowanie certyfikowanych nieiwazyjnych badań prenatalnych pozwala na ograniczenie liczby przeprowadzanych amniopunkcji przy utrzymaniu wysokiego wskaźnika predykcji. Doustne przyjmowanie niektórych leków oraz miejsce zamieszkania pacjentki może wpływać na poziomy wolnej podjednostki betaHCG

Retrospective Study of the Prevalence of High-Risk Human Papillomaviruses among Croatian Women

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 monitored by typing for HR HPV types: 16, 18, 31, 33, 45, 52 and 58

Human papillomavirus 16 is an aetiological factor of scrotal cancer

Background: Squamous cell scrotal carcinoma (SCSC) is an infrequent skin cancer associated historically with occupational carcinogens. Human papillomavirus (HPV) DNA has been associated with SCSC but there is no definitive proof of its oncogenic role. Methods: Human papillomavirus-DNA and -E6*I mRNA were analysed in six invasive histologically typed SCSC. LCM-PCR was used to localise HPV DNA to tumour cells. P16(INK4a)and p53 expression were studied by immunohistochemistry. Results: In three warty or basaloid SCSC HPV16-DNA and E6*I-mRNA were detected. LCM-PCR confirmed HPV16 was in p16(INK4a)-positive malignant cells. However, of three usual-type SCSC, all were HPV-negative and two expressed p53 protein but not p16(INK4a). Conclusions: Human papillomavirus 16 was present in tumour cells and oncogenically active in basaloid and warty SCSC, whereas usual SCSC was HPV-negative and showed immunostaining, suggesting p53 mutation. The dual pathways of oncogenesis and relation between histological type of SCSC and HPV are similar to that in penile cancers

Differentiated Vulvar Intraepithelial Neoplasia-like and Lichen Sclerosus-like Lesions in HPV-associated Squamous Cell Carcinomas of the Vulva

Most human papillomavirus (HPV)-associated vulvar squamous cell carcinomas (VSCCs) originate from high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia. However, growing evidence suggests that morphologic studies have limitations in predicting HPV status in vulvar lesions. We aimed to evaluate adjacent intraepithelial lesions in a series of DNA HPV-positive VSCCs, focusing on unusual histologic patterns mimicking differentiated vulvar intraepithelial neoplasia (dVIN) or lichen sclerosus (LS). We identified 326 DNA HPV-positive VSCC with at least 1 cm of skin adjacent to the invasive tumor and analyzed HPV typing, HPV E6*I mRNA, and p16 immunohistochemistry in all cases. A careful histologic evaluation was conducted. A conclusive association with HPV was based on a positive p16 or HPV E6*I mRNA result or both in addition to the HPV DNA, whereas cases negative for both markers were classified as nonconclusively associated with HPV. One hundred twenty-one tumors (37.1%) had normal adjacent skin, 191 (58.6%) had only high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia, and unusual intraepithelial lesions were identified in 14 (4.3%) tumors. Seven cases showed dVIN-like features, 5 showed adjacent LS-like lesion, and in 2 cases dVIN-like and LS-like lesions were identified simultaneously. Six of them were conclusively associated with HPV (3 dVIN-like, 2 LS-like, 1 with combined dVIN/LS-like features). All 6 tumors were associated with HPV16 and were positive for both p16 and HPV mRNA, and p16 was also positive in the dVIN-like and LS-like lesions. In summary, a small subset of VSCCs conclusively associated with HPV may arise on intraepithelial lesions, mimicking precursors of HPV-independent VSCC

Burden of Human Papillomavirus (HPV)-Related Cancers Attributable to HPVs 6/11/16/18/31/33/45/52 and 58

Background: Many countries, mainly high- and upper-middle income, have implemented human papillomavirus (HPV) vacci- nation programs, with 47 million women receiving the full course of vaccine (three doses) in 2014. To evaluate the potential impact of HPV vaccines in the reduction of HPV-related disease, we aimed to estimate the HPV type distribution and burden of anogenital and head and neck cancers attributable to HPV types (HPVs 16/18/31/33/45/52/58/6/11) included in currently licensed HPV vaccines. Methods: In all, 18 247 formalin-fixed paraffin-embedded specimens were retrieved from 50 countries. HPV DNA detection and typing were performed with the SPF-10 PCR/DEIA/LiPA25 system. With the exception of cervical cancer, HPV DNA- positive samples were additionally subjected to HPV E6*I mRNA detection and/or p16INK4a immunohistochemistry. For cervi- cal cancer, estimates were based on HPV DNA, whereas for other sites, estimates were based on HPV DNA, E6*I mRNA, and p16INK4a biomarkers. Results: The addition of HPVs 31/33/45/52/58 to HPVs 16/18/6/11 in the nonavalent HPV vaccine could prevent almost 90% of cervical cancer cases worldwide. For other sites, the nonavalent HPV vaccine could prevent 22.8% of vulvar, 24.5% of penile, 60.7% of vaginal, 79.0% of anal cancers, 21.3% of oropharyngeal, 4.0% of oral cavity, and 2.7% of laryngeal cancer cases. Conclusions: Our estimations suggest a potential impact of the nonavalent HPV vaccine in reducing around 90% of cervical cancer cases and a global reduction of 50% of all the cases at HPV-related cancer sites