PubMed Health⌕ Search

Biomedical subjects

Diane Solomon

Publications and source records attributed to Diane Solomon.

At least 19 recordsLinked to original sources
PubMed2007

The Bethesda Interobserver Reproducibility Study (BIRST): a web-based assessment of the Bethesda 2001 System for classifying cervical cytology.

BACKGROUND: The Bethesda System (TBS) along with its companion atlas was updated in 2001 to improve standardization, clarity, and reproducibility of cervical cytology reporting. METHODS: The authors used a novel web-based format to compare assessments of 77 images demonstrating a range of classical and borderline cytologic changes by a self-selected group of United States cytotechnologists (n = 216) and pathologists (n = 185). RESULTS: Participants were highly experienced, with 71.2% of cytotechnologists and 53.0% of pathologists reporting >10 years of practice. The mean percentage of exact agreement with the panel was slightly though significantly higher for cytotechnologists (57.0%) compared with pathologists (53.4%), adjusted for experience (P = .004); cervical cytology percentage effort (P = .0005); or cervical accession volume (P = .0002). Compared with the TBS panel, exact agreement was achieved for 55.1% of image ratings compared with 82.3% agreement at the level of Negative vs non-Negative for images with a single-panel interpretation. Agreement with the panel was highest for images classified as Low-Grade Squamous Intraepithelial Lesion and lowest for Atypical Squamous Cells qualified as either of Undetermined Significance or Cannot Exclude a High-Grade Squamous Intraepithelial Lesion. Reviewers were less sensitive in identifying high-grade glandular lesions than they were in identifying high-grade squamous lesions at any threshold (P < .001). CONCLUSIONS: Morphologic appearances of images were more important determinants than participants' academic or professional degrees with regard to interobserver reproducibility in classifying cervical cytology images. Experienced cytotechnologists and pathologists performed similarly. Participants achieved higher sensitivity for identifying high-grade squamous lesions than they did for high-grade glandular lesions. These findings demonstrated that web-based studies may be useful in assessing interobserver agreement in classifying images.

Adenocarcinoma↗
PubMed2006

Cervical cytology of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H): characteristics and histologic outcomes.

BACKGROUND: The 2001 Bethesda System category of atypical squamous cells (ASC) denotes changes suggestive, but inconclusive for, a squamous intraepithelial lesion (SIL). ASC is subcategorized as: 1) "undetermined significance (ASC-US)," when changes suggest low-grade or indeterminate-grade SIL and 2) "cannot exclude high-grade squamous intraepithelial lesion (ASC-H)," when a cancer precursor is suspected. METHODS: To better define the characteristics of ASC-H, the authors analyzed and compared human papillomavirus (HPV) testing data and outcomes after 2 years for participants in the Atypical Squamous Cells of Undetermined Significance Low-Grade SIL Triage Study (ALTS), a randomized trial of 5060 women. RESULTS: Among women with thin-layer cytology findings of ASC-H, 84% tested positive for HPV, 50% (95% confidence interval [95% CI], 41%-60%) were diagnosed with cervical intraepithelial neoplasia (CIN) type 2+, and 30% (95% CI, 22-39%) were diagnosed with CIN3+. Positive HPV tests and diagnoses of CIN2+ and CIN3+ were found to be more common among women with ASCH compared with those with ASC-US, but the highest frequencies were found to be associated with high-grade SIL. For women age < 35 years with ASC-H, HPV detection exceeded 85%, whereas only 4 of 10 women (40%) age >/=35 years tested positive for HPV (P = 0.009). CONCLUSIONS: A finding of ASC-H seems to confer a substantially higher risk for CIN2+ and CIN3+ than ASC-US. Immediate colposcopy may be the appropriate management for young women with ASC-H, but the utility of HPV testing for managing older women with ASC-H requires additional study.

Colposcopy↗
PubMed2006

Comparison of human papillomavirus distribution in cytologic subgroups of low-grade squamous intraepithelial lesion.

BACKGROUND: Low-grade squamous intraepithelial lesion (LSIL) subsumes the formerly delineated cytologic categories of human papillomavirus (HPV)-associated cell changes (koilocytotic atypia) and low-grade dysplasia/cervical intraepithelial neoplasia (CIN) Grade 1 (CIN1). In this study, the objective was to determine whether these 2 morphologic subcategories are characterized by differences in risk for CIN3 and/or HPV type distribution. METHODS: Within the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study, all cytologic interpretations of HPV cellular changes and CIN1 rendered by any of the pathology reviewers (community laboratory, clinical center, or Pathology Quality-Control Group) on referral Papanicolaou (Pap) tests or enrollment ThinPrep Pap tests were included for analysis. HPV testing was performed by Hybrid Capture 2 (HC2) and by polymerase chain reaction based reverse-line blot analysis for 27 HPV types. The absolute risks of cumulative detection of CIN3 or cancer (CIN3 +) and CIN2 or worse (CIN2 +) over 2 years of follow-up were calculated for the various cytologic interpretations. RESULTS: For each review group and cytology preparation, most LSIL interpretations (from approximately 2 of 3 interpretations to 3 of 4 interpretations) were subcategorized as CIN1 rather than HPV cellular changes. HPV type 16 (HPV-16) was the most common HPV type and was identified in 21% to 24% of CIN1 and in 14% to 18% of HPV cellular changes. Nononcogenic types were identified alone in from 9% to 11% of CIN1 compared with 17% to 20% of HPV cellular change. The absolute risks of CIN1 and HPV cellular changes for cumulatively detected CIN3 + ranged from 12% to 16% for CIN1 and from 6% to 9% for HPV cellular changes. CONCLUSIONS: Both cytologic subcategories of LSIL were associated predominantly with oncogenic HPV types; however, the proportion of nononcogenic HPV types was lower and the absolute risks for CIN3 + were higher for CIN1 compared with HPV cellular changes. The concordance in subcategorizing LSIL was low, and the authors concluded that the diagnostic distinction is of limited clinical utility for individual patient management.

Female↗
PubMed2006

Scientific issues related to the cytology proficiency testing regulations.

The member organizations of the Cytology Education and Technology Consortium believe there are significant flaws in current cytology proficiency testing regulations. The most immediate needed modifications include lengthening the required testing interval, utilizing stringently validated and continuously monitored slides, changing the grading scheme, and changing the focus of the test from the individual to laboratory level testing. Integration of new computer-assisted and located-guided screening technologies into the testing protocols is necessary for the testing protocol to be compliant with the law.

Journal Article↗
PubMed2006

Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS).

BACKGROUND: The ALTS (atypical squamous cells of undetermined significance [ASCUS] and low-grade squamous intraepithelial lesion [LSIL] Triage Study) suggests that, for women diagnosed with ASCUS, human papillomavirus (HPV) DNA testing followed by referral to colposcopy of only those women with oncogenic HPV (i.e., HPV DNA testing) is as effective at detecting cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN3+) as referring all women with ASCUS for immediate colposcopy. We conducted a cost-effectiveness analysis of the ALTS trial to determine whether HPV DNA testing is a cost-effective alternative to immediate colposcopy or conservative management with up to three cytology examinations. METHODS: Data from the ALTS trial were used in conjunction with medical care costs in a short-term decision model. The model compared the incremental costs per case of CIN3+ detected as measured by the incremental cost-effectiveness ratio (ICER) for the following management strategies for women with ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up to three cytology examinations. RESULTS: The least costly and least sensitive strategy was conservative management with one repeat cytology examination using a threshold of high-grade squamous intraepithelial lesion (HSIL) for referral to colposcopy. Compared with this strategy, triage to colposcopy based on a positive HPV DNA test result had an ICER of 3517 dollars per case of CIN3+ detected. Immediate colposcopy and conservative management with up to three repeat cytology visits detected fewer cases of CIN3+ and were more costly than HPV DNA testing. Immediate colposcopy became cost-effective at 20,370 dollars compared with HPV DNA testing only if colposcopy and biopsy were assumed to be 100% sensitive. CONCLUSIONS: HPV DNA testing is an economically viable strategy for triage of ASCUS cytology. The less than perfect sensitivity of colposcopy and biopsy needs to be accounted for in future clinical guidelines and policy analyses.

Adult↗
PubMed2006

Predicting absolute risk of CIN3 during post-colposcopic follow-up: results from the ASCUS-LSIL Triage Study (ALTS).

OBJECTIVE: At present, clinical management of women referred to colposcopy but found to have <CIN2 remains unclear. Using data from the ASCUS-LSIL Triage Study (ALTS) to inform clinical management, we calculated the absolute risk for developing CIN3 within 2 years of referral to an enrollment colposcopy. STUDY DESIGN: Women included in the analyses: (1) were initially referred to ALTS with a community cytologic interpretation of atypical squamous cell of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL); (2) had a colposcopic evaluation and biopsy, if indicated, resulting in a diagnosis <CIN2; and, therefore (3) were followed without treatment. Results from subsequent human papillomavirus (HPV) testing, liquid-based cytology interpretations, and a second colposcopic evaluation at least 6 months after and within 2 years of the first colposcopic evaluation were used to calculate absolute risks for CIN3. RESULTS: Women with HPV-negative test results were at low risk for CIN3 regardless of other test results. Among HPV-positive women, increasing absolute risks of CIN3 were observed with increasing cytology severity: 7% (normal), 11% (ASCUS and LSIL), and 45% (HSIL). The highest absolute risk for CIN3 (67%) was observed for HPV-positive women with HSIL and a colposcopic impression of high-grade/cancer on the second colposcopy. CONCLUSION: In the ALTS population, after the first colposcopic diagnosis of <CIN2, clear risk stratification for CIN3 outcomes was obtained among women with a subsequent HPV-positive test. Because absolute risk for histologic CIN3 outcomes was high for women with HPV positive tests, HSIL cytology, and a high-grade impression at second colposcopy, it is worth considering whether this combination of findings might warrant immediate excisional therapy in some circumstances.

Adult↗
PubMed2006

Number of cervical biopsies and sensitivity of colposcopy.

OBJECTIVE: To examine the influence that type of medical training and number of biopsies have on sensitivity of colposcopically guided biopsies. METHODS: Among 408 women with an adequate enrollment colposcopy and a diagnosis of cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN 3+) over 2 years in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions (ASCUS-LSIL) Triage Study, we evaluated factors influencing the sensitivity of the enrollment colposcopic procedure. We used contingency table analysis to examine confounding variables and chi(2) tests to ascertain statistical significance. RESULTS: Overall, 69.9% of women with a cumulative diagnosis of CIN 3+ had a "true-positive" enrollment colposcopically guided biopsy result of CIN 2 or worse (CIN 2+), the threshold that would trigger excisional therapy. The sensitivity of the procedure did not vary significantly by type of colposcopist. However, the sensitivity was significantly greater when the colposcopists took two or more biopsies instead of one (P<.01), a pattern observed across all types of colposcopists. Independent of the severity of the colposcopic impression, the frequency with which colposcopists took two or more biopsies instead of one varied (in descending order) from nurse practitioners to general gynecologists to gynecologic oncology fellows to gynecologic oncologists (P<.01). CONCLUSION: Colposcopy with guided biopsy or biopsies detects approximately two thirds of CIN 3+. Although the sensitivity of the procedure does not differ significantly by type of medical training, it is greater when two or more biopsies are taken.

Adolescent↗
PubMed2006

Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease.

BACKGROUND: Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment approximately 10% of women are diagnosed again with CIN2+, necessitating close follow-up of such patients. METHODS: Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment. RESULTS: At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9% [95% confidence interval (95% CI), 32.7-41.1%] of women were positive for carcinogenic HPV by PCR and 33.7% (95% CI, 29.7-37.9) had ASCUS or more severe (ASCUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0%; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0%, significantly higher than for other carcinogenic HPV types (10.8%, P < 0.001), noncarcinogenic types (1.5%, P < 0.001), or testing HPV negative (0%). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1% (95% CI, 60.0-90.7%) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9% for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6%, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1%, 95% CI, 64.6-73.3%) and PCR for carcinogenic HPV (67.1%, P = 0.5), yet was lower for HC2 (63.8%, P = 0.048) and combination testing (62.9%, P = 0.02). CONCLUSION: Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies.

Adult↗
PubMed2005

Determinants of human papillomavirus-negative, low-grade squamous intraepithelial lesions in the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions triage study (ALTS).

BACKGROUND: Although low-grade squamous intraepithelial lesions (LSIL) most often are the result of infection by human papillomaviruses (HPV), a small proportion of women with LSIL have negative HPV tests. Using the Atypical Squamous Cells of Undetermined Significance/LSIL Triage Study (ALTS) population, the authors evaluated the significance of HPV-negative LSIL. METHODS: Women with cytologic interpretations of LSIL by referral Papanicolaou (Pap) tests or enrollment ThinPrep tests (range, 1195-1476 women, depending on the specimen type and the reviewer) had HPV testing performed by both Hybrid Capture 2 and polymerase chain reaction (PCR)-based linear array for 27 HPV types. RESULTS: Using 4 independent cytologic definitions of LSIL, only 3-11% of women with LSIL were found to have HPV-negative results on both HPV tests. The demographic characteristics of women with HPV-negative LSIL were consistent with those of a low-risk population; many were age > 35 years, and many reported no or only 1 recent sexual partner. The absolute risk of a histologic diagnosis of cervical intraepithelial neoplasia (CIN) Grade 3/carcinoma during the 2-year trial was lower for women with HPV-negative LSIL (range, 2-4%) compared with the absolute risks for oncogenic HPV-positive women with LSIL (range, 13-19%). However, at the next 6-month follow-up visit, 12%-32% of the women with HPV-negative LSIL had a positive HPV test. Finally, visual inspection of cervigrams demonstrated a clear association between a larger os and negative HPV test results compared with women who had HPV-positive LSIL. This may have influenced HPV sample adequacy. CONCLUSIONS: Based on the ALTS data, the authors found no evidence to support the existence of HPV-negative LSIL as a distinct biologic entity related to the risk of cervical carcinoma. Such results appear to represent cytologic misinterpretations or falsely negative HPV tests.

Adult↗
PubMed2005

Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities.

BACKGROUND: The 2-year absolute risk for cervical precancer attributable to infection by human papillomavirus type 16 (HPV16), the most common and oncogenic HPV type, in the millions of women diagnosed annually with equivocal or mildly abnormal cytology has not been definitively evaluated. METHODS: Baseline cervical specimens of 5060 women with equivocal (atypical squamous cells of undetermined significance [ASCUS]) or mildly abnormal (low-grade squamous intraepithelial lesion [LSIL]) cytology were tested for HPV DNA using Hybrid Capture 2 (HC2) and type-specific L1 consensus primer polymerase chain reaction. We calculated absolute risks with 95% confidence intervals (CIs) for cumulative diagnosis, during the 2-year study period, of cervical intraepithelial neoplasia grade 3 (CIN3) (n = 535) or cancer (n = 7) (collectively referred to as > or = CIN3) and compared risk by HPV16 status and by other oncogenic HPV types using logistic regression. All statistical tests were two-sided. RESULTS: The baseline prevalences of HPV16 in women with ASCUS or LSIL cytology were 14.9% and 21.1%, respectively. Women with ASCUS or LSIL cytology who were HPV16 DNA positive at baseline had 2-year cumulative absolute risks for > or = CIN3 of 32.5% (95% CI = 28.4% to 36.8%) and 39.1% (95% CI = 33.8% to 44.7%), respectively. By comparison, women with ASCUS who were positive by HC2 for other oncogenic HPV types combined had an 8.4% (95% CI = 6.9% to 10.4%) risk for > or = CIN3, which was similar to the risk posed by having ASCUS (risk = 8.8%, 95% CI = 7.9% to 9.8%) without knowledge of the oncogenic HPV DNA status. Women with LSILs who were positive by HC2 for other oncogenic HPV types combined had a 9.9% (95% CI = 8.0% to 12.0%) 2-year risk for > or = CIN3, which was less than the risk posed by having LSILs (risk = 15.0%, 95% CI = 13.3% to 16.9%) without knowledge of the oncogenic HPV DNA status. Together, women with ASCUS or LSILs who were HPV16-positive had the highest 2-year risk for > or = CIN3 compared with women who were HPV-negative (odds ratio [OR] = 38, 95% CI = 22 to 68; P < .001 ), fivefold greater than the increased risk in women who were positive for other oncogenic HPV types (OR = 7.2, 95%CI = 4.2 to 13, P < .001). CONCLUSIONS: Distinguishing the high absolute risk for cervical precancer in HPV16-positive women from the lower risk posed by other oncogenic HPV types might have clinical implications.

Adult↗
PubMed2005

Does the interval between papanicolaou tests influence the quality of cytology?

BACKGROUND: It is commonly believed that the sensitivity of Papanicolaou (Pap) tests decreases with a short interval between cytology samplings. To the authors' knowledge, there is only limited evidence to support this belief. METHODS: For 5055 women in the Atypical Squamous Cells of Undetermined Significance (ASCUS)-Low Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS), the Pap interval was defined as the number of days between the referral Pap smear demonstrating ASCUS or LSIL ("first cytology") and the enrollment liquid-based ("repeat") cytology. The authors investigated the influence of the interval between Pap smears on repeat cytology by examining percentages of abnormal findings, cellularity, and test sensitivity among women diagnosed with histologic grade 3 cervical intraepithelial neoplasia (CIN3) during the 2-year course of the ALTS. In addition, because human papillomavirus (HPV) DNA adjunct testing is now performed, the authors evaluated HPV viral load, which was assayed using residual liquid cytology specimens, in women with CIN3. RESULTS: The Pap interval ranged from 8-30 days in 763 women, 31-60 days in 2317 women, 61-90 days in 1090 women, 91-120 days in 491 women, and 121-184 days in 394 women (mean of 61.3 days; standard deviation of 34 days). Repeat cytologic interpretations of unsatisfactory findings, ASCUS, and high-grade squamous intraepithelial lesion (HSIL) did not appear to vary among the Pap interval groups. However, low-grade cytologic regression occurred with an increasing Pap interval; negative cytology increased from 28.3% (8-30 days) to 41.6% (121-184 days) (P < 0.0001) whereas LSIL cytology decreased (P trend = 0.002). The approximate cellularity of the samples was slightly better in the interval group of 8-30 days (P trend = 0.04). Among women with CIN3, the repeat test sensitivity at a threshold of ASCUS or greater and the HPV DNA viral load was not found to vary by Pap interval (P trend = 0.80 and P trend = 0.36, respectively). CONCLUSIONS: The authors concluded that a short Pap interval (range, 15-120 days) does not significantly affect the quality of liquid-based repeat cytology, nor the viral load tested from a residual liquid-based specimen.

Adult↗
PubMed2005

The carcinogenicity of human papillomavirus types reflects viral evolution.

Persistent infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancers. Cervical HPV types (n > 40) also represent the most common sexually transmitted agents, and most infections clear in 1-2 years. The risks of persistence and neoplastic progression to cancer and its histologic precursor, cervical intraepithelial neoplasia grade 3 (CIN3), differ markedly by HPV type. To study type-specific HPV natural history, we conducted a 10,000-woman, population-based prospective study of HPV infections and CIN3/cancer in Guanacaste, Costa Rica. By studying large numbers of women, we wished to separate viral persistence from neoplastic progression. We observed a strong concordance of newly-revised HPV evolutionary groupings with the separate risks of persistence and progression to CIN3/cancer. HPV16 was uniquely likely both to persist and to cause neoplastic progression when it persisted, making it a remarkably powerful human carcinogen that merits separate clinical consideration. Specifically, 19.9% of HPV16-infected women were diagnosed with CIN3/cancer at enrollment or during the five-year follow-up. Other carcinogenic types, many related to HPV16, were not particularly persistent but could cause neoplastic progression, at lower rates than HPV16, if they did persist. Some low-risk types were persistent but, nevertheless, virtually never caused CIN3. Therefore, carcinogenicity is not strictly a function of persistence. Separately, we noted that the carcinogenic HPV types code for an E5 protein, whereas most low-risk types either lack a definable homologous E5 ORF and/or a translation start codon for E5. These results present several clear clues and research directions in our ongoing efforts to understand HPV carcinogenesis.

Cocarcinogenesis↗
PubMed2005

A study of the impact of adding HPV types to cervical cancer screening and triage tests.

Use of human papillomavirus (HPV) testing in cervical cancer prevention is increasing rapidly. A DNA test for 13 HPV types that can cause cervical cancer is approved in the United States for co-screening with cytology of women >or=30 years old and for triage of women of all ages with equivocal cytology. However, most infections with HPV are benign. We evaluated trade-offs between specificity and sensitivity for approximately 40 HPV types in predicting cervical intraepithelial neoplasia 3 and cancer in two prospective studies: a population-based screening study that followed 6196 women aged 30-94 years from Costa Rica for 7 years and a triage study that followed 3363 women aged 18-90 years with equivocal cytology in four U.S. centers for 2 years. For both screening and triage, testing for more than about 10 HPV types decreased specificity more than it increased sensitivity. The minimal increases in sensitivity and in negative predictive value achieved by adding HPV types to DNA tests must be weighed against the projected burden to thousands of women falsely labeled as being at high risk of cervical cancer.

Adult↗
PubMed2005

The distribution of neoplasia arising on the cervix: results from the ALTS trial.

OBJECTIVE: This study was undertaken to evaluate the topographic distribution of precancerous intraepithelial lesions on the cervix. STUDY DESIGN: We studied the distribution of cervical biopsies and location of acetowhite lesions as determined by cervigrams among women who underwent a colposcopic examination and biopsy during the ASCUS-LSIL Triage Study (ALTS). RESULTS: More biopsies were taken in the 12 o'clock (41.4%) and 6 o'clock (28.4%) quadrants than in 3 o'clock and 9 o'clock quadrant (15.8% and 14.5%, respectively) (P<.001). The proportion of abnormal histology per biopsy, and the grade of neoplasia, did not vary significantly by position. Cervigrams demonstrated visible intraepithelial lesions and acetowhitening more common on the anterior and posterior quadrants of the cervix. CONCLUSION: More cervical intraepithelial neoplasia might develop at the anterior and posterior lips of the cervix. However, the evidence is weak and confounded by a tendency of the anterior and posterior quadrants to be acetowhite even in the absence of cervical intraepithelial neoplasia.

Adolescent↗
PubMed2005

Evaluating the risk of cervical precancer with a combination of cytologic, virologic, and visual methods.

Several test modalities (cytologic, molecular, and visual) may be used for cervical cancer screening, triage, and follow-up. Although no currently available single test for cervical neoplasia can detect disease with both high sensitivity and specificity, combinations of available tests allow for improved risk prediction. We therefore evaluated the combination of liquid-based cytology (LBC), human papillomavirus (HPV) DNA testing, and visual inspection (cervicography), taken at a single point in time, to predict risk of subsequent cervical intraepithelial neoplasia 3 (CIN3) or cancer developing within 2 years in a triage population of 5,060 women referred for equivocal or mildly abnormal cytology. The concurrent administration of all three test modalities showed that combinations of these test modalities permitted clear and distinct risk stratification. Among HPV-positive women with high-grade LBC and high-grade cervicography results, 79.1 % [95% confidence interval (95% CI), 64.0- 90.0] were diagnosed with histologic CIN3 or cancer within 2 years, supporting a "see-and-treat" clinical application. Conversely, only 1.4% (95% CI, 0.7-2.5) of women with a negative HPV, normal cervigram, and second normal cytology result developed CIN3 or cancer. Because this low absolute risk was largely attributable to the negative HPV test, our results suggest a lack of benefit for a secondary or tertiary test result given an HPV-negative test result. Within HPV-positive women, however, we observed a steadily increasing absolute risk for cervical precancer/cancer with increasing numbers and severity of abnormal test results. We conclude that the clear discrimination of cervical cancer risk provided by multiple test modalities is consistent with our understanding of cervical etiology related to HPV natural history.

Adult↗
PubMed2005

A comparison of a prototype PCR assay and hybrid capture 2 for detection of carcinogenic human papillomavirus DNA in women with equivocal or mildly abnormal papanicolaou smears.

We evaluated Hybrid Capture 2 (HC2) and polymerase chain reaction (PCR) results for paired specimens collected at 19,187 visits from 5,026 of 5,060 women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). We examined the test agreement between HC2 and PCR detection for any of 13 carcinogenic human papillomavirus types targeted by HC2 and compared clinical performance of the 2 tests for detecting concurrent and follow-up cervical intraepithelial neoplasia (CIN) 3 or cancer. The k value for the 2 assays was 0.65 (95% confidence interval, 0.64-0.66), with 82.7% crude agreement. HC2 was more sensitive (93.6% vs 89.3%; P < .0005) but less specific (41.2% vs 48.5%; P < .0005) than PCR for detecting 2-year cumulative CIN 3 or cancer (n = 503). The presence of multiple types as detected by PCR and/or cytologic abnormality increased the likelihood of an HC2+ result. Increased sensitivity of HC2 compared with PCR was surprising, given the theoretical advantages of PCR-based methods for analytic sensitivity. Smaller amounts of material used in PCR could have limited its sensitivity, but our results demonstrate the importance of optimization and standardization of PCR-based assays for clinical applications.

Adolescent↗
PubMed2004

Second edition of 'The Bethesda System for reporting cervical cytology' - atlas, website, and Bethesda interobserver reproducibility project.

A joint task force of the American Society of Cytopathology (ASC) and the National Cancer Institute (NCI) recently completed a 2-year effort to revise the Bethesda System "blue book" atlas and develop a complementary web-based collection of cervical cytology images. The web-based collection of images is housed on the ASC website, which went live on November 5th, 2003; it can be directly accessed at http://www.cytopathology.org/NIH/.

Journal Article↗