Jeffrey Tan

Precancerous changes in the cervix and risk of subsequent preterm birth

Objective  The aims of this study were (i) to examine whether women referred for assessment of precancerous changes in the cervix had higher rates of preterm birth compared with those in the general population and (ii) to compare preterm birth rates for treated and untreated women adjusting for possible confounding factors.

Comparison of the Digene Hybrid Capture 2 Assay and Roche AMPLICOR and LINEAR ARRAY Human Papillomavirus (HPV) Tests in Detecting High-Risk HPV Genotypes in Specimens from Women with Previous Abnormal Pap Smear Results

ABSTRACT The development of cervical cancer is strongly associated with the presence of persistent high-risk (HR) human papillomavirus (HPV) infection. Recently, the commercially manufactured PCR-based Roche AMPLICOR (AMP) and LINEAR ARRAY (LA) HPV tests have become available for HPV detection. However, knowledge of their clinical performance compared to the U.S. Food and Drug Administration-approved Hybrid Capture 2 (HC2) assay is limited. This study evaluated the concordance between the HC2, AMP, and LA tests in detecting HR-HPV among a cohort of 1,679 women with previous abnormal Pap smear results. Overall, 1,393 specimens (81.3%) generated concordant results for HR-HPV presence or absence by the three assays. The concordance levels were substantial between the HC2 and AMP tests (84.4%, κ = 0.6419) and between the HC2 and LA tests (84.0%, κ = 0.6341) and nearly perfect between the AMP and LA tests (97.8%, κ = 0.9441). HR-HPV prevalence, as detected by the AMP or LA tests, was significantly higher among women with cytological or histological high-grade disease (CIN2 or greater) than that detected by HC2 (P < 0.0001). The AMP and LA tests exhibited greater sensitivity, but lower specificity, than HC2 for detecting HR-HPV among this cohort of women with underlying cervical abnormalities, particularly among subjects with histologically proven high-grade disease. Both PCR-based HPV tests may be valuable in the management of care for women with underlying cervical abnormalities, in predicting treatment success, and in studying the clearance or acquisition of new infections.

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.

ABNORMAL CERVICAL CYTOLOGY IN PREGNANCY : EXPERIENCE OF 811 CASES

Summary: This paper reviews our hospitals experience spanning 15 years and involving 811 women referred with abnormal cervical cytology in pregnancy. It supports the safety and accuracy of managing dysplasia in pregnancy with colposcopy, directed punch biopsy and deferral of treatment until the postpartum period. The histologically‐proven progression in pregnancy to a higher grade of dysplasia postpartum was 7%. None of the women are known to have developed microinvasive or invasive cancer between antenatal assessment and postpartum review. Of these 811 women, 16% were lost to follow‐up, 1 of whom subsequently represented 4 years later with invasive cervical cancer.

Persistent trophoblast disease following partial molar pregnancy

Objective:  Human chorionic gonadotrophin (hCG) follow‐up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Womens Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following partial molar pregnancy and to review the present follow‐up protocol of patients suffering from partial hydatidiform molar pregnancy (PHM).

HPV genotype prevalence in women with abnormal pap smears in Melbourne, Australia.

Carcinoma of the cervix and its precursor, high‐grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent oncogenic Human papillomavirus (HPV) infection, particularly HPV 16 and 18. HPV genotype distribution varies with severity of cervical disease, patient demographics such as age, as well as geographical location. In this study, HPV genotype prevalence was determined, using the Roche Linear Array genotyping test, among a cohort of 1,676 women being managed with ablative or excisional treatment following colposcopically directed biopsies, who were referred initially due to cytological abnormalities. HPV genotype prevalence, including presence of single and multiple infections was assessed against both histological diagnosis and age. Overall, 83.9% of women were identified as HPV positive, comprising of 32.2% single and 51.7% multiple HPV infections. Of those with an available histological diagnosis at time‐of‐treatment (n = 899), HPV positivity increased significantly with disease severity: 62.4% (normal), 77.6% (CIN1), 92.6% (CIN2), and 97.9% (≥CIN3) (P < 0.006). Similarly, a significant increase in high‐risk (HR) HPV detection was observed with severity of disease (P < 0.005). The five most prevalent genotypes were HPV 16 (35.1%), 31 (12.6%), 51 (11.1%), 52 (9.9%), and 18 (8.5%). HPV 16 was the only genotype to demonstrate a significant increase in prevalence with increasing severity of histological or cytological disease (P < 0.0001). Multiple HPV infections, including multiple HR‐HPV infections, declined significantly with age (P < 0.02). These findings provide the largest dataset of HPV genotype prevalence rates within Australian women, though are not representative of the general population. J. Med. Virol. 81:1283–1291, 2009.

Guidelines following hydatidiform mole: a reappraisal.

Objective:  The aim of this study was to determine how often patients with complete hydatidiform mole (CHM) who spontaneously achieve normal human chorionic gonadotrophin (hCG) levels subsequently develop persistent or recurrent gestational trophoblast disease.

Does experience in colposcopy improve identification of high grade abnormalities

OBJECTIVE This study investigates whether experience in colposcopy improves identification of high grade abnormalities. The sensitivity and positive predictive value (PPV) of colposcopy in identifying high grade intra-epithelial lesions (HSIL) performed by relatively inexperienced as compared to experienced colposcopists are evaluated. STUDY DESIGN Of 18,421 colposcopies performed at the Royal Womens Hospital, Melbourne, Australia, between 1999 and 2004 by 5 senior and 11 junior colposcopists, the colposcopic impression was correlated with the histopathology result of the biopsy taken at 6020 colposcopies, with respect to the experience of the colposcopist. RESULTS Colposcopy had a 60% sensitivity and 60% PPV in identifying HSIL in this study. In case of a high-grade referral smear the sensitivity and PPV in identifying HSIL were, respectively 76% and 73%, compared with 26% and 48% in case of a low-grade referral smear, no difference in overall colposcopic performance between experienced and inexperienced colposcopists was observed. However, the sensitivity of identifying HSIL was significantly higher with inexperienced colposcopists, and the PPV was significantly higher with experienced colposcopists. CONCLUSION In this study experience did not improve colposcopic performance, but differences in colposcopic strategy between the two groups were noted. The rather low overall sensitivity and PPV of colposcopy in identifying HSIL, especially in case of a low-grade referral smear, indicate that the role of colposcopy in the detection and treatment of cervical abnormalities is to assess size, site, and extent of an abnormality, rather than to assess the severity of this abnormality. Histology must remain the gold standard for treatment.

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

BackgroundThe 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. In one (sub study A), the prevalence of the vaccine-targeted human papillomavirus genotypes in a population cohort is being estimated, and will be analysed in relation to vaccination status, cervical cytology screening status, demographic, social, behavioural, medical and clinical factors. In sub study B, the distribution of human papillomavirus genotypes detected in high grade cervical intraepithelial neoplastic lesions from vaccine eligible women is being assessed.Methods/DesignSub Study A involves the recruitment of 1569 women aged 18–25, residing in Victoria, Australia, through Facebook advertising. Women who are sexually active are being asked to provide a self-collected vaginal swab, collected at home and posted into the study centre, where human papillomavirus DNA detection and genotyping is performed. Participants also complete an online questionnaire regarding sexual history, experience with, knowledge of, and attitudes towards human papillomavirus, the human papillomavirus vaccine, and cervical screening.Sub Study B will involve the collection of 500 cervical biopsies, positively identified as containing high grade cervical intraepithelial neoplastic lesions and/or adenocarcinoma in situ. Five serial sections are being taken from each case: sections 1 and 5 are being assessed to confirm the presence of the high grade cervical intraepithelial neoplastic lesions or adenocarcinoma in situ; human papillomavirus genotyping is performed on sections 2 and 3; single lesions are excised from section 4 using laser capture microdissection to specifically define causality of a human papillomavirus genotyping of each specific lesion.DiscussionAustralia is well placed to gain a clear and early insight into the effectiveness of the human papillomavirus vaccine in reducing the prevalence of human papillomavirus infection in young women, and any subsequent reduction in the prevalence of pre-cancerous cervical lesions, specifically high grade cervical intraepithelial neoplasia lesions, particularly of vaccine related types. The findings of a successful population based human papillomavirus program will have wide-reaching translational benefits across the globe.

Confocal endomicroscopy: a novel maging technique for in vivo histology of cervical intraepithelial neoplasia

Optical imaging technologies, such as reflectance and fluorescence spectroscopy, have shown the potential to provide enhanced detection of changes in the uterine cervix at clinical examination. This review focuses on fluorescence confocal endomicroscopy that enables in vivo microscopic imaging of the cervical epithelium in histological detail in real time. The microscopic imaging technique may permit ‘see-and-treat’ workflows in colposcopy through high-resolution fluorescence imaging of cellular and subcellular detail from the surface and subepithelial layers of the cervical mucosa. The device may be used in conjunction with a conventional colposcope. Preliminary data from clinical studies suggest that the device can be used to visualize features of the cervical epithelium including the squamo–columnar junction, dermal papillae and endocervical glands. Moreover, the technique has the ability to detect and grade precancerous changes of the cervical epithelium in conditions, such as cervical intraepithelial neoplasia, where prediction using colposcopy may be problematic. The early detection and diagnosis of gynecological abnormalities through the collection of ‘optical’ biopsies or targeted mucosal excisional biopsies have the potential to improve patient management through early therapeutic intervention and ‘see-and-treat’ strategies.