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 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.

Sex

Female

Minimum age

18 Years

Maximum age

100 Years

* 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.

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• BACKGROUNDCox JT, Lorincz AT, Schiffman MH, Sherman ME, Cullen A, Kurman RJ. Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologic diagnosis of atypical squamous cells of undetermined significance. Am J Obstet Gynecol. 1995 Mar;172(3):946-54. doi: 10.1016/0002-9378(95)90026-8. PMID 7892889
• BACKGROUNDDyson N, Howley PM, Munger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989 Feb 17;243(4893):934-7. doi: 10.1126/science.2537532. PMID 2537532