European guidelines for quality assurance in cervical cancer screening: recommendations for collecting samples for conventional and liquid-based cytology.

The current paper presents an annex in the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to make a satisfactory conventional Pap smear or a liquid-based cytology (LBC) sample. Practitioners taking samples for cytology should first explain to the woman the purpose, the procedure and how the result will be communicated.

Persistent high risk HPV infection associated with development of cervical neoplasia in a prospective population study.

Aims: To monitor the association between the course of high risk human papillomavirus (HR-HPV) infection and the development of cervical neoplasia over time, from a baseline of normal cervical cytology.

Methods: This paper presents the follow up data from a previous cross sectional analysis. Women from a screening population who had normal cytology and who were HR-HPV positive were recalled after two to three years for cytology and HPV genotyping.

Liquid-based cytology in cervical screening: an updated rapid and systematic review and economic analysis.

Objectives: To update an earlier published report reviewing the effectiveness and cost-effectiveness of liquid-based cytology (LBC).

Data Sources: Electronic bibliographic databases, relevant articles, sponsor submissions and various health services research-related resources.

Review Methods: The selected data were reviewed and assessed with respect to the quality of the evidence.

Multiple high risk HPV infections are common in cervical neoplasia and young women in a cervical screening population.

Aims: If human papillomavirus (HPV) testing is to be included within cervical screening programmes, the importance of multiple HPV infections in cervical neoplasia needs to be determined. This study investigated the diversity of multiple HPV types in a routine cervical screening population, and assessed associations with cervical neoplasia.

Methods: Overall HPV prevalence, type specific prevalence, and extent of multiple infection were assessed in residual material from 3444 liquid based cytology samples, using real time GP5+/GP6+ polymerase chain reaction for screening and linear array assay for genotyping.

Management of women who test positive for high-risk types of human papillomavirus: the HART study.

Background: Certain types of human papillomavirus (HPV) are the primary cause of almost all cervical cancers. HPV testing of cervical smears is more sensitive but less specific than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). HPV testing as a primary screening approach requires efficient management of HPV-positive women with negative or borderline cytology.

Cervical cancer control, priorities and new directions.

Cervical cancer is caused by infection with a range of high risk "oncogenic" human papillomavirus (HPV) types, and it is now accepted that >99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than 1 in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, screening for persistent HPV infection is effective in reducing the incidence of cervical cancer.

Rapid real time PCR to distinguish between high risk human papillomavirus types 16 and 18.

Aims: To assess the validity and practicality of real time polymerase chain reaction (PCR) for human papillomavirus (HPV) testing in combination with liquid based cytology samples for cervical screening.

Methods: Real time PCR using consensus (GPS+/6+) and type specific primers was developed to detect genital HPV types. This provides rapid, efficient amplification followed by denaturation of the product and computer analysis of the kinetics data that are generated.

The borderline cervical smear: colposcopic and biopsy outcome.

Aims: To review the outcome of women referred with smears showing borderline nuclear change (BNC), and to determine any differences in outcome if BNC was persistent, preceded by dyskaryosis, or followed treatment for cervical intraepithelial neoplasia (CIN). In addition, to determine criteria that might permit delineation of a BNC subtype, predictive of CIN.

Methods: The records of 178 women referred for colposcopy in 1993, with last smear showing BNC, were obtained from our laboratory database.

Detection of high-risk human papillomavirus nucleic acid in archival cervical smears.

Objective: To test the usefulness of a commercial DNA hybridization assay for the detection of high-risk (HR) human papillomavirus (HPV) types in archival cervical smears and to compare the sensitivity with that of polymerase chain reaction (PCR) using consensus primers.

Study Design: Stained material was scraped from archival slides and the pellet volume noted. DNA was extracted using silica/guanidinium isothiocyanate and the quality checked by amplification of the beta-globin gene.

Anal cytological abnormalities in HIV-infected homosexual men.

This study aimed to examine the prevalence of anal cytological abnormalities in groups of HIV-infected and non-infected homosexual men, and to monitor changes with time. Dyskaryosis suggestive of anal intraepithelial neoplasia (AIN) was noted in 24 (30%) of the 80 satisfactory anal smears from 66 HIV-seropositive homosexual men; such changes were found in only 7 (4.7%) of the 149 satisfactory smears from 181 HIV-seronegative homosexual men (P < 0.

Digital imagery/telecytology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

Issues: Optical digital imaging and its related technologies have applications in cytopathology that encompass training and education, image analysis, diagnosis, report documentation and archiving, and telecommunications. Telecytology involves the use of telecommunications to transmit cytology images for the purposes of diagnosis, consultation or education. This working paper provides a mainly informational overview of optical digital imaging and summarizes current technologic resources and applications and some of the ethical and legal implications of the use of these new technologies in cytopathology.

Quality assurance/control issues. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

Issues: General definitions of quality assurance and quality control (QA/C) have existed in many forms for decades, and a new discipline guides their application to diverse industrial and recently medical processes without much fanfare. However, in the field of cervical cytology screening, the range of QA/C options has recently broadened and become controversial. With the advent of new systems of terminology, larger-scale laboratories and new technologies--plus strong governmental and legal pressures in some nations--the range of extremely difficult and sometimes expensive QA/C choices our community faces is greater than ever.

Cell preparation methods and criteria for sample adequacy. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

Issues: Cell Preparation Methods Standardized fixation and optimal staining Sampling of cervix, sampling error, homogenization of sample, subsampling Assessment of liquid-based preparations: efficacy and economic impact Training and transitional procedures before full implementation of new technologies Criteria for Sample Adequacy Clinician responsibility for collecting and providing representative sample to laboratory Collection instruments, number of slides Cellular content of samples: evidence of transformation zone (TZ) sampling, number of squamous cells present, obscuring factors Screening issues CONSENSUS POSITION The conventional cervical smear remains the standard method of cervical cancer screening but has limitations in individual test sensitivity and specificity. Sample takers should: (1) receive appropriate training in sample collection, (2) be held responsible for providing the laboratory with appropriate samples, and (3) have their performance monitored. The instruments used for sampling should collect cells from both the ectocervix and endocervix; optimally, TZ sampling, represented by the presence of endocervical or squamous metaplastic cells, should be identifiable in samples other than atrophic specimens.

Expression of p21waf1/Cip1, MDM2 and p53 in vivo: analysis of cytological preparations.

The aim of this study was to test the hypothesis that expression of p21waf1/Cip1 and MDM2 could be used as indicators of the activity of wild-type p53 which can transcriptionally activate the p21waf1/Cip1 and mdm2 genes. In cytological preparations of serous fluids, the expression of p53, p21waf1/Cip1 and MDM2 protein was assessed by immunohistochemistry. A series of 50 cases was assessed for both p53 and p21waf1/Cip1 expression and a subset of 37 cases had sufficient material for analysis of MDM2.

Would monolayers provide more representative samples and improved preparations for cervical screening? Overview and evaluation of systems available.

Conventional cervical smears prepared on site by the smear taker are subject to great variation in technical quality and allow little control of the critical parameters required for optimal microscopic diagnosis. More critical, however, is that a significant proportion of the cells removed from the cervix are discarded along with the collecting device and that the material placed on the slide is not transferred in a representative way and may not fully represent the cells removed from the cervix. If the cells were placed directly into preservative fluid, all the material scraped from the cervix would be sent to the laboratory in a well-preserved state, and fully representative slides could be prepared.

A collaborative trial of a semi-automatic system for slide preparation and screening in cervical cytopathology.

We report a test of an experimental system for machine-aided screening in cervical cytology, comprising the 'CYTOPRESS' semi-automatic slide preparation system (Nijmegen) and the 'CERVIFIP' interactive scanner (Edinburgh). Material from women attending clinics in Edinburgh and Nijmegen was stratified according to the severity of the conventional laboratory diagnosis and selected randomly within strata for inclusion in the test. Monolayered slides were prepared by CYTOPRESS from cervical scrape material remaining after preparation of conventional smears and scanned by CERVIFIP to determine the positions of the most 'suspicious' objects.

A population-based, controlled study of the relation between HIV infection and cervical neoplasia.

Objective: To study a geographically defined population of women exposed to a drug-related risk for human immunodeficiency virus (HIV), together with carefully matched neighbourhood controls, in order to examine (1) the proportion of different groups having cervical cytopathology screening; (2) the association between HIV infection and cervical intraepithelial neoplasia; (3) the independent effect of CD4+ lymphocyte count and duration of HIV infection; and (4) the correspondence between cervical cytopathology and colposcopically directed biopsy.

Design: A population-based study.

Subjects: All women domiciled in Lothians with the following characteristics: between 1983 and 1987 they had a history of injection drug use or a seropositive partner with a history of injection drug use; they had a pregnancy after that exposure where their serostatus was known.

Fine needle aspiration cytology of breast in invasive carcinoma of tubular type and in radial scar/complex sclerosing lesions.

Fine needle aspirates (FNA) from 31 invasive carcinomas of tubular type and 22 radial scar/complex sclerosing lesions (RS/CSL), diagnosed in Edinburgh between 1986 and 1991, were reviewed. The lesions in this study varied in size and palpability at presentation, but are of increasing interest in the differential diagnosis of non-palpable areas of increased mammographic density. In agreement with previously published information, it was found that the tubular cancers were usually selected for biopsy following aspiration, but less often definitively diagnosed as malignant.

The cytological detection of persistent cervical intraepithelial neoplasia after local ablative treatment: a comparison of sampling devices.

Objective: To determine whether the cytological detection of persistent cervical intraepithelial neoplasia (CIN) after local ablative treatment is improved by the use of sampling devices other than the Ayre's spatula.

Design: A randomized controlled study.

Setting: Lothian Area Colposcopy Clinic.