Pre-Vaccination Human Papillomavirus Genotypes and HPV16 Variants among Women Aged 25 Years or Less with Cervical Cancer.

Background: In 2007, Australia introduced a national human papillomavirus (HPV) vaccination program. In 2017, the onset of cervical screening changed from 18 to 25 years of age, utilising human papillomavirus (HPV) nucleic acid testing. The objective of the study is to describe the HPV genotypes and HPV16 variants in biopsies from women ≤ 25 years of age with cervical carcinoma (CC) (cases), compared with those aged >25 years (controls), in a pre-vaccination cohort.

p53 immunohistochemistry in endometrial cancer: clinical and molecular correlates in the PORTEC-3 trial.

Standard molecular classification of endometrial cancers (EC) is now endorsed by the WHO and identifies p53-abnormal (p53abn) EC as the subgroup with the poorest prognosis and the most likely to benefit from adjuvant chemo(radio)therapy. P53abn EC are POLE wildtype, mismatch repair proficient and show abnormal immunohistochemical (IHC) staining for p53. Correct interpretation of routinely performed p53 IHC has therefore become of paramount importance.

Assessment of attribution algorithms for resolving CIN3-related HPV genotype prevalence in mixed-genotype biopsy specimens using laser capture microdissection as the reference standard.

To make accurate determinations regarding potential and actual impact of HPV vaccine programs, precise estimates of genotype-specific contributions to disease are required for pre- and post-vaccine populations. Definitive determination of lesion-specific genotypes, particularly where multiple genotypes are detected in a sample, can be technically demanding and resource intensive; therefore, most prevalence studies use mathematical algorithms to adjust for multiple genotype detections. There are currently several algorithms, which can produce genotype estimates within a wide range of variability.

Long-term Outcomes Following Multilevel Surgery in Cerebral Palsy.

Background: This long-term consecutive, retrospective single-center cohort study evaluates long-term outcomes of single-event multilevel surgery in diplegic cerebral palsy with respect to functional status, gait, and patient satisfaction.

Methods: All patients with diplegic cerebral palsy who underwent single-event multilevel surgery >10 years previously were included. Retrospective gait assessment was performed using the Edinburgh Visual Gait Score (EVGS) and Gillette Functional Assessment Questionnaire Walking Scale (FAQWS) preoperatively and at midterm postoperative follow-up (median 2.

Therapeutic options for mucinous ovarian carcinoma.

Objective: Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC.

The molecular origin and taxonomy of mucinous ovarian carcinoma.

Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin.

Interobserver agreement and diagnostic performance of individual MRI criteria for diagnosis of placental adhesion disorders.

Aim: To assess the diagnostic accuracy of several criteria for the diagnosis of placental adhesion disorder (PAD) on magnetic resonance imaging (MRI) and to assess interobserver agreement and reader accuracy based on years of interpretive experience.

Materials And Methods: Blinded evaluation of the placental MRI studies of 28 randomly selected women, 18 with PADs and 10 without PADs, was undertaken by three radiologists with 10, 5, and 2 years' experience in placental MRI interpretation. The presence of placenta praevia, dark intraplacental bands, heterogeneity, uterine bulging, "shaggy dog" appearance of the uterine serosa, subjective impression of extraplacental invasion, and dark intraplacental bands on diffusion-weighted imaging were assessed.

Histologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age.

Background: To explore the associations between histologic chorioamnionitis with brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm infants at term equivalent age.

Methods: Preterm infants (23-36 weeks' gestational age) were recruited into two longitudinal cohort studies. Presence or absence of chorioamnionitis was obtained from placental histology and clinical data were recorded.

Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer.

Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.

Looking beyond human papillomavirus (HPV) genotype 16 and 18: Defining HPV genotype distribution in cervical cancers in Australia prior to vaccination.

Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection.

Histological changes in the umbilical artery following severe chorioamnionitis and funisitis may be indicative of early atherosclerosis.

We investigated whether histological evidence of early atherosclerosis was present in the umbilical artery of 21 pregnancies complicated by severe perinatal inflammation, and 21 controls matched for gestational age, sex and birth weight. Severe chorioamnionitis with funisitis was associated with increased numbers of CD68 and CD45 positive cells (both P < 0.01), indicating accumulation of monocyte-derived macrophages in lesion-susceptible regions.

Inflammation, lipids and aortic intima-media thickness in newborns following chorioamnionitis.

Aim: This study investigated whether chorioamnionitis was associated with increased inflammation, dyslipidaemia and adverse cardiovascular phenotypes in the immediate postnatal period.

Methods: This prospective case-control study included preterm infants (30(+0) -35(+6) weeks gestational age, GA) whose mothers did not have pregnancy-related conditions that may influence outcomes. Chorioamnionitis was diagnosed by placental histology, and infants were divided retrospectively into cases (chorioamnionitis-exposed) and controls (unexposed).

Literature Review of Benign Müllerian Papilloma Contrasted With Vaginal Rhabdomyosarcoma.

Study Objectives: Benign müllerian papillomas of the genital tract are rare and, hence, can be mistaken for vaginal rhabdomyosarcoma on initial clinical review. This review of the literature will consolidate the previous cases of müllerian papilloma reported and looks for clues to differentiate the 2 entities.

Design And Setting: We provide a case report and literature review, with patients from a pediatric adolescent gynecology clinic in a tertiary center.

Whole-genome characterization of chemoresistant ovarian cancer.

Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance.

How best to interpret mixed human papillomavirus genotypes in high-grade cervical intraepithelial neoplasia lesions.

Objectives: This study aimed to determine human papillomavirus (HPV) genotypes present in biopsy sections from young women of vaccine eligible age living in Victoria, Australia, with confirmed cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) using laser capture microdissection (LCM).

Methods: Histologically confirmed CIN3 or AIS positive biopsies from vaccine eligible women (born after 30th June 1981, n=169), between May 2011 and March 2013, were identified. CIN3 or AIS lesions were isolated from biopsy material using LCM, and the HPV genotypes present in whole tissue sections (WTS) as well as LCM-isolated lesion tissue were determined by a sensitive reverse hybridisation assay; RHA kit HPV SPF10-LiPA25, version 1 (Labo Bio-medical Products, Rijswijk, The Netherlands).

Molecular correlates of platinum response in human high-grade serous ovarian cancer patient-derived xenografts.

Introduction: Improvement in the ability to target underlying drivers and vulnerabilities of high-grade serous ovarian cancer (HG-SOC) requires the development of molecularly annotated pre-clinical models reflective of clinical responses.

Methods: We generated patient-derived xenografts (PDXs) from consecutive, chemotherapy-naïve, human HG-SOC by transplanting fresh human HG-SOC fragments into subcutaneous and intra-ovarian bursal sites of NOD/SCID IL2Rγ(null) recipient mice, completed molecular annotation and assessed platinum sensitivity.

Results: The success rate of xenografting was 83%.

Measuring effectiveness of the cervical cancer vaccine in an Australian setting (the VACCINE study).

Background: The quadrivalent human papillomavirus vaccine has been provided in Australia through the National Human Papillomavirus Vaccination Program since April 2007. National registry data demonstrates good coverage of the vaccine, with 73% of school-aged girls having received all three doses. To evaluate the effectiveness of the program, we propose a two-pronged approach.

Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: molecular phenotype of chemoresistant ovarian tumors.

Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD) and non-adherent (NAD) cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN) and 14 chemoresistant (CR).

Predictive value of magnetic resonance imaging in assessing myometrial invasion in endometrial cancer: is radiological staging sufficient for planning conservative treatment?

Objectives: There has been an increasing interest in accurately assessing tumors preoperatively to plan appropriate surgery or, in some low-risk patients, conservative treatment. We wish to determine the accuracy of magnetic resonance imaging (MRI) in predicting myometrial invasion in endometrial cancer and whether it is a safe and suitable tool for planning conservative treatment.

Materials And Methods: We compared MRI scans and final histopathologic diagnoses of 111 patients with endometrioid adenocarcinoma over a 6-year period at a major tertiary centre.

Detection of cervical intraepithelial neoplasia in vivo using confocal endomicroscopy.

Objective: A high resolution optical imaging device may offer a clinically useful adjunct to colposcopy for the diagnosis and assessment of cervical precancer. This study describes the clinical evaluation of a miniaturised confocal endomicroscope for the quantitative and qualitative assessment of cervical intraepithelial neoplasia (CIN) in vivo.

Design: A descriptive study (n = 25) was performed to assess the usability of confocal endomicroscopy to image the cervix.

Mammary-like gland adenoma of the vulva: review of 46 cases.

Aims: Hidradenoma papilliferum (HP) of the anogenital region, which was previously thought to be an apocrine tumour, is now believed to be derived from anogenital mammary-like glands (MLG) and is more accurately termed MLG adenoma. We sought to explore any ramifications that may have resulted from the perceived change in histogenesis of this tumour.

Methods: We performed a clinicopathological audit of 46 cases.

Bilateral hip reconstruction in severe whole-body cerebral palsy: ten-year follow-up results.

The results of a functional, clinical and radiological study of 30 children (60 hips) with whole-body cerebral palsy were reviewed at a mean follow-up of 10.2 years (9.5 to 11).