Randomized Clinical Trial on Clinical Management of ASCUS and LSIL (ALTS)

NCT01131312 | Completed Phase 3 Results FDA Device

• 2 other identifiers: 99990807608-C-N076
• Study Type: interventional
• Target: 5,060
• Locations: 1 country
• Sites: 3

Brief Summary

Approximately 65 million Pap smears are performed each year in the United States. The vast majority of results are negative (no abnormality identified) but about 5 percent to 8 percent are reported as abnormal. Most low-grade changes regress spontaneously; only a minority of such lesions would progress to a cancer precursor without treatment. However, there is no way to determine morphologically which patients are at risk or progression. Therefore, both high- and low-grade lesions were often managed with colposcopy and directed biopsy. Epidemiologic, virologic and molecular studies have clearly demonstrated that human papillomavirus (HPV) is the central cause of cervical cancer. The motivation for the Atypical squamous cells of undetermined significance (ASCUS)- Low grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS) trial was to use the information we have gained about the role of HPV to design better treatment and prevention strategies to reduce the burden of cervical cancer and its precursors. ALTS consisted of three management strategies: (1) immediate colposcopy of all women; (2) repeat cytology with colposcopy only if the results show a high grade lesion; and (3) HPV testing and repeat cytology in combination, with referral to colposcopy if either the HPV test is positive or the cytology shows a high grade lesion. Four Clinical Centers University of Alabama, Birmingham Alabama (AL); Magee-Womens Hospital, Pittsburgh Pennsylvania (PA); University of Oklahoma, Oklahoma City OK; and University of Washington, Seattle Washington (WA) enrolled approximately 5,000 women with recent diagnosis of ASCUS or LSIL. Participants were followed at six month intervals for a total of 2 years. The ALTS database and ALTS specimens continue to be a valuable research resource in studies of cervical cancer precursors, screening tests, visual assessment of the cervix and investigation of biomarkers.

Conditions

Cervical Intraepithelial Neoplasia

Keywords

Cervix; CIN; HPV; Triage; ASCUS/LSIL; Pap Smear; HPV Test

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Cervical Intraepithelial Neoplasia III (CIN III)

  A cervical exam, pap test, human papilloma virus (HPV) deoxyribonucleic acid (DNA) test, and/or colposcopy was performed to detect whether or not a participant had CINIII. CINIII is defined as moderate or severe dysplasia or abnormal cells located on the cervix that can lead to cancer.

  up to 2 years

Secondary Outcomes (1)

• Percentage of Participants With Cumulative Detection of Clinical Center Histologically Confirmed Cervical Intraepithelial Neoplasia 2 (CIN2) and Above (High Grade Lesion) Over the 2 Years of the Trial.

  up to 2 years

Study Arms (3)

Cytology

EXPERIMENTAL

Referred to colposcopy if cytology is high grade

Device: Thinprep

Human Papillomavirus (HPV)

EXPERIMENTAL

Referred to colposcopy if cytology is high grade or HPV +

Device: Hybrid capture 2

Colposcopy

EXPERIMENTAL

All refer to colposcopy

Procedure: Colposcopy

Interventions

Thinprep DEVICE

Pap test

Cytology

Hybrid capture 2 DEVICE

Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Test

Human Papillomavirus (HPV)

Colposcopy PROCEDURE

Procedure performed by a healthcare practitioner to examine the cervix, vagina, and vulva.

Colposcopy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL)
• years or older
• Able to give informed consent with reasonable likelihood of follow-up

You may not qualify if:

• Previous Hysterectomy
• History of excisional or ablative treatment of cervix, such as laser treatment, radiation therapy, cauterization (burning), freezing or surgery such as cone biopsy or loop electrosurgical excision procedure (LEEP).
• Already known to be pregnant
• Already known to be human immunodeficiency virus (HIV) positive (HIV may negatively affect the clinical history of human papillomavirus (HPV), making triage less appropriate.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

University of Oklahoma

Oklahoma City, Oklahoma, 73019, United States

Location

Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (3)

• Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, zur Hausen H. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J. 1984 May;3(5):1151-7. doi: 10.1002/j.1460-2075.1984.tb01944.x.

  PMID: 6329740 BACKGROUND

• Cox JT, Lorincz AT, Schiffman MH, Sherman ME, Cullen A, Kurman RJ. Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologic diagnosis of atypical squamous cells of undetermined significance. Am J Obstet Gynecol. 1995 Mar;172(3):946-54. doi: 10.1016/0002-9378(95)90026-8.

  PMID: 7892889 BACKGROUND

• Dyson N, Howley PM, Munger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989 Feb 17;243(4893):934-7. doi: 10.1126/science.2537532.

  PMID: 2537532 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Interventions

Colposcopy

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Obstetrical and Gynecological; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Obstetric Surgical Procedures; Gynecologic Surgical Procedures; Urogenital Surgical Procedures

Results Point of Contact

• Title: Dr. Mark Schiffman
• Organization: National Cancer Institute

schiffmm@nih.gov

240-276-7259

Study Officials

• Mark H Schiffman, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Computer random assignment to HPV testing (HC2), cytology (ThinPrep), or immediate colposcopy.
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 25, 2010
• First Posted: May 26, 2010
• Study Start: February 20, 2008
• Primary Completion: February 5, 2009
• Study Completion: February 5, 2009
• Last Updated: November 20, 2018
• Results First Posted: November 20, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: Now and indefinitely.
• Access Criteria: The images are saved in encrypted files and shared under individual password protection. Images will only be shared with bonafide researchers who are verified and complete a pilot.

Locations

US (3)