Randomized Clinical Trial on Clinical Management of ASCUS and LSIL (ALTS)
Condition: Cervical Intraepithelial Neoplasia
MeSH terms: Uterine Cervical Dysplasia
Intervention: Thinprep; Hybrid capture 2; Colposcopy
Intervention description: Pap test; Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Test; Procedure performed by a healthcare practitioner to examine the cervix, vagina, and vulva.
Phase: Phase 3
Study type: Interventional
Primary purpose: Screening
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Masking description: Computer random assignment to HPV testing (HC2), cytology (ThinPrep), or immediate colposcopy.
Enrollment: 5060.0
Sex: Female
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Cervix; CIN; HPV; Triage; ASCUS/LSIL; Pap Smear; HPV Test

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.
    

Eligibility criteria:

        -  Inclusion Criteria:

               -  Diagnosis of atypical squamous cells of undetermined significance (ASCUS) or
                  low-grade squamous intraepithelial lesion (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
             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.