Searching HPV genome for methylation sites involved in molecular progression to cervical precancer.

Background: Human Papilloma Virus has been considered as the main cause for cervical cancer. In this study we investigated epigenetic changes and especially methylation of specific sites of HPV genome. The main goal was to correlate methylation status with histological grade as well as to determine its accuracy in predicting the disease severity by establishing optimum methylation cutoffs. Methods: In total, sections from 145 cases genotyped as HPV16 were obtained from formalin- fixed, paraffin-embedded tissue of cervical biopsies, conization or hysterectomy specimens. Highly accurate pyrosequencing of bisulfite converted DNA, was used to quantify the methylation percentages of UTR promoter, enhancer and 5' UTR, E6 CpGs 494, 502, 506 and E7 CpGs 765, 780, 790. The samples were separated in different groupings based on the histological outcome. Statistical analysis was performed by SAS 9.4 for Windows and methylation cutoffs were identified by MATLAB programming language. Results: The most important methylation sites were at the enhancer and especially UTR 7535 and 7553 sites. Specifically for CIN3+ (i.e. HSIL or SCC) discrimination, a balanced sensitivity vs. specificity (68.1%, 66.2% respectively) with positive predictive value (PPV) and negative predictive value (NPV) (66.2%, 68.2% respectively) was achieved for UTR 7535 methylation of 6.1% cutoff with overall accuracy 67.1%, while for UTR 7553 a sensitivity 60.9%, specificity 69.0%, PPV=65.6%, NPV=64.5% and overall accuracy=65.0% at threshold 10.1% was observed. Conclusion: Viral HPV16 genome was found methylated in NF-1 binding sites of UTR in cases with high grade disease. Methylation percentages of E6 and E7 CpG sites were elevated at the cancer group.

2017 Update on Ovarian Cancer Peritoneal Carcinomatosis Multimodal-Treatment Considerations.

Ovarian cancer peritoneal carcinomatosis requires a multimodal-treatment approach. Current treatment considerations are analyzed in this update and include the management of recurrent malignant ascites and the understanding of its pathophysiology, the role of peritoneal washing cytology in detecting peritoneal metastases, capsular invasion and ovarian cancer histologic type, interpretation of pretreatment Ca-125 levels at different time points of ovarian cancer therapeutic management, characteristics of 10-year survivors of high-grade ovarian cancer, and the role of lymphadenectomy in ovarian cancer peritoneal carcinomatosis. This update also includes current considerations on the role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian cancer peritoneal carcinomatosis as well as relevant ongoing phase III randomized controlled trial protocols.

The association between sexually transmitted infections, human papillomavirus, and cervical cytology abnormalities among women in Greece.

OBJECTIVE: To investigate the diagnosis of sexually transmitted infections (STIs) with human papillomavirus (HPV) infection and the presence of cytological changes in the cervix in a cohort of sexually active women in Greece. METHODS: Cervical cytology testing and the molecular typing of HPV and other STIs were performed for 345 sexually active women aged between 18 and 45 years (mean 33.2±7.2years) visiting a gynaecology clinic for routine cervical screening. The association of HPV and STI detection with cytological findings was investigated. RESULTS: HPV was detected in 61 women (17.7%) and STIs in 82 (23.8%). Ureaplasma spp was the most frequently detected pathogen, which was found in 63 (18.2%) women, followed by Mycoplasma spp (21 women, 25.6%) and Chlamydia trachomatis (five women, 6.1%). HPV positivity only (with no co-presence of STI) was associated with an abnormal cytology (odds ratio 6.9, p<0.001), while women who were negative for both HPV and STIs had a higher probability of a normal cytology (odds ratio 0.36, p<0.01). Sixteen out of the 63 (25.4%) women who tested positive for Ureaplasma spp, harboured a high-risk HPV type (odds ratio 2.3, p=0.02). CONCLUSIONS: In a population with a high prevalence of Ureaplasma spp, there was an association of this pathogen with high-risk HPV infection, a finding that needs further elucidation.

Falsely Elevated CA 15-3 Levels in Ovarian Sarcoidosis with Peritoneal Involvement and Ascites.

A rare case of ovarian sarcoidosis with peritoneal and omental involvement presenting as an ovarian malignancy is presented. Clinical, laboratory, and radiological evaluation of the patient revealed ascites and high levels of serum CA 125 and CA 15.3. The diagnosis of sarcoidosis was confirmed with pathology findings on tissues obtained during surgical laparotomy. Establishing the diagnosis of sarcoidosis can be treacherous and was complicated in this case by the falsely elevated biomarkers and ascites.

Leiomyomas and infertility.

Leiomyomas are the commonest benign tumor in the female reproductive tract. Even though their role on infertility is still questionable, evidence to date suggest that the anatomic location may be related to reproductive outcomes. Several possible mechanisms suggest that leiomyomas may affect fertility, especially in terms of the anatomical distortion of endometrial cavity, the abnormal uterine contractility, reduced blood supply to the endometrium and altered endometrial receptivity. The effect of leiomyomas on IVF outcomes has been the subject of many studies; however, a definitive direction is yet required to adjust clinical management accordingly. Management of leiomyomas is challenging in terms of clinical decision, especially among subfertile patients, since potential treatment complications and their consequences in endometrial dynamics should be also accounted. Expectant management is recommended for asymptomatic patients, whereas in symptomatic subfertile patients, medical and/ or surgical management is usually recommended.