Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs.

Our objective was to review current large studies of human papillomavirus (HPV) DNA testing as an adjunct to the Papanicolaou test for cervical cancer screening programs. We analyzed 10 large screening studies that used the Hybrid Capture 2 test and 3 studies that used the polymerase chain reaction test in a manner that enabled reliable estimates of accuracy for detecting or predicting high-grade cervical intraepithelial neoplasia (CIN). Most studies allowed comparison of HPV DNA and Papanicolaou testing and estimates of the performance of Papanicolaou and HPV DNA as combined tests.

Short-term urogenital effects of raloxifene, tamoxifen, and estrogen.

Objective: The purpose of this study was to assess the urogenital effects of raloxifene, tamoxifen, conjugated equine estrogen, and placebo in healthy postmenopausal women.

Study Design: This randomized, double-blind, placebo-controlled study compared the urogenital effects of 0.625 mg of conjugated equine estrogen (n = 15 women), 20 mg of tamoxifen (n = 14 women), 60 mg of raloxifene, (n = 15 women), and placebo (n = 13 women).

Proliferative activity of benign and neoplastic endocervical epithelium and correlation with HPV DNA detection.

Recent studies have indicated that the use of the MIB-1 immunostaining may be useful in distinguishing endocervical neoplasia from benign nonneoplastic lesions. We sought to investigate this finding further with a specific emphasis on the common benign processes that may result in a nonspecific increase of MIB-1 staining. In this study we quantified the MIB-1 immunostaining in the mucinous endocervical epithelium (n=45) and in tubal metaplasia (n=28) during the proliferative and secretory phases (hormonal influence), in the mucinous endocervical epithelium in cases of cervicitis (inflammation) (n=10), in cases with a history of a recent biopsy (regeneration) (n=15), endocervical polyps (benign growth) (n=8), in the endocervical glands adjacent to a squamous intraepithelial lesion (human papilloma virus [HPV] infection) (n=63), and in in situ and invasive cervical adenocarcinomas (n=30).

Sampling, sampling errors and specimen preparation.

To obtain an adequate cervical smear for making a correct cytologic diagnosis, smear taking, laboratory handling and interpretation must be optimal. Many people are involved, and only by a combined effort of all links can this target be seriously approached: the smear takers will have to be open minded about technical improvements and read the morphologic descriptions cautiously; in the laboratory, cytotechnicians and physicians will have to challenge themselves and each other. It is mandatory to discard specimens that do not meet general standards of adequacy.

Prevalence of human papillomavirus DNA in different histological subtypes of cervical adenocarcinoma.

The prevalence of human papilloma virus (HPV) DNA in different histological subtypes of cervical adenocarcinoma and related tumors was examined using formalin-fixed, paraffin-embedded tissue samples from 105 primary cervical adenocarcinomas and adenosquamous carcinomas. Broad-spectrum HPV DNA amplification and genotyping was performed with the SPF10 primer set and line probe assay (LiPA), respectively. HPV DNA was detected in 82 of 90 (91%) mucinous adenocarcinomas, encompassing endocervical, intestinal, and endometrioid histological subtypes, and in nine of nine adenosquamous tumors (100%).

Two-stage cervical cancer screening: an alternative for resource-poor settings.

Objective: We sought to introduce 2-stage cervical cancer screening in which 2 screening tests are performed sequentially (the second test is performed only if the first result is positive), followed by treatment if both test results are abnormal.

Study Design: A total of 1423 women from Cape Town, South Africa, were screened by direct visual inspection, human papillomavirus deoxyribonucleic acid testing, cytologic testing, and cervicography. If an abnormality was identified with any test, women were referred for colposcopy.

Human papillomavirus DNA testing for cervical cancer screening in low-resource settings.

Background: In many low-resource settings, there are barriers to cytologic screening for cervical cancer. This study evaluates human papillomavirus (HPV) DNA testing as an alternative screening method.

Methods: Cervical samples from 2944 previously unscreened South African women aged 35-65 years were tested for high-risk types of HPV with the use of the Hybrid Capture I (HCI) assay.

Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry.

Management of endometrial precancers is compromised by longstanding debate over the natural history of endometrial hyperplasias and inconsistencies in their diagnosis. The recent demonstration that some hyperplasias, like cancers, are phenotypically monoclonal is useful in recognizing biological precancers. A clonal analysis has been undertaken of a series of 93 endometrial tissues and their morphology has been evaluated by subjective diagnostic classification and computerized morphometric analysis.

Effect of a unique constant-estrogen, pulsed-progestin hormone replacement therapy containing 17beta-estradiol and norgestimate on endometrial histology.

Objective: To evaluate the effect of a 17beta-estradiol(E2)/norgestimate (NGM) HRT regimen, which provides constant estrogen in combination with pulsed progestin administration, on endometrial histology in healthy postmenopausal women 40 to 65 years of age who had experienced natural menopause at least 12 months before the start of the study.

Methods: A total of 1,253 postmenopausal women were randomized to receive either continuous 1 mg E2, or constant estrogen, pulsed progestin regimens of 1 mg E2/30 microg NGM, 1 mg E2/90 microg NGM, or 1 mg E2/180 microg NGM (3 days on, 3 days off) in a 12-month, multicenter, double-blind study. Endometrial biopsies were obtained pre- and post-treatment, and were evaluated by at least 2 (if required, by 3) pathologists who were blinded with respect to treatment and to each other's diagnosis.

Evaluation of Hydro ThermAblator for endometrial destruction in patients with menorrhagia.

Objective: To describe endometrial destruction with the Hydro ThermAblator.

Design: (Canadian Task Force classification II-1).

Setting: University-affiliated hospital.

Histologic studies of the effects of circulating hot saline on the uterus before hysterectomy.

Study Objective: To evaluate a new device for endometrial ablation.

Design: (Canadian Task Force classification II-1).

Setting: University-affiliated hospital.

Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears.

Objective: The study examined interrelationships between sensitivity and specificity of "reflex human papillomavirus deoxyribonucleic acid testing" from liquid-based cervical cytologic specimens by means of receiver operator characteristics curves.

Study Design: A cohort study was performed on 265 women evaluated by colposcopy because of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion found on Papanicolaou smear.

Results: At a positive threshold of 0.

Cigarette smoking and cervical dysplasia among non-Hispanic black women.

This is the first case-control study to determine whether smoking is associated with cervical dysplasia, after adjustment for human papillomavirus (HPV) infection, among a group of non-Hispanic black women. Subjects were interviewed and asked questions about smoking and other risk factors for cervical cancer. HPV infection was determined by hybrid capture.

Comparison of two tests for detecting carcinogenic HPV in women with Papanicolaou smear reports of ASCUS and LSIL.

Background: The detection of cancer-associated types of human papillomavirus (HPV) in cervical specimens predicts the presence and future development of cervical intraepithelial neoplasia (CIN). The purposes of this study were (1) to determine the efficacy of a second-generation assay by hybrid capture (HC II) to detect carcinogenic HPV from residual cervical cells of a liquid-based cervical cytologic specimen, and (2) to compare the performance of this second-generation test with the first-generation hybrid capture (HCT) HPV test of material from direct cervical sampling to detect CIN in women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap) smear reports.

Methods: Women with a recent Pap smear report of ASCUS or LSIL had a sampling of the cervix using either an Ayre's spatula and cytobrush or an Accellon device sampling for liquid-based cytologic system HC II HPV testing, followed by a Dacron swab sampling of the cervix for standard HCT HPV testing of the paired specimens.

Triage of women with ASCUS and LSIL on Pap smear reports: management by repeat Pap smear, HPV DNA testing, or colposcopy?

Background: The purpose of this study was to determine the efficacy of a repeat Papanicolaou (Pap) smear and the Hybrid Capture tube-based (HCT) HPV DNA test for detecting cervical intraepithelial neoplasia (CIN) grade 2 or 3 in women with recent atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) Pap smear reports.

Methods: Women with a recent Pap smear report of ASCUS (n = 169) or LSIL (n = 110) had a repeat Pap smear, sampling of the cervix for HCT HPV DNA assay and a colposcopy examination. Data were evaluated using three different triage thresholds for colposcopy examination: a repeat Pap smear of persistent ASCUS or more severe dysplasia, a finding of persistent LSIL or more severe dysplasia, and a carcinogenic HPV test result.

Computerized screening devices and performance assessment: development of a policy towards automation. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

Issues: The extension of automation to the diagnostic assessment of clinical materials raises issues of professional responsibility, on the part of both the medical professional and designer of the device. The International Academy of Cytology (IAC) and other professional cytology societies should develop a policy towards automation in the diagnostic assessment of clinical cytologic materials.

Consensus Position: The following summarizes the discussion of the initial position statement at the International Expert Conference on Diagnostic Cytology Towards the 21st Century, Hawaii, June 1997.

Human papillomavirus. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

Issues: Cervical squamous cell carcinomas, adenocarcinomas and their precursors are caused by the human papillomavirus (HPV). Although HPV appears to be essential to the transformation of these epithelial cells, it is not sufficient, and a variety of cofactors and molecular events must take place between when an HPV infection occurs and a cervical cancer or its precursor develops. This review examines the data supporting these contentions, briefly outlines the molecular events that occur, considers the epidemiology and natural history of the disease, and details the implications of using HPV detection and typing in both clinical management and population-based screening programs.

Colposcopy, cervicography, speculoscopy and endoscopy. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

Issues: The colposcope was developed in 1925 and is well established in clinical gynecologic practice for defining and delineating cytologically detected lesions mainly of the cervix but also the vagina and vulva. Additionally, various endoscopic procedures in gastroenterology, pulmonary and urologic lesions enhance the cytologic detection and histologic verification of precancerous and cancerous lesions. The cost-effectiveness of all these devices and their applicability, particularly in countries with a limited health budget, is a major issue.

The AutoPap 300 QC System multicenter clinical trials for use in quality control rescreening of cervical smears: II. Prospective and archival sensitivity studies.

Background: The AutoPap 300 QC System is an automated device for the analysis of conventional cervical cytology slides. The AutoPap selects an enriched population of cases for quality control review. These studies evaluated the overall sensitivity of AutoPap device to a wider variety of cytologic abnormalities than could be analyzed in the prospective portion of the clinical trials.

The AutoPap 300 QC System multicenter clinical trials for use in quality control rescreening of cervical smears: I. A prospective intended use study.

Background: The AutoPap 300 QC System is an automated device for the analysis of conventionally prepared cervical cytology slides. The AutoPap System selects an enriched population of cases for human quality control (QC) review. The device assigns a score based on the likelihood that a slide is abnormal.

Prospects for automated cytology.

Rescreening of Pap smears using automated devices offers the ability to re-examine Paps initially interpreted as within normal limits and to use cell-sorting technology to increase the detection of missed abnormal smears. Only recently has the development of high-resolution imaging techniques and advances in computer sciences and cell classifiers enabled investigators to achieve sensitivity and specificity levels in automated screening and quality control devices.

Conventional cervical cytologic smears vs. ThinPrep smears. A paired comparison study on cervical cytology.

Objective: To compare the time required for evaluation, the diagnostic accuracy and quality of conventional glass slide smears vs. ThinPrep smears in 365 women.

Study Design: Both smears were obtained at the same time using the Accellon Combi cervical biosampler.

Diagnostic performance of Hybrid Capture human papillomavirus deoxyribonucleic acid assay combined with liquid-based cytologic study.

Objective: Our purpose was to determine the diagnostic performance of human papillomavirus deoxyribonucleic acid testing when performed on liquid-based (Thin-prep) cytologic samples.

Study Design: Thin-prep cytologic study, human papillomavirus deoxyribonucleic acid assay with probes for high oncogenic risk human papillomavirus types (16, 18, 31, 33, 35, 45, 51, 52, and 56), and cervical biopsies on women referred to colposcopy for an abnormal Papanicolaou smear were performed.

Results: Of the 364 patients, 186 (51.