JNCI Journal of the National Cancer Institute

JNCI Journal of the National Cancer Institute 2001 93(4):293-299; doi:10.1093/jnci/93.4.293
© 2001 by Oxford University Press

This Article Full Text FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Google Scholar Articles by Solomon, D. Articles by Tarone, R. Search for Related Content PubMed PubMed Citation Articles by Solomon, D. Articles by Tarone, R. Social Bookmarking          What's this?

Journal of the National Cancer Institute, Vol. 93, No. 4, 293-299, February 21, 2001
© 2001 Oxford University Press

Comparison of Three Management Strategies for Patients With Atypical Squamous Cells of Undetermined Significance: Baseline Results From a Randomized Trial

Diane Solomon, Mark Schiffman, Robert Tarone, For the ALTS Group

Affiliations of authors: D. Solomon (Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention), M. Schiffman (Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics), R. Tarone (Biostatistics Branch, Division of Cancer Epidemiology and Genetics), National Cancer Institute, Bethesda, MD.

Correspondence to: Diane Solomon, M.D., Executive Plaza North, 6130 Executive Blvd., Rockville, MD 20852 (e-mail: ds87v{at}nih.gov).

Background: More than 2 million U.S. women receive an equivocal cervical cytologic diagnosis (atypical squamous cells of undetermined significance [ASCUS]) each year. Effective colposcopy triage strategies are needed to identify the minority of women who have clinically significant disease while avoiding excessive follow-up evaluation for others. Methods: The ASCUS/LSIL (i.e., low-grade squamous intraepithelial lesion) Triage Study (ALTS) is a multicenter, randomized trial comparing the sensitivity and specificity of the following three management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3): 1) immediate colposcopy (considered to be the reference standard), 2) triage to colposcopy based on human papillomavirus (HPV) results from Hybrid Capture 2^TM (HC 2) and thin-layer cytology results, or 3) triage based on cytology results alone. This article summarizes the cross-sectional enrollment results for 3488 women with a referral diagnosis of ASCUS. All statistical tests are two-sided. Results: Among participants with ASCUS, the underlying prevalence of histologically confirmed CIN3 was 5.1%. Sensitivity to detect CIN3 or above by testing for cancer-associated HPV DNA was 96.3% (95% confidence interval [CI] = 91.6% to 98.8%), with 56.1% of women referred to colposcopy. Sensitivity of a single repeat cytology specimen with a triage threshold of HSIL or above was 44.1% (95% CI = 35.6% to 52.9%), with 6.9% referred. Sensitivity of a lower cytology triage threshold of ASCUS or above was 85.3% (95% CI = 78.2% to 90.8%), with 58.6% referred. Conclusions: HC 2 testing for cancer-associated HPV DNA is a viable option in the management of women with ASCUS. It has greater sensitivity to detect CIN3 or above and specificity comparable to a single additional cytologic test indicating ASCUS or above.

---

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				P. E. Castle, D. Solomon, C. M. Wheeler, P. E. Gravitt, S. Wacholder, and M. Schiffman Human Papillomavirus Genotype Specificity of Hybrid Capture 2 J. Clin. Microbiol., August 1, 2008; 46(8): 2595 - 2604. [Abstract] [Full Text] [PDF]

				B. Hall and K. Howard A Synergistic Approach: Conducting Mixed Methods Research With Typological and Systemic Design Considerations Journal of Mixed Methods Research, July 1, 2008; 2(3): 248 - 269. [Abstract] [PDF]

				J. Monsonego, G. Pollini, M. J. Evrard, P. Sednaoui, L. Monfort, D. Quinzat, R. Dachez, and K. Syrjanen Linear array genotyping and hybrid capture II assay in detecting human papillomavirus genotypes in women referred for colposcopy due to abnormal Papanicolaou smear Int J STD AIDS, June 1, 2008; 19(6): 385 - 392. [Abstract] [Full Text] [PDF]

				P. E. Gravitt, M. Schiffman, D. Solomon, C. M. Wheeler, and P. E. Castle A Comparison of Linear Array and Hybrid Capture 2 for Detection of Carcinogenic Human Papillomavirus and Cervical Precancer in ASCUS-LSIL Triage Study Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1248 - 1254. [Abstract] [Full Text] [PDF]

				A. K. Wong, R. C.-K. Chan, W. S. Nichols, and S. Bose Human Papillomavirus (HPV) in Atypical Squamous Cervical Cytology: the Invader HPV Test as a New Screening Assay J. Clin. Microbiol., March 1, 2008; 46(3): 869 - 875. [Abstract] [Full Text] [PDF]

				P. E. Castle, P. E. Gravitt, D. Solomon, C. M. Wheeler, and M. Schiffman Comparison of Linear Array and Line Blot Assay for Detection of Human Papillomavirus and Diagnosis of Cervical Precancer and Cancer in the Atypical Squamous Cell of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study J. Clin. Microbiol., January 1, 2008; 46(1): 109 - 117. [Abstract] [Full Text] [PDF]

				T. E. Schutzbank, C. Jarvis, N. Kahmann, K. Lopez, M. Weimer, and A. Yount Detection of High-Risk Papillomavirus DNA with Commercial Invader-Technology-Based Analyte-Specific Reagents following Automated Extraction of DNA from Cervical Brushings in ThinPrep Media J. Clin. Microbiol., December 1, 2007; 45(12): 4067 - 4069. [Abstract] [Full Text] [PDF]

				F. Ogunmodede, S. H. Yale, B. Krawisz, G. C. Tyler, and A. C. Evans Human Papillomavirus Infections in Primary Care Clin. Med. Res., December 1, 2007; 5(4): 210 - 217. [Abstract] [Full Text] [PDF]

				I. Sokolova, A. Algeciras-Schimnich, M. Song, S. Sitailo, F. Policht, B. R. Kipp, J. S. Voss, K. C. Halling, A. Ruth, W. King, et al. Chromosomal Biomarkers for Detection of Human Papillomavirus Associated Genomic Instability in Epithelial Cells of Cervical Cytology Specimens J. Mol. Diagn., November 1, 2007; 9(5): 604 - 611. [Abstract] [Full Text] [PDF]

				M.-H. Mayrand, E. Duarte-Franco, I. Rodrigues, S. D. Walter, J. Hanley, A. Ferenczy, S. Ratnam, F. Coutlee, E. L. Franco, and the Canadian Cervical Cancer Screening Trial Study Human Papillomavirus DNA versus Papanicolaou Screening Tests for Cervical Cancer N. Engl. J. Med., October 18, 2007; 357(16): 1579 - 1588. [Abstract] [Full Text] [PDF]

				M. Safaeian, D. Solomon, S. Wacholder, M. Schiffman, and P. Castle Risk of Precancer and Follow-up Management Strategies for Women With Human Papillomavirus-Negative Atypical Squamous Cells of Undetermined Significance Obstet. Gynecol., June 1, 2007; 109(6): 1325 - 1331. [Abstract] [Full Text] [PDF]

				G. W. Bock and B. M. Kwan Encouragement of Patient Self-management and Adherence through Use of a Computerized Tracking System for Cervical and Colon Cancer Screening J Am Board Fam Med, May 1, 2007; 20(3): 316 - 319. [Full Text] [PDF]

				S. Kjaer, E. Hogdall, K. Frederiksen, C. Munk, A. van den Brule, E. Svare, C. Meijer, A. Lorincz, and T. Iftner The Absolute Risk of Cervical Abnormalities in High-risk Human Papillomavirus-Positive, Cytologically Normal Women Over a 10-Year Period Cancer Res., November 1, 2006; 66(21): 10630 - 10636. [Abstract] [Full Text] [PDF]

				G. Ronco, N. Segnan, P. Giorgi-Rossi, M. Zappa, G. P. Casadei, F. Carozzi, P. D. Palma, A. Del Mistro, S. Folicaldi, A. Gillio-Tos, et al. Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial. J Natl Cancer Inst, June 7, 2006; 98(11): 765 - 774. [Abstract] [Full Text] [PDF]

				S.-L. Huang, A. Chao, S. Hsueh, F.-Y. Chao, C.-C. Huang, J.-E. Yang, C.-Y. Lin, C.-C. Yan, H.-H. Chou, K.-G. Huang, et al. Comparison between the Hybrid Capture II Test and an SPF1/GP6+ PCR-Based Assay for Detection of Human Papillomavirus DNA in Cervical Swab Samples. J. Clin. Microbiol., May 1, 2006; 44(5): 1733 - 1739. [Abstract] [Full Text] [PDF]

				M. A. Bidus, G. L. Maxwell, S. Kulasingam, G. S. Rose, J. C. Elkas, M. Chernofsky, and E. R. Myers Cost-effectiveness analysis of liquid-based cytology and human papillomavirus testing in cervical cancer screening. Obstet. Gynecol., May 1, 2006; 107(5): 997 - 1005. [Abstract] [Full Text] [PDF]

				K McCaffery, J Waller, J Nazroo, and J Wardle Social and psychological impact of HPV testing in cervical screening: a qualitative study. Sex. Transm. Inf., April 1, 2006; 82(2): 169 - 174. [Abstract] [Full Text] [PDF]

				S. L. Kulasingam, J. J. Kim, W. F. Lawrence, J. S. Mandelblatt, E. R. Myers, M. Schiffman, D. Solomon, and S. J. Goldie Cost-Effectiveness Analysis Based on the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS) J Natl Cancer Inst, January 18, 2006; 98(2): 92 - 100. [Abstract] [Full Text] [PDF]

				G. F. Sawaya A 21-Year-Old Woman With Atypical Squamous Cells of Undetermined Significance JAMA, November 2, 2005; 294(17): 2210 - 2218. [Full Text] [PDF]

				H.-T. Tsai, C.-H. Wu, H.-L. Lai, R.-N. Li, Y.-C. Tung, H.-Y. Chuang, T.-N. Wu, L.-J. Lin, C.-K. Ho, H.-W. Liu, et al. Association between Quantitative High-Risk Human Papillomavirus DNA Load and Cervical Intraepithelial Neoplasm Risk Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2544 - 2549. [Abstract] [Full Text] [PDF]

				S. S. Wang, J. L. Walker, M. Schiffman, D. Solomon, and for the Atypical Squamous Cell of Undetermined Sig Evaluating the Risk of Cervical Precancer with a Combination of Cytologic, Virologic, and Visual Methods Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2665 - 2668. [Abstract] [Full Text] [PDF]

				K. L. Noller Cervical Cytology Screening and Evaluation Obstet. Gynecol., August 1, 2005; 106(2): 391 - 397. [Full Text] [PDF]

				P. E. Castle, D. Solomon, M. Schiffman, C. M. Wheeler, and for the ALTS Group Human Papillomavirus Type 16 Infections and 2-Year Absolute Risk of Cervical Precancer in Women With Equivocal or Mild Cytologic Abnormalities J Natl Cancer Inst, July 20, 2005; 97(14): 1066 - 1071. [Abstract] [Full Text] [PDF]

				M. J. Khan, P. E. Castle, A. T. Lorincz, S. Wacholder, M. Sherman, D. R. Scott, B. B. Rush, A. G. Glass, and M. Schiffman The Elevated 10-Year Risk of Cervical Precancer and Cancer in Women With Human Papillomavirus (HPV) Type 16 or 18 and the Possible Utility of Type-Specific HPV Testing in Clinical Practice J Natl Cancer Inst, July 20, 2005; 97(14): 1072 - 1079. [Abstract] [Full Text] [PDF]

				M. A. P. C. van Ham, J. M. J. E. Bakkers, G. K. Harbers, W. G. V. Quint, L. F. A. G. Massuger, and W. J. G. Melchers Comparison of Two Commercial Assays for Detection of Human Papillomavirus (HPV) in Cervical Scrape Specimens: Validation of the Roche AMPLICOR HPV Test as a Means To Screen for HPV Genotypes Associated with a Higher Risk of Cervical Disorders J. Clin. Microbiol., June 1, 2005; 43(6): 2662 - 2667. [Abstract] [Full Text] [PDF]

				L. A. Boardman, C. Stanko, S. Weitzen, and C. J. Sung Atypical Squamous Cells of Undetermined Significance: Human Papillomavirus Testing in Adolescents Obstet. Gynecol., April 1, 2005; 105(4): 741 - 746. [Abstract] [Full Text] [PDF]

				T. Molden, I. Kraus, F. Karlsen, H. Skomedal, J. F. Nygard, and B. Hagmar Comparison of Human Papillomavirus Messenger RNA and DNA Detection: A Cross-sectional Study of 4,136 Women >30 Years of Age with a 2-Year Follow-up of High-Grade Squamous Intraepithelial Lesion Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 367 - 372. [Abstract] [Full Text] [PDF]

				S. S. Wang, M. Schiffman, and for The ALTS Group Medication Use, Medical Conditions, and the Risk of Human Papillomavirus Infection and Subsequent Cervical Intraepithelial Neoplasia 3 Among Women with Mild Cytologic Abnormalities Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 542 - 545. [Full Text] [PDF]

				J. Wallace, B. A. Woda, and G. Pihan Facile, Comprehensive, High-Throughput Genotyping of Human Genital Papillomaviruses Using Spectrally Addressable Liquid Bead Microarrays J. Mol. Diagn., February 1, 2005; 7(1): 72 - 80. [Abstract] [Full Text] [PDF]

				M. Schiffman, M. J. Khan, D. Solomon, R. Herrero, S. Wacholder, A. Hildesheim, A. C. Rodriguez, M. C. Bratti, C. M. Wheeler, R. D. Burk, et al. A Study of the Impact of Adding HPV Types to Cervical Cancer Screening and Triage Tests J Natl Cancer Inst, January 19, 2005; 97(2): 147 - 150. [Abstract] [Full Text] [PDF]

				M. Arbyn, J. Dillner, M. Van Ranst, F. Buntinx, P. Martin-Hirsch, and E. Paraskevaidis Re: Have We Resolved How To Triage Equivocal Cervical Cytology? J Natl Cancer Inst, September 15, 2004; 96(18): 1401 - 1402. [Full Text] [PDF]

				C. Y. Muller, J. O. Schorge, G. E. Tomlinson, and R. Ashfaq BRCAPAP: Feasibility of Clinical BRCA Testing on Liquid-Based Cervical Cytology: Implications for Biomarker Development Cancer Epidemiol. Biomarkers Prev., September 1, 2004; 13(9): 1534 - 1537. [Abstract] [Full Text] [PDF]

				R. Flores-Munguia, E. Siegel, W. T. Klimecki, and A. R. Giuliano Performance Assessment of Eight High-Throughput PCR Assays for Viral Load Quantitation of Oncogenic HPV Types J. Mol. Diagn., May 1, 2004; 6(2): 115 - 124. [Abstract] [Full Text] [PDF]

				S. J. Goldie, M. Kohli, D. Grima, M. C. Weinstein, T. C. Wright, F. X. Bosch, and E. Franco Projected Clinical Benefits and Cost-effectiveness of a Human Papillomavirus 16/18 Vaccine J Natl Cancer Inst, April 21, 2004; 96(8): 604 - 615. [Abstract] [Full Text] [PDF]

				C. M. Zahn Human Papillomavirus DNA Testing as an Adjunct in Primary Screening: Is It Prime Time? Obstet. Gynecol., April 1, 2004; 103(4): 617 - 618. [Full Text] [PDF]

				S. J. Goldie, J. J. Kim, and T. C. Wright Cost-Effectiveness of Human Papillomavirus DNA Testing for Cervical Cancer Screening in Women Aged 30 Years or More Obstet. Gynecol., April 1, 2004; 103(4): 619 - 631. [Abstract] [Full Text] [PDF]

				M. Arbyn, F. Buntinx, M. V. Ranst, E. Paraskevaidis, P. Martin-Hirsch, and J. Dillner Virologic Versus Cytologic Triage of Women With Equivocal Pap Smears: A Meta-analysis of the Accuracy To Detect High-Grade Intraepithelial Neoplasia J Natl Cancer Inst, February 18, 2004; 96(4): 280 - 293. [Abstract] [Full Text] [PDF]

				J. L. Benedet, J. P. Matisic, and M. A. Bertrand The Quality of Community Colposcopic Practice Obstet. Gynecol., January 1, 2004; 103(1): 92 - 100. [Abstract] [Full Text] [PDF]

				D. M. Harper, M. R. Longacre, W. W. Noll, D. R. Belloni, and B. F. Cole Factors Affecting the Detection Rate of Human Papillomavirus Ann. Fam. Med, November 1, 2003; 1(4): 221 - 227. [Abstract] [Full Text] [PDF]

				G. F. Sawaya, K. J. McConnell, S. L. Kulasingam, H. W. Lawson, K. Kerlikowske, J. Melnikow, N. C. Lee, G. Gildengorin, E. R. Myers, and A. E. Washington Risk of Cervical Cancer Associated with Extending the Interval between Cervical-Cancer Screenings N. Engl. J. Med., October 16, 2003; 349(16): 1501 - 1509. [Abstract] [Full Text] [PDF]

				M. E. Sherman, S. S. Wang, C. M. Wheeler, L. Rich, P. E. Gravitt, R. Tarone, and M. Schiffman Determinants of Human Papillomavirus Load among Women with Histological Cervical Intraepithelial Neoplasia 3: Dominant Impact of Surrounding Low-Grade Lesions Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 1038 - 1044. [Abstract] [Full Text] [PDF]

				N. F. Schlecht, R. W. Platt, E. Duarte-Franco, M. C. Costa, J. P. Sobrinho, J. C. M. Prado, A. Ferenczy, T. E. Rohan, L. L. Villa, and E. L. Franco Human Papillomavirus Infection and Time to Progression and Regression of Cervical Intraepithelial Neoplasia J Natl Cancer Inst, September 3, 2003; 95(17): 1336 - 1343. [Abstract] [Full Text] [PDF]

				P. E. Castle, A. T. Lorincz, D. R. Scott, M. E. Sherman, A. G. Glass, B. B. Rush, S. Wacholder, R. D. Burk, M. M. Manos, J. E. Schussler, et al. Comparison between Prototype Hybrid Capture 3 and Hybrid Capture 2 Human Papillomavirus DNA Assays for Detection of High-Grade Cervical Intraepithelial Neoplasia and Cancer J. Clin. Microbiol., September 1, 2003; 41(9): 4022 - 4030. [Abstract] [Full Text] [PDF]

				S. L. Kulasingam and E. R. Myers Potential Health and Economic Impact of Adding a Human Papillomavirus Vaccine to Screening Programs JAMA, August 13, 2003; 290(6): 781 - 789. [Abstract] [Full Text] [PDF]

				K. L. Noller, B. Bettes, S. Zinberg, and J. Schulkin Cervical Cytology Screening Practices Among Obstetrician-Gynecologists Obstet. Gynecol., August 1, 2003; 102(2): 259 - 265. [Abstract] [Full Text] [PDF]

				G Gallo, M Bibbo, L Bagella, A Zamparelli, F Sanseverino, M R Giovagnoli, A Vecchione, and A Giordano Study of viral integration of HPV-16 in young patients with LSIL J. Clin. Pathol., July 1, 2003; 56(7): 532 - 536. [Abstract] [Full Text] [PDF]

				M. E. Sherman Chapter 11: Future Directions in Cervical Pathology J Natl Cancer Inst Monographs, June 1, 2003; 2003(31): 72 - 79. [Abstract] [Full Text] [PDF]

				T. Iftner and L. L. Villa Chapter 12: Human Papillomavirus Technologies J Natl Cancer Inst Monographs, June 1, 2003; 2003(31): 80 - 88. [Abstract] [Full Text] [PDF]

				E. L. Franco Chapter 13: Primary Screening of Cervical Cancer With Human Papillomavirus Tests J Natl Cancer Inst Monographs, June 1, 2003; 2003(31): 89 - 96. [Abstract] [Full Text] [PDF]

				D. Solomon Chapter 14: Role of Triage Testing in Cervical Cancer Screening J Natl Cancer Inst Monographs, June 1, 2003; 2003(31): 97 - 101. [Abstract] [Full Text] [PDF]

				C. P. Crum, D. W. Abbott, and B. J. Quade Cervical Cancer Screening: From the Papanicolaou Smear to the Vaccine Era J. Clin. Oncol., May 15, 2003; 21(90100): 224s - 230. [Abstract] [Full Text] [PDF]

				Y. Chen, C. Miller, R. Mosher, X. Zhao, J. Deeds, M. Morrissey, B. Bryant, D. Yang, R. Meyer, F. Cronin, et al. Identification of Cervical Cancer Markers by cDNA and Tissue Microarrays Cancer Res., April 15, 2003; 63(8): 1927 - 1935. [Abstract] [Full Text] [PDF]

				M. E. Sherman, S. S. Wang, R. Tarone, L. Rich, and M. Schiffman Histopathologic Extent of Cervical Intraepithelial Neoplasia 3 Lesions in the Atypical Squamous Cells of Undetermined Significance Low-grade Squamous Intraepithelial Lesion Triage Study: Implications for Subject Safety and Lead-time Bias Cancer Epidemiol. Biomarkers Prev., April 1, 2003; 12(4): 372 - 379. [Abstract] [Full Text] [PDF]

				M. H. Schiffman and P. Castle Epidemiologic Studies of a Necessary Causal Risk Factor: Human Papillomavirus Infection and Cervical Neoplasia J Natl Cancer Inst, March 19, 2003; 95(6): E2 - E2. [Full Text]

				E. I. O. Garner Cervical Cancer: Disparities in Screening, Treatment, and Survival Cancer Epidemiol. Biomarkers Prev., March 1, 2003; 12(3): 242S - 247. [Full Text]

				N. M. Lonky, J. C. Felix, Y. M. Naidu, and G. Wolde-Tsadik Triage of Atypical Squamous Cells of Undetermined Significance With Hybrid Capture II: Colposcopy and Histologic Human Papillomavirus Correlation Obstet. Gynecol., March 1, 2003; 101(3): 481 - 489. [Abstract] [Full Text] [PDF]

				E. M. Burd Human Papillomavirus and Cervical Cancer Clin. Microbiol. Rev., January 1, 2003; 16(1): 1 - 17. [Abstract] [Full Text] [PDF]

M. E. Sherman, A. T. Lorincz, D. R. Scott, S. Wacholder, P. E. Castle, A. G. Glass, I. Mielzynska-Lohnas, B. B. Rush, and M. Schiffman Baseline Cytology, Human Papillomavirus Testing, and Risk for Cervical Neoplasia: A 10-Year Cohort Analysis J Natl Cancer Inst, January 1, 2003; 95(1): 46 - 52. [Abstract]