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National Cancer Institute Questions and AnswersNational Cancer Institute Questions and Answers
  • Posted: 02/20/2001
  • Updated: 10/18/2006

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ASCUS/LSIL Triage Study (ALTS) Findings: Questions and Answers

Puntos clave

  • What is ALTS? ALTS was a clinical trial designed to find the best way to manage the mild abnormalities that often show up on Pap tests. The study began enrolling patients in November 1996 and completed enrollment in December 1998. The ALTS trial concluded at the end of 2000. Over 30 publications have since resulted from this study. (Question 1)
  • What are ASCUS and LSIL? ASCUS and LSIL are acronyms for two mild abnormalities detected by Pap tests. ASCUS stands for atypical squamous cells of undetermined significance and LSIL for low-grade squamous intraepithelial lesion. (Question 2)
  • Why did NCI initiate ALTS? NCI initiated this trial to help resolve the controversy over what physicians and women should do about ASCUS and LSIL Pap test results. Most of these mild abnormalities will go away without treatment, but some may lead to a precancerous condition or cancer. (Question 3)
  • How was the study designed? Women who enrolled in the study were divided into those with ASCUS and those with LSIL diagnoses. Patients in each category were then assigned randomly to one of three groups or study arms. (Question 4)
  1. What is ALTS?
    ALTS was a clinical trial designed to find the best way to manage the mild abnormalities that often show up on Pap tests. The study began enrolling patients in November 1996 and completed enrollment in December 1998. The ALTS trial concluded at the end of 2000. Over 30 publications have since resulted from this study.

    ALTS, which stands for the ASCUS/LSIL Triage Study, was organized and funded by the National Cancer Institute (NCI), the U.S. government's principal agency for cancer research. It was conducted at four major medical centers: the University of Alabama at Birmingham; the University of Oklahoma in Oklahoma City; Magee-Womens Hospital of the University of Pittsburgh Medical Center in Pittsburgh, Pa.; and the University of Washington in Seattle.

  2. What are ASCUS and LSIL?
    ASCUS and LSIL are acronyms for two mild abnormalities detected by Pap tests. ASCUS stands for atypical squamous cells of undetermined significance and LSIL for low-grade squamous intraepithelial lesion.

    A diagnosis of ASCUS means that the nature of the abnormality is uncertain or equivocal. A diagnosis of LSIL means that there is a more definite, but still mild, abnormality.

  3. Why did NCI initiate ALTS?
    NCI initiated this trial to help resolve the controversy over what physicians and women should do about ASCUS and LSIL Pap test results. Most of these mild abnormalities will go away without treatment, but some may lead to a precancerous condition or cancer.

    The ALTS study looked at three different ways to manage ASCUS and LSIL: immediate colposcopy, conservative management, and HPV triage. Researchers compared the three different groups to learn: 1) how effective each management option is in early detection of the serious abnormalities that can progress to cancer; 2) how acceptable each option is to patients; and 3) how cost effective each option is.

  4. How was the study designed?
    Women who enrolled in the study were divided into those with ASCUS and those with LSIL diagnoses. Patients in each category were then assigned randomly to one of three groups or study arms.

    Immediate Colposcopy: Women in this arm were referred to colposcopy (examination with a magnifying instrument) to identify abnormal tissue for biopsy and, if necessary, treatment. This is the aggressive management option used commonly in the United States. Women in this arm, as in the others, also had a repeat Pap test every six months.

    Conservative Management: Women in this arm were closely followed with repeat Pap tests (or, to use the more scientific term, cervical cytology) every six months. Patients had a colposcopy and a biopsy only if the repeat Pap test results suggested they had more severe abnormalities. This conservative approach is now common in Canada and in some European countries.

    HPV Triage: Women in this arm were managed based on results of the Pap test plus a test for the human papillomavirus (HPV), which is the cause of most cervical cancers. If their Pap test showed more severe abnormalities or if their cervical cells contained DNA from certain HPV types associated with cancer, they had colposcopy. The HPV Triage arm tested the hypothesis that HPV testing is effective at determining which women with ASCUS need colposcopy.

  5. What are the main findings of ALTS?
    Following are some of the major findings of ALTS:

    • HPV testing is sensitive in detecting underlying precancerous lesions among women with a Pap test diagnosis of ASCUS. This study looked at the ALTS patients with ASCUS who were found to have a precancerous lesion when they underwent colposcopy and biopsy. Its purpose was to find out how sensitive HPV testing was at identifying these women compared to repeat Pap testing. The study found that HPV testing was 96-percent sensitive -- that is, it identified 96 percent of the women with ASCUS who had a precancerous lesion. The authors conclude that HPV testing is a viable option for the management of ASCUS.
    • HPV testing is not useful for women with a Pap test diagnosis of LSIL. This study focused on the 642 women in the ALTS study who had an LSIL diagnosis, seeking to determine whether HPV testing could be used to decide which of them needed to undergo colposcopy and which could wait, pending the outcome of a repeat Pap test in six months. The authors found that 82.9 percent of women with LSIL tested positive for HPV. They conclude that this high prevalence of HPV limits the usefulness of HPV testing in deciding how to manage LSIL.
    • Expert interpretations of Pap tests vary substantially. The purpose of this analysis was to determine how often pathologists agree in their interpretations of both Pap tests and cervical biopsy specimens. The researchers compared different pathologists' diagnoses of the thin-layer Pap tests and biopsy specimens that were collected when women enrolled in ALTS. They found substantial differences among expert pathologists in interpreting both thin-layer Pap tests and biopsies; agreement (reproducibility) was only moderate. They conclude that variability among experts in interpreting Pap tests and biopsies should be taken into consideration when using these interpretations and when developing standards of practice.
    • Colposcopically directed biopsy is not completely sensitive in detecting precancerous lesions. The sensitivity of the colposcopy procedure is increased when the colposcopist takes more than one biopsy.

    For more information, go to the Division of Cancer Prevention web site. http://www3.cancer.gov/prevention/alts/results.html

    Reference: Stoler, M.H. and Schiffman, M., Interobserver Reproducibility of Cervical Cytologic and Histologic Interpretations: Realistic Estimates From the ASCUS-LSIL Triage Study, Journal of the American Medical Association, 285(11), Mar. 21, 2001.