The Epidermal Growth Factor system is present in human organs and plays an important role in cell proliferation, differentiation and apoptosis during embryogenesis and postnatal development. It has four receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and numerous ligands. Dysregulation of the Epidermal Growth Factor signaling network is implicated in the pathogenesis of various disorders. Especially in cancer, the Epidermal Growth Factor system becomes hyperactivated with various mechanisms (ligand overproduction, receptor overproduction, constitutive receptor activation). EGFR overexpression may have a dual role in endometrial cancer. It seems that in type I endometrial cancer, EGFR overexpression did not affect disease progression. However in type II endometrial cancer, EGFR overexpression associated with high grade disease and adverse clinical outcome. Moreover ΕrbB-2 overexpression especially in type II endometrial cancer, is an indicator of a highly aggressive disease with poor overall survival. The potential role of ErbB receptors (especially EGFR and ErbB-2) as targets for cancer therapy has been investigated for over 20 years. There are 2 major classes of ErbB targeted therapies: anti-ErbB monoclonal antibodies (MoAbs) and ErbB-specific tyrosine kinase inhibitors (TKIs). ErbB targeted therapies have still shown modest effect in unselected endometrial cancer patients. However, they may be clinically active as adjuvant therapy in well-defined subgroups of type II endometrial cancer patients with EGFR and ErbB-2 overexpression.

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Within the previous decades, following the widespread implementation of HPV-related biomarkers and computerization in liquid-based cytology, screening for lower genital tract malignancies has been optimized in several parts of the world. Many organized anogenital cancer prevention systems have reached a point at which efficacy is more a matter of population coverage and less of available infrastructures. Meanwhile, self-sampling modalities in which biologic material (vaginal secretions, urine, etc.) is obtained by the individual and not the clinician and subsequently undergoes examination for HPV biomarkers enjoy appreciating acceptance. Bygone the initial skepticism that vaginal or urine HPV represents “passenger” transient infections, extensive scientific work has been conducted to optimize high-risk HPV (hrHPV) detection from this “novel” biologic material. Nowadays, several state-of-the-art meta-analyses have illustrated that self-sampling techniques involving urine self-sampling represent a feasible alternative strategy with potentially enhanced population coverage possessing excellent performance and sensitivity. Recently published scientific work focusing on urine HPV was reviewed, and after a critical appraisal, the following points should be considered in the clinical application of hrHPV urine measurements; (i) use of first-void urine (FVU) and purpose-designed collection devices; (ii) using a preservation medium to avoid human/HPV DNA degradation during extraction and storage; (iii) using polymerase chain reaction (PCR) based assays, ideally with genotyping capabilities; (iv) processing of a sufficient volume of whole urine; and (v) the use of an analytically sensitive HPV test/recovery of cell-free HPV DNA in addition to cell-associated DNA.

The objective of this study was to investigate the hypothesis that HPV vaccination administered in patients with low-grade (LG) cytology shortly after an initial colposcopic assessment could prospectively alter HPV-related biomarkers. This was a prospective pilot observational study involving women attending a colposcopy clinic for evaluation of abnormal LG cytology that were advised to undergo HPV vaccination and proceeded accordingly. These women were compared with a matched unvaccinated group. Women requiring cervical biopsies or CIN treatment were excluded. Intervention: A full three-dose HPV vaccination was undertaken with either the 2-valent or the 4-valent anti-HPV VLP vaccine. LBC samples were obtained prior and after the completion of the vaccination regimen and tested for HPV DNA genotyping (CLART-2 HPV test) and E6 and E7 mRNA (NASBA technique). Results: Alterations of HPV-related biomarkers at a colposcopy reassessment appointment 12 months later. Analysis: The p-values, relative risk (RR), absolute relative risk (ARR), number needed to treat (NNT) and 95% confidence intervals for each biomarker in each group were assessed. Results: A total of 309 women were included in the analysis. One hundred fifty-two women received the vaccine. HPV vaccination reduced in a statistically significant manner (p < 0.05) HPV DNA positivity rates for genotypes 16, 18, and 31, RR = 1.6 (95% CI: 1.1 to 2.3), RR = 1.7 (95% CI: 1.1 to 2.8), and RR = 1.8 (95% CI: 1.0 to 2.9), in women who only tested DNA-positive for HPV16, 18, and 31 genotypes, respectively, prior to vaccination. A less pronounced, statistically insignificant reduction was shown for women who tested positive for both HPV DNA and mRNA E6 and E7 expression for HPV16, 18, and 33 subtypes. Statistically significant reduction in HPV mRNA positivity was solely documented for genotype 31 (p = 0.0411). Conclusions: HPV vaccination appears to significantly affect the rates of HPV16, 18, and 31 DNA-positive infections in the population testing HPV DNA-positive for the aforementioned genotypes. The above findings deserve verification in larger cohorts.

The aim of this study was to investigate the feasibility of texture analysis in characterizing endometrial tissue as depicted in two-dimensional (2D) grayscale transvaginal ultrasonography. Digital transvaginal ultrasound endometrial images were acquired from 65 perimenopausal and post-menopausal women prior to gynaecological operations; histology revealed 15 malignant and 50 benign cases. Images were processed with a wavelet-based contrast enhancement technique. Three regions of interest (ROIs) were identified (endometrium, endometrium plus adjacent myometrium, layer containing endometrial-myometrial interface) on each original and processed image. 32 textural features were extracted from each ROI employing first and second order statistics texture analysis algorithms. Textural features-based models were generated for differentiating benign from malignant endometrial tissue using stepwise logistic regression analysis. Models' performance was evaluated by means of receiver operating characteristic (ROC) analysis. The best logistic regression model comprised seven textural features extracted from the ROIs determined on the processed images; three features were extracted from the endometrium, while four features were extracted from the layer containing the endometrial-myometrial interface. The area under the ROC curve (A(z)) was 0.956+/-0.038, providing 86.0% specificity at 93.3% sensitivity using the cut-off level of 0.5 for probability of malignancy. Texture analysis of 2D grayscale transvaginal ultrasound images can effectively differentiate malignant from benign endometrial tissue and may contribute to computer-aided diagnosis of endometrial cancer.