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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01131312
First received: May 25, 2010
Last updated: August 1, 2014
Last verified: July 2014
  Purpose

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. It was anticipated that determining alternative management strategies would yield important potential benefits including fewer medical complications from over treatment, reduced patient anxiety associated with referral for cytologic abnormalities, as well as cost savings.

Epidemiologic, virologic and molecular studies have clearly demonstrated that human papillomavirus (HPV) is the central cause of cervical cancer. The motivation for the 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 AL; Magee-Womens Hospital, Pittsburgh PA; University of Oklahoma, Oklahoma City OK; and University of Washington, Seattle 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 main results from ALTS showed that for women with ASCUS cytology, HPV triage was at least as safe as universal immediate colposcopy in the detection of high-grade lesion and would allow approximately half of women to return to routine follow up without additional procedures (colposcopy). No efficient triage strategy was identified for women with LSIL cytology.

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.


Condition Phase
Cervical Intraepithelial Neoplasia
Cervical Smears
HPV DNA Probes
Phase 3

Study Type: Observational
Official Title: Randomized Clinical Trial on Clinical Management of ASCUS and LSIL (ALTS)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Cumulative detection of pathology QC histologically confirmed CIN3 (cervical precancer) over the 2 years of the trial.

Secondary Outcome Measures:
  • Cumulative detection of clinical center histologically confirmed CIN2 and above (high grade lesion) over the 2 years of the trial.

Estimated Enrollment: 5060
Study Start Date: February 2008
Detailed Description:

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 of progression. Therefore, both high- and low-grade lesions were often managed with colposcopy and directed biopsy. It was anticipated that determining alternative management strategies would yield important potential benefits including fewer medical complications from over treatment, reduced patient anxiety associated with referral for cytologic abnormalities, as well as cost savings.

Epidemiologic, virologic and molecular studies have clearly demonstrated that human papillomavirus (HPV) is the central cause of cervical cancer. The motivation for the 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 AL; Magee-Womens Hospital, Pittsburgh PA; University of Oklahoma, Oklahoma City OK; and University of Washington, Seattle 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 main results from ALTS showed that for women with ASCUS cytology, HPV triage was at least as safe as universal immediate colposcopy in the detection of high-grade lesion and would allow approximately half of women to return to routine follow up without additional procedures (colposcopy). No efficient triage strategy was identified for women with LSIL cytology.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • Inclusion Criteria:

Diagnosis of ASCUS or LSIL

18 years or older

Able to give informed consent with reasonable likelihood of follow-up

Exclusion Criteria:

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 LEEP.

Already known to be pregnant

Already known to be HIV positive (HIV may negatively affect the clinical history of HPV, making triage less appropriate.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01131312

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
Magee Womens Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Investigators
Principal Investigator: Mark H Schiffman, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01131312     History of Changes
Other Study ID Numbers: 999908076, 08-C-N076
Study First Received: May 25, 2010
Last Updated: August 1, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
HPV Test
Cervix
Cytology
Triage
Pap Smear

Additional relevant MeSH terms:
Carcinoma in Situ
Cervical Intraepithelial Neoplasia
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on October 22, 2014