Have we resolved how to triage equivocal cervical cytology?
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Carcinoma, Squamous Cell↗
Biomedical subjects
Diane Solomon
Publications and source records attributed to Diane Solomon.
Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening.
Human papillomavirus (HPV) DNA testing was recently approved by the Food and Drug Administration for use as an adjunct to cytology for cervical cancer screening. To help provide guidance to clinicians and patients when using HPV DNA testing as an adjunct to cervical cytology for screening, a workshop was cosponsored by the National Institutes of Health-National Cancer Institute, American Society of Colposcopy and Cervical Pathology (ASCCP), and American Cancer Society. Consensus was reached based on a literature review, expert opinion, and unpublished results from large ongoing screening studies. The conclusions of the workshop were that HPV DNA testing may be added to cervical cytology for screening in women aged 30 years or more. Women whose results are negative by both HPV DNA testing and cytology should not be rescreened before 3 years. Women whose results are negative by cytology, but are high-risk HPV DNA positive, are at a relatively low risk of having high-grade cervical neoplasia, and colposcopy should not be performed routinely in this setting. Instead, HPV DNA testing along with cervical cytology should be repeated in these women at 6 to 12 months. If test results of either are abnormal, colposcopy should then be performed. This guidance should assist clinicians in utilizing HPV DNA testing in an effective manner, while minimizing unnecessary evaluations and treatments.
Adult↗
Interlaboratory reliability of Hybrid Capture 2.
We evaluated the interlaboratory reproducibility of the Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD), a test for oncogenic human papillomavirus (HPV) DNA, using data from 4 clinical center (CC) laboratories and the quality control (QC) laboratory participating in the ASCUS (atypical squamous cells of undetermined significance) and LSIL (low-grade squamous intraepithelial lesion) Triage Study (ALTS). Residual liquid cytology specimens were tested routinely throughout the duration of ALTS at CC laboratories, and a stratified (by time in the study) random sample of specimens was retested by the HPV QC laboratory using equivalent protocols. Of the specimens selected (N = 1,175, 5.50% of all specimens obtained), 1,072 (91.23%) had sufficient specimen volume for retesting. The kappa value between all CC laboratories and the HPV QC laboratory was 0.84 (95% confidence interval, 0.78-0.89), with kappa values for individual CCs and the HPV QC laboratory ranging from 0.79 to 0.89. Agreement between test results was lowest among results for women with negative cytologic findings (0.73); among those with equivocal or abnormal cytologic findings, kappa values were 0.80 or more. These data show that HC2 is a reliable test for detecting clinically relevant oncogenic HPV DNA.
Cytodiagnosis↗
Stability of archived liquid-based cervical cytologic specimens.
BACKGROUND: Exfoliated cervical cell specimens collected in PreservCyt, a methanol-based medium used in ThinPrep liquid-based cytology, have been archived in epidemiologic studies. However, long-term DNA stability and cytologic stability of these biospecimens have not been evaluated. METHODS: Cervical specimens were collected into PreservCyt from participants in a natural history study of human papillomavirus (HPV) infection and cervical carcinoma in Guanacaste, Costa Rica (1993-2000), and stored at ambient temperatures. Thirty specimens classified as low-grade squamous intraepithelial lesions by liquid-based cytology were randomly chosen from each collection year (except for 1994) and selectively assessed for molecular and cytologic stability. Specimens were tested in 2001 for 1) HPV DNA by the Hybrid Capture 2 test, 2) beta-globin DNA by polymerase chain reaction amplification of multiple length fragments (268, 610, and 1327 bp), and 3) nuclear preservation by visual inspection of newly made liquid-based cytology slides. All testing was done masked to year of collection. Associations of stability and storage time were evaluated using standard contingency tables and chi-square tests for trend. RESULTS: Human papillomavirus DNA, as detected by the Hybrid Capture 2 test, was unaffected by storage time. Stability of beta-globin DNA (P(Trend) < 0.0001) and nuclear preservation (P(Trend) < 0.0001) declined with increasing storage time. Approximately 15% of specimens could not be amplified for any beta-globin DNA fragment after 5 years of storage (collected in 1996). In addition, cytology slides made from 41% specimens were rated as marginal (32%) or unsatisfactory (9%) after 8 years of storage (collected in 1993). CONCLUSIONS: Cervical specimens archived in PreservCyt underwent partial DNA and cytologic degradation after several years of storage. Methodologic studies to optimize long-term storage of cervical cells for epidemiologic studies of cervical carcinoma are needed.
Adult↗
Postcolposcopy management strategies for women referred with low-grade squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined significance: a two-year prospective study.
OBJECTIVE: This study was undertaken to compare postcolposcopy management strategies for women referred for low-grade squamous intraepithelial lesions (LSIL) or oncogenic human papillomavirus (HPV) DNA-positive atypical squamous cells of undetermined significance (ASCUS), with cervical intraepithelial neoplasia (CIN) grade 1 or less found at initial colposcopy. STUDY DESIGN: A 2-year prospective follow-up of 1539 women was designed to assess the percentage sensitivity of different postcolposcopy management strategies to detect subsequent CIN grade 2 or 3 and percentage referral to repeat colposcopy. RESULTS: HPV testing at 12 months was sensitive (92.2%) for detection of CIN grade 2 or 3 with a referral rate to repeat colposcopy of 55.0%. Repeat semiannual cytology with referral to colposcopy at an ASCUS threshold demonstrated similar sensitivity (88.0%) but with a higher rate of referral to colposcopy (63.6%). Combining cytology and HPV testing did not increase sensitivity and hurt specificity. Baseline viral load and colposcopic impression were not helpful. CONCLUSION: The most efficient test for identifying women with CIN grade 2 or 3 after colposcopy might be an HPV test alone at 12 months.
Adolescent↗
Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy.
OBJECTIVE: The purpose of this study was to determine the risk of cumulative cervical intraepithelial neoplasia (CIN) grade 2 or 3 according to initial colposcopy and directed biopsy results among women with low-grade squamous intraepithelial lesions (LSIL) or human papillomavirus (HPV) DNA positive atypical squamous cells of undetermined significance (ASCUS). STUDY DESIGN: A 2-year follow-up of 897 cases of LSIL and 1193 cases of HPV DNA positive ASCUS from the ASCUS/LSIL Triage Study was used to simulate American Society for Colposcopy and Cervical Pathology Consensus Conference recommendations. Women with CIN grade 1 or less were followed up for 2 years by semiannual cytologic examination, with universal exit colposcopy. The clinical end point was a cumulative clinical center histologic diagnosis of CIN grade 2 or 3. RESULTS: The cumulative risk of CIN grade 2 or 3 was equivalent for LSIL (27.6%) and HPV positive ASCUS (26.7%). After excluding the women with a diagnosis of CIN grade 2 or 3 at initial colposcopy and directed biopsy (17.9%), the remaining women were at nearly identical risk for subsequent CIN grade 2 or 3 regardless of initial colposcopy result (completely negative colposcopy-11.3%; negative colposcopically directed biopsy-11.7%; and CIN grade 1 biopsy-13.0%). CONCLUSION: LSIL and HPV positive ASCUS are clinically equivalent. Initial colposcopic detection of obviously prevalent CIN grade 2 or 3 reduces risk. However, for the remaining women who have CIN grade 1 or less on colposcopy and directed biopsy, the risk for subsequent CIN grade 2 or 3 (whether missed, prevalent, or truly incident) is approximately 12% over 2 years. This risk does not vary meaningfully by initial distinction of histologic CIN grade 1 from negative colposcopy and biopsy.
Adolescent↗
Chapter 14: Role of triage testing in cervical cancer screening.
The classic model of cervical cancer prevention-primary screening with cytology, followed by diagnostic colposcopically directed biopsy, and finally treatment of cancer precursors-is undergoing dynamic change. The introduction of human papillomavirus (HPV) DNA testing and other new modalities provides more options but increases complexity in the sequence of screening, triage, diagnosis, and patient management. This chapter will focus on the role of triage and risk stratification in management. The utility of HPV testing has been established for triage of cytologic findings of atypical squamous cells of undetermined significance but not for low-grade squamous intraepithelial lesions or worse. Countries without established cytology services may consider alternative screening, triage, and treatment programs that may be more readily implemented than a resource-rich "cytology followed by colposcopy" paradigm requiring an infrastructure of highly trained personnel. The diagnostic step of colposcopy and directed biopsy is not completely sensitive in the detection of cervical intraepithelial neoplasia (CIN) 2 or 3 as is sometimes assumed. The partial insensitivity of this diagnostic step results in a population of women with negative colposcopically directed-biopsy findings but at increased risk for missed prevalent disease: these women may require additional triage rather than resumption of routine screening. As more efficient screening, triage, and diagnosis increase the sensitivity of detection of even very small CIN2 or CIN3, overtreatment of lesions that might otherwise regress becomes a concern and highlights the need to identify accurate markers of risk of progression to cancer. Markers of molecular events further along the pathway from HPV infection to development of cancer may ultimately provide more specificity in triage and diagnosis.
Biomarkers, Tumor↗
American cancer society guideline for the early detection of cervical neoplasia and cancer.
An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical neoplasia and cancer, based on recommendations from a formal review and recent workshop, is presented. The new screening recommendations address when to begin screening, when screening may be discontinued, whether to screen women who have had a hysterectomy, appropriate screening intervals, and new screening technologies, including liquid-based cytology and HPV DNA testing.
Journal Article↗
Findings to date from the ASCUS-LSIL Triage Study (ALTS).
Controversy exists in the United States regarding the proper evaluation and management of low-grade squamous intraepithelial lesion (LSIL) and equivocal (atypical squamous cells of undetermined significance [ASCUS, now ASC-US]) cervical cytologic interpretations. To address this issue, the National Cancer Institute initiated the ASCUS-LSIL Triage Study (ALTS). ALTS is a multicenter, randomized clinical trial designed to evaluate 3 alternative methods of management, namely, immediate colposcopy, cytologic follow-up, and triage by human papillomavirus (HPV) DNA testing. This article summarizes the major findings of ALTS that have been published to date. Patients with ASCUS (n = 3488) or LSIL (n = 1572) were randomly assigned to research arms between November 1996 and December 1998, and were monitored for 2 years. The disease outcome was histologic cervical intraepithelial neoplasia (CIN) 3/cancer. The prevalence of oncogenic HPV was too high to permit effective triage of LSIL using HPV DNA testing by Hybrid Capture 2. However, for the women referred with a cytologic interpretation of ASCUS, HPV triage proved useful, with sensitivity equivalent to immediate colposcopy and a halving of colposcopic referrals. Among older women with ASCUS, HPV testing remained sensitive for detecting CIN 3 and cancer, but the referral percentage was dramatically lower compared to younger women. ALTS yielded insight into the performance of cytology and histopathology; experienced pathologists differed significantly in their interpretations of cervical abnormalities, especially histologic CIN 1 and cytologic ASCUS. Nonetheless, it was possible to distinguish a relatively uncommon type of ASCUS, equivocal for high-grade squamous intraepithelial lesion, that has a high positive predictive value for identifying women with underlying high-grade CIN. Many additional analyses are underway.
Carcinoma, Squamous Cell↗
The 2001 Bethesda System: terminology for reporting results of cervical cytology.
OBJECTIVES: The Bethesda 2001 Workshop was convened to evaluate and update the 1991 Bethesda System terminology for reporting the results of cervical cytology. A primary objective was to develop a new approach to broaden participation in the consensus process. PARTICIPANTS: Forum groups composed of 6 to 10 individuals were responsible for developing recommendations for discussion at the workshop. Each forum group included at least 1 cytopathologist, cytotechnologist, clinician, and international representative to ensure a broad range of views and interests. More than 400 cytopathologists, cytotechnologists, histopathologists, family practitioners, gynecologists, public health physicians, epidemiologists, patient advocates, and attorneys participated in the workshop, which was convened by the National Cancer Institute and cosponsored by 44 professional societies. More than 20 countries were represented. EVIDENCE: Literature review, expert opinion, and input from an Internet bulletin board were all considered in developing recommendations. The strength of evidence of the scientific data was considered of paramount importance. CONSENSUS PROCESS: Bethesda 2001 was a year-long iterative review process. An Internet bulletin board was used for discussion of issues and drafts of recommendations. More than 1000 comments were posted to the bulletin board over the course of 6 months. The Bethesda Workshop, held April 30-May 2, 2001, was open to the public. Postworkshop recommendations were posted on the bulletin board for a last round of critical review prior to finalizing the terminology. CONCLUSIONS: Bethesda 2001 was developed with broad participation in the consensus process. The 2001 Bethesda System terminology reflects important advances in biological understanding of cervical neoplasia and cervical screening technology.
Female↗
ASCUS LSIL Triage Study (ALTS) conclusions reaffirmed: response to a November 2001 commentary.
Explore the source record for details and available documents.
Carcinoma, Squamous Cell↗
American Cancer Society guideline for the early detection of cervical neoplasia and cancer.
An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical neoplasia and cancer, based on recommendations from a formal review and recent workshop, is presented. The new screening recommendations address when to begin screening, when screening may be discontinued, whether to screen women who have had a hysterectomy, appropriate screening intervals, and new screening technologies, including liquid-based cytology and HPV DNA testing.
Adolescent↗