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Mark Schiffman - One of the best experts on this subject based on the ideXlab platform.
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risk of precancer and follow up management strategies for women with human papillomavirus negative atypical squamous cells of undetermined significance
Obstetrics & Gynecology, 2007Co-Authors: Mahboobeh Safaeian, Mark Schiffman, Diane Solomon, Sholom Wacholder, Philip E CastleAbstract:OBJECTIVE: To investigate the relative performances of follow-up cytology and carcinogenic human papillomavirus (HPV) DNA testing among carcinogenic HPV-negative women with atypical squamous cells of undetermined significance (Ascus), for detection of cervical precancer. METHODS: Twelve-month follow-up management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) or worse using cytology or HPV testing or both were compared among women with HPV-negative Ascus in the Atypical Squamous Cells of Undetermined Significance‐ Low-Grade Squamous Intraepithelial Lesion (Ascus‐LSIL) Triage Study. RESULTS: Overall only 22 of 1,559 (1.4%) HPV-negative Ascus women developed CIN grade 3 or worse during follow-up compared with 269 of 1,767 (15.2%) HPVpositive Ascus women (P<.001). Because of the low risk of disease among HPV-negative Ascus women, only 7 cases of CIN3 were diagnosed between 12 and 24 months of follow-up, limiting power to distinguish meaningful differences in sensitivity among 12-month testing strategies. The specificity of HPV testing (84%) was significantly higher than cytology using an Ascus threshold (71%) (P<.001). Cotesting with cytology and HPV testing at 12 months resulted in even lower specificity (61%). Because cases were uncommon, the positive predictive value for subsequent CIN3 or worse was low for cytology (2.6%), Hybrid Capture 2 (3.8%), and cotesting with cytology and HPV testing (2.2%). The negative predictive value for all three management strategies was very high (99.70%, 99.82%, and 100.0% for HPV testing, cytology, or cotesting, respectively.) CONCLUSION: Women with HPV-negative Ascus have very low absolute risk of subsequently detected CIN3 or worse in the subsequent 2 years, similar to women with a negative cytology in the absence of HPV testing. The results suggest that women with HPV-negative Ascus should return to routine screening intervals which may be longer than 1 year depending on age and screening history. However, if increased surveillance is chosen, a single HPV test for carcinogenic types at 12 months has significantly higher specificity and lower referrals than cytology.
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human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease
Cancer Epidemiology Biomarkers & Prevention, 2006Co-Authors: Aimee R Kreimer, Mark Schiffman, Diane Solomon, Cosette M Wheeler, Richard Guido, Sholom Wacholder, Jose Jeronimo, Philip E CastleAbstract: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 ∼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. (Cancer Epidemiol Biomarkers Prev 2006;15(5):908–14)
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human papillomavirus type 16 infections and 2 year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities
Journal of the National Cancer Institute, 2005Co-Authors: Philip E Castle, Mark Schiffman, Diane Solomon, Cosette M WheelerAbstract: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 defi nitively evaluated. Methods: Baseline cervical specimens of 5060 women with equivocal (atypical squamous cells of undetermined signifi cance [Ascus]) or mildly abnormal (low-grade squamous intraepithelial lesion [LSIL]) cytology were tested for HPV DNA using Hybrid Capture 2 (HC2) and typespecifi c L1 consensus primer polymerase chain reaction. We calculated absolute risks with 95% confi dence 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 ≥ 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 ≥ 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 ≥ 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 ≥ 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 HPV16positive had the highest 2-year risk for ≥ CIN3 compared with women who were HPV-negative (odds ratio [OR] = 38, 95% CI = 22 to 68; P <.001 ), fi vefold 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. [J Natl Cancer Inst 2005;97:1066 – 71]
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findings to date from the Ascus lsil triage study alts
Archives of Pathology & Laboratory Medicine, 2003Co-Authors: Mark Schiffman, Diane SolomonAbstract:Abstract 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 ...
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effects of age and human papilloma viral load on colposcopy triage data from the randomized atypical squamous cells of undetermined significance low grade squamous intraepithelial lesion triage study alts
Journal of the National Cancer Institute, 2002Co-Authors: Mark E. Sherman, Mark SchiffmanAbstract:Background: Testing for oncogenic human papillomavirus (HPV) DNA at a 1.0-pg/mL threshold represents a promising approach for colposcopy triage of atypical squamous cells of undetermined significance (Ascus), but not for low-grade squamous intraepithelial lesions (LSIL). Considering age or viral load could improve colposcopy triage. Methods: We determined the sensitivity for detecting Cervical Intraepithelial Neoplasia 3 (CIN3) and cancer and the percentage of referrals for colposcopy using HPV testing and repeat thinlayer cytopathology in 2198 women with Ascus and in 848 women with LSIL enrolled in ALTS from November 1996 through December 1998. We analyzed results by age and at two thresholds for HPV load and repeat cytopathology. Results: For Ascus, the overall sensitivity of HPV testing at 1.0 pg/mL was 96.1% (95% confidence interval [CI] = 92.8 to 99.5%) and varied minimally with age (range, 93.9% to 97.8%). HPV testing at this threshold would refer 31.2% (95% CI = 28.0% to 34.3%) of women aged 29 years or older as compared with more than 65% of younger women. Among women aged 29 years or older with Ascus, referral for repeat cytopathology of Ascus had a sensitivity of 90.9% (95% CI = 81.1% to 100.0%) and would refer 50.1% (95% CI = 46.7 to 53.5%). Among all Ascus, HPV testing using a 10.0-pg/mL threshold decreased sensitivity to 91.5% and referrals to 41.7%. More than 63% of LSIL would have been referred using any strategy achieving 90% sensitivity. Conclusion: For women with Ascus, HPV testing was highly sensitive for detecting CIN3 and cancer with dramatically fewer referrals of older women. Neither a single HPV test nor repeat cytopathology provides useful triage for women with LSIL. [J Natl Cancer Inst 2002;94:102–7]
Diane Solomon - One of the best experts on this subject based on the ideXlab platform.
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risk of precancer and follow up management strategies for women with human papillomavirus negative atypical squamous cells of undetermined significance
Obstetrics & Gynecology, 2007Co-Authors: Mahboobeh Safaeian, Mark Schiffman, Diane Solomon, Sholom Wacholder, Philip E CastleAbstract:OBJECTIVE: To investigate the relative performances of follow-up cytology and carcinogenic human papillomavirus (HPV) DNA testing among carcinogenic HPV-negative women with atypical squamous cells of undetermined significance (Ascus), for detection of cervical precancer. METHODS: Twelve-month follow-up management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) or worse using cytology or HPV testing or both were compared among women with HPV-negative Ascus in the Atypical Squamous Cells of Undetermined Significance‐ Low-Grade Squamous Intraepithelial Lesion (Ascus‐LSIL) Triage Study. RESULTS: Overall only 22 of 1,559 (1.4%) HPV-negative Ascus women developed CIN grade 3 or worse during follow-up compared with 269 of 1,767 (15.2%) HPVpositive Ascus women (P<.001). Because of the low risk of disease among HPV-negative Ascus women, only 7 cases of CIN3 were diagnosed between 12 and 24 months of follow-up, limiting power to distinguish meaningful differences in sensitivity among 12-month testing strategies. The specificity of HPV testing (84%) was significantly higher than cytology using an Ascus threshold (71%) (P<.001). Cotesting with cytology and HPV testing at 12 months resulted in even lower specificity (61%). Because cases were uncommon, the positive predictive value for subsequent CIN3 or worse was low for cytology (2.6%), Hybrid Capture 2 (3.8%), and cotesting with cytology and HPV testing (2.2%). The negative predictive value for all three management strategies was very high (99.70%, 99.82%, and 100.0% for HPV testing, cytology, or cotesting, respectively.) CONCLUSION: Women with HPV-negative Ascus have very low absolute risk of subsequently detected CIN3 or worse in the subsequent 2 years, similar to women with a negative cytology in the absence of HPV testing. The results suggest that women with HPV-negative Ascus should return to routine screening intervals which may be longer than 1 year depending on age and screening history. However, if increased surveillance is chosen, a single HPV test for carcinogenic types at 12 months has significantly higher specificity and lower referrals than cytology.
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human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease
Cancer Epidemiology Biomarkers & Prevention, 2006Co-Authors: Aimee R Kreimer, Mark Schiffman, Diane Solomon, Cosette M Wheeler, Richard Guido, Sholom Wacholder, Jose Jeronimo, Philip E CastleAbstract: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 ∼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. (Cancer Epidemiol Biomarkers Prev 2006;15(5):908–14)
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human papillomavirus type 16 infections and 2 year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities
Journal of the National Cancer Institute, 2005Co-Authors: Philip E Castle, Mark Schiffman, Diane Solomon, Cosette M WheelerAbstract: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 defi nitively evaluated. Methods: Baseline cervical specimens of 5060 women with equivocal (atypical squamous cells of undetermined signifi cance [Ascus]) or mildly abnormal (low-grade squamous intraepithelial lesion [LSIL]) cytology were tested for HPV DNA using Hybrid Capture 2 (HC2) and typespecifi c L1 consensus primer polymerase chain reaction. We calculated absolute risks with 95% confi dence 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 ≥ 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 ≥ 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 ≥ 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 ≥ 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 HPV16positive had the highest 2-year risk for ≥ CIN3 compared with women who were HPV-negative (odds ratio [OR] = 38, 95% CI = 22 to 68; P <.001 ), fi vefold 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. [J Natl Cancer Inst 2005;97:1066 – 71]
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findings to date from the Ascus lsil triage study alts
Archives of Pathology & Laboratory Medicine, 2003Co-Authors: Mark Schiffman, Diane SolomonAbstract:Abstract 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 ...
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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
American Journal of Obstetrics and Gynecology, 2003Co-Authors: Thomas J Cox, Diane SolomonAbstract:Abstract 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. (Am J Obstet Gynecol 2003;188:1406-12.)
Ruediger Ridder - One of the best experts on this subject based on the ideXlab platform.
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p16 ki 67 dual stain cytology in the triage of Ascus and lsil papanicolaou cytology
Cancer Cytopathology, 2011Co-Authors: D Schmidt, Christine Bergeron, Karin Denton, Ruediger RidderAbstract:BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (Ascus) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquid-based cytology material from 776 retrospectively collected Ascus/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (Ascus) and 94.2% (LSIL), while specificity rates were 80.6% (Ascus) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with Ascus or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
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p16 ki 67 dual stain cytology in the triage of Ascus and lsil papanicolaou cytology
Cancer Cytopathology, 2011Co-Authors: D Schmidt, Christine Bergeron, Karin Denton, Ruediger RidderAbstract:BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (Ascus) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquid-based cytology material from 776 retrospectively collected Ascus/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (Ascus) and 94.2% (LSIL), while specificity rates were 80.6% (Ascus) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with Ascus or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
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p16 ki 67 dual stain cytology in the triage of Ascus and lsil papanicolaou cytology results from the european equivocal or mildly abnormal papanicolaou cytology study
Cancer Cytopathology, 2011Co-Authors: D Schmidt, Christine Bergeron, Karin Denton, Ruediger RidderAbstract:BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (Ascus) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquid-based cytology material from 776 retrospectively collected Ascus/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (Ascus) and 94.2% (LSIL), while specificity rates were 80.6% (Ascus) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with Ascus or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
D Schmidt - One of the best experts on this subject based on the ideXlab platform.
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p16 ki 67 dual stain cytology in the triage of Ascus and lsil papanicolaou cytology
Cancer Cytopathology, 2011Co-Authors: D Schmidt, Christine Bergeron, Karin Denton, Ruediger RidderAbstract:BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (Ascus) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquid-based cytology material from 776 retrospectively collected Ascus/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (Ascus) and 94.2% (LSIL), while specificity rates were 80.6% (Ascus) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with Ascus or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
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p16 ki 67 dual stain cytology in the triage of Ascus and lsil papanicolaou cytology
Cancer Cytopathology, 2011Co-Authors: D Schmidt, Christine Bergeron, Karin Denton, Ruediger RidderAbstract:BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (Ascus) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquid-based cytology material from 776 retrospectively collected Ascus/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (Ascus) and 94.2% (LSIL), while specificity rates were 80.6% (Ascus) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with Ascus or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
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p16 ki 67 dual stain cytology in the triage of Ascus and lsil papanicolaou cytology results from the european equivocal or mildly abnormal papanicolaou cytology study
Cancer Cytopathology, 2011Co-Authors: D Schmidt, Christine Bergeron, Karin Denton, Ruediger RidderAbstract:BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (Ascus) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquid-based cytology material from 776 retrospectively collected Ascus/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (Ascus) and 94.2% (LSIL), while specificity rates were 80.6% (Ascus) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with Ascus or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
Christine Bergeron - One of the best experts on this subject based on the ideXlab platform.
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p16 ki 67 dual stain cytology in the triage of Ascus and lsil papanicolaou cytology
Cancer Cytopathology, 2011Co-Authors: D Schmidt, Christine Bergeron, Karin Denton, Ruediger RidderAbstract:BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (Ascus) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquid-based cytology material from 776 retrospectively collected Ascus/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (Ascus) and 94.2% (LSIL), while specificity rates were 80.6% (Ascus) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with Ascus or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
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p16 ki 67 dual stain cytology in the triage of Ascus and lsil papanicolaou cytology
Cancer Cytopathology, 2011Co-Authors: D Schmidt, Christine Bergeron, Karin Denton, Ruediger RidderAbstract:BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (Ascus) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquid-based cytology material from 776 retrospectively collected Ascus/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (Ascus) and 94.2% (LSIL), while specificity rates were 80.6% (Ascus) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with Ascus or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
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p16 ki 67 dual stain cytology in the triage of Ascus and lsil papanicolaou cytology results from the european equivocal or mildly abnormal papanicolaou cytology study
Cancer Cytopathology, 2011Co-Authors: D Schmidt, Christine Bergeron, Karin Denton, Ruediger RidderAbstract:BACKGROUND: The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16INK4a and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (Ascus) or low-grade squamous intraepithelial lesions (LSIL). METHODS: Residual liquid-based cytology material from 776 retrospectively collected Ascus/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. RESULTS: Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (Ascus) and 94.2% (LSIL), while specificity rates were 80.6% (Ascus) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged <30 years versus women aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. CONCLUSIONS: The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with Ascus or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
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triage of women with Ascus and lsil cytology use of qualitative assessment of p16ink4a positive cells to identify patients with high grade cervical intraepithelial neoplasia
Cancer, 2006Co-Authors: Nicolas Wentzensen, Christine Bergeron, Frederic Cas, Svetlana Vinokurova, Magnus Von Knebel DoeberitzAbstract:BACKGROUND. The identification of a small percentage of high-grade cervical intraepithelial neoplasias (HGCIN) among patients with minor cytological abnormalities (atypical squamous cells of undetermined significance [Ascus] and/or low-grade squamous intraepithelial lesions [LSIL] group) is a major problem in cytology-based cervical cancer screening. The authors investigated the efficacy of p16INK4a as a biomarker to identify samples of patients with HGCIN among those with an Ascus or LSIL result in Papanicolaou cytology. METHODS. Consecutive liquid-based cytology specimens of 137 Ascus and 88 LSIL results were selected from gynecologists who adopted a triage regimen with biopsy under colposcopy 2 months later, independent of the p16INK4a result. p16INK4a stained slides were prepared and independently read by 2 observers, who used a recently described score to categorize p16INK4a stained squamous cells. The endpoint of the study was detection of a biopsy-confirmed HGCIN. RESULTS. The overall sensitivity and specificity of p16INK4a positive cells with a nuclear score >2 for diagnosis of HGCIN in Ascus and LSIL cases combined was 96% and 83%, respectively. The sensitivity and specificity in the Ascus group was 95% and 84%, and 100% and 81% in the LSIL group, respectively. Two observers had a high concordance in assessing p16INK4a stained cells (κ value of 0.841). CONCLUSIONS. These data suggested that the use of p16INK4a as a biomarker combined with nuclear scoring of p16INK4a positive cells in cervical cytology to triage Ascus and/or LSIL cases allows identification of HGCIN with good sensitivity and specificity. Cancer (Cancer Cytopathol) 2007. © 2006 American Cancer Society.
