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

Phase 3
18 Years
Not Enrolling
Cervical Intraepithelial Neoplasia, Cervical Smears, HPV DNA Probes

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Trial Information

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

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

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.


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.

Type of Study:


Study Design:


Outcome Measure:

Cumulative detection of pathology QC histologically confirmed CIN3 (cervical precancer) over the 2 years of the trial.

Principal Investigator

Mark H Schiffman, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

February 2008

Completion Date:

Related Keywords:

  • Cervical Intraepithelial Neoplasia
  • Cervical Smears
  • HPV DNA Probes
  • HPV Test
  • Cervix
  • Cytology
  • Triage
  • Pap Smear
  • Neoplasms
  • Cervical Intraepithelial Neoplasia
  • Carcinoma in Situ



University of Alabama Birmingham, Alabama  
University of Oklahoma Oklahoma City, Oklahoma  73190
University of Washington Seattle, Washington  98195
Magee Womens Hospital Pittsburgh, Pennsylvania  15213