Cervical screening adjuncts: Recent advances☆,☆☆,★
Section snippets
False-negative Papanicolaou smears
The concerns with regard to cervical cytologic testing center around the perception that its sensitivity is unacceptably low. However, it should be remembered that the Papanicolaou smear is a highly specific test with regard to high-grade squamous intraepithelial lesions (SILs) and cancers, although somewhat less specific in low-grade SILs. Furthermore, because sensitivity and specificity are a tradeoff, increasing the sensitivity will likely result in a decrease in specificity.
A screening test
Technique of cervical cytologic studies
Before we explore many of the new and sophisticated ways to reduce the false-negative rate of Papanicolaou smear testing, attention should be focused on maximizing the quality of the smear by the use of proper technique.
Smears are obtained before any digital examination. Lubricants and douches should be avoided for 24 hours before the examination. The patient should not be bleeding and should not have marked vaginitis. An ectocervical scrape should be obtained with a moistened Ayres spatula,
Automated cytologic screening
Mathematic models10 have suggested that 100% manual rescreening is the most effective method for reducing cytologic screening errors, and this has always been considered the “gold standard” with which other rescreening modalities have been compared. However, screening results are dependent on the test screening environment. Bosch et al11 tested cytotechnologists to determine whether they were able to detect disease on slides originally identified as positive and those falsely identified as
Effectiveness of automated cytologic screening as a rescreening tool
When all negative smears were processed by the AutoPap system and the smears with the highest quality control scores (top 10%) were rescreened manually, AutoPap detected 52.4% of the low- grade and high-grade lesions and carcinomas that were originally read as negative and were detected by a parallel 100% manual rescreening of the slides.20 In other words, under these circumstances AutoPap is half as sensitive to false-negative smear results as 100% manual rescreening but 5 times better than
Effectiveness of automated cytologic tests as a primary screening tool
PapNet is not currently approved by the Food and Drug Administration for primary screening, whereas AutoPap was recently approved for this use. Also, the method by which they would function as primary screeners differs between the two systems. The AutoPap system functions to remove a certain percentage (currently 25%) of adequate and normal smears from the cytotechnologist’s workload. Future advances may also mark the location of the significant cellular abnormalities by means of a computer
Cost-effectiveness of automated cytologic studies
AutoPap and PapNet function differently in their approach to cost savings. As a primary screener, AutoPap aims to remove a percentage of slides from the cytotechnologists’ workload, thereby saving money. Lee et al25 showed that AutoPap was able to maintain 96.9% sensitivity among a training set of 4174 slides while eliminating 30% of slides from the workload. As a primary screener, PapNet aims to reduce costs by presenting the most diagnostic cells to the cytotechnician in a well-organized
Fluid-based technology
Fluid-based technology (monolayers) also uses cytologic studies to detect cervical neoplasia; however, it changes the methods by which the cells are collected and processed. Its aim is to reduce the incidence of false-negative cytologic findings by optimizing the collection and preparation of cells.
Two systems are currently available, which create a monolayer for cervical cytologic studies. One (ThinPrep, Cytyc Corporation, Boxborough, Mass) is approved by the Food and Drug Administration,
Effectiveness of fluid-based technology
Before the clinical experience with monolayers is reviewed, it is important to note that the cytologic collection device can have a major impact on the number of cells deposited in both conventional smears and monolayers. Although the combination of an endocervical brush and a spatula deposited more cells on the slide with a conventional smear, the Cervex-Brush (Unimar, Wilton, Conn), which is used in many of the monolayer trials, collects almost twice as many epithelial cells compared with any
Cost-effectiveness of fluid-based technology
The cost of ThinPrep may be twice the cost of conventional cytologic studies when all the variables are considered, including the greater cost of supplies, longer slide preparation time, and shorter slide evaluation time for ThinPrep.36 Because the area on the slide that is covered by the monolayer is only 20 mm in diameter (13 mm for CytoRich), monolayers are routinely assessed in half the time required for conventional smears.39, 43 However, experience with monolayers suggests that the
HPV testing
Most of the present data derived from clinical and epidemiologic studies support the preeminent role of HPV in cervical carcinogenesis.44, 45 We know that >80 different genotypes of HPV exist. Approximately 20 of them infect the cervix. These can be divided into high-risk HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58) and low-risk types (HPV 6, 11, 42, 43, and 44). A number of studies46, 47 have shown that women infected by HPV 16 or 18 have a higher rate of progression of
Techniques for HPV detection
A crucial factor in analyzing the value of HPV testing is the sensitivity of the test being used. Several tests are available for detecting HPV. A brief summary of the various methods available for the detection of HPV is outlined inTable I.
Method Sensitivity Specificity Comment Cytology Low Low Easy, relatively inexpensive, but subjective, insensitive, and nonspecific Dot blot Moderate Moderate Radioactive, commercially available as ViraPap,
Uses of HPV testing
To understand the potential role that HPV testing may have in cervical cancer screening, our knowledge of the natural history of HPV infection must be reviewed. The prevalence of HPV varies dramatically, depending on the population studied. In a population-based study with cervical cytologic studies to detect HPV, Syrjanen et al68 found HPV in 0.8% of 63,115 women aged 20 to 65 years. De Villiers et al,69 with Papanicolaou smear and filter in situ hybridization, found HPV in 9% of women aged 15
Cervicography
As far back as 1958, Navratil et al88 showed that the combination of cytologic examination and colposcopy detected 98% of all lesions compared with 88% for cytologic examination alone. These studies were confirmed by Limburg89 and by Kern.90 However, screening colposcopy has limitations because it requires a considerable amount of expertise, the equipment is expensive and not portable, and it is time-consuming.
In 1981 a technique called cervicography was introduced by Adolf Stafl.91 By the use
Speculoscopy
Speculoscopy is a new visual endoscopic examination that uses specialized “blue- white” chemiluminescent light, along with acetic acid and low-power magnification, to screen patients for cervical disease.104
The cervix and the vagina are washed with 3% to 5% acetic acid. An activated blue-white chemiluminescent light that uses peroxyoxalate chemical means is attached to the inner aspect of the upper speculum blade. The room lights are dimmed, and the cervix and vagina are inspected with
Polarprobe (Polartechnics Ltd, Sydney, Australia)
This adjunctive test is different than all those previously described. Almost all diagnostic and screening tests in clinical medicine have as their basis pattern recognition skills or biochemical information. This is certainly true of manual and automated cytologic testing, histologic examination, monolayer cytologic studies, cervicography, colposcopy, and speculoscopy (all of which have as their basis automated or manual pattern recognition skills) and HPV DNA testing (which has as its basis
Comment
In the United States today, 60% of women with invasive cancer have not had a Papanicolaou smear in the previous 5 years (or have never had a Papanicolaou smear at all). Without question, the most clinically effective and cost-effective approach to reducing the incidence of cervical cancer would be to screen this unscreened population.
However, attention must also be focussed on the 4500 to 6500 women in the United States each year who have cervical cancer develop despite regular screening. Some
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Risk factors for and prevention of human papillomaviruses (HPV), genital warts and cervical cancer
2013, Journal of InfectionCitation Excerpt :Cervical cancer screening programs are designed to identify and offer treatment to females with precancerous cervical lesions and early invasive cancers in order to reduce incidence and mortality rates of ICC.87 Therefore, cervical cancer progression can be prevented through early detection of HPV and treatment of precancerous lesions.88 In 2004, an IARC Working Group on the Evaluation of Cancer Preventive Strategies concluded there was sufficient evidence that high-quality cervical cancer screening for 35–64 year old females every three to five years could reduce ICC incidence by 80%.87
Human papillomavirus detection and utility of testing
2007, Clinical Microbiology NewsletterComparison of computer-assisted and manual screening of cervical cytology
2007, Gynecologic OncologyCitation Excerpt :Two computer screening systems were approved by the U.S. Food and Drug Administration (FDA) in the 1990s. The PAPNET system (Neuromedical Systems Inc., Suffern, NY) and AutoPap 300 QC (NeoPath, Redmond, WA) were approved to screen previously (manually) screened conventional Pap smears to identify screening false-negative results [3]. The AutoPap system was later approved for primary screening and is currently marketed as FocalPoint™ (Tripath Imaging, Inc., Burlington, NC).
A clinical study of optical biopsy of the uterine cervix using a multispectral imaging system
2005, Gynecologic OncologyCorrelation of metabolites in saliva and in vivo tissue of oral cancer patients based on fluorescence spectral deconvolution
2020, Progress in Biomedical Optics and Imaging - Proceedings of SPIEHuman papillomavirus genotyping by surface plasmon resonance-based test
2016, Clinical Laboratory
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From the Department of Obstetrics and Gynecology, Queens Hospital Center affiliated with the Mount Sinai School of Medicine.
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Reprint requests: Mark Spitzer, MD, Director, Department of Obstetrics and Gynecology, Queens Hospital Center, 82-68 164th St. B Building, Room 210, Jamaica, NY 11432.
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