Cervicography for triage of women with mildly abnormal cervical cytology results.

OBJECTIVE: To estimate the sensitivity and specificity of cervicography in detecting cervical cancer precursor lesions in women participating in the National Cancer Institute's multicenter atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion triage study (ALTS). STUDY DESIGN: Cervigrams were obtained from 3134 women with a referral Papanicolaou smear diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. Cervigram and cervical histology results were compared by using cervical intraepithelial neoplasia (CIN) 2 and CIN 3 disease end points. RESULTS: Of 3134 women, 444 had histologic findings of more than or equal to CIN 2 and 222 had CIN 3. Cervicography interpretation by using a threshold of greater than or equal to atypical had a sensitivity, specificity, and positive and negative predictive values of 79.3%, 61.0%, 13.4%, and 97.5%, respectively, for detecting greater than or equal to CIN 3. Cervicography was more sensitive (80.8% vs 57.1%), but less specific (55.7% vs 81.8%), for detecting CIN 3 in women younger than 35 years compared with women 35 years or older, respectively. CONCLUSIONS: Cervicography functioned moderately well at detecting CIN 2 or CIN 3 in women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Papanicolau smear results. Cervigram sensitivity was better for younger women.

Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia.

OBJECTIVE: To determine the ability of Multimodal Hyperspectral Imaging (MHI) to noninvasively detect, localize and diagnose cervical neoplasia. MATERIALS AND METHODS: The cervical epithelium was interrogated by MHI using tissue fluorescence and reflectance measurements after the probe was placed on the ectocervix. A Papanicolaou smear was taken, and a colposcopic examination was performed and cervical histologic specimens were collected, when indicated. MHI and Pap smear sensitivity and specificity data were compared with colposcopic and histologic results. RESULTS: Nineteen patients had CIN2 or higher, 30 had CIN1, 34 had benign cellular changes or metaplasia, and 28 were normal by both Pap smear and colposcopic examination. At equal specificity (70%) for both tests, the sensitivity of MHI was 97%, compared to 72% for the Pap smear. CONCLUSION: MHI detected cervical cancer precursors at a rate greater than that obtained by a simultaneously collected Pap smear.

Identification of cervical neoplasia using a simulation of human vision.

OBJECTIVE: To determine whether a computer simulation of human vision could detect and discriminate cervical cancer precursors and cancer from normal epithelium. METHODS: The Georgia Tech Vision (GTV) system was trained to recognize normal and abnormal cervical features. GTV then assessed a new series of images to determine whether it could detect and diagnose cervical neoplasia without any a priori information about the images. RESULTS: After training on one set and testing on another set of images, GTV demonstrated 100% sensitivity and 98% specificity to detect cervical intraepithelial neoplasia 3 (CIN3). GTV also had 88% sensitivity and 93% specificity to detect cervical cancer following training on one set and testing on another set of digitized cervical colposcopic images. CONCLUSION: This study demonstrated that GTV can detect CIN3 and cancer from digitized cervical colposcopic images. Furthermore, GTV could discriminate cervical cancer precursors and cancer from normal cervical epithelium, including immature metaplasia.

The efficacy of liquid-based cervical cytology using direct-to-vial sample collection.

BACKGROUND: Previous studies of liquid-based cervical cytology (LBCC) have used a split sample collection technique that creates a potential negative bias for its evaluation. Thus, the full diagnostic potential of LBCC has not been established. The purpose of our study was to determine rates of specimen adequacy and cervical cytologic and histologically confirmed diagnoses obtained with a liquid-based Papanicolaou (Pap) test using a direct-to-vial sample collection technique and compare these results with those obtained using the conventional Pap test (CPT). METHODS: A total of 1004 nonpregnant women aged 18 years or older with an intact cervix had Pap tests collected with an Ayre spatula and cytobrush, and the sample was placed in a preservative solution. The specimens were processed as thin layer Pap tests according to the manufacturer's specifications. Another group of 2110 women with a similar patient profile had a CPT collected immediately preceding the initiation of the trial. The subjects in each group consisted of an equal percentage of women presenting for a routine Pap test or a colposcopy examination. We compared the distributions of diagnostic categories between the groups using a chi-square test. RESULTS: A significantly greater percentage of satisfactory Pap tests were obtained using LBCC (84.0%) compared with the CPT (60.5%, P < .001). Fewer satisfactory but limited by (SBLB, 14.8%) and unsatisfactory (1.2%) Pap tests were reported using LBCC compared with the CPT (35.7% and 3.8%, respectively, chi2 = 170.7, P < .001). A significantly greater percentage of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Pap test results were reported using LBCC (7.4% and 3.7%, respectively) compared with the CPT (1.7% and 1.7%, respectively, chi2 = 74.4, P < .001). The predictive value of a positive LBCC test (93.9%) was similar to that for a positive CPT (87.8%) when compared with histology results. CONCLUSIONS: Compared with the CPT, LBCC detected a significantly greater percentage of satisfactory Pap tests and significantly reduced the number of unsatisfactory and SBLB tests. Four times the percentage of LSIL and twice the percentage of HSIL Pap test results were obtained using LBCC compared with the CPT. These findings demonstrate that LBCC significantly improves the adequacy of Pap tests and may increase the rate of detection of cervical neoplasia compared with the CPT.

The natural history of cervical cryosurgical healing. The minimal effect of debridement of the cervical eschar [see comment].

BACKGROUND: Cryosurgery is a favored treatment method for cervical intraepithelial neoplasia (CIN) among family physicians, in part because it is inexpensive and requires the least technical training and skill. Although cervical cryosurgery has been used for more than 30 years, the natural history of the postprocedure process has never been described. The primary purpose of our study was to describe the natural history of the healing process after cervical cryosurgery. A secondary purpose was to determine the effect of mechanical debridement of the cervical eschar on the symptoms of healing. METHODS: We conducted a prospective multicentered trial in which women who had a histologic ally documented CIN lesion underwent cervical cryosurgery. Forty-six women were randomized to undergo eschar debridement at 48 hours after cryosurgey, and 38 women received standard care. All women were followed up and given preweighed sanitary pads for hydrorrhea (watery discharge) collection and a diary to record the severity and number of days of odor, pain, cramping, and hydrorrhea that were experienced. RESULTS: The average total amount of hydrorrhea or discharge was 288 g, which required using an average of 41 sanitary pads during a period of 12.4 days. The duration of odor was 8.9 days, and the pain and cramping experienced after cryosurgery lasted 4.7 days. Women who were obese had greater hydrorrhea and pad usage than nonobese women. Debridement of the cervical eschar did not significantly change the signs and symptoms of healing after cryosurgery. CONCLUSIONS: There are significant symptoms patients experience after cryosurgery that are not ameliorated by debridement. The expectations of the cryosurgical healing process should be disclosed to women before the procedure.

A comparison of colposcopy using optical and video colposcopes.

OBJECTIVE: To compare the colposcopic adequacy, colposcopic impressions, histologic sampling intent, biopsy site location, procedural complications, and difficulty of colposcopic examinations using optical and video colposcopes. MATERIALS AND METHODS: Women and men presenting consecutively for colposcopy were examined independently by two colposcopists using alternately either an optical or video colposcope. Colposcopists individually recorded their exam adequacy, colposcopic impression, biopsy intent and site, procedural complications, and difficulty of examination. Most colposcopists had no prior experience with video colposcopes. RESULTS: Of 300 patients, mean age 35.3 years (±12.2 SD), examined, 29.7% were nulliparous, 4.9% pregnant, 52.5% had a previous biopsy and 34.3% had prior cervical treatment. Agreement between colposcopes was excellent for visualizing the complete squamocolumnar junction (75.6%, x = 6.40, p = 0.09). Colposcopists using the video colposcope had more unsatisfactory exams of the endocervical canal (36.6%, 97/265) than did colposcopists using optical colposcopes (24.9%, 66/265, x = 16.65, p = 0.001). Colposcopic impression agreement with pathology results were not significantly different between the video (58.1%) and optical (57.0%) colposcopes (x = 0.09, p = 0.8). Biopsy intent (79.9% agreement, x = 0.20, p = 0.7) and biopsy site selection by cervical quadrant were not significantly different for the two colposcopes. Both types of colposcopes were rated extremely easy to use, but colposcopy in general (T = 3.97, p < 0.001), visualization (T = 2.98, p = 0.002), assessment (T = 2.76, p = 0.004), and sampling (Wilcoxon = 2.27, p = 0.02) were determined to be easier when using optical colposcopes. CONCLUSIONS: Video colposcopes have similar, clinically relevant outcomes when compared with optical colposcopes. Colposcopists using optical colposcopes reported easier colposcopy exams and fewer unsatisfactory examinations of the endocervical canal. These findings may represent a learning curve effect as colposcopists become familiar with operating the video colposcope.▪.

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 0.2 pg/ml (1000 copies of human papillomavirus per test), human papillomavirus deoxyribonucleic acid testing detected 86% of women with cervical intraepithelial neoplasia and 93% of women with high-grade cervical intraepithelial neoplasia with a specificity of 30%. Decreasing the sensitivity of the human papillomavirus test to 1 pg/ml (5000 copies of human papillomavirus per test) improved the specificity of a positive result to 44% but decreased the clinical sensitivity to 78% for cervical intraepithelial neoplasia grade 2 or 3. Relationships between sensitivity and specificity were influenced by patient age and referral diagnosis. For example, limiting the analysis to only women with a referral for atypical squamous cells of undetermined significance found on Papanicolaou smear and a positive human papillomavirus test threshold of 0.5 pg/ml produced a sensitivity of 90% for cervical intraepithelial neoplasia grade 2 or 3 and a test specificity of 55%. CONCLUSION: Human papillomavirus deoxyribonucleic acid testing of residual cellular material from liquid cytologic specimens appears to be more appropriate for older women (>30 years old) and women with atypical squamous cells of undetermined significance, as opposed to low-grade squamous intraepithelial lesion, on their Papanicolaou smears.

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. RESULTS: The sensitivity, specificity, and positive and negative predictive values for detecting CIN 2/3 were 70%, 45%, 7%, and 96% for a repeat Pap smear using an ASCUS-positive threshold and 20%, 86%, 8%, and 94% for a repeat Pap smear using an LSIL-positive threshold, respectively, when women with an initial ASCUS Pap smear were considered. HPV testing for carcinogenic viruses alone or in combination with a repeat Pap smear (using ASCUS as a positive threshold) yielded results of 50%, 67%, 9%, and 96%, respectively, and 70%, 37%, 7%, and 95%, respectively, for detecting CIN 2/3. In women with an initial LSIL Pap smear, respective values for detecting CIN 2/3 by a repeat Pap smear with an ASCUS threshold were 92%, 26%, 14%, and 96%, and for an LSIL threshold 23%, 64%, 8%, and 86%, respectively. Hybrid Capture HPV testing alone or in combination with a repeat Pap smear yielded 69%, 43%, 14%, and 91%, respectively, and 100%, 21%, 14%, and 100%, respectively. CONCLUSIONS: A Pap smear triage threshold restricted to LSIL or more severe dysplasia for women with prior ASCUS or LSIL Pap smear results was clearly ineffective for detecting high-grade cervical precancerous lesions. In contrast, when the repeat Pap smear triage threshold was expanded to include persistent ASCUS as abnormal, 83% of the women with CIN 2/3 were detected. Detection of carcinogenic HPV DNA using the HCT test was almost as sensitive for detecting CIN 2/3 as a solitary repeat Pap smear using an ASCUS or more severe positive threshold. Combining the HPV test with a repeat Pap smear did not significantly improve the sensitivity of cytology for detecting high-grade CIN. This study suggests that women with ASCUS and particularly LSIL Pap smears should be referred for a colposcopy examination until better triage methods become available.

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. All women received colposcopy examinations including cervical biopsy and endocervical curettage, when indicated, to determine criterion standards for comparison. RESULTS: Paired swabs and liquid-based cervical specimens from 242 women were available for testing by standard HCT and the newer HC II HPV DNA assays. The sensitivity, specificity, and positive and negative predictive values for detecting CIN grade 2 or 3 (CIN 2/3) were 61.9%, 57.0%, 12.0%, and 94.0%, respectively, for the HCT test, and 90.5%, 29.4%, 10.9%, and 97.0%, respectively, for the liquid-based cytology HC II assay. When only women with an initial ASCUS Pap smear report were considered, the HC II test results were 88.9%, 40.3%, 9.1%, and 98.2%, respectively. CONCLUSIONS: Testing for lower genital tract carcinogenic HPV DNA using a cervical cytology liquid transport media residual sample is clinically feasible. The new HC II microplate HPV test achieved a greater test sensitivity for detecting carcinogenic HPV and correspondingly of CIN 2/3 compared with the currently available first-generation HC HPV test. Use of a liquid-based cervical cytology system combined with intermediate triage by HC II testing of residual cells for carcinogenic HPV alone may help to efficiently identify CIN 2/3 in women who have a prior screening Pap smear report of ASCUS.

Colposcopy Quality Control: Establishing Colposcopy Criterion Standards for the National Cancer Institute ALTS Trial Using Cervigrams.

OBJECTIVES: The colposcopy quality control (QC) group of the Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesions (ASCUS/ LSIL) Triage Study (ALTS) monitors colposcopists at four clinical centers by direct observation and indirectly by assessment of digitized computer colposcopic images transferred nightly by modem. The purpose of this preclinical study was to determine the agreement among colposcopy QC monitors' colposcopic impressions and biopsy site placement through evaluation of cervical photographic images. MATERIALS AND METHODS: A nonparticipant selected 100 Cervigram slides representing four pathologically confirmed categories: cervical intraepihelial neoplasia 1(CIN), CIN2 and CIN3, normal, and cancer. our colposcopy QC monitors and two certified Cervigram evaluators independently interpreted the images for colpocopic impression on two separate occasions. Measures of agreement were calculated for intraobserver, pairwise interobserver, and observer versus histological diagnoses. Participants also indicated the most severe biopsy site by marking an χ on a 4 × 6-inch color print duplication. Mean distances between biopsy site annotations for each pair of evaluators were calculated. RESULTS: The ALTS observer agreement with histology ranged from 75.3% (K = .66) to 47.4% (K = .36) for the first evaluation and 71.1 % (K = .63) to 50.5% (K = .38) for the second evaluation. ALTS interobserver agreement varied between 71 % and 57% for the first interpretation and 76% and I2% for the second evaluation. ALTS intraobserver agreement varied from 86% (K = .86) to 68.0% (K = .60). The mean listances between biopsy site annotations for each pair of ALTS observers varied from 0.99 ± 0.93 mm to 1.44 ± 1.19 nm. CONCLUSIONS: The ALTS colposcopy QC monitors achieved poor to good observer agreement with histology, fair to excellent interobserver agreement, and good to excellent intraobserver agreement in assessing the severity of cervical images. These levels of agreement are similar to many reported by pathologists for cervical cytology and histology interpretations. Monitors also demonstrated a very narrow variation of distance (< 2 mm) for ideal biopsy site placement.

Cryotherapy of the cervix.

Cryotherapy is an office-based ablative procedure for treating premalignant cervical disease. The procedure may be easily performed and serious complications occur rarely. When compared with other types of cervical neoplasia surgical therapies, cryotherapy is relatively inexpensive and comparably effective when properly conducted.

Women's triage and management preferences for cervical cytologic reports demonstrating atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions.

OBJECTIVE: To determine women's triage test preferences for the evaluation and management of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) Papanicolaou smear reports. DESIGN: A 35-item questionnaire. SETTINGS: Primary care clinic waiting rooms. PARTICIPANTS: A convenience sample of 968 women. INTERVENTION: Women received standardized descriptions of the meaning of ASCUS and LSIL Papanicolaou smear classifications and uniform descriptions of the 4 triage tests: Papanicolaou smear, human papillomavirus DNA test, cervicography, and colposcopy. MAIN OUTCOME MEASURES: Subjects' responses to questionnaire. RESULTS: More women (58.4%) preferred a repeat Papanicolaou smear for an ASCUS report than would choose human papillomavirus DNA testing (7.3%), cervicography (20.6%), or colposcopy (13.8%) (P < .001, chi 2). Alternatively, 51% of women wanted colposcopy to evaluate an LSIL report compared with the other 3 options (P < .001, chi 2). Test accuracy was the most important factor that influenced women's decisions for each test, compared with cost, discomfort, and other reasons (P < .001, chi 2). Positive predictors for women's selection of colposcopy to evaluate a Papanicolaou smear showing LSIL included older age (P < .01, logistic regression analysis), higher level of income (P < .001, chi 2), greater level of education (P < .001, logistic regression analysis), greater level of knowledge of colposcopy and Papanicolaou smears (P < .001, logistic regression analysis), family history of cervical cancer (P < .01, chi 2), and history of cervical dysplasia (P = .02, chi 2). CONCLUSIONS: Most women preferred a repeat Papanicolaou smear to further evaluate an initial Papanicolaou smear demonstrating ASCUS and colposcopy to evaluate a report of LSIL. Women identified test accuracy as the most important reason for triage test selection. Multiple factors, primarily involving patient and family history of cervical neoplasia, level of education, income, age, and knowledge of tests, influence women's desire for specific triage tests. Because no optimal management of women with ASCUS and LSIL Papanicolaou smear reports has been determined, consideration of women's triage test preferences should complement overall patient care.

Office procedures. Colposcopy.

Colposcopy is a clinical procedure to examine the epithelium of the uterine cervix and surrounding anogenital area with a magnifying instrument to detect the presence of cervical neoplasia and to identify abnormal tissue for biopsy. The procedure is enhanced by the use of chemical solutions that assist discrimination of normal tissue and abnormal lesions. Colposcopic examination and directed biopsy of the most severe focus of cervical neoplasia ensure a valid representation of the status of cervical disease. The results from the cytologic smear, histologic evaluation, and colposcopic impression collectively determine appropriate patient management.

Video colposcopy.

Video colposcopy is a new method for examining the lower genital tract. The video colposcopy system includes a video colposcope on a center pole or overhead boom, a high-resolution video monitor, and an optional image (data) management system. Because the video colposcope has no eyepieces, the technique differs from traditional colposcopy in that the colposcopist views the target only on the video monitor. A modified colposcopy technique is employed to assist depth perception, as the system does not permit stereoscopic viewing. The video colposcopy system, like other traditional optical colposcopes with attached video systems, enhances resident training and patient education.

The efficacy of topical benzocaine gel in providing anesthesia prior to cervical biopsy and endocervical curettage.

OBJECTIVES: Our goal was to determine the effectiveness of topical 20% benzocaine gel in providing anesthesia prior to cervical biopsy and endocervical curettage (ECC) and to identify specific patient characteristics that would predict which patients would be more likely to benefit from the application of benzocaine gel before cervical procedures. MATERIALS AND METHODS: Women requiring cervical biopsy and ECC completed a questionnaire that obtained demographical and pertinent gynecological information, perceived pain thresholds, and anxiety levels prior to the cervical biopsy procedures. Either benzocaine gel or a placebo was applied to the ectocervix and endocervical canal in a doubleblinded fashion. After each procedure, subjects reported the type, intensity, character, and duration of the sensation via visual analog scales (VAS) (0 = no sensation, 100 = maximum sensation). RESULTS: No difference was noted in the mean VAS scores reported by the placebo and benzocaine cohorts for the sensation felt at the time of cervical biopsy (30.1 SD ± 28.2 and 35.3 SD ± 24.3, respectively; p = .33). No significant difference in mean VAS scores was noted after ECC by the placebo cohort (53.0 SD ± 26.8) and the benzocaine cohort (41.0 SD ± 28.2; p = .09). Pain experienced with prior Papanicolaou (Pap) smears correlated significantly with the level of sensation noted during cervical biopsy (r = 0.395; p = .0001). The mean VAS scores for sensation experienced during cervical biopsy also were significantly greater among women who reported a history of dyspareunia (42.2 vs 27.7; p = .0059) and who reported a history of painful pelvic examinations (45.0 vs 29.8; p = .0125) than among women who did not report these painful experiences. CONCLUSIONS: Topical benzocaine gel was ineffective in reducing discomfort reported on cervical biopsy and ECC as compared with a placebo. Biopsy instrument sharpness may be a critically important factor that determines invoked pain. Discomfort associated with prior Pap smears, history of dyspareunia, and history of painful pelvic examinations correlated significantly with a greater perceived biopsy sensation. Prebiopsy recognition of these indicators may help clinicians to determine which women may be more likely to experience greater pain with cervical biopsy and enable them to intervene with other pain prevention measures.

A neglected lesbian health concern: cervical neoplasia.

Many health care providers believe that lesbian women do not need routine Papanicolaou smears. This erroneous assumption fails to recognize that the majority of lesbian women have had prior heterosexual relationships and thus may be at risk for developing cervical neoplasia. The following case report describes a lesbian woman who denied prior heterosexual intercourse but who developed cervical intraepithelial neoplasia grade 2 (CIN 2) associated with a high oncogenic risk human papillomavirus (HPV) type. Sexual contact with multiple lesbian partners who had previous heterosexual relationships likely explains her cervical disease.