Randomized Clinical Trial on Clinical Management of ASCUS and LSIL (ALTS)
Condition: Cervical Intraepithelial Neoplasia
MeSH terms: Uterine Cervical Dysplasia
Study type: Interventional
Phase: Phase 3

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.
    

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.
    

Intervention name(s): Thinprep; Hybrid capture 2; Colposcopy
Intervention type(s): Device; Device; Procedure
Intervention description(s): Pap test; Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Test; Procedure performed by a healthcare practitioner to examine the cervix, vagina, and vulva.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Screening
Keywords: Cervix; CIN; HPV; Triage; ASCUS/LSIL; Pap Smear; HPV Test